U.S. Markets for Wound Management Products

Transcription

U.S. Markets for
Wound Management Products
#RP-181303
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Table of Contents
EXECUTIVE SUMMARY............................................................................................... ES-1
1.
i.
Cleansing Agents and Patient Preparation Supplies,
Cleansing and Debridement Agents............................................................ ES-2
ii.
Wound Closure Devices.............................................................................. ES-6
iii.
Hydrogel Dressings ..................................................................................... ES-6
iv.
Pressure-Relief and Pressure-Reduction Equipment .................................. ES-9
MARKET OVERVIEW .......................................................................................... 1-1
1.1
Impacts of Managed Care .............................................................................. 1-1
1.1.1
1.2
Innovation in Perspective ............................................................................... 1-3
1.3
Purchasing Environment ................................................................................ 1-3
1.3.1
Outcomes Studies......................................................................... 1-5
1.4
Medicare......................................................................................................... 1-5
1.5
Minimally Invasive Surgery........................................................................... 1-7
1.6
Hospital and Alternate Site Markets .............................................................. 1-9
1.7
2.
Differentiation to Commoditization ............................................. 1-2
1.6.1
Hospitals....................................................................................... 1-9
1.6.2
Physician Networks and Ambulatory Care ................................ 1-10
1.6.3
Nursing Homes .......................................................................... 1-10
1.6.4
Home Health Care...................................................................... 1-11
1.6.5
Subacute Care Facilities ............................................................. 1-12
1.6.6
Wound Care Centers .................................................................. 1-13
The FDA ...................................................................................................... 1-15
CLINICAL ISSUES ................................................................................................. 2-1
2.1
2.2
Anatomy and Physiology of Soft Tissue........................................................ 2-1
2.1.1
Epidermis ..................................................................................... 2-2
2.1.2
Dermis .......................................................................................... 2-2
2.1.3
Subcutaneous Tissue .................................................................... 2-3
2.1.4
Normal Skin Changes Associated with Aging............................. 2-3
Types of Wound ............................................................................................. 2-4
2.2.1
©1997, Medtech Insight, LLC
Surgical Wounds .......................................................................... 2-4
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2.2.2
Trauma-Induced Injuries ............................................................ 2-10
2.2.3
Burns .......................................................................................... 2-10
2.2.3.1
Classification of Burns .......................................... 2-12
2.2.3.2
Therapeutic Intervention for Burns ....................... 2-14
2.2.4
Proliferative Scars ...................................................................... 2-17
2.2.5
Pressure Ulcers........................................................................... 2-18
2.2.6
2.2.5.1
Staging of Pressure Ulcers .................................... 2-18
2.2.5.2
Incidence of Pressure Ulcers ................................. 2-19
2.2.5.3
Therapeutic Intervention for Pressure Ulcers ....... 2-20
Venous Ulcers ............................................................................ 2-21
2.2.6.1
2.2.7
Arterial Ulcers ............................................................................ 2-23
2.2.7.1
2.3
2.4
Therapeutic Intervention for Venous Ulcers......... 2-23
Diabetic Ulcers...................................................... 2-24
2.2.8
Amputations ............................................................................... 2-24
2.2.9
Acquired Immune Deficiency Syndrome .................................. 2-24
Wound Healing Biological Factors .............................................................. 2-25
2.3.1
Inflammatory Phase ................................................................... 2-26
2.3.2
Proliferative Phase ..................................................................... 2-27
2.3.3
Maturation Phase........................................................................ 2-28
Complications Affecting Wound Healing.................................................... 2-28
2.4.1
2.4.2
Local Factors .............................................................................. 2-29
2.4.1.1
Surgical Technique ............................................... 2-29
2.4.1.2
Blood Supply......................................................... 2-29
2.4.1.3
Hypoxia ................................................................. 2-29
2.4.1.4
Infection ................................................................ 2-29
2.4.1.5
Radiation ............................................................... 2-30
Systemic Factors ........................................................................ 2-30
2.4.2.1
Advanced Age ....................................................... 2-30
2.4.2.2
Nutritional Status .................................................. 2-31
2.4.2.3
Pharmacological Medications ............................... 2-31
2.4.2.4
Diabetes and Other Diseases ................................. 2-32
2.4.2.5
Emotional Stress ................................................... 2-32
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Table of Contents
3.
CLEANSING, DEBRIDEMENT AND GRANULATION AGENTS ................. 3-1
3.1
3.2
4.
Cleansing Agents ........................................................................................... 3-1
3.1.1
Common Cleansing Agents ......................................................... 3-4
3.1.2
Drug-Resistant Bacteria and the Effects
of Wound Cleaners....................................................................... 3-4
3.1.3
Competitors and Products ............................................................ 3-5
3.1.4
Market Analysis ........................................................................... 3-5
3.1.5
Competitive Analysis ................................................................... 3-8
Debridement and Granulation Agents............................................................ 3-8
3.2.1
Mechanical Debridement ............................................................. 3-8
3.2.2
Autolytic Debridement............................................................... 3-10
3.2.3
Enzymatic/Chemical Debridement ............................................ 3-11
3.2.3.1
Competitors and Products ..................................... 3-11
3.2.3.2
Enzymatic/Chemical Debridement
Development Status .............................................. 3-14
3.2.3.3
Market Analysis .................................................... 3-14
3.2.3.4
Competitive Analysis ............................................ 3-15
WOUND CLOSURE DEVICES ............................................................................. 4-1
4.1
4.2
Needled and Non-Needled Sutures ................................................................ 4-1
4.1.1
4.1.2
Development Status ..................................................................... 4-3
4.1.3
Market Analysis ........................................................................... 4-4
4.1.4
Competitive Analysis ................................................................... 4-4
Tissue Glues ................................................................................................... 4-6
4.2.1
Pooled Plasma-Derived Sealants ................................................. 4-9
4.2.2
Autologous-Processed Sealants ................................................. 4-10
4.2.3
Collagen-Based Sealants ............................................................ 4-11
4.2.4
Cyanoacrylate-Based Sealants ................................................... 4-12
4.2.5
Polymer-Based Sealants............................................................. 4-13
4.2.6
Recombinant and Genetically Engineered Sealants................... 4-14
4.3
Delivery of Fibrin Glue ................................................................................ 4-14
4.4
Market Potential of Tissue Glues ................................................................. 4-14
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Table of Contents
5.
WOUND DRESSINGS ............................................................................................ 5-1
5.1
Non-Occlusive Dressings............................................................................... 5-3
5.1.1
5.2
Occlusive Dressings ....................................................................................... 5-5
5.2.1
5.2.2
5.2.3
5.2.4
5.2.5
6.
Film Dressings ............................................................................. 5-5
5.2.1.1
Market Analysis ...................................................... 5-6
5.2.1.2
Competitive Analysis .............................................. 5-6
Hydrogel Dressings ...................................................................... 5-9
5.2.2.1
Market Analysis ...................................................... 5-9
5.2.2.2
Hydrocolloid Dressings.............................................................. 5-13
5.2.3.1
Market Analysis .................................................... 5-16
5.2.3.2
Foam Dressings .......................................................................... 5-21
5.2.4.1
Market Analysis .................................................... 5-21
5.2.4.2
Calcium Alginates ...................................................................... 5-26
5.2.5.1
Market Analysis .................................................... 5-26
5.2.5.2
SYNTHETIC/BIOSYNTHETIC DRESSINGS AND SKIN
REPLACEMENTS .................................................................................................. 6-1
6.1
Autologous Skin Grafts and Flaps ................................................................. 6-1
6.2
Synthetic and Biosynthetic Dressings ............................................................ 6-1
6.3
6.2.1
6.2.2
Synthetic/Biosynthetic Dressing Market Analysis ...................... 6-3
Skin Replacements and Substitutes................................................................ 6-7
6.3.1
Regulatory Status ......................................................................... 6-7
6.3.2
6.3.2.1
Advanced Tissue Sciences ...................................... 6-9
6.3.2.2
Genzyme Tissue Repair .......................................... 6-9
6.3.2.3
LifeCell ................................................................. 6-10
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6.3.2.4
6.3.3
6.3.4
7.
Development Status ................................................................... 6-12
6.3.3.1
Organogenesis ....................................................... 6-12
6.3.3.2
Ortec ...................................................................... 6-13
6.3.3.3
Purdue University ................................................. 6-14
Skin Replacement and Substitute Market Analysis ................... 6-15
GROWTH FACTORS............................................................................................. 7-1
7.1
Normal Effects of Growth Factors ................................................................. 7-2
7.2
Categorization of Growth Factors .................................................................. 7-4
7.3
7.2.1
Fibroblast Growth Factors ........................................................... 7-5
7.2.2
Transforming Growth Factors...................................................... 7-7
7.2.3
Epidermal Growth Factor............................................................. 7-8
7.2.4
Platelet-Derived Growth Factors ................................................. 7-9
7.2.5
Platelet-Derived Wound Healing Formula .................................. 7-9
7.2.6
Insulin-like Growth Factors ....................................................... 7-10
7.2.7
Interleukins................................................................................. 7-12
7.2.8
Other Growth Factors................................................................. 7-12
Development Status ..................................................................................... 7-13
7.3.1
7.4
8.
Integra LifeScience ............................................... 6-12
Concerns about Growth Factors................................................. 7-13
Growth Factor Market Potential .................................................................. 7-14
INSTRUMENTED WOUND HEALING .............................................................. 8-1
8.1
Compression Devices..................................................................................... 8-1
8.1.1
Passive Compression.................................................................... 8-1
8.1.2
Sequential Compression Devices ................................................. 8-4
8.1.3
Dynamic Compression Devices ................................................... 8-4
8.2
Whirlpool Therapy Devices ........................................................................... 8-5
8.3
Lavage Devices .............................................................................................. 8-6
8.4
Electrical Stimulation Products...................................................................... 8-7
8.5
Electromagnetic Stimulation Devices ............................................................ 8-9
8.6
Ultraviolet Wound Healing Devices ............................................................ 8-10
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9.
8.7
Hyperbaric Oxygen Chambers ..................................................................... 8-10
8.8
Mechanically Assisted Wound Healing Devices ......................................... 8-11
8.9
Thermography .............................................................................................. 8-13
8.10
Emerging Technologies ............................................................................... 8-14
Ultrasonic Wound Healing Devices........................................... 8-14
8.10.2
Laser-Based Wound Healing Devices ....................................... 8-16
PRESSURE RELIEF AND PRESSURE REDUCTION EQUIPMENT ............ 9-1
9.1
9.2
10.
8.10.1
Developmental Considerations ...................................................................... 9-2
9.1.1
Pressure ........................................................................................ 9-2
9.1.2
Shear............................................................................................. 9-3
9.1.2.1
Patient Movement ................................................... 9-3
9.1.2.2
Nurse Movement of Patient .................................... 9-3
9.1.2.3
Bed Movement ........................................................ 9-4
9.1.3
Support Surface Requirements..................................................... 9-4
9.1.4
Pressure Relief versus Pressure Reduction .................................. 9-7
Specialty Beds ................................................................................................ 9-7
9.2.1
Air-Fluidized Beds ....................................................................... 9-7
9.2.2
Low Airloss Beds ......................................................................... 9-8
9.3
Mattress Replacements .................................................................................. 9-8
9.4
Mattress Overlays .......................................................................................... 9-8
9.5
Market Analyses ............................................................................................ 9-9
9.5.1
Specialty Bed Market Analysis .................................................. 9-10
9.5.2
Specialty Bed Competitive Analysis.......................................... 9-12
9.5.3
Mattress Replacement Market Analysis .................................... 9-15
9.5.4
Mattress Replacement Competitive Analysis ............................ 9-15
9.5.5
Mattress Overlay Market Analysis ............................................ 9-16
9.5.6
Mattress Overlay Competitive Analysis .................................... 9-21
COMPANY PROFILES ........................................................................................ 10-1
10.1
3M Corporation ............................................................................................ 10-1
10.2
Advanced Tissue Sciences, Inc. ................................................................... 10-2
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10.3
Bristol-Myers Squibb Company/ConvaTec ................................................. 10-3
10.4
Cardio Systems ............................................................................................ 10-4
10.5
Carrington Laboratories, Inc. ....................................................................... 10-5
10.6
Coloplast Corporation .................................................................................. 10-6
10.7
ConMed Corporation ................................................................................... 10-8
10.8
C.R. Bard, Inc. ............................................................................................. 10-9
10.9
Cryolife, Inc. .............................................................................................. 10-10
10.10 Curative Health Services, Inc..................................................................... 10-11
10.11 Genzyme Tissue Repair ............................................................................. 10-12
10.12 Haemacure Corporation ............................................................................. 10-13
10.13 Hillenbrand Industries/Hill-Rom ............................................................... 10-14
10.14 Integra LifeSciences Corporation .............................................................. 10-15
10.15 Invacare Corporation.................................................................................. 10-16
10.16 Johnson & Johnson .................................................................................... 10-19
10.17 Kinetic Concepts, Inc. ................................................................................ 10-20
10.18 LifeCell Corporation .................................................................................. 10-20
10.19 Mylan Laboratories, Inc./Dow Hickam Pharmaceuticals .......................... 10-22
10.20 Organogenesis, Inc. .................................................................................... 10-23
APPENDIX: COMPANY LISTING ................................................................................ A-1
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List of Exhibits
Exhibit ES-1:
1996 Wound Incidence by Etiology in the United States ..................... ES-3
Exhibit ES-2:
U.S. Wound Cleanser Market Forecast, 1996-2002 ............................. ES-4
Exhibit ES-3:
U.S. Chemical/Enzymatic Debridement Market Forecast,
1996-2002 ............................................................................................. ES-5
Exhibit ES-4:
U.S. Suture Market Forecast, 1996-2002.............................................. ES-7
Exhibit ES-5:
U.S. Hydrogel Dressing Market Forecast, 1996-2002 .......................... ES-8
Exhibit ES-6:
U.S. Pressure-Relief and Pressure-Reduction Market
Forecast, 1996-2002 ............................................................................ ES-10
Exhibit 1-1:
Sales Approaches in a Managed Care Environment ................................ 1-4
Exhibit 1-2:
Surgical Dressing Durable Medical Equipment Regional Carrier
Utilization Guidelines .............................................................................. 1-6
Exhibit 1-3:
U.S. Rate of Conversion Rate to Endoscopic or Other Minimally
Invasive Surgeries by 2000 ...................................................................... 1-8
Exhibit 2-1:
Classification of Wounds by Severity...................................................... 2-5
Exhibit 2-2:
Classification of Wounds by Morphology ............................................... 2-6
Exhibit 2-3:
Classification of Wounds by Etiology ..................................................... 2-7
Exhibit 2-4:
1996, Wound Incidence by Etiology in the United States ....................... 2-8
Exhibit 2-5:
Incidence of Wound Care Procedures, 1994............................................ 2-9
Exhibit 2-6:
Types of Burns Referred to Burn Centers.............................................. 2-11
Exhibit 2-7:
Lund and Browder Chart for Measuring Extent of Burn Wounds......... 2-13
Exhibit 2-8:
Classification of Burns According to Mechanisms of Injury ................ 2-15
Exhibit 2-9:
An Ideal Dressing................................................................................... 2-22
Exhibit 3-1:
Recommendations for Wound Cleaning .................................................. 3-2
Exhibit 3-2:
Evaluation of Irrigation Device................................................................ 3-3
Exhibit 3-3:
Selected Manufacturers of Wound Cleansers .......................................... 3-6
Exhibit 3-4:
U.S. Wound Cleanser Market Forecast, 1996-2002 ................................ 3-7
Exhibit 3-5:
1996 Wound Cleanser Market, Share by Supplier................................... 3-9
Exhibit 3-6:
Chemical/Enzymatic Debridement Agents ............................................ 3-13
Exhibit 3-7:
U.S. Chemical/Enzymatic Debridement Market
Forecast, 1996-2002 ............................................................................... 3-16
Exhibit 3-8:
1996 Chemical/Enzymatic Debridement Market,
Share by Supplier ................................................................................... 3-17
Exhibit 4-1:
U.S. Suture Market Forecast, 1996-2002................................................. 4-5
Exhibit 4-2:
1996 Suture Market, Share by Supplier ................................................... 4-7
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List of Exhibits
Exhibit 5-1:
Selected Manufacturers of Gauze and Impregnated
Gauze Dressings....................................................................................... 5-4
Exhibit 5-2:
U.S. Film Dressing Market Forecast, 1996-2002 .................................... 5-7
Exhibit 5-3:
Selected Manufacturers of Film Dressings .............................................. 5-8
Exhibit 5-4:
1996 Film Dressings, Share by Supplier................................................ 5-10
Exhibit 5-5:
U.S. Hydrogel Dressing Market Forecast, 1996-2002 ........................... 5-11
Exhibit 5-6:
Selected Manufacturers of Hydrogel Dressings..................................... 5-14
Exhibit 5-7:
1996 Hydrogel Dressings, Share by Supplier ........................................ 5-15
Exhibit 5-8:
U.S. Hydrocolloid Dressing Market Forecast, 1996-2002..................... 5-17
Exhibit 5-9:
Selected Manufacturers of Hydrocolloid Dressings .............................. 5-19
Exhibit 5-10:
1996 Hydrocolloid Dressing Market, Share by Supplier ....................... 5-20
Exhibit 5-11:
U.S. Foam Dressing Market Forecast, 1996-2002 ................................. 5-22
Exhibit 5-12:
Selected Manufacturers of Foam Dressings........................................... 5-24
Exhibit 5-13:
1996 Foam Dressings, Share by Supplier .............................................. 5-25
Exhibit 5-14:
U.S. Alginate Market Forecast, 1996-2002 ........................................... 5-27
Exhibit 5-15:
Selected Manufacturers of Alginates ..................................................... 5-29
Exhibit 5-16:
1996 Alginate Dressing Market, Share by Supplier ............................. 5-30
Exhibit 6-1:
U.S. Synthetic/Biosynthetic Dressing Market Forecast,
1996-2002 ................................................................................................ 6-5
Exhibit 6-2:
1996 Synthetic/Biosynthetic Dressing Market,
Share by Supplier ..................................................................................... 6-6
Exhibit 6-3:
U.S. Skin Replacement and Substitute Market Forecast,
1996-2002 .............................................................................................. 6-16
Exhibit 6-4:
1996 Skin Replacement and Substitute Market,
Share by Supplier ................................................................................... 6-17
Exhibit 7-1:
Sequence of Biological Events in the Repair of Soft Tissues .................. 7-3
Exhibit 8-1:
U.S. Market for Instrumented Wound Healing Devices,
1996 and 2002 .......................................................................................... 8-2
Exhibit 8-2:
Selected Manufacturers of Pulsed Lavage Systems................................. 8-8
Exhibit 8-3:
Selected Manufacturers of Hyperbaric Oxygen Chambers.................... 8-12
Exhibit 8-4:
Selected Manufacturers of Thermography Systems .............................. 8-15
Exhibit 9-1:
U.S. Specialty Bed Market Forecast, 1996-2002 ................................... 9-11
Exhibit 9-2:
Selected Manufacturers of Specialty Beds............................................. 9-13
Exhibit 9-3:
1996 Specialty Bed Market, Share by Supplier ..................................... 9-14
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List of Exhibits
Exhibit 9-4:
U.S. Mattress Replacement Market Forecast, 1996-2002 ..................... 9-17
Exhibit 9-5:
Selected Manufacturers of Mattress Replacements ............................... 9-18
Exhibit 9-6:
1996 Mattress Replacement Market, Share by Supplier ........................ 9-19
Exhibit 9-7:
U.S. Mattress Overlay Market Forecast, 1996-2002 ............................. 9-20
Exhibit 9-8:
Selected Manufacturers of Mattress Overlays ....................................... 9-22
Exhibit 9-9:
1996 Mattress Overlay Market, Share by Supplier ................................ 9-24
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Executive Summary
EXECUTIVE SUMMARY
This report examines the market in the United States for wound care products, including
wound cleansers, debridement agents, wound closure products, wound dressings, skin
replacements, growth factors, instrumented technologies and pressure-relieving equipment,
from the year 1996 to the year 2002. Each of these markets is discussed in detail, with special
attention given to current practices, products in development, competitors and market
forecasts.
Many wound care products have undergone a gradual transition from specialty to commodity
products, but in certain segments, the industry has fought against commodization and
resultant pricing pressures. Many manufacturers of dressings successfully resisted some of
the pressure by focusing on products that promoted healing in moist environments. This
technological innovation, however, invited new companies into the dressing market which
produced fierce competition with even more pricing pressure in the various dressing
segments.
Managed care has also had a major effect on most wound care markets. With managed care,
the hospital knows what its revenues for the year will be and expects its providers to manage
the costs of that care. When working as a cost center instead of a revenue center, the
paradigm of care moves from a treat/repair mode to a prevention/treatment/rehabilitation
model. Manufacturers of wound care products must, therefore, be able to demonstrate that
their products are more cost effective and provide better outcomes.
Minimally invasive surgery (MIS) is having an impact on the wound market due to the
smaller size and severity of wounds in these procedures. As fewer large incisions are made,
fewer large dressings are required. It is likely that the move to less invasive procedures will
also lower the number of infections and hard-to-heal wounds which occasionally result from
surgical procedures. This trend will certainly have major impact for the suture segment of the
market because; minimally invasive procedures require fewer sutures.
As the average life expectancy grows and the number of elderly persons increase in the
United States, patients with chronic wounds are expected to significantly increase as shown
in Exhibit ES-1. Arterial and diabetic ulcers are expected to grow at an annual rate of 14%,
and the cost for diabetic ulcer treatment is approximately $16-$21 billion per year. Pressure
ulcers are also costly to treat, with annual expenditures for these types of wounds at
ES-1
#RP-181303
Executive Summary
approximately $3 billion per year. While there were about 2.9 million persons with pressure
ulcers in 1996, approximately 2 million of these were preventable.
i.
Cleansing Agents and Patient Preparation Supplies, Cleansing and
Debridement Agents
Prior to any invasive intervention, and as an adjunct to any therapeutic management of
wounds and ulcers, the skin and wound must be cleansed. In addition, debridement of
devitalized tissue, especially in traumatic injuries, must be completed before wound closure
and healing can occur. Several different types of products are used to accomplish these goals,
including cleansing, debridement and granulation agents.
Open wounds have delicate wound beds, and must be handled with care. A variety of
appropriate methods and cleaning agents are used to cleanse skin, wounds and ulcers. The
caregiver must take care in the choice of these agents as the very act of cleansing the wound
could cause harm. Before cleansing the wound, the clinician must weigh the potential for
traumatizing the wound bed against the benefits of a clean wound. In addition, due to the
increased incidence of drug-resistant bacteria, wound care experts are adhering to stringent
infection control and exercising judicious use of antibiotic cleansers. As the cytotoxicity of
these traditional cleansers becomes more evident, the market for cleansers is expected to
increase at an annual growth rate of 13.6% as shown in Exhibit ES-2.
Chemical and enzymatic debridement agents are experiencing less growth than cleansers
because their use is limited by the increased utilization of surgical debridement, which helps
decrease the patients length of stay in hospitals. As shown in Exhibit ES-3, chemical and
enzymatic debridement agents are expected to grow at a modest 3.6%, from $74.2 million in
1996 to $91.0 million in 2002. While discount pricing will also limit this market, a more
important trend will be the influence of managed care. In this environment, providers will
quickly determine which products only require application once per day. Nursing homes
must reduce the time allocated for skilled care, while home health agencies will adopt care
paths that will focus on the ability of a home caregiver to reduce the number of skilled visits.
ES-2
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Executive Summary
Exhibit ES-1: 1996 Wound Incidence by Etiology (Chronic and Acute) in the United States
Wound Type
Surgical wounds
Traumatic wounds
Percentage of Annual
Total
Growth Rate
Incidence
24,370,000
725,000
44.3%
1.3
3.0%
1.2
Burn wounds (non-hospitalized)
Burn wounds (hospitalized)
1,200,000
680,000
2.2
1.2
1.0
1.0
Pressure ulcers
Venous ulcers
Arterial/diabetic ulcers
2,900,000
1,250,000
2,350,000
5.3
2.3
4.3
5.0
6.0
14.0
530,000
1.0
0.8
Procedure-based wounds
21,000,000
38.2
3.0
Total
55,005,000
100.0
3.5
Amputations
Source: Medtech Insight, LLC
ES-3
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Executive Summary
Exhibit ES-2: U.S. Wound Cleanser Market Forecast, 1996-2002
Year
Sales
Growth
1996
1997
1998
1999
2000
2001
2002
$16.4M
18.5
21.2
24.6
28.1
31.5
35.0
—
12.8%
14.6
16.0
14.2
12.1
11.1
CAGR 1997-2002
13.6%
ES-4
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Executive Summary
Exhibit ES-3: U.S. Chemical/Enzymatic Debridement Market Forecast, 1996-2002
Year
Sales
Growth
1996
1997
1998
1999
2000
2001
2002
$74.2M
76.4
79.0
81.9
85.1
88.1
91.0
—
3.0%
3.4
3.7
3.9
3.5
3.3
CAGR 1997-2002
3.6%
ES-5
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Executive Summary
ii.
Wound Closure Devices
Sutures are a mature market even though manufacturers continue to produce new and
different products as line extensions every year. While one of the largest markets in the
wound care industry with sales of $668.2 million in 1996, the suture market is expected to
grow at a minimal 1.3% per year, reaching $730.5 million. This modest growth is partially
due to the substitution of other types of wound closure devices, including staplers and
adhesives, and also due to the rise of procedures performed through minimally invasive
techniques, which use less suture material to close the wound. In addition, managed care will
have its usual price erosion impact, causing intense price competition in this commodity
market. Exhibit ES-4 presents the suture market forecast in the United States from 1996 to
the year 2002.
Tissue glues and adhesives, which are expected to be approved in 1998, will not only impact
the suture market, but are expected by some experts to revolutionize the care of lacerations.
Sales in 1998 are expected to reach as high as $10 million, increasing to $30 million in 1999.
Average annual growth thereafter is forecasted in excess of 100% until some degree of
maturity is achieved. Tissue glues will primarily be used in the hospital setting; however, by
2000, approximately 10% of tissue glue sales will be distributed among alternate site
locations. Some industry experts even predict a day when coaches will apply adhesives to
wounded sports players on the field, and families will take tissue glues on camping trips.
iii.
Hydrogel Dressings
A previously rapidly growing market, hydrogels experienced a major setback due to changes
in Medicare reimbursement in the fourth quarter of 1995. As a result of this change and cost
containment pressures from hospitals, and this market became increasingly cost conscious,
causing major manufacturers to reduce prices and offer greater discounts to maintain
customer accounts. Carrington, the traditional leader in this segment with a 36% market
share, had to cut their prices to distributors by 19.1% in 1996. As a result of this and other
pricing discounts, the sales in the market plunged to $32.1 million in 1996, while industry
estimates the year before were approximately $75 million to $95 million. As shown in
Exhibit ES-5, this market is expected to slowly increase to $39.5 million in 2002 as
competitors introduce new products or perhaps use hydrogels as delivery systems with
liposomes. Competitors are also expected to more actively pursue the alternate and home care
markets.
ES-6
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Executive Summary
Exhibit ES-4: U.S. Suture Market Forecast, 1996-2002
Year
Sales
Growth
1996
1997
1998
1999
2000
2001
2002
$668.2M
685.1
697.8
707.9
716.5
724.0
730.5
—
2.5%
1.9
1.4
1.2
1.0
0.9
CAGR
1997-2002
1.3%
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Executive Summary
Exhibit ES-5: U.S. Hydrogel Dressing Market Forecast, 1996-2002
Year
Sales
Growth
1996
1997
1998
1999
2000
2001
2002
$32.1M
33.4
34.7
35.9
37.2
38.3
39.5
—
4.0%
3.8
3.6
3.4
3.2
3.0
CAGR
1997-2002
3.4%
ES-8
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Executive Summary
iv.
Pressure-Relief and Pressure-Reduction Equipment
Specialty beds, mattress replacements and overlays are the primary products used for the
relief and reduction of pressure for patients with chronic wounds. Manufacturers in these
markets offer low-, medium- and high-tech products which in many cases can be purchased
or rented. Consumers are understandably confused in making the difficult decisions
concerning the correct support surfaces for patients. Manufacturers of these products are
continually debating the best product for the treatment and prevention of pressure ulcers. The
purchaser must balance the technological advantages of the products with various other
factors, including cost, decreased hospital waste and reduced labor costs.
In 1996, manufacturers in the pressure-relief and pressure-reduction equipment market had to
review their product and marketing strategies due to changes in Medicare reimbursement in
the home care segment. Group 2 reimbursement was changed to add non-airloss forms of air
floatation, which allowed these manufacturers to be reimbursed at high rates. However, for
manufacturers of traditional low-airloss products, this meant more competition in the home
market and loss of reimbursement for pressure ulcer treatment. In some cases, this change
caused low-air loss manufacturers sales to significantly decrease. However, for some lowairloss manufacturers, the home market continued to grow due to the introduction of new
products and marketing strategies which were specifically targeted at the home care
environment.
The pressure-relief and pressure-reduction market forecasts are presented in Exhibit ES-6.
Full-framed specialty beds are the largest market with $520 million in sales in 1996;
however, this market is forecasted to experience the slowest growth at 2.6% Pricing pressure
is a major limiter in this market, and manufacturers in this segment must often compete with
less costly mattress replacements. Thus, mattress replacements are projected to experience
the highest growth at 5.7% due to the use of some of this segments powered devices as costeffective alternatives to specialty beds. Unit volume will continue to increase in the overlay
market with the aging of the American population and higher acuity of patients. The dollar
growth is attributed to increasing unit volume of static and dynamic air overlays, as foam
products exhibit a slight decline in unit volume. The overall, estimated sales for overlays is
expected to grow from $210.3 million in 1996 to $272.2 million in 2002 at an average annual
growth rate of 4.3%.
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Executive Summary
Exhibit ES-6: U.S. Pressure-Relief and Pressure-Reduction Market Forecast, 1996-2002
Year
Total
Growth
Beds
Growth
—
$520.1M
—
1996
$865.4M
1997
898.2
3.8%
536.0
3.1%
1998
931.3
3.7
551.5
2.9
1999
965.5
3.7
567.2
2000
999.8
3.6
2001
1034.6
2002
1070.4
CAGR
Mattresses
$135.0M
Overlays
Growth
—
$210.3M
—
5.3%
220.1
4.7%
149.9
5.5
229.9
4.5
2.8
158.5
5.7
239.8
4.3
582.4
2.7
167.8
5.9
249.6
4.1
3.5
596.7
2.5
177.5
5.8
260.4
4.3
3.5
610.8
2.4
187.4
5.6
272.2
4.5
3.6%
142.1
Growth
2.6%
5.7%
4.3%
1997-2002
Note: Beds includes full-framed specialty beds, while mattresses include all devices that can replace a conventional mattress.
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Chapter 1: Market Overview
1.
MARKET OVERVIEW
Manufacturers are seeking to create well-rounded, advanced offerings in all aspects of wound
care. To offer clinicians a wider variety of choices and to offset risk associated with too great
a dependence on any one technology, manufacturers have created a situation where product
comparisons are breeding price sensitivities. Even those companies that feel their products
have feature advantages over the competitors’ similar products cannot price their product
significantly above the competitors because of managed care buying practices.
What is happening to wound care companies, beyond simple price pressure, is common to
many other areas of medical product innovation. Like other highly innovative, clinicianpreference products, such as orthopedic implants and cardiovascular devices, real technical
differentiation in advanced wound care is no longer protection against the leveling forces of a
cost-conscious buyer. Rapid technological innovation creates alternatives to existing therapy
without allowing clinicians the time to prove, from both a clinical and an economic point of
view, which approach works best. Eventually, the clinician becomes numbed to the new array
of products and begins to force the manufacturer to prove the value of a new technology on
more than just clinical efficacy. While transparent film was a definite advance over
traditional dry approaches, and hydrocolloids were advances over films, subsequent
innovations in advanced wound care such as calcium alginates have largely been seen as
alternatives to currently available advanced approaches rather than better ways of healing.
These latest products are not the quantum leap as with dry-to-moist dressings; they are only
incremental advances.
1.1
Impacts of Managed Care
The uncertainty of today's healthcare environment makes finding a way to succeed in the face
of cost-conscious managed care no longer a choice for wound care manufacturers, but a
necessity. As Medicare beneficiaries enroll in Medicare risk plans at an increasing rate,
wound care is certain to become a target for increased cost containment by managed care
organizations. This is sure to be precipitated by the high costs associated with the care of
certain wounds. For example, each year it costs as much as $60 million to treat burn wounds;
as, in the U.S. approximately 100,000 burns are treated in the hospital environment. Forwardthinking suppliers can bring their organizations to preferred supplier status with a managed
care organization by reducing the cost of wound care treatment through clinical support and
outcomes data.
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1.1.1
Differentiation to Commoditization
It has been the less than happy fate of most medical/surgical supply product segments over
the past 15 years to undergo a gradual transition from sustainable clinical differentiation to
general commoditization, from price protection to price pressure. Two decades ago, even
products like surgeons’ gloves were considered appropriately a matter of surgeon preference;
today an increasing number of products including gloves, are finding themselves covered
under hospital group purchasing agreements, which all but ignore features and benefits in the
name of securing lower prices or meeting practice guidelines.
The wound care industry has fought against the trend toward commoditization and price
pressures. Many manufacturers of dressings have successfully resisted some of this pressure
by focusing on a key technological shift in the treatment of wounds—the shift from dry to
moist healing. Today, advanced wound care markets such as hydrocolloids and calcium
alginates are increasing, taking more and more market share from traditional dressings. This
rapid technological innovation, however, is inviting new companies into the market, which in
turn introduces a fierce competitive environment. Advanced care companies are discovering,
however, that technological innovation in a managed care environment presents singular
problems. A more crowded technological portfolio creates skepticism on the part of
clinicians about the value of new approaches. Suppliers of traditional dressing products are
providing product lines that include both dry and moist healing in the hopes that this move
will best position them to deal with the new buyer, while advanced dressing manufacturers
are seeking to broaden the scope of advanced technologies in their product line.
The manufacturers of other wound care products such as pressure reduction equipment are
facing similar managed care pricing pressures and are striving to differentiate their products
out of their commodity status by continually adding features. Perhaps the only segments
where the individual products continue to have brand identity and differentiation are those of
growth factors and skin replacements.
Even as these firms resist the trend toward commoditization and blurred differentiation by
moving into advanced product lines, the key issue for wound care companies, including all
manufacturers of products illustrated in this report, is not the assault of biotech or synthetics,
but the larger industry dynamic of group purchasing and managed care. The key players in
the market are bound to become smaller in number and more entrenched. In addition,
companies will have to switch their marketing style from selling on the basis of features and
benefits, and learning to play in the arena of managed care contracting.
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1.2
Innovation in Perspective
Perhaps the biggest challenge for wound care companies is to put technological innovation in
perspective, to resist the temptation to place too great a faith in the ability of technology
alone to heal wounds. Clinicians state that wound healing is an art, not a science. In many
cases traditional gauze will heal a wound as effectively as some advanced products as long as
the care provider pays the same amount of attention to the wound. Thus, with some advanced
products, it’s the marketing that is important, not technological advances.
Compliance is a critical issue in wound care. If the clinician does not change the dressings
when appropriate, or if the clinician does not remove the pressure from a pressure sore, the
wound will not heal no matter the technology of the wound care products applied. All
factors—dressings, nutrition, support surfaces and nursing care—have to come together.
1.3
Purchasing Environment
Healthcare providers are moving from a system that was revenue driven to a cost-driven
system. With managed care, the hospital or integrated healthcare delivery network (IHDN)
knows what its revenues for the year will be, and expects its providers to manage the costs of
that care. When working as a cost center instead of a revenue center, the paradigm of care
moves from a treat/repair mode to a prevention/treatment/rehabilitation model.
Manufacturers of wound care products must, therefore, be able to demonstrate that their
products are more cost effective and provide better outcomes.
Manufacturers of wound care products are learning that a partnership approach works best
with this newly emerging managed care customer. The customer interface must become more
collaborative and less transactional. Some specific suggestions to enhance this collaboration
are presented in Exhibit 1-1. Many manufacturers are replacing their commissioned sales
personnel with account teams, which include middle management personnel from the
corporate office. As the customer base consolidates, manufacturers are finding that
purchasing decisions are being made at higher levels within the customer’s company and
more empowered manufacturers’ representatives are necessary to negotiate contracts on an
appropriate level.
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Exhibit 1-1:
Sales Approaches in a Managed Care Environment
•
Differentiate the customers. Identify those most important in meeting the
manufacturer’s goals and objectives and treat those customers with special care and
deliberation;
•
Develop high-level, well-trained, knowledgeable and empowered executives to
interface with major customers;
•
Develop “customer specific” proposals and contracts that emphasize cost
effectiveness, improved outcomes and improved product standardization and
utilization;
•
Make a true commitment to “customer satisfaction” and “customer-specific” needs;
•
Develop skills in consultative selling and relationship building to augment existing
transactional sales skills; and,
•
Consider “risk-sharing” contracts and agreements that exhibit a true commitment to
reducing the IHDN’s costs of care.
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1.3.1
Outcomes Studies
With cost and price pressures a fact of life, clinical research will be more and more
important; research must show not only improved clinical outcomes, but must also prove
better economic outcomes while establishing protocol that results in faster healing at a
measurably reduced cost. Hospital buying groups and managed care organizations will be
requesting these studies and much work will go into validation of manufacturers’ product
claims. Capitation and risk sharing will be dangerous unless the manufacturer has knowledge
that the company’s products do indeed result in overall lowered cost-per-covered life.
1.4
Medicare
In addition to the growing effects of managed care, surgical dressing benefits for Medicare
have been revised through durable medical equipment regional carrier (DMERC) coverage,
sometimes causing radical changes in specific markets. For example, changes in
reimbursement for hydrogels in 1996 resulted in a sharp decline in sales in this segment.
Exhibit 1-2 reviews the DMERC utilization guidelines for surgical dressings.
In mid 1997, the House Ways and Means Subcommitee in Congress unanimously approved a
package of changes in the Medicare system, entitled the Medicare Amendments Act of 1997.
Growth in federal spending on the program would be trimmed by over $100 billion over the
next five years. The majority of the savings will come from reducing payments to providers
and health plans. Hardest hit by the deficit reduction plan would be HMOs, with an average
22% reduction, nursing homes with an average 16% reduction and home health services with
a 14% reduction.
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Exhibit 1-2:
Surgical Dressing Durable Medical Equipment Regional Carrier Utilization
Guidelines
Primary Dressing
Frequency of Dressing Change
Alginates
Once daily
Film, transparent
Three times per week
Foam dressings
Foam wound fillers
Once daily
Gauze (non-impregnated)
Three times per day, no more than two pads
on a wound
Once daily
Gauze (impregnated with other than saline
or water)
Hydrocolloids
Hydrogel wound cover
Once daily or three times per week if using
adhesive border
Only daily and no more than 3 ounces per
month
Hydrogel wound filler
Source: DMERC Utilization Guidelines, 1996.
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1.5
Minimally Invasive Surgery
The wound care product marketplace has been affected by the move to less -invasive surgical
procedures, due to the smaller size and severity of wounds in these procedures. The
continuing conversion of open surgical procedures to endoscopically directed and other lessinvasive treatments will continue to impact this industry, but at a moderate pace.
The demand for minimally invasive surgical (MIS) procedures will be driven by the efforts to
cut cost, provide quality care and good patient outcomes. In each surgical specialty, surgeons
continue to seek new and increasingly less-invasive techniques to offer their patients in the
interest of reducing costs, lessening patient trauma and reducing length of stay in the hospital
by the surgical patient. The number of potential patients for these procedures will increase as
the U.S. population ages, and as patients that originally were not candidates for open
procedures become candidates for therapy that is less invasive.
Endoscopically directed minimally invasive therapies can significantly lower overall costs of
care for individual patients. Adoption of some procedures may, however, increase overall
societal costs due to increases in procedure volume. This occurred with laparoscopic
cholecystectomy. When consumers became aware of the reduced pain and shorter
recuperation time, many more patients than expected sought treatment. Manufacturers and
market analysts predicted that all general surgery procedures would rapidly follow the same
trend as cholecystectomy in conversion to the laparoscopic approach; however, this expected
trend has not occurred.
There are two areas, however, where procedural conversion to MIS will still enjoy large
increases: vascular surgery and neurosurgery. This will be due to new opportunities in
laparoscopic technology that are likely to emerge as minimally invasive abdominal
approaches to spinal fusion and aortic surgery are developed. Exhibit 1-3 presents the
conversion rates expected by the year 2000, by surgical specialty.
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Exhibit 1-3:
U.S. Rate of Conversion Rate to Endoscopic or Other Minimally Invasive
Surgeries by 2000
Specialty
Cystoscopy
Converted
100%
Total MIS Procedures
1,767,000
Endogynecology
100
473,000
Endothoracic
100
662,000
Endourology
100
375,000
General surgery (endoscopic)
100
112,000
Orthopedics (other)
98
1,500,000
Plastic surgery
93
721,000
Gynecology (laparoscopic)
86
1,540,000
Ear, nose and throat
82
720,000
Thoracic
78
173,000
General surgery (laparoscopic)
71
3,350,000
Orthopedics (spine)
50
195,000
Neurosurgery
41
18,000
Urology (laparoscopic)
23
112,000
Cardiovascular
16
114,000
Totals
83%
11,832,000
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1.6
Hospital and Alternate Site Markets
End-user markets for wound care products can be categorized into various sites, including
hospitals, nursing homes and home health. Physician offices and freestanding clinics usually
purchase through some type of group purchasing or hospital group purchasing programs and
contracts. Their unit volumes and dollar volumes are relatively low compared to the total unit
and dollar volumes of the “Big 3” (e.g., hospitals, nursing homes and home healthcare
organizations).
The wound care provider can choose from a dizzying array of products available on the
market. In addition, the market is becoming more difficult to differentiate, with more and
more products sold in the fragmented and difficult-to-reach alternate site market. For many
manufacturers, their biggest challenge has not been assembling a line of advanced care
products, but finding a cost-effective way to get to the alternate site market.
The alternate site market is not only fragmented, it is extremely price sensitive, and, in the
case of home care, can utilize completely different distribution channels such as retail
pharmacies. It is also a segment where getting information to clinicians and patients about
advances in product design is a cumbersome and labor-intensive process.
1.6.1
Hospitals
The Sachs Group’s study, Health Care 1999, provides a framework for understanding
managed care’s effect on inpatient utilization. The study used as its basis a group model
managed care market with the practice pattern of California, recognized as the most
aggressive state with respect to managed care. According to this analysis, total inpatient days
will decrease 34% nationwide from 1994 to 1999, due primarily to a dramatic (26%)
decrease in admissions. The Northwest could potentially see the largest drop in utilization;
the West will experience the smallest drop.
Regional differences in patient days are even more profound at the product line level. For
instance, general surgery patient days are projected to hold fairly constant in the Midwest,
with a drop of 1%, from 3.4 million to 3.3 million. Patient days in the South, however, will
decline 18%, from 5.9 million to 4.9 million. In the West patient days are expected to decline
19%, from 2.6 million days in 1994 to 2.1 million days in 1999.
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Inpatient volume, as measured by discharges, will decline 26%, from 32.5 million to 24.2
million. Outpatient procedures will increase. Average lengths of patient stay will decrease
11%, from 6.1 days to 5.5 days between 1994 and 1999.
Several conclusions can be drawn from this study. First, there are too many hospital beds. In
1994, the demand for beds was 643,000. A 34% reduction in bed days would result in a 1999
bed demand of 424,000. In 1996, the number of beds in U.S. hospitals totaled 1.2 million.
Without a significant decrease in capacity, by the end of the century, there will more than
double the beds needed.
Second, traditional hospital providers will continue to consolidate. Excess bed capacity will
be corrected through provider mergers to achieve economies of scale. This downsizing will
trickle down throughout the healthcare industry. In addition, networks will be the entities
destined to succeed. Hospitals that choose either to create or buy alternate site delivery
facilities, and form or join integrated healthcare delivery networks, have a greater chance of
surviving. Affiliations or partnerships with home health agencies and long-term care
providers will ensure that services are in place throughout the entire cost-effective continuum
of care.
1.6.2
Physician Networks and Ambulatory Care
As part of the trend toward a cost-effective continuum of care, there will be more
outpatient/ambulatory networks. In addition, as prevention and wellness become more
attractive financially, demand for primary care physicians will skyrocket and the
development of physician practice management (PPM) companies will increase. These
entities pool the doctors’ skills and practices, handle administration, purchase medical/
technical products, and, more importantly, negotiate contracts with HMOs and other
managed care groups.
1.6.3
Nursing Homes
The nursing home industry can be characterized as fairly fragmented, with occupancy rates
running between 90% -95% in most states. Improvements in the industry’s finances has
encouraged growth through facility acquisition by the larger chains; however, the 30 largest
chains accounted for about 25% of all nursing home beds in 1996. The nursing home
industry is unlike most other healthcare sectors because of its high occupancy levels and its
reimbursement mix. The industry has experienced significant rebound since the mid 1980s as
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a rising Medicare census, improved Medicaid rate reimbursement in many states and
moderate labor cost increases bolstered margins.
The high occupancy levels are partly the result of state limitations on new construction and
bed additions. Such limits are imposed as a means to limit the states’ expense for care as
evidenced in runaway Medicaid budgets. Industry occupancy levels have not increased
significantly as lower acuity patients are transitioned to other alternate sites, such as assisted
living and home care. The higher acuity patients often have acute conditions that improve
quickly and allow for discharge directly home, thereby decreasing the average length of stay.
The aging population is also responsible for the increased demand for home care as the over
65 year old population is expected to approach 35 million people by 2000. The over 85 year
old population, the group most likely to require nursing home care, is expected to grow to 4.6
million people from 3.2 million people in 1990.
Nursing home that provide skilled nursing services to Medicare and Medicaid beneficiaries
are classified as skilled nursing facilities (SNFs) for reimbursement purposes. The majority
of nursing homes are not owned or operated by hospitals and are classified as freestanding
skilled nursing facilities. The nursing home market is projected to reach $500 million in
2000, while SNFs are forecasted to reach $350 million.
1.6.4
Home Health Care
The major segments within the home market include nursing services, infusion therapy and
respiratory therapy. The increasingly burdensome Medicare paperwork demands, the tight
limits on reimbursement and unreliable interpretations of the Medicare home care benefits by
the Health Care Financing Administration (HCFA) increases the barriers for future market
entry. However, as a result of products that have been adapted for home care use and the
need to discharge to alternative healthcare sites to reduce costs, the market potential for home
care is enormous.
Home health care has also moved to the forefront of public policy debates. According to
study released by the U.S. General Accounting Office, expenditures for home health care
services and products are out of control: $18 billion in 1996, from just $2.1 billion in 1988.
Recent publicity regarding fraudulent claims has highlighted some potential drawbacks of the
current Medicare reimbursement structure.
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As a result, Medicare policy may be moving toward a prospective “case rate” reimbursement
structure for home health care, similar to that used to pay hospitals. In fact, part of the
proposed legislation in the Medicare Amendments Act of 1997 establishes a prospective
payment system in fiscal year 2000, and a significantly downward redefinition of the home
health benefit is also included.
Within the home health care market, wound care management is required by over 30% of
patients. Wound care is an integral part of the home health care market, and the potential for
wound care products in this segment is encouraging. These markets will be the growth areas
for many of the mature markets, such as for debridement agents. Cleansers and dressings will
also expand in this sector. However, in the last several years, insurance providers have been
concerned with the increasing intensity of nurse visits and utilization of wound care products.
Medicare reimbursement in this sector has also been scrutinized. For example some
manufacturers in the pressure-reduction market experienced a flattening in the home care
segment due to changes in Medicare codes in 1996.
1.6.5
Subacute Care Facilities
The primary goals of subacute care facilities are multifaceted and offer patients continued
quality of care while payers are able to use a cost-effective healthcare source. For acute
health care providers, the use of subacute care facilities means earlier discharges of stable
patients in order to reduce costs.
Subacute care facilities are defined by the kind of care performed. These entities can be
categorized into three types: medical, rehabilitative and combined facilities.
Competition in this market comes from medical product manufacturers that focus on the
home health care, as well as companies that focus on products used for acute care. Both of
these manufacturer groups can service this market if they are able to modify their products
and adapt to the specific needs of the subacute care facility. For the home healthcare
manufacturers, this means redesigning to incorporate more sophisticated parameters and
storage capability than that found in current home healthcare products. Conversely, acute
care manufacturers must streamline acute care products/devices to meet the cost criteria and
subacute care clinical needs.
Healthcare performed in subacute facilities costs significantly less than similar services
delivered in the acute care setting. Revenue per patient day in a subacute bed is between $300
and $500, compared to $600-$1200 in a full-service acute or rehabilitation hospital.
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A subacute wound care program provides the support and services necessary to manage and
prevent wounds. Wound care may include complex treatment and dressing procedures;
whirlpool debridement, electrical stimulation, specialty beds and pressure-reducing devices,
frequent laboratory evaluation, teaching wound care to the patients, and ongoing assessment
of the effective treatment by changes in wound status. The goal of a wound care program is
to facilitate healing of wounds of various types, while managing potential complications and
reducing risk factors. Effective wound care programs incorporate nutrition and hydration
services with specific treatment protocols.
Subacute wound care programs typically focus on treatment of large surgical wounds that
have not closed, infected wounds, multiple stage III and IV decubitus ulcers, recent
debridement, second- or third-degree burns and unstable wound healing. In addition, patients
with recent amputations or skin grafts and patients with impaired healing processes,
including those with medical complications, digestive disorders, cancer or AIDS, are
candidates for admission to a wound care program.
Patients recovering from surgery, complicated wounds, burns, decubitus ulcers, vascularrelated tissue breakdown, grafts or amputations receive specialized services, including
advanced wound care management, specialized beds, nutritional support and physical therapy
services. In addition, wound care programs treat patients infected by certain forms of
antibiotic-resistant bacteria. These kinds of patients must be isolated under strict infection
control procedures to prevent the spread of the disease. These patients are ideal candidates
for a subacute care facility, since treatment of this condition is not practical at home.
1.6.6
Wound Care Centers
Hospitals, healthcare professionals and medical suppliers are establishing wound care
services designed to attract a strong client base and generate additional revenues. As wound
care continues to move from an inpatient to an outpatient service, this expansion of existing
services and creation of new outpatient centers is a natural.
Wound care centers are a way to attract new clients and provide innovative treatment to
many patients who have been shifted from provider to provider, often without satisfactory
coordinated treatment. Hospital-based centers are an excellent way of drawing communitybased patients into the network of care provided by an institution. There is no perfect model
or formula for establishing a wound care center. Each facility or agency will be unique in its
settings, goals and marketing.
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Any institution or provider should consider a number of market issues prior to establishing
their individual wound center. One model for a wound care center is a hospital-owned and
operated center, billing and receiving payment from a fiscal intermediary while using the
hospital provider number. Another mechanism is a hospital-owned center which operates
under a separate provider number. A third type is a center under separate ownership and
management. Reimbursement and billing procedures are different for each type of clinic.
Other privately managed delivery models are appearing to take advantage of the growing
interest in advanced wound healing. Specialized wound care centers have been established by
independent providers and cater to the highest acuity, hardest-to-heal wounds. Curative
Health Services claims market leadership, with approximately 109 such centers. What impact
these centers will have on the market remains to be seen. Some critics feels these centers are
simply “marketing ploys,” achieving high success rates and impressive revenue levels by
carefully screening patients to find those most desperate, and therefore, most willing to be
compliant with established protocols. Curative Health Services, however, has grown
significantly over the last several years; revenues in 1996 alone increased 29% to $67.4
million compared to $52.4 million in 1995.
Centers charge for a visit as brief, intermediate or comprehensive based on the procedure
performed and the length of time spent with the patient. Ambulatory patients are often seen
weekly in a wound care center. Those who are homebound are followed by a home health
agency after the wound care treatment plan is established. Health maintenance organization
patients usually have prior approval for a specified number of visits, so the director of
nursing and the patient decide together how best to utilize the allocated benefit.
One of the major advantages of wound care centers is that they are able to conduct outpatient
clinical studies. Research generates additional revenue per patient and often means that
treatment supplies are provided by the sponsor of the study.
An aging population and strong emphasis on reducing utilization of more expensive services
mean that treatment of wound care patients at the outpatient/clinic level will grow and be
accepted positively by payers. However, facilities contemplating the establishment of a
wound care center must conduct a thorough analysis of reimbursement issues to ensure
success.
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1.7
The FDA
This government agency’s decisions can have life or death consequences on new products
being developed for the wound care market. While 1996 has seen some improvement in the
speed with which new products are evaluated, the process of 510(k) approvals is still a
lengthy one.
Changes in FDA policy can also have drastic consequences for manufacturers. For example,
in April 1996, the FDA issued new regulations to govern products that are derived from cells
and tissues. Over a three-year period, the FDA will institute new rules to prevent unwitting
use, processing or handling of contaminated tissue that could carry and transmit infectious
disease. According to the FDA, the three-tiered approach effects an appropriate level of
control that is equal to the perceived risk for the materials. Products that are considered novel
or are extensively processed require FDA approval before they are marketed. All tissue
processing facilities will be required to register with the FDA and to list their products.
The policy does not impact cells or tissue removed from and transplanted to the same person
in a single surgical procedure. Further, minimally processed conventional and reproductive
tissue would not be subject to FDA concern in areas of handling and ensuring they are not
contaminated. But for certain tissues, controlled clinical trials and premarket approval will be
required to demonstrate safety and efficacy of the matter.
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Chapter 2: Clinical Issues
2.
CLINICAL ISSUES
Understanding the wound healing market must start with a thorough understanding of the
anatomy and physiology of skin, types of wounds and healing processes. This section of the
report covers the clinical side of the wound care marketplace.
2.1
Anatomy and Physiology of Soft Tissue
To correctly treat acute and chronic wounds, it is necessary to understand normal skin, its
structures, functions, and changes, both intrinsic and extrinsic, throughout life. In many
ways, the skin is the mirror of the body. It reflects disease, trauma, nutrition, metabolism,
perfusion, oxygenation and emotional status.
The skin is the largest organ of the body, covering over 20 square feet in the average
American adult. It weighs approximately 12 pounds (in a 150 pound person). The complexity
of the skin is demonstrated when one considers that 1cm 2 of skin contains 15 sebaceous
glands, 1 yard of blood vessels, 100 sweat glands, 3,000 sensory cells, 4 yards of nerves,
300,000 epidermal cells and 10 hairs. Skin thickness varies, from the thinnest covering the
eyelids to the thickest covering the hands and the soles of the feet. The skin can harden to
form fingernails, and it can elongate to form hair. The skin is not a passive structure that
holds the inner organs, but rather, it is an active organ that continually undergoes biological
and biochemical activity.
The skin has several functions: 1) it provides the interface between the body and the
environment (protection from micro-organisms and traumatic injury to bones, muscles and
other organs); 2) it transmits sensation of touch, pain and pressure endured from the
environment; 3) it regulates the body temperature, assisting in fluid excretion as well as
retention of fluid; and, 4) it assists in vitamin D production, in the presence of sunlight.
The skin has three distinct layers, each with their own functions, but all are interrelated and
interdependent upon each other. The skin is comprised of the epidermis (outer layer), the
dermis (middle layer) and the subcutaneous tissue (inner layer).
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2.1.1
Epidermis
There are five layers in the epidermis, starting from the skin layer closest to the environment:
•
Stratum corneum is the tough acidic layer which retards certain fungal and bacterial
growth;
•
Stratum lucidum is found only in the palms and soles and is a dense, translucent layer
of flat cells (this layer may be minimal or not present at all in thin, old or fragile
skin);
•
Stratum granulosum is a granular layer consisting of macrophage cells which affect
the immune reactions and inflammatory phases of wound healing;
•
Stratum spinosum is a wavy layer that contains spine-like extensions of the basal
layer; and,
•
Stratum germinativum, also called basal stratum; is the only layer that has the ability
to regenerate new cells through mitosis.
Although there are five layers in epidermis, it is relatively thin and avascular. The epidermis
proliferates rapidly, continually pushing new cells from the basal layer to the surface. Cells
produced by the basal layer migrate upward, losing their nucleus and transforming via
keratinization into a flat, tough, nonliving layer of cells that becomes part of the stratum
corneum or horny layer. The epidermis is replaced with new cells every 4-6 weeks.
Melanocytes are contained in the epidermal layer, releasing granules of melanin pigment,
which provide skin tone colors and protect the body from solar radiation. Darkly pigmented
skin has increased number of melanocytes, and hypopigmentation of wounds and ulcers
frequently occurs in dark-skinned persons. Although these wounds appear to be healed, time
is often required for the melanin to reach the stratum corneum layer and return skin to its
normal color.
2.1.2
Dermis
The dermis consists of two layers. The papillary dermis is closest to the epidermis, consists
of collagen and reticular fibers, and is integrated with capillaries. It provides nourishment and
oxygenation to the epidermal layer and appendages, such as the nails, hair and skin glands.
The reticular dermis is a thick layer of large collagen fibers organized into bundles. This
layer anchors the skin to the subcutaneous tissue and provides for elasticity of the skin.
The dermis provides the skin with the necessary elasticity and structural and mechanical
strength. It is integrated with capillary blood vessels, nerves and appendages. A superficial
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burn will stimulate nerve endings in this layer and generate an acute sensation of pain.
Deeper burns will destroy nerve endings and make the wound insensitive to pain. The most
predominant cells in the dermis are fibroblasts which produce collagen.
Collagen gives the skin strength and elastic stretch. At the microscopic level, collagen
consists of three identical polypeptide chains that form a helix. There are more than 11
identified forms of collagen protein which are made by fibroblasts. Four types of collagen
have been identified and are associated with body tissue. Type I is found in bone, skin and
tendons; type II is found in cartilage; type III is associated with healing and embryonic tissue
and type IV is found in certain membranes. Although newly formed collagen is type III in the
proliferative phase, during the maturation phase it is remodeled into type I collagen.
2.1.3
Subcutaneous Tissue
The subcutaneous tissue consists of dense connective and adipose tissue. Its functions are to
house major blood vessels, lymphatics and nerves; serve as a heat insulator and shock
absorber; relinquish its nutritional storage during periods of illness or starvation; provide a
cushioning effect; and to facilitate mobility of the skin over underlying structures.
2.1.4
Normal Skin Changes Associated with Aging
The impact of aging is more noticeable on the skin than on any other organ or structure in the
body. Aging causes atrophy and thinning of both epithelial and fatty layers. Only small
amounts of subcutaneous fat are present on the legs and forearms of the elderly. Fat atrophy
causes noticeable bony prominences in the thorax, scapulae, trochanters, knees, ankles and
toes. It is this loss of fatty padding which can predispose elderly people to pressure ulcers.
Other changes include the shrinkage of collagen and elastic fibers, and depletion of sweat
glands, resulting in dry, thin and inelastic skin. The attachment of the epidermis to the dermis
weakens and predisposes the epidermis to slide over the dermis. Even minor friction and
shearing force can result in a skin tear for the elderly. Both friction and shear contribute to
the mechanical destruction of tissue. Shear, which primarily effects deep tissue; occurs when
tissues attached to bones are pulled in one direction as a result of body weight, while surface
skin remains stationary. Friction occurs when two surfaces move across one another, wearing
away the outer layer of the skin, ultimately causing skin abrasion and tissue damage.
The elderly frequently complain about dry and itchy skin, as well as being cold. This results
from a depletion of insulating subcutaneous fat and smaller cutaneous blood vessels. Cellular
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changes include the depletion of melanocytes, causing the graying of hair, increased
whitening of Caucasian skin and the loss of body hair.
2.2
Types of Wound
There are three methods to classify wounds, using either wound severity, morphology or
etiology. As shown in Exhibit 2-1, classification by severity identifies wounds as either tidy,
untidy, wounds with tissue loss, or infected. Tidy wounds are the most common, including
surgical incisions and simple cuts; untidy wounds and wounds with tissue loss are the next
most common forms and are usually the result of an accident or burn injury. Infected wounds
are the smallest category and include infections in the form of abscesses, cellulitis, or those
so contaminated by foreign materials that they will certainly become infected.
As presented in Exhibit 2-2, classification by morphology identifies wounds as either partialthickness or full-thickness. This classification has displaced the classification of first-,
second- and third-degree wound ranking. Classification by etiology identifies wounds by
origin which includes surgery, trauma, burns, pressure, venous and diabetic ulcers, radiation
and HIV patients. Exhibit 2-3 outlines the classifications of wounds by etiology, while
Exhibit 2-4 presents the wound incidence by etiology. Exhibit 2-5 lists the incidence of
wound care procedures by ICD-9 code.
In 1995, the National Center for Health Statistics reported the average life expectancy at 75.8
years, a record high. As life expectancy grows and the number of elderly persons increase,
patients with chronic wounds is expected to grow by 6% from 1996 to 2000. In addition, the
cost associated with treating chronic wounds was estimated at $12-$14 billion in 1996.
2.2.1
Surgical Wounds
As shown in Exhibit 2-4, 24 million patients had surgical operations that resulted in skin and
tissue incision. These types of wounds will grow at an annual rate of approximately 3%, but
surgical wounds will likely be smaller as a result of the increase in minimally invasive
surgical techniques. The surgical wound category can be divided into either inpatient or
outpatient surgeries. In many instances, the wound closure method and wound care covering
will be determined by whether the patient will be treated on an inpatient or outpatient basis.
The majority of acute wounds are treated initially in an acute care facility, while most chronic
wounds and ulcers are treated through physicians’ offices, outpatient clinics, nursing homes
and home health care.
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Exhibit 2-1:
Classification of Wounds by Severity
Classification
Wound Characteristics
Wound Etiology
Tidy Wound
Clean wound with edges only
minimally damaged; minimal tissue
loss; no infection apparent
Surgical incisions;
accidental, simple
lacerations
Untidy wound
Significant tissue damage or
destruction (crushed, torn); disruption
of neurovascular, muscle or bony
structures; foreign materials often
present
Crushing injuries,
abrasions and
traumatic vehicle
injuries
Wounds with tissue loss
Loss or severe damage of tissue,
including subcutaneous tissue,
neurovascular components, muscles,
tendons or bony structures
Excisions, burns
and ulcerations
Infected wounds
Any wound that is infected, such as a
tidy wound that shows signs of
infection or an untidy wound free of
infection initially, yet so contaminated
with foreign matter that infection is
likely
Wounds with
cellulitis,
lymphangitis,
abscesses, burns
and contamination
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Exhibit 2-2:
Type
Classification of Wounds by Morphology
Cellular
Characteristics
Common Cause
Prognosis for
Healing
Partial
Thickness
Involves entire epidermis
and portions of dermis.
Very severe sun burns,
contact with hot liquids
and flash burns from
gasoline flames.
Healing within 10-18
days, epidermal element
germinates and migrates
up to the epithelial layer.
Heals without significant
scarring or functional
impairment.
Deep PartialThickness
Involves entire epidermis
and almost entire dermis.
Fire and thermal burns, car
injuries.
Healing within 20-35
days, may produce
unacceptable scarring.
Full-Thickness
Involves epidermis,
dermis; may extend into
subcutaneous tissue.
Sweat glands and hair
follicles are destroyed.
Fourth-degree
or complete
burns
Considered more
extensive than fullthickness wounds.
Involves subcutaneous
tissue, muscle, fascia and
bone.
Extremely small wounds
may be allowed to heal
through wound border
epithelialization.
Electrical burns and
certain thermal burns, such
as molten metal or severe
scalding.
Complete debridement of
wound to viable, bleeding
tissue, removing all
necrotic tissue, bone.
Systemic antibiotic
therapy and grafts/flap
skin replacement.
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Exhibit 2-3:
Classification of Wounds by Etiology
•
Surgical Wounds
•
Traumatic Wounds
•
Burn Wounds
•
Proliferative Scars
•
Ulcerations, including venous, arterial/diabetic and pressure
•
Immunosuppressive Wounds
•
Pharmacological Therapeutics
•
Disease-Associated
•
Radiation Wounds
•
Keloids
•
Hypertrophic
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Exhibit 2-4:
1996, Wound Incidence by Etiology in the United States
Wound Type
Incidence
Surgical wounds
24,370,000
Traumatic wounds
725,000
Percentage of
Total
Annual Growth
Rate
44.3%
3.0%
1.3
1.2
Burn wounds(non-hospitalized) 1,200,000
Burn wounds (hospitalized)
680,000
2.2
1.2
1.0
1.0
Pressure ulcers
Venous ulcers
Arterial/diabetic ulcers
2,900,000
1,250,000
2,350,000
5.3
2.3
4.3
5.0
6.0
14.0
Amputations
530,000
1.0
0.8
Procedure-based wounds
21,000,000
38.2
3.0
Total
55,005,000
100%
3.5%
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Exhibit 2-5:
ICD-9 Code
Incidence of Wound Care Procedures, 1994
Description
Number of Procedures
86.01
Aspiration of skin and subcutaneous
10,000
86.04
Other skin and subcutaneous
96,000
86.05
Skin incision/foreign body removal
20,000
86.09
Skin and subcutaneous incision
28,000
86.11
Skin and subcutaneous biopsy
26,000
86.22
Wound debridement
261,000
86.27
Debridement of nail
22,000
86.28
Non excision, debridement of wound
66,000
86.3
Other local skin destruction
77,000
86.4
Radical excision of skin lesion
16,000
86.69
Free skin graft
58,000
86.72
Pedicle graft advancement
86.74
Attach pedicle graft
86.89
Skin repair and plasty
7,000
14,000
7,000
Total
708,000
Source: National Center for Health Statistics, National Hospital Discharge Survey, 1994
(latest available year)
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2.2.2
Trauma-Induced Injuries
The National Center for Health Statistics reported traumatic injury is the fifth leading cause
of death in the United States in 1995 (the latest year available). In 1996, there were
approximately 725,000 traumatic wounds, and the incidence of these types of wounds is
expected to increase by 1.2% annually.
Traumatic wounds have a classification all their own and are described as either abrasions,
simple lacerations, lacerated wounds with tissue loss or contusion-sustaining injuries.
Abrasions usually result from a shearing type of injury, such as a traffic accident victim being
thrown across the road surface. This injury usually results in a partial-thickness wound. A
simple laceration usually results from an object that penetrates the skin and is classified as a
full-thickness wound. A laceration with tissue loss could involve amputation of the digits or
even a limb. A contused wound ranges from minor bruising to severe tissue destruction, such
as a crushing injury or a bullet wound.
2.2.3
Burns
More than 1.8 million Americans sustain burns which must be treated in the hospital or
physician’s office each year. Burn wounds cost approximately $70 million per year, with
some individual costs reaching as high as $60,000. More than 35% of all fire/burn injuries
and deaths occur to children. However, burns are known to be one of the most common
accidental injuries, occurring in any environment to victims of all ages.
Approximately 680,000 people will sustain major burns that are serious and life-threatening,
requiring hospitalization. These burns are unquestionably among the most devastating types
of injury known to man. Burns are a total physical assault to the body. Emergency techniques
include resuscitation, hemodynamic stabilization, nutritional and oxygen support, ventilation,
patient comfort, accelerated proper healing, and prevention against infection and secondary
complications. Burn patients not only have dramatic physiological dysfunctions that are
multi-system, but also psychological and psychosocial alterations that challenge and require
the expertise of a burn team, often in a comprehensive burn center. The types of burns that
are referred to a burn center are listed in Exhibit 2-6.
Patients that do survive require rehabilitation that is a minimum of seven times longer than
their stay in the hospital, and they may require years of psychological intervention. The
average length of stay for a hospital burn patient is 24 days, although it can be months for the
severely burned patient. In the past ten years the length of stay has declined by 50%.
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Exhibit 2-6:
Types of Burns Referred to Burn Centers
•
Full-thickness burns covering more than 10% of body surface area (BSA)
•
Partial-thickness burns exceeding 20% of BSA and full-thickness burns exceeding
10% of BSA in the adult
•
Burns involving the face, hands, feet, perianal, genitalia or joints
•
Circumferential burns of an extremity or chest wall
•
Chemical burns
•
Electrical burns
•
Inhalation burns
•
Burns complicated with another major injury
Source: American Burn Association, Medtech Insight, LLC
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There is controversy whether burn centers can be profitable or if they only provide a much
needed community service. Some reports conclude hospitals that market their product well,
maintain full occupancy, efficiently utilize staff and market a payer-mix having a large
number of commercially covered patients, can reap a profit. Other reports suggest that burn
units can sometimes cause institutions to lose hundreds of millions of dollars annually.
2.2.3.1 Classification of Burns
Burns are classified according to the extent of body surface involved and the depth of injury
to the skin. Data collected from these scoring systems can assist in determining whether the
burn can be categorized as major, moderate or minor for identification of treatment and
facility needed for proper care.
One commonly used guide in determining extent of injury is the Rule of Nines and Nineteen.
The Rule of Nine is used for adults, while the Rules of Nineteen are used for pediatric
patients. These systems divide the body into sections by percentage. The Rule of Nines
provides the quickest assessment of total body surface injury and is used for initial
emergency patient status.
Another guide for determining the extent of injury is The Lund and Browder Chart. This
guide is presented in Exhibit 2-7. The Lund and Browder Chart is a more specific and
accurate estimate in determining what percentage of body surface has been injured as it
assesses hands, feet and upper arms separately. The Lund and Browder Chart is retained as a
permanent patient record after treatment is well established.
The depth (degree) of a burn was classically coined as first, second, third and fourth degree
and has now been superseded by the classification of partial-thickness, full-thickness and
complete burn wounds. First-degree burns are not included in the current evaluation of
extent-of-burn-injury unless they comprise over 30% total body surface (TBS). In these
wounds, the skin is fiery red, very painful and not blistered. First-degree burns usually heal in
3-5 days.
Partial-thickness wounds (formerly second-degree) involve destruction of all epidermal
layers with destruction of various layers of the dermis. Full-thickness (formerly third-degree)
denotes destruction of all dermal and epidermal layers and can extend into the subcutaneous
tissue. The sweat gland and hair follicles that foster re-epithelialization are completely
destroyed; therefore, any healing must now occur through epithelial migration from the
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Exhibit 2-7:
Lund and Browder Chart for Measuring Extent of Burn Wounds
Age 0-1
Years
Age 1-4
Years
19%
2%
13%
13%
2.5%
17%
2%
17%
13%
2.5%
13%
2%
13%
13%
2.5%
10%
2%
13%
13%
2.5%
7%
2%
13%
13%
2.5%
Left Buttocks
Genitalia
Right Upper Arm
Left Upper Arm
Right Lower Arm
Left Lower Arm
Right Hand
Left Hand
Right Thigh
Left Thigh
Right Leg
2.5%
1%
4%
4%
3%
3%
2.5%
2.5%
5.5%
5.5%
5%
2.5%
1%
4%
4%
3%
3%
2.5%
2.5%
5.5%
5.5%
5%
2.5%
1%
4%
4%
3%
3%
2.5%
2.5%
5.5%
5.5%
5%
2.5%
1%
4%
4%
3%
3%
2.5%
2.5%
5.5%
5.5%
5%
2.5%
1%
4%
4%
3%
3%
2.5%
2.5%
5.5%
5.5%
5%
Left Leg
Right Foot
Left Foot
5%
3.5%
3.5%
5%
3.5%
3.5%
5%
3.5%
3.5%
5%
3.5%
3.5%
5%
3.5%
3.5%
Area
Head
Neck
Anterior Trunk
Posterior Trunk
Right Buttocks
Age 5-9
Years
Age 10-15
Years
Adult
Source: American Burn Association
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periphery and from wound contracture. Grafting is required if the wound is extensive. There
is also a complete (fourth-degree) burn classification, which denotes extension into the
subcutaneous tissue, muscle, fascia and even the bone. Although such a burn on the surface
may appear at first inspection to be a full-thickness wound (third-degree), if improperly
diagnosed, it can result in severe systemic toxicity or systemic infection/sepsis. Between 44
degrees C and 51 degrees C, the rate of cellular destruction doubles with each degree increase
in temperature. Above 51 degrees C, brief exposure produces rapid tissue destruction; while
70 degrees C and above provides full-thickness burns with a one-second exposure. As shown
in Exhibit 2-8, burns may also be categorized according to the primary mechanism for injury:
thermal, electrical, radiation and chemical.
2.2.3.2 Therapeutic Intervention for Burns
Accurate assessment of burn depth usually requires one to three days of observation. It is
critical that the clinician treat burns differently than other traumatic injury. Differences in the
two types of injuries are:
•
Burns are rapidly infiltrated by bacteria;
•
Burns frequently have large portions of nonviable tissue;
•
Burns excrete large quantities of water, serum and blood; and,
•
Burns frequently require tissue grafts or flaps for permanent closure.
Although a surgical wound heals by primary intention (sutured incision), a burn wound heals
by secondary intention (filling the tissue defect through new connective tissue, blood
vasculature and epithelium). Secondary intention increases repair time, causes greater
scarring and increased susceptibility to infection. Although burn wounds are generally sterile
following the initial burn, bacterial contamination will result within 48 hours if topical
antibacterial therapy is not promptly initiated. Bacterial counts greater than 100,000 or 10 5
per gram of tissue, will result in a predictable course of gram positive bacterial invasion
followed by gram-negative bacterial invasions. Contamination can be caused by endogenous
flora (from the patient's own skin or respiratory tract) or from exogenous flora (in the
environment or on the hands of healthcare workers).
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Exhibit 2-8:
Mechanism of
Injury
Classification of Burns According to Mechanisms of Injury
Probable Cause
Thermal
Steam, scalding liquids, flames, semi-solids and hot metal
Electrical
Direct electrical current traveling through the body, arcing of electrical
current, or the effects of electrical current combined with flames from
clothing ignition. Most often associated with industrial injuries. Electrical
injuries are frequently fatal.
Radiation
Industrial use of ionizing radiation or from therapeutic radiation sources
(for example, in treatment of oncology patients).
Chemical
Strong acids and alkalis cause tissue destruction by denaturing tissue
proteins and/or interfering with normal cellular metabolism. Alkali burns
are more serious than acid burns because alkali penetrates deeper and
burns longer.
Source: American Burn Association
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Although the major goal of burn management is to close the wound as soon as possible,
several objectives must be met for optimal wound closure. These objectives include the
prevention of wound infection through meticulous cleansing and debridement, promoting the
development of granulation tissue and re-epithelialization, preparing the wound for grafting,
providing for patient pain comfort, and reducing the amount of scarring and contractures.
Clinical experiences at burn centers reveal that the removal or debridement of eschar as
quickly as possible reduces the likelihood of bacterial infection and other iatrogenic
problems. Debridement provides for removal of devitalized tissue or burn eschar, and
removes bacterial and foreign-body contaminated tissue as a means to further protect against
bacterial infection. Debridement can be accomplished through mechanical, surgical or
enzymatic procedures.
Mechanical debridement involves the use of scissors and forceps to encourage separation of
eschar from wound. These procedures are usually performed in conjunction with daily wound
cleansing and dressing activity. Mechanical debridement can also be achieved through the
use of coarse “mesh” dressings applied via either “dry” or “wet-to-dry” technique. As the
wound begins to develop granulation tissue and epithelial budding, this method should be
avoided, to protect granulation formation.
Surgical debridement involves primary excision of full-thickness skin or tangential excision
of thin layers of the dermis until freely bleeding viable tissue is achieved. It usually is
initiated a few days after the burning or as soon as the patient is hemodynamically stable and
can undergo anesthesia. The wound is grafted immediately by either temporary or permanent
grafting techniques. Risks include prolonged anesthesia and excessive blood loss. Surgical
debridement is the procedure of choice for large burns, reducing the likelihood of wound
sepsis.
Enzymatic debridement occurs when topically applied proteolytic and fibrinolytic enzymes
are used to debride the wound. It is a slower method, a major disadvantage. It is not
antibacterial, so topical antibacterial agents should be used in conjunction. Enzymatic action
softens the eschar and dissolves devitalized tissue; however, these enzymes can produce pain
and bleeding when necrotic vessels are digested. In addition, wounds can not be immediately
grafted after enzymatic debridement because of the possibility of skin graft rejection. Some
enzymatic products are used for maintenance cleansing and cannot debride eschar.
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Topical antibacterial agents are preferred over systemic antibiotic agents. Topical
antibacterial agents reduce the number of bacteria present, keeping the bacterial population to
less than 100,000 or 105 per gram of tissue, and allowing the body's own defense mechanism
to fight off invasion. Systemic antibiotics are used when systemic sepsis is likely or the
body's own defense mechanism is compromised. The use of topical antibacterial agents on
burn patients gives the clinician the necessary time to remove devitalized tissue, promote
spontaneous wound healing and to keep the wound in low bacterial population counts so
grafting can be accomplished.
The indications for grafting burn wounds is determined by the depth of the wound (fullthickness), the anatomical site of the wound and the extent of body surface that the wound
covers. If re-epithelialization is not achievable, a skin transplant is necessary. Priority areas
for skin grafting are the face (for cosmetic and psychological perception), the hands (for
increased patient activity and self-esteem), and the feet (to encourage quicker mobility and
reduce the possibility of contractures). However, when burns are extensive, the chest and the
abdomen are usually grafted first to reduce the wound surface area, superseding cosmetic and
functional considerations.
2.2.4
Proliferative Scars
Improper wound healing can result in abnormal formation or excessive formation of scar
tissue. Proliferative scars can be classified as keloids or hypertrophic scars. The primary
differentiation between these two is that hypertrophic scars remain in the wound
circumference or borders, whereas keloid scars extend beyond the wound borders.
Hypertrophic scars are more likely to occur when the injury has gone to or beyond the level
of the deep dermis, replacing normal integumentary tissue with metabolically highly active
tissue lacking the normal architecture of the skin. In hypertrophic scars, collagen bundles are
laid down in random, tight, wavy patterns, and resemble a supercoiled appearance. The
hypertrophic scar is red, raised and hardened.
Most keloids appear in darkly-pigmented skin, and may grow for years after injury. Keloids
are also prone to reoccur even after surgical excision of the initial keloid. Keloids can form
on any part of the body, but the most common sites are the neck, face, ear lobes, sternum and
upper back. Therapies for keloids include laser surgery, cryotherapy and surgical excision.
Minor scratches and vaccinations have been documented as keloid-producing. Keloids of the
earlobes are a common problem of Afro-American women and multiple holes in the ear
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increase the likelihood of keloid formation. Young children and older adults rarely produce
keloids.
2.2.5
Pressure Ulcers
The US Public Health Service through its Agency for Health Care Policy and Research has
published a series of Clinical Practice Guidelines for Pressure Ulcer Treatment. In its 1994
Quick Reference Guide for Clinicians (#15), this agency defines a pressure ulcer as “any
lesion caused by unrelieved pressure resulting in damage of underlying tissue.” Stated
another way, pressure ulcers are localized necrotic areas of tissue as a result of vascular
insufficiency in an area under continuous pressure. The term pressure ulcer has now
displaced the common historical terms of bedsore, decubitus ulcer and pressure sore.
Pressure sufficient enough to close a capillary (25-32 mm Hg) is thought to be the primary
cause of pressure ulcers. There is an inverse relationship between the amount of pressure
exerted and the time before tissue damage. Pressure ulcers are more likely to evolve from low
pressure for long periods of time, rather than high pressure for short periods.
There are two other factors that also contribute to the development of pressure ulcers:
friction and shear. An example of friction is when a patient's feet are dragged across the bed.
Shear injuries result when the head of the patient's bed is elevated, the skin stays in place but
the internal tissues and skeleton slide downward, ripping the skin away from its underlying
blood supply.
2.2.5.1 Staging of Pressure Ulcers
Usually pressure ulcers are located over bony prominences and are graded or staged to
classify the degree of tissue damage observed; however, pressure ulcers do not necessarily
progress from Stage I to Stage IV or heal from Stage IV to Stage I. Staging of pressure ulcers
in order to define the best treatment protocol is recommended by the Pressure Ulcer Advisory
Panel Consensus Development Conference.
Stage I is defined when there is non-blanchable erythema of intact skin. In individuals with
darker skin, discoloration of the skin, warmth, edema, induration or hardness may also be
indicators. Stage II defines those ulcers where there is partial-thickness skin loss involving
epidermis, dermis or both. The ulcer is superficial and presents clinically as an abrasion,
blister or shallow crater. A Stage III ulcer is diagnosed with there is full-thickness skin loss
involving damage to or necrosis of subcutaneous tissue which may extend down to, but not
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through, underlying fascia. The ulcer presents clinically as a deep crater with or without
undermining of adjacent tissue. A Stage IV ulcer is defined as a full-thickness skin loss with
extensive destruction, tissue necrosis or damage to muscle, bone or supporting structures.
These staging definitions recognize a number of limitations. Stage I ulcers may be
superficial, or they may be a sign of deeper tissue damage. Stage I pressure ulcers are not
always reliably assessed, especially in patients with darkly pigmented skin. When eschar is
present, a pressure ulcer cannot be accurately staged until the eschar is removed. Pressure
ulcer assessment in patients with casts, other orthopedic devices, or support stockings is
difficult.. Extra vigilance is required to assess ulcers under these circumstances.
Pressure ulcers usually occur over bony prominences and are scored, staged or classified
according to the degree of damage observed. However, there are many clinicians who oppose
this staging system, indicating that a pressure ulcer much like an iceberg, with just the top of
the pressure ulcer actually observed. Many clinicians and researchers would like to use a
classifying system that would graphically detail the damage from the bottom of the iceberg
and which would portray the actual tissue damage.
Stage I ulcers may be superficial, or they may be a sign of deeper tissue damage.
Stage I pressure ulcers are not always reliably assessed, especially in patients with darkly
pigmented skin.
When eschar is present, a pressure ulcer cannot be accurately staged until the eschar is
removed.
It may be difficult to assess pressure ulcers in patients with casts, other orthopedic devices, or
support stockings. Extra vigilance is required to assess ulcers under these circumstances.
Source: Pressure Ulcer Treatment, Clinical Practice Guideline, US Department of Health
and Human Services, Agency for Health Care Policy and Research, 1994
2.2.5.2 Incidence of Pressure Ulcers
Pressure ulcers are an all-too-familiar problem in medical history and, in particular, nursing
experience. Pressure ulcers and diabetic ulcers constitute the two largest categories of chronic
non-healing wounds. In 1996, there were approximately 2.9 million pressure ulcers in the
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United States, and annual costs for these types of wounds were approximately $3 billion. In
its Quick Reference Guide for Clinicians, # 15 Pressure Ulcer Treatment, the U.S.
Department of Health and Human Services (1994) states that pressure ulcers are a serious
problem that affects approximately 9% of all hospitalized patients and 23% of all nursing
home patients. Many sources indicate that approximately 2 million people per year develop
pressure ulcers that, for the most part, are preventable.
Patients especially at risk for pressure ulcers include hospitalized quadriplegic patients,
elderly patients admitted for femoral fracture and the critically ill patients. Other high-risk
patients include the entire elderly population and all orthopedic fracture patients. The most
common sites for pressure ulcer to develop are the sacrum, coccyx, ischial tuberosities,
greater trochanters, elbows, scapulae, heels, occipital skull bones, iliac crests, knees and
ankles. The majority of pressure ulcers occur in the lower half of the body, which absorbs
more of the body's weight.
The incidence of pressure ulcers in extended-care facilities is expected to increase, primarily
attributable to increased acuity of the patients. This increased acuity in extended-care
facilities is the result of shorter hospital stays, use of nursing homes for intermediate care and
an increasingly aged population with more associated multi-system diseases. The elderly
suffer 50% of the total tabulated number of pressure ulcers because of the higher prevalence
of debilitating conditions such as immobility, incontinence, poor nutritional status and other
high-risk conditions. Although the prevalence of pressure ulcers will continue to grow, it is
not expected to be proportional to the increased growth of the aged population, primarily as a
result of aggressive prevention and early treatment programs.
As pressure ulcer prevalence is increases in the acute and chronic healthcare setting,
morbidity and mortality secondary to pressure ulcer formation is also increasing. Bedfast and
chairfast patients, because of injury, surgical operation or disease/illness, are at a much
higher risk than their healthy counterparts, and can develop ulcers in as little as one to two
hours, depending on individual risk factors. The risk of pressure ulcers further increase with
immobility, nutritional deficiencies, lower mental awareness and moisture caused by
incontinence, perspiration, or wound drainage.
2.2.5.3 Therapeutic Intervention for Pressure Ulcers
Therapeutic intervention presents a significant problem for healthcare workers. Some
pressure ulcers will completely heal with a certain product while other pressure ulcers on
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either the same or different individual will not heal completely, or will not heal at all using
the same product. Just as no single technology will be therapeutic for all types of wounds, no
one product will be able to irradiate all pressure ulcers. This dilemma could possibly explain
the existence of so many wound care products available in today's marketplace. These
choices are confusing to the patient, caregiver, clinician, researcher and to medical product
manufacturers.
The treatment for pressure ulcers will be diverse, depending upon: 1) the patient's long-term
health (a terminally ill patient should not undergo aggressive and painful treatment, but rather
supportive care through positioning, oxygen delivery, nutritional supplementation, and pain
medication); 2) nutritional status; 3) perfusion and oxygenation status; 4) age; 5) normal skin
status; 6) lifestyle status (a recent quadriplegic patient or an elderly patient who has lost
his/her caregiver); 7) anatomical site on the body; and, 8) the potential for contamination
(pressure ulcers on the sacrum are at higher risk for bacterial contamination than on the
scapulae).
Pressure ulcers are open, chronic wounds, which require dressings that protect and maintain
their physiologic environment. Exhibit 2-9 lists the properties of an ideal wound dressing.
The cardinal rule for clinicians is to keep moist tissue moist and dry tissue dry. The condition
of the wound bed will predicate which type of dressing to use. Moist, not wet, dressings
provide the optimum conditions for re-epithelialization and rapid wound healing. Drying
causes scabbing to form, interfering with effective migration of epithelial cells. Drying also
causes dehydration and cellular death.
2.2.6
Venous Ulcers
Venous disease is described as an alteration in the vein integrity, resulting in decreased
venous return or thrombosis. Deep vein thrombosis combined with chronic venous valve
insufficiency is thought to be the precipitator for increased pressure in veins and venous
stasis. Over a period of time, this higher pressure causes increased stretching and weakening
of the veins, and may lead to the development of venous ulcers. However, the
pathophysiology and pathogenesis of venous disease and venous ulcer formation is not fully
understood. One hypothesis that has received much attention suggests that high venous
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Exhibit 2-9:
An Ideal Dressing
Function
Rationale
Provides moist wound
environment
Moisture promotes re-epithelialization and cellular migration
and reduces cellular death from dehydration.
Absorbs excessive fluid
Removes excessive drainage to maintain a moist environment
but not a “swamp-like” wound environment.
Permeable to air
Absorbs excessive skin moisture.
Provides protection against
microbes and further
wound trauma
Provides a bacterial barrier and supportive wound environment.
Removal of dressing
without trauma or
contamination
Protects against tissue destruction during changes and dressing
particulate/lint from entering the wound.
Provides for a drugdelivery vehicle
Able to incorporate, maintain and effectively release drug
therapies to the wound.
Provides pain relief
Provides a cooling sensation and protects against discomfort
from circulating air.
Provides thermal insulation
Prevents heat loss from the wound.
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pressure (venous hypertension) causes distention and weakening of dermal capillary beds,
consequently enlarging the endothelial pores. This allows large molecules, such as
fibrinogen, to leak out to the extravascular space and polymerize to form a peripapillary
fibrin cuff. This cuff acts as a barrier to the diffusion of oxygen and nutrients, causing
cellular death and ultimately ulceration. Precapillary fibrin is present in and around most
venous ulcers and persists over time, in spite of documented ulcer healing. Fibrin cuff
formations may simply predispose venous ulcer development. These ulcers are irregularly
shaped and have brown-colored hemosiderin pigmentation with surrounding edematous
tissue. In 1996, there were approximately 1,250,000 venous ulcers, and the rate of increase is
approximately 6% per year. For a patient with recurrent venous ulcers, the cost over a
lifetime is estimated at $50,000 with higher costs should repeated hospitalizations or
amputation be required.
2.2.6.1 Therapeutic Intervention for Venous Ulcers
Unna boots, compression dressings and wet-to-dry dressings are the most common
modalities of treatment for venous ulcers. Unna boot therapy is the continuous use of a soft
cast, applied once a week. It functions to promote venous return and prevent edema of the
leg. The main disadvantage of the Unna boot is the technical skill necessary for proper
application and fit so as to prevent leg macerations. Other disadvantages include the inability
of the patient to observe the skin during treatment and the inability to bathe while wearing
the boot.
Compression dressing methods use absorbent dressings under compression support
stockings. An even heavier support stocking can be used over the compression stocking
during periods of activity. The advantages of this treatment modality are that the patient can
remove the dressing daily, assess the status of the ulcer and surrounding skin, bathe without
concern and wear ordinary shoes. The disadvantages center on the patient’s inability to
follow directions and comply with treatment.
Wet-to-dry dressing are used for excess drainage from venous ulcers. The application of the
Unna boot or compression dressing/stocking are usually initiated once exudate is moderate.
2.2.7
Arterial Ulcers
Patients with intermittent claudication and arteriosclerosis are predisposed to arterial leg and
foot ulcers resulting from tissue hypoxia in the area of arterial insufficiency. Arterial ulcers
are common in diabetic patients who have both arteriosclerotic disease and diabetic
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peripheral neuropathy. Arterial ulcers are painful, occur most often in the lower legs
(especially toes and heels) and have well-defined wound borders. If chronic non-healing
arterial ulcers persist, the primary therapeutic focus will be to first correct the underlying
arterial insufficiency by vascular reconstructive surgery. Unsuccessful vascular surgery with
continued non-healing wounds could result in surgical amputation of the limb or appendage.
2.2.7.1 Diabetic Ulcers
Diabetic ulcers are a large and significant subtype of arterial ulcers. In the United States,
diabetic ulcer treatment costs approximately $16-$21 billion per year. Diabetic ulcers do not
heal as fast as skin ulcers on non-diabetic populations and have increased likelihood of
associated infection. Many times these ulcers become infected and traumatized, with
amputation being the only medical choice for the patient.
2.2.8
Amputations
Amputations are surgical procedures performed for multiple indications including gangrene,
peripheral arterial occlusion, non-healing ulcers, severe soft tissue infections, osteomyelitis,
trauma, tumors and deformities. In 1996, there were approximately 530,000 amputations in
the United States, and treatment costs associated these procedures are about $1.5 billion per
year.
Amputation, as a result of a non-healing ulcer or wound, represents a significant clinical
problem. In addition, the personal and societal costs of an amputation include the time lost
from work during hospitalization and rehabilitation, loss of future earning power, increased
reliance on social programs and frequently a reduction in the quality of life.
Although in many situations, amputation is the most appropriate course of action (chronic,
infected, non-healing or gangrenous wounds), unilateral amputations increase the risk of
contralateral amputations, particularly in diabetic patients. The unilateral diabetic amputee
changes walking and weightbearing patterns, causing the remaining foot to become
deformed, and frequently results in pressure points and ulcerations.
2.2.9
Acquired Immune Deficiency Syndrome
Acquired Immune Deficiency Syndrome (AIDS) is an immune deficiency acute/chronic
disease which will significantly effect the market for wound care products and wound healing
services. Due to the immunosuppression of patients with AIDS, even small bug bites can
evolve into deep crater-like ulcers. These wounds must be treated aggressively to reduce
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further involvement and microbial contamination. Skin care products (adhesive dressings,
tapes and antiseptics) will need to be modified to protect the often fragile skin of the AIDS
patient. Such patients are treated in hospitals, nursing homes and the home care environment.
The skin of the AIDS patient becomes drier as the syndrome progresses. As the CD4 positive
T-cell count falls below 400 cells/mm3, pruritus and erythematous patches appear on the skin,
progressing to ichthyosis, manifested by thick, large, polygonal scales on the skin. Ichthyosis
is typically found on lower extremities. Histological changes include hyperkeratosis with a
thinner granular layer. Treatment includes application of emollients containing alpha hydroxy
acids or urea to improve skin appearance, and topical corticosteroids to heal eczematoid
lesions. If pruritus is unresponsive to antihistamines, ultraviolet light phototherapy may
reduce the itching. Seborrheic dermatitis is the most common skin disease in AIDS patients
at a frequency of 40% to 83% of all cases and is often the initial symptom of HIV infection.
From 1981 to the end of 1996, a total of 573,800 persons with AIDS over the age of 13 had
been reported to the Centers for Disease Control. Lifetime costs of treating AIDS have
increased to greater than $150,000, and it is conservatively expected that lifetime AIDS
treatment expenses will exceed $200,000 by the year 2000. From the point of diagnosis, HIV
patients are living an average of 15 years, making this disease both a chronic and catastrophic
one in description.
2.3
Wound Healing Biological Factors
Wound healing is a complex process, with no single factor responsible for normal healing.
Understanding of cellular and biochemical events involved for wound healing is incomplete,
but knowledge of the wound healing process is mounting. This is an exciting era for wound
healing. Much of the current research is devoted to understanding the biochemical
interconnections and cascade mechanisms for wound healing and determining at what level
in this cascade process intervention will have the greatest impact on wound management.
Wound healing begins the moment a wound is made and continues for years. The Wound
Healing Society defines a wound as a disruption of normal anatomic structure and function.
An ideally healed wound proceeds through an orderly and timely reparative process which
results in sustained anatomical restoration and functional integrity. Chronic wounds fail to
proceed through this process, resulting in poor anatomical restoration and/or reduced
functional integrity.
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Wounds can be divided into two groups: wounds without tissue loss (primarily surgical
wounds which heal by direct union, also referred to as primary intention) and wounds with
tissue loss (such as burns and ulcers, which must heal by indirect union or secondary
intention). Wound healing has three major phases: inflammatory phase, proliferative phase
and maturation phase.
2.3.1
Inflammatory Phase
The initial response of the body to wounding is vasoconstriction of the blood vessels, which
lasts 5 to 10 minutes. During this process several different types of cells are recruited to the
wound area to defend and revitalize traumatized tissue. Platelets first aggregate and promote
the deposition of fibrin for clot formation. Although the actual role of platelets in subsequent
phases has been debated, it is well accepted that platelets produce many substances that
induce other wound healing events. Platelets release collagenase (an enzyme that breaks
down/degrades collagen) and a collagenase inhibitor (to stop the degradation of collagen).
Platelets are necessary for the ensuing proliferative phase to occur. After the initial
vasoconstriction event, the surrounding tissues become ischemic and release chemicals
including histamines and kinins to induce vasodilation.
Vasodilation increases vascular permeability and results in leakage of elements (proteins,
enzymes and fluid) into the wound space and surrounding tissue. Fibrin is deposited into
lymphatic systems, which causes lymphatic blockage and subsequent edema and tissue
warmth. The classic signs of inflammation swelling, redness and heat are apparent. Next,
both leukocytes (neutrophils) and macrophages migrate to the wound area and up the hair
shafts. Leukocytes function to digest and transport organic debris from the wound site.
Macrophages originate from blood monocytes, and their function is to debride the wound,
regulate fibroplasia and to degrade collagen in the healing process.
Neutrophils are effective in phagocytizing or destroying bacteria, if the bacterial count is less
than 105 per gram of tissue. However, should bacterial contamination occur, the acute
inflammation phase will persist and interfere with the next phase of wound healing. In a
chronically inflamed wound, neutrophils and wound debris are the chief components of pus.
Infection initially is the most important obstacle to alleviate before proper wound healing will
begin. Infection can result from endogenous and exogenous bacterial flora. Additionally,
macrophages also function to release angiogenic factors stimulating the formation of new
blood vessels while releasing growth factors that stimulates cellular growth during the
proliferative phase. Macrophages also produce and release enzymes, inhibitors, and
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complement factors. When experimentally removed from a wound, debridement becomes
inhibited and wound repair slows. Experimental removal of neutrophils from a wound does
not retard repair but does increase the risk of bacterial invasion.
The replacement of dead or damaged tissue by new and healthy tissue begins with a process
known as epithelialization. Epithelial cells migrate from the wound's border, moving across
the wound from all edges to form a seal over the wound. Migration continues until the
epithelial cells from the edges make contact with one another, inducing a process called
contact inhibition (prohibiting further cellular migration). Epithelial cells are guided in their
migration by scaffolding, which is the formation of a network of fibrin strands. In a primary
healing wound, fibrin closes the wound in a few hours, and epithelialization begins within 1
to 2 days. In secondary healing wounds, the epithelialization process is much slower. Once
epithelialization is complete, the wound will stop weeping body fluid and electrolytes, and
will be protected from bacterial invasion. Exudate contains active leukocytes. It is produced
during the inflammatory phase, acts as a culture medium to enhance the migration and
mitosis of epithelial cells and protects against bacterial invasion. Moist exudate prevents the
wound from dehydration, cellular death and scab formation, and eliminates increased woundborder maceration. The main function of the inflammatory process is to recruit needed cells,
remove debris, seal the wound and prepare the wound for the regeneration of new tissue.
2.3.2
Proliferative Phase
While wound healing is a cascade process, the steps are not discrete, they overlap one
another. The proliferative phase, angiogenesis, begins on the third day following wounding
and continues for the next 14 days. The primary function of the proliferative phase is to
develop tissue as epithelial cells continue to migrate across the wound. The main cell type in
this phase is the fibroblast, a multiplier and synthesizer of collagen. Fibroblasts also
synthesize proteoglycans or ground substance, which forms the scaffolding matrix for the
migration of cells. Macrophages are still present in the wound site.
Collagen, as the principle component of connective tissue, fills the tissue and provides wound
strength. Bud-like capillary structures form, penetrating the wound and providing the
nutritional support for the newly generated tissue. This tissue appears bright red and granular.
Granular tissue is very fragile and produces a difficult terrain for advancing epithelial cells.
Granulation tissue contains a dense population of macrophages, fibroblasts and new capillary
vasculature embedded in a loose matrix of collagen, fibronectin and hyaluronic acid.
Granulation tissue causes the wound edges to contract and begin to form scar tissue. As the
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production of collagen dissipates, these vascular channels regress, and the wound transforms
from a vascular-rich, cellular tissue to avascular, cell-free scar composed of dense collagen
bundles. The main functions of the proliferative phase are collagen synthesis and tissue
growth.
2.3.3
Maturation Phase
During the maturation phase of wound healing , the wound takes on its permanent form. As
the wound matures, its collagen undergoes remodeling. This usually begins on day 14,
although primary and secondary wounds progress differently in this phase. In the primary
wound, maximum collagen synthesis is at day 42, establishing an equilibrium between
collagen synthesis and collagen degradation. During this time, the collagen fibrils and fibers
become dehydrated and re-weave into a tight pattern, and the scar fades to silvery white This
color results from the regression of capillary beds and fibroblasts. The scar becomes less
bulky and continues to gain tensile strength, although no wound will ever regain the full
strength found in the original tissue. Most wounds will reach a maximum of 70% of the
original tissue’s tensile strength within two years after injury.
Secondary wounds may not begin to differentiate collagen for months or years after injury
because they heal by wound contraction. Myofibroblasts are specialized cells that appear in
contracting wounds, functioning to provide collagen synthesis and contractility. Contraction
begins on the fifth day after wounding, overlapping both the proliferative and maturation
phases. The contraction process occurs by the movement of the surrounding skin to the center
of the wound. The main functions of the maturation phase in both primary and secondary
wounds is the growth and development of new tissue and the strengthening of scar tissue.
2.4
Complications Affecting Wound Healing
Factors that inhibit or prevent proper wound healing can be categorized as local or systemic
factors. The local environment of the wound needs to have optimal conditions of
temperature, hydration, nutrients, oxygenation and waste removal for mechanism of wound
healing to progress. These mechanisms include epithelialization, collagen formation,
angiogenesis and wound contracture. Systemic factors that inhibit proper wound healing
include patient age, nutrition status, pharmacological medications, other disease conditions
and emotional stress.
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2.4.1
Local Factors
Local factors affecting wound healing include surgical technique, blood supply, hypoxia,
infection and radiation. Each of these are discussed in the sections below.
2.4.1.1 Surgical Technique
Good surgical technique is more than just proper handling of the tissue; it also involves
meticulous hemostasis, eliminating dead space between tissue layers when closing the
surgical wound and preventing collection of serum or formation of hematomas, which are
excellent media for bacterial growth. If sutures are too tightly tied, wound tension will be
increased, leading to decreased blood flow and necrosis of the tissue.
2.4.1.2 Blood Supply
Adequate blood circulation to the wound controls wound healing. Blood supplies the wound
with oxygen, cells and nutrients for wound repair. Decreased blood supply, due to disease,
anatomical location of wound or the amount of circulating blood, affects the ability and the
length of time for wounds to heal. If blood volume is low, nutrients and tissue oxygenation
will be inadequate resulting in impaired wound healing.
2.4.1.3 Hypoxia
Adequate tissue oxygenation is vital for the healing process. Hypoxia conditions may result
either from inadequate blood flow to the wound site or from decreased blood oxygen.
Diseases that provide inadequate oxygen intake or alkalemia states contribute to hypoxia.
The most significant wound-tissue hypoxia occurs in surgical patients with radical
mastectomy or abdominal, cardiac or vascular wounds because they have not received
enough oxygen during surgery.
2.4.1.4 Infection
Infection is the root of most “evils” that occur in the wound healing process; it leads to
serious complications, prolonged healing and increased healthcare costs. Acute wounds such
as surgical incisions require vigilant care. Many surgical wound infections result from poor
aseptic technique. Proper cleansing of the skin prior to incision and regular cleaning of the
site and areas surrounding the wound will assist to reduce bacterial invasion of acute wounds.
The cost of infections acquired while the patient is hospitalized, nosocomial infections, are
not reimbursed to the hospital. The added hospital stay to treat a surgical wound infection
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averages 7 extra days, with the maximum at 68 days. The additional cost to treat the surgical
wound infection averages $2,800, with the maximum at $28,000. An average 250-bed acute
care hospital accounts for $1 million in non-reimbursed expenses to treat nosocomial
infections.
When an infection is diagnosed, the wound must be debrided before normal wound healing
can occur. Care should be exercised in the prescribing of antibiotics; rampant or
indiscriminate use of antibiotics on wounds increases the proliferation of antibiotic-resistant
bacteria. Both hypoxic conditions and poor blood circulation in the wound increase the risk
for tissue necrosis and infection. Systemic antibiotics are recommended for cellulitis, sepsis
or osteomyelitis.
2.4.1.5 Radiation
Side effects from radiation treatments include suppression of leukocyte production, which
increases the risk of infection in ulcers. Radiation for treatment of cancer causes secondary
complications to the skin and underlying tissue. Early signs of radiation side effects include
acute inflammation (redness, heat and pain), exudation (skin weeping) and scabbing. Later
signs, four to six months after radiation, includes woody, fibrous and edematous skin.
Advanced radiated skin appearances can include avascular tissue and ulcerations in the
circumscribed area of the original radiation. The radiated wound may not manifest until 1020 years after the termination of radiation therapy.
2.4.2
Systemic Factors
A number of systemic factors can influence the rate of wound healing. This section of the
report considers the most important of these factors: age, nutrition, pharmacologic
influences, diabetes and other diseases, and emotional stress.
2.4.2.1 Advanced Age
The physiologic changes occurring with advanced age generally cause the elderly to heal
more slowly than younger persons. Wound healing in the elderly occurs at a much slower
pace and wound separation or dehiscence occurs up to three times more often in people over
the age of 60. This slower rate of wound healing is attributable to the aging process itself,
multiple medical conditions, frequent surgical procedures, inadequate hydration and poor
nutritional status. The elderly experience decreased epidermal turnover for new skin
replacement, increased skin fragility and decreased tissue tensile strength. In addition, the
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number of dermal blood vessels is diminished with advanced aged, making the elderly more
susceptible to injury.
Most of the elderly have at least one chronic condition and many have multiple conditions.
The most frequent diseases or conditions for the elderly are: arthritis (48%); hypertension
(38%); hearing impairment (29%); heart disease (28%); cataracts and orthopedic impairment
(16% each); sinusitis (15%); diabetes (9%); and visual impairment and varicose veins (8%
each).
The elderly account for 33% of all hospital stays and 45% of all days of care in hospitals.
With the baby boomer generation nearing age 65 and over, these statistics are expected to
increase. By the year 2030, it is estimated that the over 65 population will represent 20% of
the entire population (60 million senior citizens).
2.4.2.2 Nutritional Status
A critical role in the wound healing process is attributed to nutrition. Malnutrition, often
present in critically ill patients, can develop from a variety of factors and can lead to harmful
effects, including poor wound healing. Malnutrition in patients with wounds can be caused
by inadequate intake, absorption and or utilization difficulties with nutrients, particularly
protein and calories, in relation to increased metabolic demands that may occur with
concurrent disease states.
Caregivers must be concerned with appropriate physical assessment and intervention related
to nutrition to improve the patient’s wound healing process while minimizing the potential
for related complications such as infection. Nutritional support in a patient with a wound
includes adequate intake provided by a balance of carbohydrates, fat, protein, electrolytes,
vitamins (especially Vitamin C) and trace elements (especially zinc). Specific nutrient needs
in the critically ill or elderly patient with a wound are different from those in patients who are
younger and less ill. Caloric energy needs are increased in these patients
2.4.2.3 Pharmacological Medications
The inflammatory phase is inhibited by steroid therapy causing prolonged healing time.
Topically applied vitamin A may counteract the effect of steroid therapy on wound healing;
therefore, it may be a useful adjunct therapy for patients requiring steroid therapy during
wound healing. Other drugs, such as anticoagulants, phenytoin, anti-neoplastic agents,
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penicillamine and nonsteroidal anti-inflammatory drugs delay or impair the wound healing
process.
2.4.2.4 Diabetes and Other Diseases
Diabetics suffer from impaired circulation and neuropathy, which can result in trauma and
hypoxia of the skin. Insulin deficiency impairs leukocyte function, increasing the risk of
infection and reduced cellular proliferation in both acute and chronic wounds. Therefore,
diabetics have more difficulty resisting wound infections and heal more slowly than patients
without diabetes. Diabetics have a five-fold greater risk of developing infection than
nondiabetic persons.
Patients with hemophilia, hepatic disease, thrombocytopenia and clotting factor deficiencies
are predisposed to prolonged bleeding and delayed wound healing.
Uremic patients have increased risk of infection, delayed granulation, faulty collagen
deposition and increased wound dehiscence; therefore, patients in renal failure will have
delayed or impaired wound healing.
2.4.2.5 Emotional Stress
Although the exact mechanism is not fully understood, emotional stress is thought to slow
wound healing. During times of increased negative stress, increased adrenaline is produced
and released in the body, resulting in decreased rate of epidermal cell division and
maturation. When sleep and relaxation are enhanced, there is a decreased production of
adrenaline and increased rates of epidermal cell division and maturation.
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Chapter 3: Cleansing, Debridement and Granulation Agents
3.
CLEANSING, DEBRIDEMENT AND GRANULATION AGENTS
Prior to any invasive intervention, and as an adjunct to any therapeutic management of
wounds and ulcers, the skin and wound must be cleansed. In addition, debridement of
devitalized tissue, especially in traumatic injuries, must be completed before wound closure
and healing can occur. Several different types of products are used to accomplish these goals,
including cleansing, debridement, and granulation agents. Each of these products are
discussed in the sections below.
3.1
Cleansing Agents
Before most wounds can be permanently closed, the clinician must meticulously cleanse the
wound or ulcer. However, open wounds have delicate wound beds and must be handled with
care. A variety of appropriate methods and cleaning agents are available, and the clinician
must take care in the choice of these agents, as the very act of cleaning the wound could
cause harm. The caregiver must weigh the potential for traumatizing the wound bed by
cleaning it against the benefits of a clean wound. In its December 1994 clinical practice
guideline for treating pressure ulcers, the Agency for Health Care Policy and Research
(AHCPR) tried to settle this issue, as recommendations are supplied in Exhibit 3-1.
Soap and water cleansing is often used in conjunction with a saline solution irrigant. The
combination of the detergent/surfactant and flushing mechanism provides adequate cleaning
of non-infected wounds as well as skin cleansing. Wounds should be cleaned on first
encounter and at each dressing change. Normal saline is generally the best cleaning solution,
and the use of topical antiseptics such as iodine or povidone-iodine are discouraged.
Irrigation of the wound is recommended to remove debris.
When irrigating a wound, flushing with a bulb syringe delivers only two pounds per square
inch (psi) of pressure, which is an insufficient amount of pressure for wound cleansing.
Water-Piks, on the other hand, can introduce 50-70 psi, which traumatize wound beds.
The ideal pressure for wound cleansing is 8 psi, which can be achieved with a 35 cc syringe
and a 19-gauge needle (or 19-gauge angio-catheter) with the tip at one to two inches from the
wound surface. Exhibit 3-2 illustrates various mechanisms used to irrigate wounds.
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Exhibit 3-1:
Recommendations for Wound Cleaning
•
Clean a wound initially and at each dressing change. If cleaning with gauze, cloth or
sponges, use minimal mechanical force—traumatized wounds are more susceptible to
infection and are slower to heal. Also, aggressive mechanical force can disrupt the
growth of new granulation tissue. Coarse wound-cleaning materials can cause greater
friction and trauma, so choose the least-coarse product available.
•
Normal saline is generally the best cleaning solution because it is physiologic, will
not harm tissue, and will adequately clean most pressure ulcers. Do not use skin
cleansers or antiseptic agents such as povidone-iodine, sodium hypochlorite solution,
hydrogen peroxide, or acetic acid. These solutions are cytotoxic. However, consider a
wound cleanser without these harmful chemicals if normal saline cannot adequately
clean the wound.
•
Irrigate the wound with enough pressure to enhance wound cleaning without
traumatizing the wound bed. This is generally between 4 and 15 pounds per square
inch (psi). Pressures below 4 psi might not adequately clean the wound; pressures
greater than 15 psi may cause trauma and drive bacteria into the tissue. Irrigation
devices that deliver 8 psi of pressure are significantly more effective than a bulb
syringe in removing bacteria and preventing infection.
•
Consider whirlpool treatments to clean a pressure ulcer (or wound) containing thick
exudate, slough, or necrotic tissue. Be careful; the high-pressure water jets can
traumatize the wound if they are too close to the wound. Discontinue the whirlpool
when the wound is clean.
Source: Quick Reference Guide for Clinicians, Clinical Practice Guideline, Pressure Ulcer
Treatment, US Department of Health and Human Services, December 1994
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Exhibit 3-2:
Evaluation of Irrigation Device
Irrigation Impact
Pressure
Adequacy
Device
Not enough pressure
Spray bottle
1.2
Bulb syringe
2.0
Piston irrigation syringe (60 ml) with
catheter tip
4.2
Saline squeeze bottle (250 ml) with
irrigation cap
4.5
Adequate pressure
Water Pik at lowest setting
6.0
35 ml syringe with 10 gauge needle
or angio-catheter
8.0
Too much pressure
Water Pik at middle setting
42.0
Water Pik at highest setting
>50.0
Note: Irrigation impact pressures are reported in pounds per square inch.
Source: Beltran, K., Thacker, J. and Rodeheaver, G., “Impact Pressures Generated by
Commercial Wound Irrigation Devices,” unpublished research report, Charlottesville, VA,
University of Virginia Health Sciences Center, 1994
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Mild cleansers consisting of liquid preparations of surfactants are also used to remove wound
debris. These cleansers may also contain antiseptic (which inhibits bacterial growth) or antimicrobial (which destroy and suppress microorganisms) ingredients.
3.1.1
Common Cleansing Agents
There are three categories of cleaning agents: soap and water, mild skin cleansers, and topical
antiseptic and antibiotic agents. Antiseptics include products such as povidone-iodine,
hydrogen peroxide, Dakin's solution (sodium hypochlorite), acetic acid, and boric acid.
Povidone-iodine is a broad-spectrum drug, with microbiocidal action on gram-positive,
gram-negative, yeast, virus, and protozoa bacteria. However, full-strength povidone-iodine
has a deleterious effect on wounds and healing tissues. In addition, high concentrations of
acetic acid, hydrogen peroxide and Dakin's solution are 100% cytotoxic to fibroblasts: these
solutions interact with the cell membrane causing cellular death.
While indiscriminate use of antiseptics on wounds can delay wound healing, topical
antibiotics appear to better prevent bacterial contamination. Antibiotics should be applied to
wounds only after cleansing with an irrigant used for specific treatment regimens and only
for a short period of time. Antibiotics are biologically derived products that inhibit microbial
function, and full-strength use of bacitracin, neomycin, and kanamycin are not cytotoxic to
human fibroblasts. Neomycin absorption from deep wounds, however, may lead to
cytotoxicity and nephrotoxicity: this antibiotic should be used in superficial wounds only.
Fladyl (metronidazole), a bactericidal agent, is used for anaerobic infections.
3.1.2
Drug-Resistant Bacteria and the Effects of Wound Cleaners
With the increasing threat of drug-resistant bacteria, many clinicians are concerned with the
possibility of the development of pathogens resistant to all available drugs in the near future.
For instance, the incidence of vancomycin-resistant enterococci (VRE) infections have grown
dramatically in hospitals over the last several years, and treatment options are often limited to
experimental antimicrobial compounds because many strains of VRE are also resistant to
penicillin and other antibiotics. In response to this growing problem, wound care experts are
adhering to stringent infection control measures and exercising judicious use of antibiotics.
These clinicians are returning to a regime that stresses the basics, such as hand washing,
restrained use of antibiotics, proper cleansing and debridement of wounds, and the use of
gloves and gowns.
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Of primary concern with wound care professionals are VRE and methicillin-resistant
Staphylococcus aureus (MRSA). These bacteria can be found on equipment and other
surfaces, and can be spread from the unwashed hands of healthcare workers to the patients in
their care. S. aureus, the most common cause of postoperative wound and skin infections,
was treated with antibiotics until the 1980s when strains resistant to methicillin and other
antibiotics began to appear. Today, MRSA can be treated successfully with vancomycin;
however, scientists are predicting that a resistance to vancomycin may be imminent.
Epidemiologists theorize that VRE may transfer its vancomycin resistance genetically to
S. aureus, creating vancomycin-resistant Staphylococcus aureus (VRSA).
3.1.3
Competitors and Products
ConvaTec’s SAF-Clens is a dual surface surfactant system for cleansing wounds with
moderate- to high-foaming capabilities, while Bard’s Biolex provides an acidic pH and a
moist environment to promote wound healing. Carrington Laboratories has several types of
wound cleansers for use on intact skin and for cleansing stage I-IV ulcers. The first product,
Carra-Klenz, has aloe for removing necrotic tissue, while their second product, Ultra-Klenz,
is a gentle cleanser with physiological pH and osmolality. Carrington also has a antimicrobial
cleanser called MicroKlenz which is used for infected wounds. In addition, the company has
products for treating radiation dermatitis: RadiaCare Klenz and RadiaCare Oral Wound
Cleanser. The latter product is a freeze-dried powder with aloe vera gel extract and
acemannan hydrogel which relieves pain in the mouth by adhering to tissue and protecting
against further irritation. These competitors and other manufacturers in the wound care
cleanser market (excluding antibiotics and antiseptics) are presented in Exhibit 3-3.
3.1.4
Market Analysis
Wound cleansers are likely to experience significant growth over the next several years due
to more advanced products being introduced to the market. As the cytotoxicity of traditional
cleansers becomes more evident and the restrained use of antiseptics is encouraged, the
market for specialized cleansers will increase, fueling overall wound cleanser growth. In
addition, as the use of hydrogels and hydrocolloids increase, specialized wound cleansers
may be required for their removal, thus boosting demand for these wound cleansers.
Managed care, however, will take a critical look at pricing and efficacy. Providers in this
environment may begin to substitute cheaper, self-made saline products instead of using the
ready-made, more costly cleansers. Exhibit 3-4 presents the forecast for the wound cleanser
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Exhibit 3-3:
Selected Manufacturers of Wound Cleansers
Company
Product
Bard
Biolex
Carrington Laboratories
CarraKlenz, Ultra-Klenz, RadiaCare Klenz,
and DiaB Klenz
Coloplast
Sea Clens
ConvaTec
SAF-Clens; Shure-Clens
DermaRx
DermaMend
Derma Sciences
Dermagran
Gentell
Gentell Wound Cleanser
Healthpoint
Curasol
Kendall
Curaklense
MPM
MPM Wound & Skin Cleanser
Sherwood/Davis & Geck
Constant-Clens Dermal Wound Cleanser
Swiss America
Elta Dermal
Note: Exhibit excludes antiseptics and antibiotics.
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Exhibit 3-4:
U.S. Wound Cleanser Market Forecast, 1996-2002
Year
Sales
Growth
1996
$16.4M
—
1997
18.5
12.8%
1998
21.2
14.6
1999
24.6
16.0
2000
28.1
14.2
2001
31.5
12.1
2002
35.0
11.1
CAGR 1997-2002
13.6%
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market from 1996 to 2002. This forecast assumes an increased prevalence in MRSAs and
possibly VRSAs, thereby increasing the need to reduce bacteria colonization by using wound
cleansers.
In 1996, approximately 61% of wound cleansers were used in the hospital environment,
while 39% were applied in non-hospital sites. In the non-hospital sites, 39% of cleansers
were used in subacute and long-term care facilities, 31% were administered in the home and
30% were applied in physicians’ offices and ambulatory clinics. By the year 2002, the nonhospital mix is expected to grow to 42%, while the hospital segment will decrease to 58%.
Within the non-hospital mix in 2002, 27% will be used in subacute and long-term
facilities, 36% will be applied in physicians’ offices and ambulatory clinics and 37% will be
administered in the home environment.
3.1.5
Competitive Analysis
Most of the competitors in this arena have products in other segments of the wound care
market; for example, ConvaTec competes in the dressing market as well. The largest
competitors in this market include ConvaTec with 31% of the market and Carrington
Laboratories with 19% of the market. Due to Carrington’s expansion of its product line in
1996, this company is expected to increase in market share over the next year. Specific
products that will help boost Carrington’s market share include RadiaCare Klenz and the
DiaB Klenz. The company estimates that DiaB Klenz will target a market of 1.2 million
diabetics who suffer with lower extremity skin ulcers. As shown in Exhibit 3-5, other
competitors in the market include Bard, Sherwood-Davis & Geck and Coloplast.
3.2
Debridement and Granulation Agents
Traumatic injuries are frequently associated with dirt and foreign debris in a wound bed, and
chronic wounds are likely to have necrotic tissue in the wound. There are various methods for
debridement, but all can be classified as either mechanical, autolytic or chemical/ enzymatic.
3.2.1
Mechanical Debridement
Mechanical debridement can be achieved using surgical instruments, lasers, moist-to-dry
dressings, maggot therapy, vigorous irrigation of wound beds or hydrotherapy. Moist-to-dry
dressings, the most common method, use sterile gauze which is dampened with normal saline
and placed in the wound. As the gauze dries, the necrotic tissue sticks to the gauze. When the
gauze is removed, usually eight hours later, the necrotic tissue is removed with the gauze.
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Exhibit 3-5:
1996 Wound Cleanser Market, Share by Supplier
Supplier
ConvaTec
Carrington
Laboratories
Sales
Market Share
$5.1M
3.1
31%
19
Bard
Sherwood/Davis &
Geck
1.6
10
0.8
5
Coloplast
0.8
5
Other*
5.0
30
Total
$16.4M
100%
*Other includes DermaRx, Derma Sciences, Gentell, Healthpoint, Kendall, MPM and Swiss
America.
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Mechanical debridement is usually used when necrotic tissue must be removed faster than
autolytic or chemical debridement. Moist-to-dry debridement can be painful, and it can also
remove both nonviable and viable tissues.
Maggot therapy is used by some clinicians for debriding necrotic wounds because it is
usually painless and is selective for necrotic tissue. The larvae of blowflies is put into the
wound, and usually within one week, the larvae have cleared the wound of necrotic tissue. In
addition to eating necrotic tissue, the maggots secrete antibacterial enzymes and stimulate the
growth of granulation tissue through their movement.
The disadvantage of hydrotherapy or irrigation of wound beds is that they debride nonselectively and may injure or remove new epithelial tissue along with the necrotic tissue. In
addition, some experts believe that hydrotherapy drives organisms deeper into tissues.
Therefore, hydrotherapy and irrigation are contraindicated in hard eschar wounds and should
be discontinued once granulation tissue is apparent.
There are various types of devices used for mechanical debridement with irrigation solutions.
Ackrad Laboratories manufacturers the Irriject DS Wound Irrigation System. This device
provides mechanical debridement by using a syringe device with tubing, replaceable tips and
splash guard for the irrigation solution. Stryker Instruments offers the SurgiLav Plus Hydro
Debridement System which provides a variety of tips, all under 15 psi, and splash shields in
different sizes.
Sharp debridement or surgical debridement is the most effective method to remove grossly
necrotic tissue. The wound is removed in layers until viable, bleeding tissue is obtained.
Surgical debridement (forceps/scissors or tangential excision) is a relatively long surgical
procedure, necessitating general anesthesia for the intense pain involved and results in
considerable blood loss. Often a patient is hemodynamically weak and unable to immediately
undergo such surgical debridement.
3.2.2
Autolytic Debridement
Autolytic debridement is performed with semi-occlusive and occlusive dressings, usually
hydrocolloids, hydrogels and transparent films. These dressings provide the medium for the
body's own wound exudate enzymes to liquefy necrotic tissue. They also provide a painless
debridement for degradation of thin eschar. Autolytic debridement does not damage the
surrounding skin, but may stimulate anaerobic growth when hydrocolloids are used.
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This type of debridement process uses the patient’s own phagocytic cells and proteinase
enzymes in the wound tissue. The autolytic process requires moisture so that phagocytic cells
can move freely and to promote the digesting function of the proteinases. Flushing of large
wounds on a periodic basis is also required to eliminate the inhibitory by-products of the
phagocytic cells and proteinases. Autolytic debridement is a slow process and is used where
there is minimal necrotic tissue and a low risk of infection.
Horizon Medical offers Stericare glycerin hydrogel which is formulated for partial- and fullthickness ulcers, first- and second-degree burns and venous leg ulcers. In December 1996, the
FDA approved Derma Sciences’ Dermagran Hydrophilic Wound Dressing for marketing a
new indication, as a debriding product. Prior to the approval, the dressing was used to
accelerate the healing process after surgical incisions, skin ulcerations, stage I-IV pressure
ulcers, minor lacerations, diabetic ulcers, partial-thickness burns and hypothermia burns.
Other autolytic dressing are discussed in the wound dressing chapter in this report.
3.2.3
Enzymatic/Chemical Debridement
Chemical or enzymatic debridement is achieved through non-prescriptive chemical agents or
topical prescriptive enzymes. Chemical agents are used to absorb exudate, maintain a moist
wound environment, prevent eschar formation and promote epithelialization. These types of
agents are used primarily in exudating or secreting wounds.
Enzymatic agents attack denatured collagen and liquefy necrotic tissue and usually take
effect in 3-30 days. Enzymatic debridement can be problematic because the agents are slow
acting, can cause pain, and are not tissue-specific for necrotic tissue. These agents must be
discontinued as soon as debridement is achieved, so as not to damage newly formed
granulation tissue.
Enzymatic debriding agents are generally supplied in ointment or powder form. Most
common is the ointment form applied 1-3 times per day for a period of 3 to 15 days.
Examples of enzymatic debridement agents include papain, which is a proteolytic agent, and
fibrinolysin-deoxyribonuclease, which dissolves fibrin clots and hydrolyses proteinaceous
exudate. Collagenase and streptokinase-streptodornase digest collagen and denatured protein.
3.2.3.1 Competitors and Products
Granulex (Dow Hickam) is a vasodilating, lubricating spray applied to wound beds to
enhance tissue granulation. This topical spray also contains trypsin, which results in a mild
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debriding action. Granulex is a prescription drug and is marketed as a wound stimulant, not
specifically as a debridement agent. The product is unable to debride thick eschar or hard
necrotic tissue; however, it stimulates the blood supply and maintains a moist environment
for optimum healing. Some companies in this market, however, consider Granulex a
debriding agent. Dow Hickam also markets Proderm, which has many of the therapeutic
properties of Granulex, but this product is an over-the-counter aerosol.
Parke-Davis (Warner Lambert) manufacturers Elase ointment and Elase-Chloromycetin
ointment; both of these products are marketed by Fujisawa USA. Elase contains fibrinolysin
which debrides the fibrin of blood clots and fibrinous exudates, while the deoxyribonuclease
digests DNA.
Healthpoint Medical manufactures a papain-urea debriding ointment called Accuzyme.
Papain is a proteolytic enzyme which debrides over a wide pH range of 3 to 12, but it
becomes inactive in the presence of heavy metal salts, such as lead, silver and mercury.
Contact with these substances, therefore, needs to be avoided. In addition to papain,
Accuzyme contains urea which is a protein solvent that helps in the debriding action by
exposing protein substrates to complete proteolysis. The product also contains purified water,
emulsifying wax, glycerin, isopropyl palmitate, potassium phosphate monobasic,
methylparaben and propylparaben.
Pharmacia Upjohn manufacturers Debrisan for Johnson & Johnson which has licensed the
marketing rights. Debrisan is offered as beads or paste, and is used on necrotic tissue,
infected surgical incisions and infected foot ulcers. This product debrides the wound by
absorbing bacteria and exudate.
Knoll Pharmaceutical offers Collagenase Santyl, which is the only enzymatic debridement
agent that specifically attacks collagen. This product is mentioned in the AHCPR Clinical
Practice Guideline for the Treatment of Pressure Ulcers and is usually applied once per day.
Introduced by Rystan in 1956, Panafil consists of papain, urea and chlorophyllin-copper
complex . The latter ingredient promotes healing and deodorizes the wound. The company
also makes Panafil White which does not contain chlorophyllin copper complex.
Exhibit 3-6 summarizes the chemical/enzymatic debridement manufacturers and product
brand names.
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Exhibit 3-6:
Chemical/Enzymatic Debridement Agents
Company
Product Brand
Name
Chemical/Enzymatic
Ingredient
Dow Hickam
Granulex
Trypsin
Fujisawa USA/Parke Davis
Elase
Fibrinolysin/deoxyribonuclease
Healthpoint
Accuzyme
Papain/urea
Johnson & Johnson/Pharmacia
Upjohn
Debrisan
Dextranomer hydrophilic beads
Knoll Pharmaceuticals
Santyl
Collagenase
Rystan
Panafil
Papain/urea/chlorophyll
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3.2.3.2 Enzymatic/Chemical Debridement Development Status
Genzyme Corporation has been developing Vianain, an enzymatic debridement agent.
Vianain consists of two proprietary enzymes, ananain and comosain, derived from two
pineapple stem proteases and formulated into a hydrophilic cream. Vianain rapidly removes
non-viable tissue from burn sites, minimizes blood loss and reduces the number or duration
of surgical debridement procedures. The hydrophilic-based product promotes hydration of
the burn eschar, provides efficient enzyme delivery and facilitates post-treatment cleansing.
Genzyme received an orphan drug designation for Vianain, and licensed the product to
Neozyme Corporation prior to Genzyme’s acquisition of Neozyme in late 1996. Genzyme
does not plan to commercialize the product, and is exploring licensing the product.
3.2.3.3 Market Analysis
With greater frequency, acute care hospitals are using autolytic debridement with semiocclusive and occlusive dressings for noninfected wounds, or these institutions use faster
surgical debridement because they are pressured to decrease patient length of stay. Nursing
homes and home healthcare, however, continue to use enzymatic debridement because of the
lower cost of these products. In 1996, approximately 33% of the $74.2 million
chemical/enzymatic debridement market’s products were used by hospitals, while alternate
care facilities used products in the remaining 67% of the market. Subacute and long-term
care facilities, including nursing homes and hospices, composed 60% of the non-hospital
market; physicians’ offices and ambulatory clinics were 15% of the non-hospital market; and
home healthcare was 25% of the market.
The enzymatic/chemical debridement market is forecasted to grow at an average annual
growth rate of 3.6% to $91 million in 2002. The market is being driven primarily by an
increase in the elderly population, especially those in nursing homes and in home healthcare,
whose increased acuity and need to debride wounds increase the overall debridement agent
volume. In addition, an increase in the prevalence of diabetes, along with diabetes ulcers, is
helping to boost this market. In the hospital enzymatic debridement market, some
manufacturers are marketing their enzymatic debridement agents as an adjunct to surgical
debridement. After surgical debridement is performed, the enzymatic debridement agent can
be used to clean out non-viable tissue that was missed during surgery and aid in the healing
process.
While discount pricing will continue to be a limiter in this market, a more important trend
will be the influence of managed care. In this environment, providers are quickly determining
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which products only require application once per day. Nursing homes must reduce the time
allocated for skilled care, while home health agencies will adopt care paths that will focus on
the ability of a home caregiver to reduce the number of skilled visits. Capitation will drive
the re-engineering of traditional home health as well as in other sites.
Of the total market in 2002, approximately 27% of debridement agents will be sold to the
hospital market, while 73% will compose the non-hospital market. Within the non-hospital
market, approximately 46% of products will be sold to subacute and long-term care facilities,
21% will be marketed to physicians’ offices and ambulatory clinics and 33% will be bought
by home health care. Exhibit 3-7 provides a forecast to the year 2002 for this market.
3.2.3.4 Competitive Analysis
Knoll Pharmaceutical is the market leader with 38% of the market in 1996. This leadership
position is due in part to the inclusion of the company’s product, Santyl, in the guidelines
published by the Agency for Health Care Policy and Research. In addition, other national
wound care organizations have been positive in their support of this product’s debriding
agent, collagenase, in certain applications. This product is usually only applied every 24
hours, which has also helped boost its market share.
Parke-Davis/Fujisawa is in the second-place position with 27% of the market; however, their
market share is likely to be eroded due clinicians needing to use this product every 6 hours
instead of every 24 hours. Dow Hickam’s third-place position with 21% of the market is due
in part to their traditional strong presence in home healthcare and nursing homes. In
particular, nursing homes remain loyal to Dow Hickam due to this company’s continued
support through the years.
Healthpoint has been aggressively marketing their new enzymatic debridement agent,
Accuzyme, which contains papain and urea. In addition, clinicians who were interviewed as
part of this report consider this company’s quality control and clinical study results to be
exceptional. Healthpoint is likely to gain market share because of its efforts, but there is also
an interest in papain with clinicians due to its “natural” focus. Rystan, which has a
papain/urea/chlorophyll product called Panafil, has benefited from the recent interest in
papain compounds. Traditionally a small competitor, Rystan hopes that more clinicians will
return to using their papain debridement agent which has been on the market since 1956.
Exhibit 3-8 provides a breakdown of the market by suplier.
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Exhibit 3-7:
U.S. Chemical/Enzymatic Debridement Market Forecast, 1996-2002
Year
Sales
Growth
1996
$74.2
—
1997
76.4
3.0%
1998
79.0
3.4
1999
81.9
3.7
2000
85.1
3.9
2001
88.1
3.5
2002
91.0
3.3
CAGR 1997-2002
3.6%
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Exhibit 3-8:
1996 Chemical/Enzymatic Debridement Market, Share by Supplier
Supplier
Knoll Pharmaceuticals
Sales
Market Share
$28.4M
38%
Fujisawa USA/Parke Davis
20.2
27
Dow Hickam
15.8
21
Other*
9.8
14%
Total
$74.2M
100%
*Other includes Healthpoint, Johnson & Johnson/Pharmacia Upjohn and Rystan
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Chapter 4: Wound Closure Devices
4.
WOUND CLOSURE DEVICES
The primary goal for any wound closure device is to bring the edges of the wound together
within the shortest period of time, and without further tissue traumatization. Wounds may
close by either primary intention, delayed primary intention, or by secondary intention.
Primary intention wounds are sutured immediately, and are not knowingly infected. Delayed
primary intention wounds are those that are contaminated or are at risk of becoming infected.
Closure of these wounds is delayed to allow for frequent dressing changes, for drainage of
exudate, and to observe and culture the wound bed prior to permanent closure. These wounds
are usually treated by antibiotics, locally and systematically. Secondary intention wounds are
purposefully left open allowing the cavity to fill with granulation tissue, then to contract, and
eventually to epithelialize.
Wound closure devices have undergone remarkable advances in the past 10 years. This
market segment was once completely dominated by sutures, but now includes a variety
products, including tissue glues. Most of these products are applied in the operating room,
with secondary use in delivery sites such as the emergency room and physician offices.
4.1
Needled and Non-Needled Sutures
Sutures represent one of the oldest medical products in the world. Sutures are still used in
abundance; however, they are considered a commodity item which are being replaced by
advanced technologies.
Needled and non-needled suture products can be categorized by the various materials used as
the “thread” and by the inherent characteristics of those threads: absorbable versus
nonabsorbable, coated versus non-coated, amount of tissue drag, tensile strength, and tying
ability. Most sutures have needles swedged on, that is, attached to the suture by the
manufacturer.
Absorbable sutures include synthetic and non-synthetic suture material. Synthetic
biodegradable polymers have replaced traditional absorbable catgut suture. Synthetic
absorbable sutures are now replacing nonabsorbable sutures for many surgical applications
because of their increased tensile strength over an extended period of time and because of
their improved knotting features.
 1997, Medtech Insight, LLC
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Surgical specialties, such as ophthalmology and cardiovascular, plastic and reconstructive
surgery, demand modified needles to meet the specific surgical goals of the discipline. Many
of these needs focus on needles that are strong enough to penetrate tissue without
bending/breaking, and with diameters small enough to reduce tissue damage. An ideal needle
requires low penetration force to pierce the intended tissues and maintains its sharpness
without dulling during multiple passes. The needle should bend without breaking and not
damage the tissue as it passes through. In addition, the needle diameter should closely
approximate the diameter of the suture material.
Many patient care departments are demanding needles with blunted taper-points to reduce the
risk of accidental needle stick. The development of laser drilling and induction annealing has
allowed metallurgists to provide a much stronger needle. These blunt needles slide through
tissue adequately, and when using 300-series stainless steel, replace the older carbon steel
materials.
4.1.1
Sherwood-Davis & Geck and Ethicon are the major players in the suture market; together
these companies monopolize over 80% of the market. The largest competitor in the suture
market is Ethicon with over 2,000 different types of sutures. The company’s product line
consists of three suture groups: absorbable sutures, non-absorbable sutures and specialty
sutures. The absorbable suture group includes plain and chromic surgical gut as well as
sutures made from polyglactin (Vicryl Rapide and coated Vicryl), poliglecaprone (Monocryl)
and polydioxanone (PDS II). Non-absorbable sutures are also made from a variety of
materials, including polypropylene (Prolene), polyester (Ethibond), nylon (Ethilon and
Nurolon), silk (Perma-Hand) and stainless steel. Specialty sutures include products for a
variety of applications, such as endosutures and sutures for cardiovascular surgery.
U.S. Surgical has increased its sales over the last several years through offering
technologically advanced products. One of these products, the Endo Stitch, allows the
surgeon to suture laparoscopically by using the company’s proprietary needle and suture
material between a jaw at the end of the endoscopic shaft. Endo Stitch can also be used in
open procedures for difficult surgical locations. U.S. Surgical also introduced the Biosyn
suture in 1995, which is a synthetic, absorbable suture. This suture combines the benefits of
both monofilament and braided sutures, namely, ease of handling and knot holding
capability.
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Deknatel Snowden Pencer, a smaller competitor in the suture industry, was acquired by
Genzyme in June 1996 for approximately $250 million in cash. The acquisition of Deknatel
will help Genzyme create a platform for building a specialty surgery business, increasing
Genzyme’s annual revenues by $50 million. Deknatel’s surgical sutures are the oldest
products in its product line. The company developed the Tevdek suture in 1950, followed by
the first coated Dacron-based suture and Silky Polydek, a softer suture which facilitated
tying. Deknatel specializes in sutures for cardiovascular and plastic surgeries.
4.1.2
Development Status
Lukens Medical received FDA approval in February 1997 to market its synthetic absorbable
suture material. The suture, called PGA, is made of polyglycolic acid and features a patented
coating technology to enhance performance. The suture is for use in most surgical
procedures, and is heavily used in gynecology, orthopedics and general surgery. Lukens
projected the worldwide market for synthetic absorbable sutures to exceed one-half billion
annually.
Perclose develops and markets suture-based percutaneous vascular surgery systems targeted
at the 6.9 million diagnostic and therapeutic catheterization procedures performed each year
worldwide. These systems are used to close arterial access sites following therapeutic
catheterization procedures, including angioplasty and stenting. The company’s proprietary
Prostar, Prostar Plus, Techstar and Techstar XL systems offer less invasive, cost-effective
treatment alternatives, providing the patient with significant clinical benefits including rapid
hemostasis, earlier ambulation and improved patient comfort. The Prostar Plus 9F and 11F
systems are marketed in the United States, and the Prostar Plus 8F and 10F, the Techstar 6F
and 7F and Techstar 6F XL systems are marketed internationally. Perclose is planning to
introduce the Techstar products at the end of 1997, pending FDA approval.
The Sure-Closure system was developed by Life Medical Sciences, Inc. and introduced in the
United States in late 1996. After debridement of the wound, two intradermal needle devices
are inserted, parallel to each other. The Sure-Closure system is then carefully positioned so
that its recurved hooks are centered on the subcuticular tension bars. The edges of the wound
are then approximated by repeated tightening of the system, and the edges of the wound are
closed with sutures once the system is removed.
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4.1.3
Market Analysis
Sutures are another mature market, even though the major manufacturers continue to produce
new and different products as line extensions every year. Significant product developments
may evolve from research on growth factors because these factors may provide added value
to sutures, in both effectiveness and safety. Incorporation of growth factors in suture material
may promote even faster wound repair and healing and certainly could greatly reduce the
incidence of scars.
There is ongoing debate regarding the benefits of suturing versus stapling. Some surgeons
prefer suturing over stapling for finer, delicate tissue, and to provide better closure for
various tissue planes and surfaces. Laparoscopic surgery favors stapling and clip devices
because of the difficulty surgeons have with suturing in a two-dimensional environment. In
addition, there are also newer endoscopic staplers and automatic ligating clip appliers which
facilitate surgeries using minimally invasive techniques.
Although staplers continue to be a substitute for sutures, the U.S. suture market was valued at
$668 million in 1996 and is projected to grow at a 1.3% average annual growth rate through
the close of the decade. This modest growth is partially due to the substitution of other types
of wound closure devices, including staplers and adhesives, and also due to the rise of
procedures performed through minimally invasive techniques, which use less suture material
to close the wound. In addition, managed care will have its usual price erosion impact,
causing intense price competition in this commodity market. As shown in Exhibit 4-1, the
total U.S. suture market is projected to reach $731 million in 2002.
Although the surgical department will continue to be the primary end user, the product mix
of will change toward alternate site users, with the largest growth occurring in physicians’
offices. While overall growth in the suture market will remain low, suture products will still
remain one of the largest segments in the wound closure market.
4.1.4
Competitive Analysis
Within the suture market, there is intense competition with many individual hospitals or
alliances preferring to buy their wound closure products from a single vendor. Ethicon (a
Johnson & Johnson company) and Sherwood-Davis & Geck have a variety of wound closure
products which enables them to compete effectively within the entire wound closure market.
Ethicon and Sherwood- Davis & Geck offer sutures, staplers and clip appliers, and Ethicon
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Exhibit 4-1:
U.S. Suture Market Forecast, 1996-2002
Year
Sales
Growth
1996
$668M
—
1997
685
2.5%
1998
698
1.9
1999
708
1.4
2000
717
1.2
2001
724
1.0
2002
731
0.9
CAGR 1997-2002
1.3%
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dominates the suture segment with a 71% market share. Sherwood-Davis &Geck competes in
the second place position with 12% of the market.
U.S. Surgical, with 8% of the market, has made inroads in the last several years due to
marketing agreements with large providers. For example, in mid 1997, U.S. Surgical
established supply agreements with AmeriNet as well as Health Services Corporation of
America. The company also hopes that its marketing efforts and competitive pricing will
enable it to gain market share at the expense of the larger players.
The rest of the market, with a 9% share, consists of numerous small players. Some of these
companies are broadening their product lines in an attempt to gain market share. For
example, Lukens Medical now offers a complete line of sutures, including its new,
absorbable polyglycolic acid suture. Exhibit 4-2 presents the competitors and their market
shares in the suture market.
4.2
Tissue Glues
Surgical sealants or fibrin glues are biologic sealants used during surgeries to aid clot
formation. These tissue adhesives form a temporary wound closure, and they assist in
neovascularization and fibroblast proliferation. These adhesives are made from blood
proteins which cause clotting and scabbing. Fibrin glues can be made from autologous or
multiple-donor sources.
The glues are created by combining two blood-clotting factors: fibrinogen and thrombin.
Included in the fibrinogen is Factor XIII which initiates clotting when combined with the
thrombin at the time of surgery. The fibrin glue is delivered to the wound by using a doublebarrel syringe which allows mixing of the two components at the tip before being applied to
the site by a blunt-tipped cannula or spray. Once combined, the sealant assumes a viscous
consistency, readily adheres to the wound site, and sets up a fibrin network to control
hemostasis or augment the strength of the incision. The major indications for surgical glues
and sealants include hemostasis, adhesion, sealing, and reinforcement.
Scientists first tried to create biological glue in the 1940s, but it was 1974 before an Austrian
doctor separated the useful proteins from blood, freeze dried them, and mixed then into an
adhesive. Fibrin glues and surgical sealants have long been stymied in the U.S. by the FDA's
uncertainty regarding the regulation of fibrin-based products. The agency has been
particularly sensitive to approving fibrin sealants based on the concerns of disease
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Exhibit 4-2:
1996 Suture Market, Share by Supplier
Supplier
Sales
Market Share
Ethicon
$475M
71%
Sherwood-Davis & Geck
76
12
U. S. Surgical
55
8
$62
9
$668M
100%
Others*
Total
*Others includes Alcon, Anchor Products Company, Cottrell, Deknatel (Genzyme), Lukens
Medical, S. Jackson, Surgical Specialties, W.L. Gore, among numerous others.
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transmission, consistency of product formulation, and the lack of defined clinical end-points
to assess clinical efficacy. Fibrin glues were commercially available in the U.S., but were
withdrawn in 1978, due to the possibility of viral infectivity, although they continued to be
used in the European market.
The European manufacturers, Behringwerke and Immuno International, addressed these
concerns by developing viral inactivation processes, which were achieved by subjecting the
fibrin glue products to heat. Introduction of these European-derived fibrin glue preparations
in the U.S. was again precluded by the FDA, in part due to the inclusion of aprotinin (a
bovine-derived product) in the sealant formulation to reduce fibrinolytic degradation of the
sealant after application. The FDA required data showing that the addition of this agent
significantly increased clinical efficacy was needed before the licensing to market could be
obtained. Faced with these challenges, manufacturers were unwilling to undergo the long and
arduous approval process.
With more research and development dollars being spent on fibrin sealants, the FDA seems
ready to proceed with regulatory approval. Although the FDA appears to be satisfied with the
viral safety of fibrin glue products, regulations continue to evolve regarding product efficacy,
making time frames for product approvals uncertain and difficult to predict. The FDA has
established different criteria for evaluating homologous- versus autologous-sourced products.
For homologous products, the FDA is evaluating performance issues such as tensile strength
and time to hemostasis as clinical endpoints. In the case of autologous-derived products, the
FDA is examining process controls to ensure reliability and consistency of the product
formulation. Another obstacle set forth by the FDA is the requirement that companies justify
the addition of exogenous materials, such as Factor XIII, into their fibrin preparations. Most
companies are performing clinical studies designed to show the clinical benefit of their
sealant or glue. This has not worked in Baxter’s favor; the FDA has turned down the
company’s application for the use of Sealagen for controlling bleeding from donor sites in
burn patients.
Commercial glues have been used extensively in Europe since the 1970s with beneficial
results. Wound adhesives have also been marketed in Canada, the Middle East, South
America, and Japan. In these countries, surgical sealants appear to have no tissue toxicity,
are readily absorbed, and assist in wound healing and repair. In addition, wound infection is
minimized because there is no suture or staple on the skin.
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Outside the United States, more than 30 companies compete in a market estimated at about
$250-$280 million. Approximately 60% of the market consists of Asian/Pacific countries,
while 30% and 10% of the market is European countries and the rest of the world,
respectively. The worldwide leader is Centeon, which has offered a fibrin sealant, Beriplast,
since 1983. This product is used for hemostasis, tissue adhesion, suture support, sealing of
body cavities, and controlling leakage to cerebral spinal fluid. Other companies with glues or
sealants include 3M, Cryolife, Immuno International, Research Medical, Johnson &
Johnson, and U.S. Surgical.
Manufacturers are marketing or investigating several different types of sealants or glues,
including pooled plasma-derived sealants, autologous processed sealants, collagen-based
composite sealants, cyanoacrylate-based sealants, polymer-based sealants, recombinant
sealants, and genetically engineered sealants. Each of these different types of glues are
discussed in the following sections.
4.2.1
Pooled Plasma-Derived Sealants
From the FDA’s standpoint, homologous adhesives may be easier to regulate than other types
of adhesives because the extensive manufacturing process can be evaluated using standard
investigational protocols. Due to research that ensures the viral safety of homologous glues,
the FDA finally appears to be ready to give clearance by end of the decade. The FDA’s main
concern appears to be the efficacy of tissue glues for a given indication, specifically, whether
the glue is used for hemostasis or for sealing a duct or air leak in the lung.
In a joint effort, Baxter and the American Red Cross (ARC) have completed studies on their
fibrinogen-based hemostatic agent. Examples include using the adhesive for dental extraction
in hemophilia patients, total joint replacement, circumcision, and as a topical hemostat in
infants undergoing extracorporeal membrane oxygenation. A biosafety study was also
completed on patients having skin excision and in patients with second-degree burns who
needed grafting. In this study, there was no evidence of viral antibodies to hepatitis or HIV
from the fibrin sealants. Baxter and the ARC will market the sealants under different names:
Baxter’s adhesive will be called Sealagen and the ARC’s product will be known as Fibriseal.
U.S. Surgical has entered into a worldwide distribution agreement with Vitex for this
company’s doubly virally inactivated fibrin sealant, ViGuard. Vitex, formerly Melville
Biologics, Inc., was created in 1995 as a spin-off from the New York Blood Center. Vitex
will receive financial payments from U.S. Surgical for clinical trials and regulatory costs
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while maintaining manufacturing rights. U.S. Surgical also gained rights to product
improvements and an option on other wound-healing products in development by Vitex.
To eliminate the risk of virus transmission in ViGuard’s human fibrinogen and thrombin, two
complementary viral inactivation procedures are performed. The two-stage procedure treats
each component with a solvent detergent developed by Vitex which inactivates lipidenveloped viruses such as HIV and hepatitis B and C. The components are then subjected to
short wavelength ultraviolet light which eliminates both enveloped and non-enveloped
viruses such as hepatitis A and parvovirus. Vitex has also licensed this two-stage inactivation
procedure to other fibrin glue suppliers.
Vitex has completed Phase II trials of ViGuard for wound closure after mastectomy or
lumpectomy and has received investigational new drug (IND) approval which covers the
product at five clinical sites in the United States. Vitex hopes to submit a product licensing
agreement to the FDA at the end of 1997.
Cryolife is developing two surgical bioadhesives, FibRx and BioGlue. FibRx is a fibrinogen
and thrombin adhesive and indicated for patients undergoing skin grafting for second-degree
and third-degree burns. Unlike other fibrin adhesives, this product is frozen, and after being
thawed, are delivered in a single lumen syringe or spray. BioGlue is a plasma protein-based
bioadhesive which has ten times the adhesive power of FibRx. This product is being
developed to replace suturing or stapling in some surgical procedures and is under evaluation
for artery attachment and gluing bone fragments.
Haemacure has three U.S. patents for the manufacturing of its Hemaseel technology, which is
a human-based, liquid fibrin sealant with hemostatic and adhesive properties. The product is
absorbable and contains fibrinogen and thrombin which has been isolated from human
plasma by the company’s patented processes. Haemacure is also developing a solid fibrin
sealant, Hemaseel Dressing. This product is also absorbable and has been designed to arrest
bleeding in emergency and surgical situations.
4.2.2
Autologous-Processed Sealants
Several companies are developing techniques for using the patients’ blood on a individual
basis to make an autologous sealant at the time of surgery. Biosurgical is one company that is
developing a system for processing autologous fibrin sealants, while ConvaTec has
developed Vivostat which is an automated, computerized system for centrifuging and
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processing the sample of the patient’s blood. The unit centrifuges the blood for 25 minutes,
separates the plasma, and the resultant sealant is dispensed into a vial for spraying onto the
wound site.
Thermogenesis has developed the CryoSeal system which is an automated method for
processing the blood component, cryoprecipitate AHF. This component is approved by the
FDA for the treatment of blood clotting in protein-deficient patients. The system can also be
used to make cryoprecipitate for use as a tissue adhesive and hemostatic agent.
Thermogenesis has filed for 510(k) clearance for the system; however, its specific use as
tissue adhesive in surgical procedures will require an additional FDA approval.
Plasmaseal is developing a technology for making concentrated plasma for use as a tissue
sealant during surgery. This product, Plasma Concentrate Sealant (PCS), can be made in less
than 10 minutes from the patient’s own blood. The sealant is similar in strength to other
adhesives, and the product is easy to use. Once the blood is taken from the patient, it is
injected into a single-use, disposable cartridge. The clinician pushes a button and waits 10
minutes until the plasma concentrate is ready to use.
4.2.3
Collagen-Based Sealants
Collagen, the protein that makes skin elastic, appears to strengthen the cohesive ability glues.
The French manufacturer, Saduc-Imedex, is developing a collagen-composite product called
Collagen Gel Sealant (CGS). This adhesive consists of collagen treated with periodic acid as
an oxidating agent. A solid gel at lower temperatures, CGS readily transforms into a viscous
fluid when subjected to body temperature.
In August 1996, Centeon formed a strategic alliance with Nycomed for this company’s
TachoComb adhesive. Nycomed will receive contributions toward the development of
TachoComb in the United States, while Centeon’s rights to the product will include other
countries other than Europe and Japan. TachoComb consists of equine collagen fleece coated
with purified human fibrinogen, bovine thrombin, and bovine aprotinin. The product is used
instead of suture for hemostasis and for controlling intraoperative bleeding on parenchymal
structures which are too fragile for cautery. When the fleece contacts bleeding structures and
pressure is applied for several minutes, the clotting factors dissolve and a glue is formed
which adheres the collagen fleece to the wound’s surface.
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Fusion Medical Technologies is developing wound closure products for a variety of surgical
procedures, including minimally invasive surgery. The company already offers RapiSeal,
which received clearance from the FDA in June 1996 for use in lung surgery. RapiSeal, a
biodegradable collagen patch, also received 510(k) clearance in February 1997 for the
treatment of bleeding organs, such as the spleen or liver. The patch is used in conjunction
with an energy source and closes wounds in solid organs, resulting in complete cessation of
bleeding at the wound site. In March 1997, the company submitted its 510(k) application for
the SilverBullet electrode to the FDA. This technology was developed with the focus on
enhancing the performance of the RapiSeal Patch and making the sealant easier for surgeons
to use.
Fusion is also planning to begin European and Canadian trials of its Flowable Gel surgical
sealant for cardiovascular and general surgical applications. Flowable Gel is a biodegradable,
collagen-based liquid that can stop active bleeding in about one minute. The product is
applied with a syringe, can be used to seal vessels during coronary artery bypass procedures
as well as to reinforce suture and staple lines.
As part of a project to develop adhesion and anti-adhesion products, Collagen Corporation
acquired an 80% interest in Cohesion in June 1996. Cohesion is a private company which
develops tissue adhesives, hemostats, biosealants and adhesion-prevention products.
4.2.4
Cyanoacrylate-Based Sealants
In the late 1950s, cyanoacrylate adhesives were developed for both commercial and medical
use. These adhesives consist of low-viscosity molecules, which under certain conditions,
such as the presence of moisture, form simple compounds, or polymers, with unique adhesive
properties. The most common type of this adhesive is the household product, “Super Glue,”
but some forms are used for surgical purposes because the glue polymerizes on contact with
blood to form a tight bond.
The first glue developed was methyl cyanoacrylate, but this adhesive proved to be toxic to
tissues. In 1966, cyanoacrylate adhesives were used in Vietnam to stop bleeding until
conventional surgery could be performed in overloaded combat surgical units. Since the
1970s, cyanoacrylate glues have been used in Europe for many surgical applications,
including bone and cartilage grafts, middle ear surgery, and skin closure. Manufacturers of
cyanoacrylate adhesives outside the United States include B. Braun and Loctite. In Canada,
Histoacryl Blue (n-butyl cyanoacrylate, manufactured by B. Braun in Germany and
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distributed by Davis & Geck Canada) and Tissu-Glu (Medi-West Pharmaceuticals) are used
for a variety of applications, including episiotomy repair.
Ethicon (Johnson & Johnson) has formed a worldwide distribution agreement with Closure
Medical, formerly Tri-Point Medical, for Closure Medical’s proprietary cyanoacrylate glue
technology. This adhesive is designed to be a substitute for sutures in internal and topical
wound care. The topical product, Dermabond, has been evaluated in clinical trials for sealing
wounds after the removal of trocars in laparoscopy and for skin lacerations in plastic surgery.
In January 1997, Closure Medical filed a PMA with the FDA which granted expedited
processing to the product.
The company believes that Dermabond’s adhesive technology promises a revolution in
wound closure through the decreases expected in overall treatment costs. These reductions
are predicted to come through shorter procedure times, rapid patient recovery and elimination
of follow-up visits. With traditional sutures, topical anesthesia is normally necessary. This
not only heightens the patient’s anxiety, particularly if the patient is a child or an adult with a
fear of needles, but also increases the risk of needle-stick injuries to caregivers. A return visit
is often necessary for removal of sutures.
With Dermabond, the adhesive is applied in a painless procedure. No anesthesia is necessary
and the procedure time is minimal. Delivered in single-use, disposable applicators which do
not require refrigeration, Dermabond protects the wound from infection by forming a flexible
barrier.
4.2.5
Polymer-Based Sealants
In January 1997, Ethicon (Johnson & Johnson) and Focal (Lexington, MA) announced a
reciprocal agreement to bring Focal’s polymer-based sealants to the worldwide market.
Ethicon will distribute outside the United States, while both companies will share the
responsibility of securing regulatory approval in the various countries. Focal’s unique
polymer technology includes a cross-linkable hydrogel that is being developed to seal air and
fluid leaks during lung surgeries. The company’s initial absorbable product, FocalSeal, is in
clinical trials to evaluate the product’s ability to create a leak-proof seal over sutures, staples,
and other sites during lung surgery. In April 1997, the U.S. Patent and Trademark Office
awarded a patent to Focal covering its delivery system for delivery of the company’s
synthetic absorbable materials to precise surgical locations.
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4.2.6
Recombinant and Genetically Engineered Sealants
The ARC and other research institutions, including the New York Blood Center,
Zymogenetics, and PPL Therapeutics, are developing new methods for producing human
fibrinogen. Some of these methods include recombinant techniques, placental extraction, and
transgeneic sources. In addition, Johnson & Johnson’s Ethicon division has formed a
worldwide marketing and distribution agreement with Protein Polymer Technologies for a
genetically engineered sealant. Protein Polymer Technologies sealant is a bioengineered
protein system designed to set quickly, provide high bond strength and then be absorbed by
the body.
4.3
Delivery of Fibrin Glue
A number of systems are being developed by various manufacturers for the delivery of fibrin
glues. Resorbable wound dressings lined with fibrin glue have been developed by firms such
as ARC/Baxter, Nycomed and Cohesion. In addition, other manufacturers are developing
powder sprays, blunt-nosed cannulas, self-expanding foams and collagen or cellulose
carriers. With the collagen or cellulose carriers, a sponge is soaked with fibrinogen, and the
thrombin is placed on one side to activate the glue. Other new delivery systems permit the
application of fibrin sealants through a catheter, for use in closing fistula or percutaneously
eliminating air leaks under CT guidance.
4.4
Market Potential of Tissue Glues
In a study published in The Journal of the American Medical Association in May 1997, Dr.
Alexander Trott, a professor of emergency medicine at the University of Cincinnati College
of Medicine, predicted that glues will cause a revolution in the care of lacerations. With
training anyone will be able to use the medical glue properly. He envisions a day when
coaches will apply it to wounded sports players on the field and families would take it on
camping trips. In addition, developers of tissue adhesive and glues are claiming that glues
could replace sutures for one-third of the 11 million wounds seen in emergency rooms across
the United States. As a result of this positive outlook, the potential market for glues and
adhesives is estimated at $400 million to $600 million worldwide. In the United States, the
potential market for tissue glues and adhesives is estimated at approximately $300 million,
and some manufacturers have stated that the U.S. market potential could be realized within
five years.
In June 1996, Fusion Medical Technologies received clearance for its surgical sealant used in
lung surgery, RapiSeal Patch. As of the last quarter in 1996, sales of the RapiSeal Patch were
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approximately $23,000. In February 1997, RapiSeal received 510(k) clearance for the control
of bleeding during abdominal surgeries for solid organs, such as the liver and spleen. Sales of
RapiSeal, with its specific clinical applications, are forecasted to reach over $100,000 in
1997.
Other glues or adhesives with broader applications are expected to be approved in
approximately 1998, and sales in that year are forecasted at $10 million, increasing to $30M
in 1999. Compound annual growth thereafter is forecasted in excess of 100% until some
degree of maturity is achieved.
Tissue glues will primarily be used in the hospital setting; however, by 2000, approximately
10% of tissue glue sales will be distributed among alternate site locations. Physician offices
and ambulatory clinics will be the largest user of tissue adhesives with approximately 75% of
sales in the total alternate site market, while subacute and long-term care facilities will be a
secondary user with the remaining 25% of sales.
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Chapter 5: Wound Dressings
5.
WOUND DRESSINGS
Most surgical incisions, ulcers, or traumatic wounds require some type of wound dressing or
covering. The specific type is determined by anatomical location, exudate characteristics, the
skill of the healthcare provider, the healthcare setting/environment, the protection
requirements against physical re-injury, pain control characteristics, and patient prognosis.
Wound healing is a dynamic process; therefore, wound dressings that optimize wounds in
one development stage may not be the dressing of choice during another development stage.
The wound changes its characteristics through various phases of the wound repair cycle.
In the past, companies with leadership positions in wound dressing markets have relied on
low to minimally advanced technology and have focused primarily on treating the symptoms
of wound care (that is, exudate absorption and physical and bacterial protection), rather than
making products that actively participate in wound healing. The last ten years have brought
about a new understanding of the healing process, providing the manufacturers of wound
dressings with an opportunity to become more sophisticated and active in the treatment of
wounds. Dressings are being modified to become the vehicle for the delivery of growth
factors, biochemicals, induced oxygenation, timed drug releases, and even serve as temporary
replacements for natural skin.
Wound dressings are less passive today; they absorb wound exudate, prevent the drying of
wounds and protect against microorganism contamination and physical assault. Dressings are
active participants in wound management. Although dressings will continue to maintain
passive therapy attributes, they also have added features which simulate skin replacement
barriers, provide autolytic debridement, and/or stimulate wound healing by acting as vehicles
for the delivery of drugs and oxygen to wound beds.
Of the 24 million surgical wounds estimated for 1996, most are closed by primary intention,
covered, and heal uneventfully. However, of the growing number of hard to heal wounds like
chronic ulcers, half respond poorly to existing treatments. It is this wound type, in particular,
which has contributed to the $12-$14 billion dollar healthcare cost for treatment of dermal
ulcers. With the numerous wound dressings and wound care products currently in the
marketplace, no one single dressing or type of dressing composition can provide the optimum
environment for all wounds. Important features for the ideal dressing include tissue
compatibility, adherence to the skin around the wound but not to the wound itself, and
durability without excessive cost. The array of wound dressing products in the marketplace is
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confusing to even the most sophisticated user; however, dressings can usually be classified
into two general categories: non-occlusive and occlusive.
Gauze is classified as non-occlusive, allowing air to pass and causing dehydration of the
wound bed. Occlusive dressings have moisture-retentive properties; the adequacy of
occlusion is measured by the moisture vapor transport rate (grams of moisture vapor passing
through the dressing per square meter of dressing surface per hour). The lower the moisture
vapor transport rate, the higher the occlusion ability of the dressing, and therefore, the greater
the moisture-retentive nature of the dressing. Moisture is important for increasing the rate of
wound healing; a moist wound environment facilitates migration of epithelial cells and
increases wound closure. When epithelial resurfacing is accelerated, collagen production is
greater, granulation tissue growth is rapid, and angiogenesis is stimulated under occlusion. In
all, occlusive wound management can lead to lower cost of management for wounds.
Occlusive dressings can include a variety of different coverings such as film dressings,
hydrogel dressings, hydrocolloid dressings, foam dressings and calcium alginates. These
dressing can be fully occlusive or semi-occlusive. Occlusive dressings prevent the
penetration of liquid, moisture vapor, oxygen, and bacteria to or from the wound site. Semiocclusive dressings are vapor-permeable, but do not allow liquids or bacteria to penetrate.
The following sections review each composition type separately, but combinations of two or
even three dressing types appear to have the greatest potential in the future of wound
management.
The rule of thumb for clinicians in wound management is to often adopt a “wait and see”
stance, trying a product for two weeks, then, if there are no positive results, a switch is made
to some other product. Manufacturers in the wound care product industry are working to
change this type of approach, so that the clinician’s first choice of dressing is the most
optimum dressing for the patient’s wounds/ulcers.
Clinical Practice Guidelines such as those issued by the Agency for Health Care Policy and
Research (December 1994) are helping clinicians in their decisions, but research proving the
efficacy of different types of wound dressings is needed. Manufacturers’ outcomes studies
will be a great assistance in this decision process.
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5.1
Non-Occlusive Dressings
These products were in popular clinical use until the first arrival of the more advanced wound
products. Use of gauze and impregnated gauze is still quite common, although limited mainly
to primary surgical incisions and uncomplicated wounds.
Dry dressings are commodity products, and, expected to experience little change in size. The
1996 market was estimated at $150 million, and is projected to grow only about 1.5-2% per
year through the end of the decade.
5.1.1
Gauze and impregnated gauze are commonly used to cover a surgical wound site. These
dressings excel in absorbing wound exudate, supporting wound cavities, and providing for
mechanical debridement to remove necrotic tissue, in a moist-to-dry dressing protocol. Gauze
is difficult to keep moist, does not provide a bacterial barrier, and if left on the wound to dry,
can dislodge viable granulation tissue from the wound surface during dressing removal.
Impregnated gauze dressings reduce the likelihood of inadvertent drying out of the gauze
through petroleum-based coatings, providing easier removal and less adherence to the wound
site. Both gauze and impregnated gauze need secondary dressings with a good seal to prevent
the wound or incision from drying out.
Numerous manufacturers compete in the gauze and impregnated gauze market. Johnson &
Johnson offers a full line of gauze dressings, such as their Steri product line, which includes
the popular Steri-Pad. Sherwood-Davis & Geck markets Vaseline petrolatum gauze, which is
a sterile, non-irritating dressing of fine mesh gauze impregnated with white petrolatum. This
dressing conforms to body contours and is available in four sizes.
The leaders in gauze and impregnated gauze dressing market are Johnson & Johnson,
Kendall Healthcare, and Sherwood-Davis & Geck. Johnson & Johnson is the traditional
market leader; however, Kendall, in second place, has recently gained market share due to its
acquisition of Professional Medical Products in early 1996. Professional Medical Products
had a particularly strong position in the home care market. Exhibit 5-1 reviews selected
products from this market.
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Exhibit 5-1:
Selected Manufacturers of Gauze and Impregnated Gauze Dressings
Manufacturer
Acme United
Product
Tubifast and Tubegauze
Beiersdorf-Jobst
Aquaphor gauze
Derma Sciences
Dermagran (zinc-saline) wet dressing and
Dermagran (saline) wet dressing
DeRoyal
Covaderm adhesive wound dressing,
Multipad, Dermanet, Sofsorb, and Fluftex
Horizon
DermAssist oil emulsion and DermAssist
petrolatum
Johnson & Johnson
Nu-Brede, Nu-Gauze, Steri-Pad, J&J gauze
sponges, Adaptic Non-Adhering Dressing,
Band-Aid Surgical Dressing, and Kling
Kendall Healthcare
Curity and Kerlix brand products
Molnlycke
Medpore
Intersorb, Vaseline petrolatum gauze,
Vaseline oil emulsion dressing, Xeroform
petrolatum gauze, Xeroflo, and scarlet red
ointment dressing
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5.2
Occlusive Dressings
The variety of occlusive dressings is extensive, and new combinations of
products/technologies are entering the market on a monthly basis. This section of the report
considers the most commonly used semi-occlusive and occlusive dressings including film
dressings, hydrogel dressings, hydrocolloid dressings, foam dressings and calcium alginates.
5.2.1
Film Dressings
Film dressings are made of versatile polymers which can be synthesized into a varying range
of surface hardnesses. Depending upon molecular structure, these dressings possess many
positive physical and chemical characteristics such as flexibility, resiliency, absorbency, and
elasticity.
Film dressings are synthetic, semi-occlusive, adhesive, waterproof, and usually transparent
(exudate may obscure this transparency). Although film dressings allow the free flow of
oxygen through the pores of the dressing and water to pass from the wound to the air,
bacteria cannot enter through the film pores. These products maintain a physiological
environment and provide for autolytic debridement. Epithelialization is enhanced by
preventing scabs from forming on the wound/ulcer.
Film dressings do have disadvantages; they are difficult to apply and they lack the ability to
conform to the wound crater, this resulting space under the dressing provides opportunity for
bacterial invasion. Exudate accumulation under the dressing can cause leakage of exudate,
and this action compromises the bacterial barrier property of the film. Occlusive properties
differ between products, causing confusion among clinicians. Secondary gauze dressings may
be applied to absorb the exudate, but transparency is sacrificed. When removing film
dressings, extreme caution must be taken to prevent the inadvertent removal of new
epithelium by the adhesive backing on the film dressing.
Film dressings are used for superficial wounds, burns, and shallow ulcerations. Many times
they are used prophylactically, to decrease the risk of abrasion or ulceration by decreasing the
friction between a patient’s skin and bed surface, or by keeping the skin dry from urinary or
fecal incontinence.
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Considered a mature product market, these dressings are approximately 30% of the overall
occlusive dressing market, which was about $241 million in 1996, this segment's 1996 sales
were estimated at $73.3 million.
Film dressings remain popular as covers for I.V. drips, allowing the clinician to document the
starting date and time directly on the dressing. In addition, film dressings are used as
secondary coverings, which help to boost its overall volume usage. However, as the length of
stay decreases in acute care sites, I.V. therapy is being less utilized, and patients are receiving
their medications orally at home. Clinicians often complain that films are difficult to use, and
Medicare does not reimburse for these dressings, both of which help limit their market
growth potential. Thus, growth in this market is relatively limited at an annual rate of 6.2%
per year with the market growing to $106.2 million in 2002, as shown in Exhibit 5-2.
A variety of suppliers compete in the film dressing market, with 3M, Johnson & Johnson,
and Smith & Nephew current market leaders. 3M has a product line called Tegaderm, which
is offered in different sizes and shapes, including a film with an absorbent pad which absorbs
exudate. Johnson and Johnson makes Bioclusive, a vapor-permeable film, which lets the skin
breathe, thereby reducing the risk of maceration. Smith & Nephew offers the Opsite Flexigrid
with a flexible carrier grid which allows the clinician to trace the border of the wound once
the dressing is in place. Then, the grid can be removed and put in the patient’s chart. Smith &
Nephew also offers the OpSite Post-Op with a absorbent non-adhering pad for use in
postoperative wound care. Exhibit 5-3 reviews product selections by manufacturer.
Carrington Laboratories is a relatively new participant in the film dressing market with their
Carra Film, launched in early 1996, and CarraSmart Film, introduced in March 1997. Carra
Film is designed to be used with the company’s Carrasyn hydrogel dressing or low exudating
wounds, such as superficial pressure ulcers, skin grafts, donor sites, and closed surgical
wounds.
Sherwood-Davis & Geck’s Blisterfilm transparent dressing has a unique adhesive border
which prevents the adhesive from touching the wound, thus it avoids re-injury when
removed.
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Exhibit 5-2:
U.S. Film Dressing Market Forecast, 1996-2002
Year
Sales
Growth
1996
$73.3M
—
1997
78.5
7.1%
1998
83.8
6.8
1999
89.3
6.5
2000
94.8
6.2
2001
100.5
6.0
2002
106.2
5.7
CAGR 1997-2002
6.2%
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Exhibit 5-3:
Selected Manufacturers of Film Dressings
Manufacturer
Product
3M
Tegaderm
Acme United
ACU-derm
Carra Film and CarraSmart film
ConvaTec
Pro-Clude
DeRoyal
Transeal
Horizon
DermAssist film
Johnson & Johnson
Bioclusive
Kendall
Polyskin II
Molnlycke
Alldress
ProCyte
ProCyte film
Viasorb and Blisterfilm
Smith & Nephew
OpSite Flexigrid, OpSite Flexifix, and OpSite
Post-Op
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3M monopolizes the market with $40M or a 55% market share. 3M’s leadership position is a
reflection of its dominance in both the acute care and alternate sites. Johnson & Johnson and
Smith & Nephew follow with 20% and 16% of the market, respectively. These other two
companies have strength in only one of these markets: Johnson & Johnson’s is effective in its
marketing to acute care sites, while Smith & Nephew is especially aggressive in alternate
sites. Exhibit 5-4 depicts market competition.
5.2.2
Hydrogel Dressings
Hydrogel dressings provide immediate cooling effects on painful wounds, cooling the wound
as much as five degrees. Hydrogels contain water- or glycerin-based amorphous gels, which
help to maintain a moist wound bed. Hydrogels range from transparent to translucent and
may obscure the wound when exudate accumulates. These dressings are permeable when the
backing is removed and require a secondary dressing to avoid spreading of the hydrogel and
to ensure contact with the wound bed. Hydrogels can be squeezed onto the wound and
smoothed down or may be supplied on a patch with a semi-occlusive film. Evaporation
occurs through the gel surface. Hydrogels are fairly easy to remove through irrigation.
The advantages of hydrogels are many. They are biocompatible, non irritating, provide for
pain relief, will not macerate wound borders, can be used in conjunction with topical drugs,
and are cost effective. However, these dressings usually are not able to absorb large amounts
of exudate because of their high concentration of water, and they are difficult to keep in place
on superficial wounds. Clinical indications include donor sites, superficial burns, tattoo
removal, fragile skin, skin susceptible to allergies, and chronic wounds/ulcers.
The market forecast for hydrogel dressings is presented in Exhibit 5-5. Hydrogel dressings
are approximately 13% of the $241 million occlusive dressing market, with approximately
$32 million in sales in 1996. This market experienced a major setback due to changes in
Medicare reimbursement in the fourth quarter of 1995. Specifically, the reimbursement rate
for hydrogels was reduced from one ounce per day to three ounces per month, causing a
slowing of unit growth in this market. As a result of this change as well as cost containment
measures by hospitals and acute care providers, this market became increasingly cost
conscious, causing major manufacturers to cut prices and offer greater discounts to maintain
customers. For example, Carrington cut their pricing to distributors by 19.1% in 1996. As a
result, dollar sales in this market plunged in 1996; however, the market is expected to slowly
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Exhibit 5-4:
Supplier
3M
1996 Film Dressings, Share by Supplier
Sales
Market Share
$40.3M
55%
Johnson & Johnson
14.7
20
Smith & Nephew
11.7
16
Other*
6.6
9
Total
$73.3M
100%
*Other includes Acme United, Carrington, ConvaTec, DeRoyal, Horizon, Kendall,
Molnlycke and Sherwood-Davis & Geck.
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Exhibit 5-5:
U.S. Hydrogel Dressing Market Forecast, 1996-2002
Year
Sales
Growth
1996
$32.1M
1997
33.4
4.0%
1998
34.7
3.8
1999
35.9
3.6
2000
37.2
3.4
2001
38.3
3.2
2002
39.5
3.0
—
CAGR 1997-2002
3.4%
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increase to over $39 million in the year 2002, as competitors introduce new products, perhaps
using hydrogels as delivery system with liposomes. Competitors are also expected to more
actively pursue the alternate and home care markets. However, because hydrogels need to be
changed more often than other dressings, use of this dressing could increase labor costs,
which is a significant disadvantage in nursing homes and alternate care sites.
Carrington Laboratories, the first competitor in the market with a primary hydrogel which
used complex carbohydrates, has a broad product line based on products derived from the
Aloe vera plant. Carrasyn hydrogel wound dressing is used for the management of Stage I-IV
pressure ulcers, stasis ulcers and first- and second-degree burns. The company also offers
other hydrogel products such as CarraGauze Strips, CarraGauze Pads, and Carrasyn Spray
Gel. In January 1996, Carrington launched its new, freeze-dried hydrogel wound dressing
called CarraSorb M. This product is made with an Aloe vera extract containing acemannan
which absorbs wound exudate, up to 20 times its own weight. Indications for CarraSorb
include pressure ulcers, diabetic ulcers, foot ulcers, post-surgical incisions, radiation
dermatitis, and abrasions. In November 1996, Carrington launched a new acemannan product
called RadiaCare Gel which is used in radiation therapy for the treatment of radiation induced
dermatitis. The company also introduced its DiaB Gel which is formulated for diabetic and
foot ulcer care.
This hydrogel is composed primarily of water, plasticizer/humectant, and propylene glycol.
In July 1996, ProCyte introduced its Iamin hydrating gel, a patented tripeptide complexed
with copper. This product attracts macrophages and monocytes as well as increases
angiogenesis and collagen synthesis. In March 1997, the FDA granted marketing clearance
via a 510(k) for ProCyte’s GraftCyte moist dressing, which also uses the company’s copper
peptide technology in a gel-impregnated gauze for use in hair restoration procedures.
In October 1996, AcryMed received FDA approval for their AcryDerm Advanced Wound
dressing for the management of cavitated acute and chronic wounds with moderate to heavy
exudate. This product enhances autolytic debridement and is offered in a hydrogel sheet
format as well as a bound, strand-like format. This strand format, which received 510(k)
clearance from the FDA in November 1996 and was launched in the United States in March
1997, is called AcryDerm Strand. This product is classified as a wound filler and has the
flexibility to be placed deeply into a wound.
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New Dimensions in Medicine (NDM), which was acquired by ConMed in 1996, offers a
hydrogel called ClearSite. Other hydrogel products are outlined in Exhibit 5-6.
Carrington Laboratories, with a 36% market share, is the traditional market leader with its
natural Aloe vera product line. There is a preference in today’s market for natural products;
however, for Carrington to remain market leader, it will need to become more aggressively in
making purchasing agreements with larger providers. ConMed/NDM follows in second place
with 18% of the market due partly to its success in making these types of national purchasing
agreements. Healthpoint’s third-place position with 14% of the market is due to its recent
aggressive marketing, while Molnlycke is especially strong in the home market. DeRoyal,
although a minor competitor at present in this market, is actively marketing its hydrogel
product along with other dressings in its product line to large, national providers. Other
hydrogel competitors are included in Exhibit 5-7.
5.2.3
Hydrocolloid Dressings
Hydrocolloid dressings are waterproof and provide a bacterial barrier. These dressings have
been derived from the same materials commonly used for ostomy barriers. Hydrocolloids
consist of hydrophilic particles (that is, gum, karaya, gelatin, pectin, carboxymethylcellulose), that interact with wound moisture to form a gel. The wound is in constant contact
with the gel, providing a continuous wound bath.
Infected wounds are diagnosed by classical symptoms and supportive microbiology. The
likelihood of infection occurring with the use of occlusive dressings compared to
nonocclusive dressings has been studied and results indicate that occlusive dressings are less
likely to become infected than their nonocclusive counterpart. Hydrocolloids are an effective
bacterial barrier, and they do not allow for the transmission of oxygen, carbon dioxide, or
significant amounts of moisture vapor. Although hydrocolloids are highly absorbent, they
have the ability to conform to difficult anatomical sites. On the wound bed, the hydrocolloid
forms a soft gel as it absorbs exudate and simultaneously provides moisture to the wound.
Caution is advised when removing hydrocolloid dressings so as not to disrupt newly formed
granulation tissue.
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Exhibit 5-6:
Selected Manufacturers of Hydrogel Dressings
Manufacturer
AcryMed
Bard
Coloplast/Sween
ConMed/New Dimensions in Medicine
ConvaTec
DermaRx
Derma Sciences
DeRoyal
Dow Hickam
Gentell
Healthpoint Medical
Hollister
Horizon Medical
Johnson & Johnson
Kendall
Medi-Tech International
Molnlycke
ProCyte
Smith & Nephew
Southwest Technologies
Swiss-American Products
Product
AcryDerm Advanced Wound Dressing
Biolex wound gel and Vigilon primary
wound dressing
Carrasyn hydrogel wound dressing,
CarraGauze Strips, CarraGauze Pads,
Carrasyn spray gel, CarraSorb M, RadiCare,
and DiaB
Woun’Dress natural collagen hydrogel
wound dressing
ClearSite Gel and ClearSite HydroGauze
dressing
DuoDerm hydroactive gel and SAF-Gel
DermaMed
Dermagran Hydrophilic and Dermagran
(zinc-saline) hydrogel
Aquasorb
Flexderm
Gentell Hydrogel
Curasol, Iodosorb and Iodoflex
Restore Hydrogel
Stericare glycerin hydrogel
Nu-Gel
Curafil and Curagel
Spand-gel
Hypergel and Normlgel
Iamin hydrating gel and GraftCyte
TransiGel, SoloSite, and IntraSite
Elasto-Gel
Elta Dermal
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Exhibit 5-7:
Supplier
Carrington
1996 Hydrogel Dressings, Share by Supplier
Sales
Market Share
$11.4M
36%
ConMed/NDM
5.8
18
Healthpoint
4.6
14
Molnlycke
3.1
10
Other*
7.2
22
Total
$32.1M
100%
*Other includes Bard, Coloplast/Sween, ConvaTec, DermaRx, Derma Sciences, DeRoyal,
Dow Hickman, Gentell, Hollister, Horizon Medical, Johnson & Johnson, Kendall, MediTech International, ProCyte, Smith & Nephew, Southwest Technologies and Swiss-American
Products.
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Hydrocolloid dressings are generally not indicated for heavily exudating wounds/ulcers or
fistulas. Fowl-smelling exudate, in conjunction with hydrocolloid dressings or bacterial
build-up in the exudate on the wound surface, can result in malodorous fluids. This will
require frequent dressing changes. However, the adhesive backing on the hydrocolloid
dressings is designed to stay in place for up to five days, thus frequent dressing changes may
indicate the use of another type of dressing for a patient so as not to injure newly forming
granulation tissue. Hydrocolloid dressings are opaque; therefore, the caregiver is unable to
observe the healing process without first removing the dressing. Another disadvantage is the
relative thickness of the dressing; however, some manufacturers have significantly reduced
the thickness of hydrocolloids in recent years. In addition, the hydrocolloid material may
dissolve into the wound bed, making cleansing more difficult.
The hydrocolloid dressing market is about 35% of the $241 million occlusive dressing
market, with $83 million in sales in 1996. Due to this dressing’s ability to stay on the wound
for up to 5 days, it has high-volume use in long-term care sites, which helps make
hydrocolloids the largest market within the occlusive dressing category. However,
hydrocolloids are losing product volume to alginates, causing its growth to begin to slow in
recent years. As a result, the overall market is forecasted to grow at an average annual growth
rate of 7.9% to $133 million in the year 2002. Exhibit 5-8 presents the market forecast for
hydrocolloid dressings.
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Exhibit 5-8:
U.S. Hydrocolloid Dressing Market Forecast, 1996-2002
Year
Sales
Growth
1996
$83.4M
1997
90.9
9.0%
1998
98.8
8.7
1999
107.0
8.3
2000
115.3
7.8
2001
124.0
7.5
2002
133.0
7.3
—
CAGR 1997-2002
7.9%
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As presented in Exhibit 5-9, competitors in the hydrocolloid dressing market include
ConvaTec, Hollister and other prominent dressing manufacturers. ConvaTec manufacturers
several hydrocolloids including DuoDerm CGF, the company’s key hydrocolloid dressing, as
well as SignaDress for the home care market. DuoDerm CGF creates an acidic environment
and promotes anti-infective effective in the wound. SignaDress is an easy-to-use dressing
because of its tear drop in the center of the dressing which allows for easy centering of the
dressing on the wound. As the dressing absorbs exudate, a bubble is formed in the tear drop.
When the bubble reaches a visible indication line, the dressing is ready to be changed.
Hollister also offers several hydrocolloids, including Restore Wound Dressing, Restore Cx
and Restore Extra Thin. The latter dressing is a unique hydrocolloid with a flexible film
backing which is resistant to urine and other contaminants.
In April 1995, Brennen Medical began marketing their B-G-C Matrix wound dressing which
is a beta-glucan and hydrocolloid matrix combined with multifilament mesh. This mesh is
applied to a smooth, gas permeable polymeric layer. This dressing is available in various
sizes and can be held in place with flexible net or gauze. The dressing may remain on the
wound for as long as three days. If the wound appears to be re-epithelializing, it may remain
on the patient longer as a simple barrier or protective dressing.
Market shares for the hydrocolloid dressing market are shown in Exhibit 5-10. ConvaTec is
by the far the industry leader with 76% of the market, mainly to due its well-known
DuoDerm hydrocolloid. All other players in this market compete with under a 10% market
share; some companies, like Kendall, compete in the bottom part of the market due primarily
to their concentration in the non-hospital market.
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Exhibit 5-9:
Selected Manufacturers of Hydrocolloid Dressings
Manufacturer
3M
Product
Tegasorb and Tegasorb Thin
Beiersdorf-Jobst
Cutinova
Brennen
BGC Matrix
Coloplast/Sween
Comfeel Plus
ConvaTec
DuoDerm CGF,CombiDerm and SignaDress
Dow Hickam
Hydrocol
Gentell
Dermatell and Dermatell Secure
Hollister
Restore Wound Care Dressing, Restore Extra
Thin and Restore Cx
Horizon
DermAssist hydrocolloid
Kendall
Curaderm
Ultec and Ultec Thin
Smith & Nephew
RepliCare
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Exhibit 5-10: 1996 Hydrocolloid Dressing Market, Share by Supplier
Supplier
Sales
Market Share
ConvaTec
$63.4M
76%
Smith & Nephew
6.7
8
3M
5.0
6
Other*
8.3
10
Total
$83.4M
100%
*Other includes Beiersdorf-Jobst, Brennen, Coloplast/Sween, Dow Hickman, Gentell,
Hollister, Horizon, Kendall and Sherwood-Davis & Geck.
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5.2.4
Foam Dressings
Foams are semi-occlusive, made from inert ingredients such as polyurethane, and have a high
degree of thermal insulation. In addition, foams provide controlled moisture to the wound
bed while absorbing exudate. Foams consist of one hydrophilic side, which is placed on the
wound while the other untreated side provides a barrier for bacteria. Foam dressings allow
oxygen and vapor permeability which help to reduce the risk of infections. These dressings
require a secondary dressing and a sealed edge in order to maintain wound moisture.
Foam dressings are used for heavily exudating wounds, especially during the inflammatory
phase. They are also used for wounds with deep cavities to prevent premature closure while
keeping the wound moist and absorbing exudate. Other advantages to these dressings include
increased patient comfort, nonadherence to the wound, and decreased maceration due to the
dressing holding the exudate away from the wound and surrounding tissue. Foams can be
drying if there is not enough drainage.
Foam dressing are one of the fastest growing segments of the occlusive and semi-occlusive
dressing market, with an average 8.6% annual growth rate through the end of the decade.
Although foams are starting to reach maturity, they may be one of the first dressings used
with growth factors because they are easy to impregnate. However, their growth is not as
solid as alginates, partly because they are difficult to use; they sometimes dislodge and do not
contour to the wound as well as other dressings. Regardless, the market is expected to grow
from $18 million in 1996 to $29.5 million in 2002, as shown in Exhibit 5-11.
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Exhibit 5-11: U.S. Foam Dressing Market Forecast, 1996-2002
Year
Sales
Growth
1996
$18.0M
1997
19.5
8.5%
1998
21.3
9.1
1999
23.2
8.9
2000
25.2
8.6
2001
27.3
8.3
2002
29.5
8.1
CAGR
8.6%
1997-2002
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Johnson & Johnson, a major competitor in the foam dressing market, offers Tielle
hydropolymer dressing which absorbs up to 15 times its own weight and requires no
secondary dressing. This company also offers Biopatch, an antimicrobial dressing consisting
of a hydrophilic polyurethane foam with chlorhexidine, which has antimicrobial and
antifungal properties.
Dow Hickman offers Flexzan, a ultra-thin, highly conformable foam dressing with an opencell foam and a closed-cell outer surface. This dressing is indicated for skin tears, early-stage
pressure ulcers, and dermatologic and plastic surgery procedures.
Carrington Laboratories introduced its new CarraSmart foam dressing in 1996 which is made
up of three layers. The first layer consists of a hydrophilic polyurethane to maintain moisture
in the wound, while the second layer is a hydrophilic, open-cell foam which also helps to
manage moisture. The last layer is a porous, pressure-sensitive adhesive. CarraSmart is
indicated for venous stasis ulcers, diabetic ulcers, pressure sores, partial-thickness and fullthickness wounds, first- and second-degree burns, and donor sites. Exhibit 5-12 summarizes
these competitors and others in the foam dressing market.
Market shares for the foam dressing market are shown in Exhibit 5-13. One factor in this
segment of the market is the increased use of advanced dressings, such as Smith & Nephew’s
Allevyn Cavity dressing. This dressing is a matrix of absorbent hydrocellular foam chips
which are kept separate from the wound by a perforated film sack. Smith & Nephew is the
market leader with 32% of the market, followed by ConvaTec with 21% of the market.
ConvaTec promises to be an even stronger competitor in this market, especially after its
purchase of the rights to Lyofoam from Acme United in July 1997. Johnson & Johnson,
currently a smaller player in the market, may become a major competitor if it can combine its
research in growth factors with its foam dressings.
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Exhibit 5-12: Selected Manufacturers of Foam Dressings
Manufacturer
Acme United
Product
Lyofoam
CarraSmart Foam
ConvaTec
Mitraflex and Hydrasorb
DeRoyal
Polyderm Border
DermaRx
DermaMend Foam
Dow Hickman
Flexzan
Ferris
PolyMem
Gentell
Low Profile foam
dressing
Johnson & Johnson
Sof-foam, Biopatch and
Tielle
Kendall
CuraFoam
Smith & Nephew
Allevyn
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Exhibit 5-13: 1996 Foam Dressings, Share by Supplier
Supplier
Sales
Market Share
Smith & Nephew
$5.7M
32%
ConvaTec
3.7
21
Dow Hickam
3.3
18
Acme United
1.4
8
Ferris
1.3
7
Other*
2.6
14
Total
$18M
100%
*Other includes, Carrington, DeRoyal, DermaRx, Gentell, Johnson & Johnson and Kendall.
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5.2.5
Calcium Alginates
Calcium alginate contains naturally occurring polysaccharide salts of alginic acid, a
carbohydrate which occurs in brown seaweed. This non-woven twisted fiber is placed into
the wound and absorbs 20 times it own weight in exudate fluid. It is the dressing of choice
for heavily exudating wounds. However, like most other wound filler and absorptive
products, it needs a secondary dressing for wound covering. Calcium alginates are very
comfortable for patients, absorb without pathology to healthy surrounding tissue, are easy to
use, and are especially useful for packing exudating wounds. Alginate dressings are also a
very poor medium for microbial growth and can be easily removed from the wound site with
saline irrigation to the area. Calcium alginate dressings are used on chronic wounds, partialthickness burns, skin graft donor sites, dermabrasion, acute wounds, and dermal ulcers.
Alginates, the fastest growing segment in the occlusive and semi-occlusive dressing market,
are expected to increase from $34 million in 1996 to $64.4 million by 2000. The 11.7%
average annual growth rate is being driven by a number of factors. First, these dressings are
popular in home and long-term care, and they have an ability to conform to the wound while
absorbing and containing drainage better than foam dressings. Second, their inclusion as part
of nation-wide contracts with large providers with fuel growth until the end of the decade,
when this market is expected to begin to reach maturity. The forecast for alginates is
presented in Exhibit 5-14.
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Exhibit 5-14: U.S. Alginate Market Forecast, 1996-2002
Year
Sales
Growth
1996
$34.0M
1997
37.0
8.8%
1998
40.5
9.5
1999
45.0
11.1
2000
51.6
14.7
2001
58.0
12.4
2002
64.4
11.0
—
CAGR
11.7%
1997-2002
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In 1989, Dow Hickman introduced the first calcium alginate dressing called Sorbsan.
Through sodium ion exchange, this dressing transforms into an absorbent, conformable
sodium alginate gel when the dressing contacts the sodium-rich exudate in the wound bed.
Sorbsan is indicated for all wet wounds, including those that are infected. Another major
competitor is ConvaTec, with their Kaltostat product, which is available as a wound dressing
or wound packing. Kaltostat offers the advantages of an alginate as well as the structural
support of collagen.
In 1995, DeRoyal purchased the rights to the Kalginate dressing from Chem/Orbital, Inc. and
subsequently introduced the dressing in November 1995. According to DeRoyal, Kalginate is
made with heavier fibers which help to absorb more exudate and hold the dressing together
when it is removed. The company is also able to manufacture the fibers in their own textile
mills while most other competitors rely on fibers that are manufactured in England and
France.
In January 1996, Carrington Laboratories introduced its first calcium alginate product,
CarraSorb H. This dressing is made for wounds with heavy exudate, and the corresponding
indications include pressure ulcers, stasis ulcers, diabetic ulcers, arterial and venous ulcers,
foot ulcers, post-surgical incisions, radiation dermatitis, donor sites, trauma wounds, dermal
lesions, and abrasions. Exhibit 5-15 summarizes the major competitors and their products in
the alginate market.
Market shares for the alginate market are shown in Exhibit 5-16. Dow Hickam, with the first
alginate dressing in the industry, still enjoys market leadership with a 44% market share.
However, ConvaTec may gain market share in the next several years due to its contracting
agreement with national providers; currently, ConvaTec holds a 34% market share.
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Exhibit 5-15: Selected Manufacturers of Alginates
Manufacturer
Product
3M
Tegagen HI and Tegagen HG
Bard
Algiderm
Carrington
CarraSorb H
Coloplast/Sween
Comfeel SeaSorb and
Comfeel SeaSorb filler
ConvaTec
Kaltostat
DeRoyal
Kalginate
Dow Hickam
Sorbsan
Hollister
Restore CalciCare
Horizon
DermAssist alginate
Kendall
Curasorb
Dermacea alginate
Smith & Nephew
AlgiSite
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Exhibit 5-16: 1996 Alginate Dressing Market, Share by Supplier
Supplier
Dow Hickman
ConvaTec
Sales
Market Share
$15.0M
44%
11.5
34
Kendall
1.6
5
Other*
5.9
17
Totals
$34.0M
100.%
*Other includes 3M, Bard, Carrington, Coloplast/Sween, DeRoyal, Hollister, Horizon,
Sherwood-Davis & Geck, and Smith & Nephew.
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Chapter 6: Synthetic/Biosynthetic Dressings and Skin Replacements
6.
SYNTHETIC/BIOSYNTHETIC DRESSINGS AND SKIN
REPLACEMENTS
Much of the current wound healing research and clinical investigation is concentrated on
biosynthetic dressings and skin replacements. Large venture capital investment indicates that
expectations are high for these products. There is much controversy over indications for use,
efficacy, effectiveness in wound healing and cost/benefit ratios.
While traditional skin coverings have included skin grafts and flaps, the newer products
range from synthetic and biosynthetic coverings to in vitro cultured tissue for epidermal and
dermal replacement. These skin coverings can be applied for temporary or permanent skin
replacement, or a combination of both. Although the primary market focus of skin
replacement is for severe burn patients, these products are also being considered for the
chronic skin ulceration marketplace.
6.1
Autologous Skin Grafts and Flaps
The autograft (a patient's own skin) includes split-thickness grafts and full-thickness pedicle
flaps and free flaps. Split-thickness grafting is most common and is used in the early stages
of burn injury for wound closure. Split-thickness grafts can be applied in sheets or meshed
for greater wound coverage. Although meshed grafts cling to wound beds easier and prevent
accumulation of blood, serum or purulent material under grafts, the meshed-look pattern may
remain. The patterned look results from the lack of the epidermal basal layer for regeneration
of epithelial cells, causing scar tissue to develop.
Full-thickness pedicle flaps and free flaps are commonly used later (months to years after
injury) and are usually reserved for reconstructive purposes. A pedicle flap is a section of the
patient's skin (epidermis, dermis and subcutaneous layers) moved from one area to another
while maintaining a vascular attachment to the original location. Free flaps contain various
tissue types which are disconnected from their original vasculature and reconnected to blood
vessels at wound injury sites via micro-surgery techniques. The advantages of flaps are that
they maintain their own blood supply, provide superior facial cosmesis and are superior in
repairing poorly vascularized defects and covering bony prominences.
6.2
Synthetic and Biosynthetic Dressings
In the past, synthetic and biosynthetic dressing have been used as temporary coverings for
burns until autograft is feasible or until allograft skin or cultured skin is available. These
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dressings are now used for partial-thickness wounds, donor sites, decubitus ulcers and
abrasions. They are used as a barrier which protects the wound from infection and allows
healing to progress naturally. In order to further reduce the likelihood of infection, some
temporary dressings have been introduced with silver sulfadiazine cream. Porcine skin with
silver sulfadiazine cream is commercially available, as well as amniotic membranes
incorporating silver nitrate.
6.2.1
Biobrane, a dressing offered by Dow Hickam, is intended for meshed autografts, donor sites
and partial-thickness wounds. This dressing is translucent, allowing for easy wound
visualization, and is a nylon-knit fabric bonded to a silicone-plastic membrane. Collagen
peptides are also bonded to the surface. Biobrane is non-toxic, non-antigenic and permeable
to anti-bacterial creams. This dressing has many small pores in its silicone membrane for
exudate drainage, but with infected wounds, there can be fluid build-up beneath the dressing.
Regardless, Biobrane is a temporary dressing, ultimately subject to immune rejection.
Brigham and Women's Hospital in Boston has been using Biobrane for seven years reported
that Biobrane adheres well to scald burns. According to the Regional Burn Center at the
University of California, San Diego Medical Center, the combination of Biobrane and
airflow specialty beds can enable successful treatment of posterior donor site wounds.
Ormed, a division of Synthes-Hug-Straumann Group of Germany, is the U.S. distributor of
the Epigard dressing which has been sold in the United States since 1992. This dressing was
developed by Becton-Dickinson in France which sold the marketing rights to Synthes-HugStraumann. Epigard is a synthetic skin substitute for temporary coverage, debridement and
conditioning of soft tissue wounds. The dressing consists of a double-layered textile, which is
microporous and non-medicated. The 2.5 micron upper layer is a polytetrafluoroethylene
(PTFE) membrane with a controlled microporosity which permits ventilation but not
bacterial penetration. The lower layer is an open matrix of reticulated polyurethane. These
two layers are laminated together without the use of adhesives or solvents; lamination is
achieved by a polyethylene net bonded together by heat and pressure.
The foam side of the Epigard dressing produces intimate thrombogenic adhesion to the
plasma-wet surface of the wound’s viable tissue. This inhibits any further loss of plasma and
binds the necrotic debris to the foam. By changing the dressing every 24 hours, there is
selective debridement of necrotic tissue, inducing a highly vascularized granulation tissue.
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Removal of Epigard just prior to grafting leaves a viable capillary bed suitable for reception
of the homograft.
Epigard is not categorized as a traditional dressing and is included in the
synthetic/biosynthetic category because it has been recognized as a substitute for temporary
wound coverage. This product is particularly well suited as a temporary covering in preparing
wounds prior to skin grafting and as a primary covering of burn wounds after surgical
debridement.
A traditional competitor in the synthetic/biosynthetic dressing market, Brennen Medical
offers several different dressings. The company manufactures E-Z Derm, a biosynthetic
wound dressing which is a porcine-derived xenograft. With this dressing, the collagen has
been chemically crosslinked with an aldehyde to provide strength, durability and convenient
storage at room temperature. This product can be used on partial-thickness wounds, donor
sites and as a test graft to ensure a proper wound bed for autografting. E-Z Derm also protects
the interstices when used on meshed autografts and can be used for treatment of skin loss
injuries such as abrasion, scalds and avulsions on an outpatient basis.
Mediskin Porcine Biological Dressing is another Brennen Medical product; this dressing is
immediately soothing and adheres to a clean, eschar-free wound surface, protecting sensitive
nerve endings. Mediskin also eliminates daily painful dressing changes because it is left in
place until it sloughs off. Mediskin can be stored in any freezer and will thaw at room
temperature in 1 to 2 hours.
BioMed Sciences' biosynthetic dressing, Silon-TSR, consists of network of silicone and
polytetrafluoroethylene. This dressing is "self-clinging," but non-adhering; therefore, it
requires a secondary gauze dressing which may need to be changed while leaving Silon-TSR
in place as the wound heals. Silon-TSR is indicated for laser resurfacing, dermabrasion
wounds, second-degree burns and skin tears.
Another manufacturer in this category is Sherwood-Davis & Geck. This company offers
Inerpan which incorporates amino acids, L-leucine and methyl L-glutamate.
6.2.2
Synthetic/Biosynthetic Dressing Market Analysis
In the past, synthetic/biosynthetic dressings like Dow Hickam’s Biobrane have been in a
class of their own because their use as a covering on critically burned patients was vital to
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keep the patient’s electrolytes in balance and to stabilize the patient. The growth in this $47.8
million market is expected to begin to slow due to the introduction of skin replacements and
skin substitutes. Not all patients will require skin replacement products, which will help to
keep this market growing in the future. As shown in Exhibit 6-1, the market will continue to
increase at 5.5% average annual growth rate to $38.6 million in 2002.
As shown in Exhibit 6-2, Dow Hickam is the leader in this segment of the dressing market,
with a 46% market share. Ormed is in second place with 29% of the market, followed by
other smaller players with 25% of the market.
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Exhibit 6-1:
U.S. Synthetic/Biosynthetic Dressing Market Forecast, 1996-2002
Year
Sales
Growth
1996
$27.8M
—
1997
29.6
6.3%
1998
31.4
6.1
1999
33.2
5.8
2000
35.0
5.5
2001
36.8
5.1
2002
38.6
.9
CAGR 1997-2002
5.5%
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Exhibit 6-2:
1996 Synthetic/Biosynthetic Dressing Market, Share by Supplier
Supplier
Sales
Market Share
Dow Hickam
$12.8
46%
Ormed
8.1
29
Others*
6.9
25
Total
$27.8M
100%
*Others includes Bio Med Sciences, Brennen and Sherwood-Davis & Geck.
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6.3
Skin Replacements and Substitutes
Skin replacements and skin substitutes are mainly used for severe burn patients; however,
these products are also gaining momentum for the treatment of dermal ulcerations, in
particular venous stasis and diabetic ulcers. Manufacturers are focusing on these market
segments in order to expand their market scope. Although more expensive than conservative
wound therapy, there are numerous advantages to these products, including reduced need for
donor sites in burn patients, faster closure for larger wounds and better dermal quality and
less risk of scarring.
Manufactures will need to justify the increased costs of these products by outcomes studies
which substantiate these advantages as well as document faster healing rates and improved
overall cost effectiveness. Indirect costs, such as nursing time and improvement in the quality
of life, will also need to be considered. In addition, to maximize cost effectiveness, these
products must be able to accelerate healing in chronic lesions.
At the present time, manufacturers of this unique technology are racing to either get FDA
approval or a better share of the market. Participants in the current market and those in
development include: LifeCell Corporation, Advanced Tissue Sciences, Genzyme Tissue
Repair, Organogenesis and Integra LifeSciences.
6.3.1
Regulatory Status
In April 1996, FDA Commissioner David Kessler issued new regulations to govern products
which are derived from cells and tissues. Over a three-year period, the FDA will institute new
rules to prevent unwitting use, processing or handling of contaminated tissue which could
carry and transmit infectious disease. These rules are designed to ensure clinical safety and
effectiveness for certain cells and tissues and vary in their application depending on the
potential risk involved.
"Human tissues have wide uses in medicine, including skin replacement after severe burns,
tendons and ligaments to repair injuries, and corneas to restore eyesight," said Health and
Human Service Secretary Donna E. Shalala. "Now that science is providing even more new
ways of using tissues, FDA has developed an innovative regulatory approach to allow these
novel products to benefit patients as soon as possible."
According to the FDA, the three-tiered approach effects an appropriate level of control that is
equal to the perceived risk for the materials. Products that are considered novel or are
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extensively processed require FDA approval before they are marketed. All tissue processing
facilities will be required to register with the FDA and to list their products.
The policy puts in place requirements for infectious disease testing, donor screening and
processing controls for tissue that is transplanted from one patient to another. All such tissues
would be handled according to "good tissue practices" which would include testing tissue for
infectious agents and donor screening for exposure to disease agents.
The policy does not impact cells or tissue removed from and transplanted to the same person
in a single surgical procedure. Further, minimally processed conventional and reproductive
tissue would not be subject to FDA concern in areas of handling and contamination. But for
certain tissues, controlled clinical trials and premarket approval will be required to
demonstrate safety and efficacy of the material. Such requirements will apply to tissues and
cells in which characteristics have been altered biologically or functionally. Labeling would
also be required for tissue containers to protect healthcare workers and advise handlers of the
potential biohazard.
6.3.2
When considering skin replacements and substitutes, current products and investigational
therapies can be categorized by the following:
•
Epidermal replacements - keratinocytes grown on tissue culture or on a carrier, such
as bioresorbable matrix;
•
Dermal replacements - fibroblasts or endothelial cells grown on a support structure to
aid in proliferation; and,
•
Skin substitutes - a combination of epidermal and dermal replacements which are able
to support both the dermal and epidermal components.
Competitors with skin replacement and skin substitute products include Advanced Tissue
Sciences, Genzyme Tissue Repair, Integra LifeSciences and LifeCell. Each of these
companies and their products are discussed in the following sections.
6.3.2.1 Advanced Tissue Sciences
In March 1997, Advanced Tissue Sciences received approval from the FDA to market its
Dermagraft product. Dermagraft is a bioengineered human dermal tissue replacement product
and designed to provide permanent replacement of the inner layer of skin. Advanced Tissue
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Sciences has been working in conjunction with Smith & Nephew on a joint venture to
develop the product.
Dermagraft is engineered human dermal tissue combined with a synthetic epidermal layer
which is designed to treat patients with third-degree burns on more than 20% of the body’s
surface. The product also provides a protective cover for burn patients to help retain fluids
and reduce the risk of infection until a sufficient amount of the patient's own skin becomes
available for grafting.
Dermagraft production begins by culturing human dermal fibroblasts onto a semipermeable
membrane which is bonded to nylon mesh. The nylon mesh provides structure as a threedimensional scaffold for the growth of dermal tissue, and the membrane forms the synthetic
epidermis. As the dermal fibroblasts grow on the mesh, they secrete growth factors and
structural components. The resultant product is then frozen which kills the cells, but leaves
the tissue matrix and cell growth factors intact. Later in the operating room, the surgeon
unfreezes the dermal patch as a temporary skin replacement for the patient’s destroyed
dermis. This product uses living human tissue, namely neonatal foreskin, which does not
elicit an allergic or immune response because the basic component has not developed
antibodies to cause a reaction.
Clinical trial data demonstrated that Dermagraft successfully reached its primary endpoint,
which was the ability to adequately prepare the burn wound bed for successful autografting
and performing equal to or better than the cadaver allograft control. In addition, Dermagraft
performed significantly better than the control with respect to important secondary endpoints
such as ease of removal, amount of excision required, amount of bleeding upon excision and
overall satisfaction ratings as a temporary covering among investigators.
6.3.2.2 Genzyme Tissue Repair
Genzyme Tissue Repair is the only company in the world to successfully provide cultured
tissue technology as a commercial service, delivering therapeutically viable cells to a large
number of patients on a reproducible basis. The Epicel service was developed at BioSurface
and consists of a sheet of proliferative cultured autologous keratinocytes, ranging from 2 to 8
cell layers thick. The autologous keratinocytes are harvested from the patients’ own skin
tissue and are processed to isolate specific cell types for epidermal autografts. Each cultured
epidermal autograft is approximately 30 cm2 in size and is individually packaged with a
small amount of buffered serum-free nutrient medium. The company has processed more
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than 1,500 individuals patient biopsies, treated over 800 burn patients with Epicel skin grafts
in more than 120 cities around the world.
Epicel lies outside of FDA regulations because it is an autologous therapy which does not
involve manipulation of cells in such a way as to significantly change their biological
properties. However, Genzyme employs rigorous quality standards and all processing
procedures are controlled to ensure safety and tractability of operations.
An article by in the Annals of Surgery in 1996 by A.M. Munster MD, reported the results of a
controlled trial which compared the outcome of therapy in patients with massive burns, with
and without cultured autologous epithelial autografts . During a 5-year period, 22 patients
with an average burn size of 71.8% were treated with cultured keratinocytes and compared
with a group of 42 controls with an average burn size of 61.6%. The results showed a
reduction in mortality in the cultured epithelial autograft group compared with controls, from
48% to 14%. There was no difference between the two groups in other major complications,
or in readmission for breakdown.
Acticel is a wound dressing that is intended to limit infection and promote healing of severe
burns. It is composed of living epidermal tissue grown in laboratories that is then attached to
a synthetic dressing. The company announced that the results of a 77-patient study of Acticel
in the treatment of partial-thickness burns were significant enough for marketing this
application. Acticel's potential is being reviewed by the company, thus casting doubt as to
whether the product will ever reach the U.S. market. An earlier study using Acticel in treating
skin graft donor sites was also halted following an interim analysis because it had only
borderline efficacy compared to the placebo.
6.3.2.3 LifeCell
LifeCell employs a patented process to manufacture a cryopreserved allograft skin for
temporary burns called AlloDerm. This product has been on the market since June 1995.
Using donated cadaveric skin grafts, the patented process removes all cells while preserving
the dermal matrix. The cells of these grafts normally maintain the matrix which are also the
targets of the body's immune response. The end result is a totally intact, acellular matrix. The
matrix contains all the facilities for cell residence and function so that when the nonviable
processed matrix is transplanted, the patient's own cells repopulate it and create a
permanently integrated living tissue graft. The grafts are effective in helping skin heal and
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promoting the growth of fibroblasts which are the key maintenance cells of dermis. By using
AlloDerm, integrated living tissue grafts can be formed which are invisible to the immune
system.
A porcine equivalent called XenoDerm is being developed, and a number of universities and
burn centers have shown that XenoDerm decreases wound contraction and improves
cosmesis compared to conventional treatment. By using an immune-deficient mouse
reconstituted with human immune system cells, LifeCell is evaluating the immune response
to XenoDerm. If successful, human clinical applications will then take place.
LifeCell is also developing a composite, bi-layered AlloDerm graft for burn wound treatment
in order to eliminate the need for self-donated skin to graft burn wounds. Also, the National
Science Foundation has provided LifeCell with the funding to develop a composite skin by
combining AlloDerm and the cells of the epidermis. This program focuses on using stem
cells in skin to create the readily available composite skin from AlloDerm and a patient's own
epidermal cells, eliminating patient autograft requirements.
In January 1997, the company announced the award of over $1 million from the U.S. Army
Medical Research and Material Command in order to fund the development of new tissue
transplant products for use in neurological, dermatological and cardiovascular surgery.
Investigation of AlloDerm grafts to repair dura mater and the membrane lining of the brain,
as well as investigation of its use in conjunction with micro-skin grafting to cover large
wound surfaces with small, biopsy-sized skin grafts, will be the focus of this two-year
cooperative agreement.
Results from a study conducted by David J. Wainwright M.D. of the University of Texas
Health Science Center, were published in the June, 1995 issue of Burns. The study compared
test sites using AlloDerm to control sites using the patient's own skin or autografts. AlloDerm
sites demonstrated high "take rates" and results indicated that AlloDerm would reduce the
amount of donor skin required for split-thickness autografts in full-thickness burn injuries.
Only a single application of AlloDerm was required, and was considered a major treatment
benefit.
At 1997 Annual Meeting of the American Burn Association, AlloDerm was presented as
beneficial in treating wound contracture complications for reconstruction of burn wounds
previously grafted with the patient's own skin. The product also was shown to offer benefits
in initial permanent dermal graft in elderly persons.
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6.3.2.4 Integra LifeScience
Integra LifeSciences received PMA approval for its Integra Artificial Skin in March 1996.
This product is designed to grow new skin and permanently replace damaged skin on severe
burn victims. The product is a dermal composite which consists of a porous lattice of fibers
of a cross-linked bovine collagen and glycosaminoglycan (GAG), and a synthetic epidermal
layer of polysiloxane polymer (silicone). The GAG that is used is chondroitin-6-sulfate. The
product was originally approved by the FDA to be manufactured in 4" by 10" sheets. The
company applied to the FDA and was granted a PMA approval supplement to manufacture
additional sizes of 4" x 5" and 8" x 10". This will accommodate physicians' requirement to
use the product in more applications.
The product is manufactured in the United States and has been marketed domestically as well
as internationally to such countries as Denmark, Hong Kong, Singapore, Switzerland, Ireland
and parts of Germany. The product is sold only after medical professionals have been trained
in the use of the product. Specialized registered nurses are employed to provide in-hospital
training for operating room and burn unit personnel. By early 1997, more than 300 surgeons
had been trained in the United States and Canada, as well as an additional 300 in Europe and
Asia in the use of Integra Artificial Skin.
6.3.3
Development Status
Other companies are moving swiftly to develop and commercialize additional skin
replacements and substitutes. Investigational products from Organogenesis, Ortec and Purdue
University are discussed in the following sections.
6.3.3.1 Organogenesis
Apligraf, being developed by Organogenesis, is a full-thickness living skin substitute which
contains both dermal and epidermal layers. The product is intended for the treatment of
wounds, including chronic wounds, skin surgery wounds and burns.
In 1996, Organogenesis launched a clinical trial to assess the efficacy and safety of Apligraf
for the treatment of diabetic ulcers. The FDA has granted expedited review status of the
company's PMA for the product's use in diabetic ulcers. A PMA for the treatment of venous
ulcers was also given expedited review status by the FDA.
Apligraf is a organotypic tissue product which consists of complex tissue with living cells
organized like native tissue. The upper layer of Apligraf is composed of living human
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epidermal cells (keratinocytes), and the lower layer consists of living human dermal cells
(fibroblasts) in an organized dermal matrix. These cells can interact with the wound bed and
directly contribute to the wound healing process.
Among the fundamental raw materials needed to manufacture Apligraf are keratinocytes and
fibroblasts which are derived from donated infant foreskins. The lab separates the different
cell types and keeps them growing so that a dozen donations could provide enough material
to treat the world. One postage stamp-sized piece of human foreskin can produce 200,000
(approximately four acres) of Apligraf.
Organogenesis entered into a marketing agreement with Sandoz (Novartis) in January 1996.
The agreement entered into with Sandoz Ltd. grants the company global marketing rights to
Apligraf in exchange for bearing all sales and marketing costs and giving Organogenesis per
unit manufacturing payments as well as royalties on all Apligraf sales. Sandoz also
contributes strong representation in key markets as well as extensive expertise in marketing
breakthrough medical products. In April 1997, Apligraf was approved in Canada, and
Novartis is preparing to launch the product in this country.
6.3.3.2 Ortec
In April 1996, Australian physician, Mark Eisenberg, MD, reported findings on a new
cultured skin technology to the National Conference of the Australian Wound Management
Association. The study showed that an experimental skin replacement technology, Composite
Cultured Skin (CCS), is a promising treatment for children suffering from recessive
dystrophic epidermolysis bullosa, a congenital skin conditional characterized by painful
ulceration and widespread permanent scarring resulting in deformity of the hands and feet.
The results suggested that CCS can be an effective addition to the surgical management of
the disease’s deformities, and it can reduce the need for autografts. In addition, CCS also
helped restore the functioning and appearance of the children's fingers. Ortec holds exclusive
worldwide rights to the CCS technology under a licensing agreement with Dr. Eisenberg,
who is the developer of CCS.
In the United States, CCS is being evaluated in a clinical trial for treatment of burns, under an
Investigational Device Exemption (IDE) granted by the FDA. This product will also be
evaluated in patients with chronic dermal ulcers at Rockerfeller University Hospital in New
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York. Enrollment of patients in that trial is targeted for completion by the end of the third
quarter 1997.
The product is derived from human dermal and epidermal cells (infant foreskins), which can
be grown in large quantities and cryopreserved. After thawing, the two cell types are cultured
on a proprietary collagen matrix, forming a "biologically active dressing." The dressing is
then applied directly on a wound site. According to Ortec, CCS differs from Organogenesis'
Apligraf in its collagen matrices and the methods used in culture and cells onto the collagen
matrices.
6.3.3.3 Purdue University
In a study that is being conducted at Purdue University, a biomaterial derived from small
intestinal submucosa (SIS) is being used to induce the healing of recalcitrant skin wounds
resulting from the use of prosthetic devices. Treatment options for these patients are limited,
and repeat reconstructive surgical procedures are often necessary. Since continued use of the
prosthetic device is a necessity for these patients, a suitable exogenous material that could fill
subcutaneous spaces, promote vascularization in ischemic tissues, and serve as a skin
covering would be a significant benefit. Small intestinal submucosa has the ability to
stimulate or induce host tissue to proliferate, remodel and even regenerate into a type of
connective tissue that is appropriate for the particular location in the body where the material
is placed. SIS supports epithelial growth, neovascularization and infection resistance. The
implanted SIS is resorbed within 60 to 90 days leaving no material against which the host can
mount an inflammatory response.
The study aims to optimize these properties for the local treatment of skin wounds caused by
prosthetic devices. Various forms of xenogeneic SIS will be used to treat these wounds,
including SIS with attached growth factors EGF, FGF and PDGF. Measured variables will
include wound contraction, vascularization, epithelialization, infection resistance and
mechanical properties of the remodeled tissue.
6.3.4
Skin Replacement and Substitute Market Analysis
Skin replacements and skin substitutes compete mainly in a discrete section of the overall
burn market, namely, the severe burn segment. These innovative products will have a
marketing edge over the next few years; however, their rapid growth is bound to be
somewhat impeded by the introduction of growth factors, possibly as soon as 1998 or 1999.
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Although these skin replacements and growth factors will compete in the same market
segments, they can also be used to complement one another. For example, growth factors
could be used on replacement skin to enhance angiogenesis, skin replacement acceptance,
and remodeling using patient's own cells. As shown in Exhibit 6-3, the skin replacement and
substitute market is expected to increase from $10 million in 1996 to $15 million in 2002 at
an average annual rate of 6.9%.
As shown in Exhibit 6-4, there were three competitors in the market in 1996: Genzyme
Tissue Repair, Integra LifeSciences and LifeCell. Genzyme Tissue Repair was the market
leader with a 50% share, while Integra and LifeCell composed the remaining half of the
market with 30% and 20% of the market, respectively. These market positions are bound to
change over the next several years as new products, such as Advanced Tissue Sciences and
Organogenesis, are used for both burn and ulcer applications.
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Exhibit 6-3:
U.S. Skin Replacement and Substitute Market Forecast, 1996-2002
Year
Sales
Growth
1996
$10M
—
1997
11
6.7%
1998
12
7.5
1999
13
8.0
2000
14
7.1
2001
14
6.4
2002
15
5.6
CAGR 1997-2002
6.9%
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Exhibit 6-4:
1996 Skin Replacement and Substitute Market, Share by Supplier
Supplier
Sales
Market Share
Genzyme Tissue Repair
$5.1
50%
Integra LifeSciences
3.1
30
LifeCell
2.0
20
$10.2M
100%
Total
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Chapter 7: Growth Factors
7.
GROWTH FACTORS
The process of wound healing is orchestrated in part by the release of and response to peptide
mediators. These macro-molecules are released at the time of original injury by platelets,
leukocytes and local tissue to stimulate the proliferation of new connective tissue, blood
vessels and epithelium in the injury site. As inflammation proceeds to tissue replacement,
local expression of these growth factors controls the rate and extent of repair. Since these
proteins are all distinct gene products, elaborate regulation can occur at the cellular level. In
addition, many growth factors are produced in latent forms or linked to carrier molecules.
Growth factors can be released from the extracellular matrix during its turnover, and they can
be sequestered by the newly deposited tissue matrix. These potent molecules are involved in
normal and pathologic healing, and there are substantial experimental data demonstrating
their ability to alter the rate of repair.
Despite the knowledge gained through experimental data, much needs to be learned about
delivering and combining growth factors as well as protecting them from degradation to
obtain clinically effective results. New modalities such as gene therapy, use of anti-proteases
and wound pretreatment could improve the utility of these potent molecules.
Growth factors have caused a good deal of clinical and manufacturing interest. Some
observers feel that too much attention has been devoted to a technology that may never be
fully realized. They note that growth factors may not reduce hospital costs, may not heal all
wounds or ulcers, cannot prevent wound/ulcer reoccurrence, and may, in fact, be harmful
because of their close interrelationship with carcinogenic cell stimulation. Many also think
the advantages of growth factors are exaggerated due to the body's own miraculous ability to
heal itself by natural pathways.
Others believe the time is right and growth factor technology will change not only how
chronic wounds are healed, but speed the healing of normal incisions and wounds and
possibly eliminate proliferative scarring (that is, keloid and hypertrophic scar formations).
Although numerous growth factors have been identified, this chapter will be limited to those
that have been established in the wound healing literature. These growth factors include
fibroblast growth factors (aFGF and bFGF), transforming growth factors (TGF-alpha and
TGF-beta), epidermal growth factor (EGF), platelet-derived growth factors (PDGF), insulinlike growth factors (IGF-I and IGF-II) and interleukins (IL-1 and IL-2).
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7.1
Normal Effects of Growth Factors
Normal wound healing progresses through a series of specific growth factor secretions and
specific cell stimulations. At injury, platelets degranulate at the site and release their alpha
granules into the wound. Platelet-derived growth factor, TGF-alpha and EGF are then
released. After arriving at the wound site, neutrophils are attracted to these cytokines and
produce TGF-beta and interleukins. Macrophages appear and secrete large quantities of
TGFs, PDGF, FGFs, interleukins and macrophage angiogenesis factors throughout the
wound healing process. This combination of factors produces the granulation tissue which
fills the wound cavity. Fibroblasts and endothelia produce IGFs and endothelins.
Additionally, PDGF stimulates wound contraction, and both EGF and PDGF stimulate
epidermal cells to cover the granulation tissue with epithelium. Exhibit 7-1 presents a
summary of the biological events in the repair of soft tissues.
Recombinant growth factors are exact copies of cloned peptides; however, recombinant
growth factors may have subtle biochemical differences. Human recombinant PDGF is a
homodimer of two B chains, whereas in the natural state in the body (in vivo), it is found as a
three-dimeric chain. Additionally, in the natural state some peptides are heavily glycosylated
peptides, whereas in the recombinant state they are nonglycosylated, such as with
granulocyte macrophage colony stimulating factor (GM-CSF). Recombinant growth factor
manufacturers are aware of these differences and strive to make growth factors of the same or
greater bioactivity. As more manufacturers enter this market and more growth factors are
produced for future commercialization, the ability to maintain the correct bioactivity to
achieve specific therapeutic results will be an issue.
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Exhibit 7-1:
Sequence of Biological Events in the Repair of Soft Tissues
Phase
Amount of Time Following
Injury
Mechanisms
Coagulation
Immediate
Release of growth factors to
initiate healing cascade
Acute inflammatory
0-4 days
Macrophages clear wound of
debris; release of growth
factors
Collagen synthesis
3-30 days
First phase of collagen repair
with fibroblasts producing
scar collagen; mediated by
growth factors
Remodeling
14 days-1 year
Second phase of collagen
repair; remodeling and crosslinking of collagen fibrils
Completion of repair
Beyond 1 year
Unknown mechanisms
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7.2
Categorization of Growth Factors
There are many different types of growth factors. Initially, these proteins were named for
their tissue of origin, target cell specificity or activity in cell cultures. Unfortunately, much
confusion has occurred as research revealed that growth factors have multiple functions,
target cells, and tissue and cellular origins. As with transforming factors alpha and beta, the
proteins have similar names but do not share the same molecular homology and are
chemically distinct. In fact, TGF-alpha shares a similar homology with EGF. As more
products emerge from clinical trials and approach commercialization, the nomenclature will
need to be standardized.
Growth factors are small polypeptide molecules (that is, proteins) which are secreted by a
group of cells through autocrine (produced and utilized by the same cell, such as EGF),
paracrine (produced by one cell and utilized by another, such as TGF and PDGF) or
endocrine (delivered through the blood system, such as IGF I and IGF II) control. Unlike
blood-borne hormones (that is, insulin or epinephrine), growth factors act locally or near their
point of secretion. Growth factors do not cross cell membranes because they are proteins, and
therefore, these polypeptide bind to receptors on the outer surface of the cells. The bound
growth factor activates the receptor to transmit a message to the intracellular components.
Based on the message, a biochemical response causes the stimulation or inhibition of cell
growth.
Growth factors perform one or more of the following functions: stimulating cells to
proliferate, attracting cells to move and proliferate or altering the phenotypic state of the cell.
Mitogen activity, regulating cell division/proliferation, can be further classified into
competence or progressive factors. Before a cell can divide, it must be stimulated to move
from a resting stage (GO) to a state of readiness to replicate DNA and divide (G1).
Competence factors stimulate cells to transform from the GO to G1 state. Once the cells enter
the G1 state, progressive factors are needed to complete the cellular division cycle. Plateletderived growth factor and EGF are competence factors which stimulate cells in the GO state.
IGF-I is a progressive factor, stimulating cells to divide once they have achieved the G1 state.
Factors that alter the phenotypic state of the cell are called transforming factors.
Chemoattractants make cells move, by either chemotactic or chemokinetic factors.
Chemotactic factors work through cell receptors on the surface or cell membrane. Higher
concentrations on one side of the cell cause a target cell to move in a given direction.
Chemokinetic factors increase the rate of movement.
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Most knowledge of growth factors has been learned through isolated in vitro cellular cultures
and in vivo animal models. Animal models provide the most significant data regarding the
complex interaction of growth factors with systemic functions of the body. Performance of
growth factors may differ between in vitro and in vivo studies, indicating that another growth
factor or cellular presence may be needed to stimulate certain growth factors. Additionally, in
the presence of some other peptides, growth factors may exhibit stimulatory or inhibitory
activities. For example, TGF-beta stimulates the growth of fibroblasts in the presence of
PDGF, but inhibits the growth of fibroblasts in the presence of EGF.
In vitro studies reveal that control of growth factor effects depends on the concentration of
growth factors as well as receptor sensitivity. For example, FGF and PDGF are stimulatory at
low concentrations but are inhibitory at higher concentrations.
While recombinant growth factors are not commercially available, a number of companies
are developing specific growth factors which promise to impact all phases of wound repair.
These growth factors include FGFs, TGF-alpha and TGF-beta, EGF, PDGF, IGF-I and IGFII and interleukins.
7.2.1
Fibroblast Growth Factors
Fibroblast growth factors (FGFs) were one of the first growth factors to be isolated and
identified. FGF is a term that describes a number of heparin-binding growth factors. In 1985,
the amino acid structures and molecular weights for FGFs were determined. The amino acid
polypeptides for basic FGF (bFGF) was 146, and the molecular weight was 18,000 daltons.
The amino acid polypeptides for acidic FGF (aFGF) is 140, and the molecular weight was
16,000 daltons. The structural homology of the two FGFs share 50-55% homology. The
bFGF gene is located on human chromosome 4, and aFGF is on chromosome 5. The
homology likeness and close chromosomal approximation indicate that they share a common
ancestral gene and possibly became separate gene products through the process of gene
duplication and evolutionary divergence.
The broad specificity of both aFGF and bFGF for a number of target cells, such as
endothelial and connective tissue cells, coupled with their widespread distribution within the
body, suggests that they have reparative functions. However, aFGF appears to be 30-100
times less potent than bFGF. It is not known how FGF reaches the cell exterior because
neither the bFGF or aFGF gene codes for a typical single polypeptide sequence. Current
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hypotheses are that FGF may be released during cell lysis after tissue injury or during cellular
death.
If FGF is primarily released in accordance with either one of these two hypotheses, it further
substantiates the factors’ role in tissue repair and wound healing. bFGF stimulates various
cell types, including endothelial (endocardium, capillaries and large blood vessels) cells,
vascular smooth muscles, fibroblasts, myoblasts, chondrocytes, osteoblasts, melanocytes and
mesothelial cells, to either proliferate and migrate or be inhibited and repressed. Of all the
growth factors currently under investigation, only bFGF can trigger all of the phenomena
associated with angiogenesis. FGFs are potent mitogens for endothelial cells and have been
used to create autogenous endothelial cell linings for vascular prostheses. FGF is bound
strongly by heparin-related matrix components and has been identified in significant amounts
in the extracellular matrix. This widespread inactive pooling of FGF suggests that it is ready
to be released at any site of injury in the body. Such widespread cell stimulation or inhibition
may indicate that FGF is a primary stimulating factor in early embryonic development.
Recombinant bFGF used on full-thickness wounds stimulates significant dermal healing,
increased granulation tissue thickness, capillary formation and increased tensile strength.
bFGF is mitogenic for epidermal cells as well as connective tissue cells and has been used for
culturing human epidermal keratinocytes by adhering bFGF to a collagen matrix in order to
formulate a collagen-based dermal skin replacement.
Scios scientists were first to clone and produce recombinant human bFGF. Scios holds
patents in the United States and Europe covering the manufacture, use and sale of
recombinant human bFGF. In October 1996, Scios Inc. and Wyeth-Ayerst, the
pharmaceutical division of American Home Products Corporation, announced the signing of
a collaboration agreement for the joint development and commercialization of Scios' Fiblast
(bFGF), for the treatment of neurological and cardiovascular disorders. Fiblast is in Phase I/II
clinical trials for stroke and coronary artery disease (CAD) and in preclinical studies for
peripheral vascular disease (PVD).
Under the terms of the agreement, Wyeth-Ayerst and Scios will collaborate in the
development and commercialization of Fiblast in North America, where the companies will
share development costs and profits. Scios has granted Wyeth-Ayerst exclusive marketing
rights outside of North America and certain Pacific Rim countries and will receive royalties
on sales outside of North America and payments for bulk drug supply worldwide.
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Wyeth-Ayerst will make a $12 million upfront payment in cash and will also pay Scios
milestone payments upon achievement of all key development events. In addition, WyethAyerst will provide a $12 million line of credit that Scios may draw upon from time to time
to fund expansion of its manufacturing facility for Fiblast. The total of all payments
including the line of credit could reach $56 million.
7.2.2
Transforming Growth Factors
Transforming growth factors (TGFs) have the ability to alter the phenotype of some cells into
transformed cells. Although TGFs have the ability for angiogenesis in vivo, TGF-alpha and
TGF-beta are structurally distinct. TGF-alpha is synthesized as a transmembrane protein
precursor. It is a 50-amino-acid polypeptide with a molecular weight of 5,700 daltons.
Although structurally different than TGF-beta, it does share a 35-42% homology to EGF and
binds to the EGF receptor. It also shares a 30 percent homology to the vaccinia growth factor
and can bind to the same cell surface receptor. The gene for TGF-alpha is located on
chromosome 2.
TGF-alpha is produced by keratinocytes, activated macrophages and degranulating platelets.
TGF-alpha has mitogenic, angiogenic and chemotactic influences on endothelial and
epidermal cells. TGF-alpha also accelerates the healing of burns, and increases the area of
regenerated epithelium.
TGF-beta is a 112-amino-acid polypeptide with a molecular weight of 25,000 daltons. TGFbeta stimulates the production of fibronectin and collagen by fibroblasts. This function
suggests that its role is in the latter stages of wound repair, for strengthening and remodeling
of the wound. In the presence of other growth factors, it has either mitogenic or inhibitory
actions. For example, TGF-beta, in vitro, stimulates the growth of fibroblasts in the presence
of PDGF, but inhibits their growth if EGF is present.
Genzyme Tissue Repair has licensed recombinant TGF-beta-2 from Celtrix Pharmaceuticals
for use in the treatment of chronic skin ulcers. Genzyme Tissue Repair is collaborating with
Celtrix on the use of this growth factor, which supplements the body’s own production of
TGF-beta-2. Using a collagen sponge as a delivery vehicle, a consistent dose of the growth
factor is released into the wound over time. Genzyme Tissue Repair will manufacture the
required amount of growth factor needed for Phase III clinicals, and after market
introduction, the company will provide Celtrix with royalty payments based on cumulative
sales.
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7.2.3
Epidermal Growth Factor
In 1986, Levi-Monthalcini and Cohen were awarded the Nobel prize for their work in
unraveling the role of EGF and other growth factors. EGF is synthesized as a transmembrane
protein precursor. It is a 53-amino-acid polypeptide with a molecular weight of 6,000
daltons. The EGF gene is located on chromosome 4 and was first detected in 1962, when Dr.
Stanley Cohen injected rodent salivary gland extract into newborn mice. He found that the
eyes of the EGF-treated mice opened earlier than those of the control group.
Having noted that most animals tended to lick their wounds and EGF is present in significant
quantities in the saliva, researchers in 1979 investigated the effects of EGF on open wounds.
Removing the submandibular glands of mice, resulted in a reduced rate of spontaneous
wound closures. Repeated application of EGF further substantiated EGF's role in wound
closure because the wounds healed at a faster rate.
EGF is a competence factor that stimulates epithelial and mesenchymal cells to replicate
DNA. EGF is angiogenic and chemotactic for endothelial cells and has mitogenic influences
over epithelialization and keratinization. EGF apparently affects mesenchymal cells by
stimulating proliferation of the dermis in partial-thickness wounds and increasing tensile
strength of surgical incisions. EGF may also affect wound healing indirectly by enhancing
the production of several growth factors, such as TGF-alpha, or by modulating the activity of
growth factors delivered to the wound.
EGF appears to promote the rate of migration in structures of the skin which do not normally
undergo rapid proliferation, such as the hair follicles, sweat glands, and arrectores pilorum
muscles. This characteristic may lead to further investigation of this growth factor for
conditions such as male baldness. A major concern regarding EGF use is the possibility that
abnormal cell transformations will be permanently induced, and therefore, continually
regenerated.
Growth control mechanisms in cutaneous wound healing using EGF are the central focus of a
study being conducted at Vanderbilt University. EGF and EGF-like ligands, their common
receptor (EGF-r tyrosinekinase), and subsequent phosphorylated substrates are being studied
within unique wound healing environments. To define epidermal wounding responses, the
EGF signaling cascade are being compared in migrating and proliferating populations of
wound keratinocytes, both in vitro and in vivo superficial trauma (mouse tail tape stripping).
Deeper wound environments (excisional porcine wounds, human burns and human chronic
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wounds) are being used to define and contrast cytokine mechanisms which control the
extracellular matrix proteins.
7.2.4
Platelet-Derived Growth Factors
Platelet-derived growth factor (PDGF) is primarily a human serum growth factor. It is a 124amino-acid, cationic glycoprotein with a molecular weight of 30,000 to 32,000 daltons.
Although originally discovered in platelets, it is also found in monocytes, macrophages,
endothelial cells, smooth muscle cells and various transformed cells.
PDGF has mitogenic, chemotactic and angiogenic activity; however, the mitogenic activity is
dependent on the presence of other growth factors in the serum, whereas its chemotactic
activity is not dependent on other growth factors. Studies indicate that PDGF is a potent
mitogen for fibroblasts, glial cells and smooth muscle cells. It is also a significantly strong
chemoattractant for neutrophils and macrophages. A combination of growth factors, such as
PDGF and the IGFs, stimulates greater collagen deposition in the wound chamber than does
PDGF alone. This suggests that PDGF requires progressive factors such as the IGFs in order
to complete cellular replication. PDGF has no effect on the growth of epithelial cells or
endothelial cells; these cells have no receptors for PDGF.
Regranex, a wound healing agent manufactured by Chiron and in clinical development by
Johnson & Johnson, is showing promising results. Regranex (becaplermin) is a formulation
containing recombinant human platelet-derived growth factor (rhPDGF-B). Its development
is being fostered by a partnering in which Chiron manufactures the growth factor and
Johnson & Johnson conducts the trials and is responsible for regulation, marketing and sales.
Chiron and Johnson & Johnson filed Biologics Licensing Applications (BLAs) with FDA for
Regranex Gel in early 1997. In September 1996, preliminary Phase III trial results showed
promise for the wound healing agent.
7.2.5
Platelet-Derived Wound Healing Formula
Platelet-derived wound healing formula is a mixture of growth factors obtained specifically
from platelets. This mixture stimulates rapid formation of capillary-dense granulation tissue
which covers exposed soft tissue and bone. After granulation tissue forms, rapid reepithelization occurs, followed by epithelial maturation and function.
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Curative Health Services, formerly known as Curative Technologies, Inc. prescribes its
platelet-derived wound healing formula, Procuren, as part of its own wound care center
treatment protocols. Procuren contains at least five locally acting growth factors from the
alpha granules of platelets: PDGF, PDAF, platelet-derived EGF, TGF-beta and platelet
factor 4 (PF-4).
Procuren does not require FDA approval because it is an autologous treatment using the
patient's own platelets. Approximately two ounces of the patient’s blood is drawn and sent to
Curative’s laboratory where a special process is used to extract the platelets from the blood.
The growth factors are then prepared in a colorless liquid which protects them from damage.
This serum is used for a patient's own treatment, thus, eliminating transmission of disease
from other human blood products.
7.2.6
Insulin-like Growth Factors
Insulin-like growth factor (IGF) is a somatomedin, an anabolic polypeptide with a molecular
weight of 7,500 daltons. Somatomedins circulate in the plasma in an inactive state bound to a
larger protein. No other tissue growth factor is found in such significant quantities in the
bloodstream. Somatomedins function in the synthesis of glycogen, protein and
glycoaminoglycans as well as promote the transport of glucose and amino acids across the
cell membrane. Fibroblasts and endothelial receptors have a high affinity for somatomedins.
This has resulted in further investigation for its possible role in wound repair. Somatomedins
appear to stimulate collagen synthesis in cultured fibroblasts, and therefore, they may be a
primary factor in the development of proliferative scar formation such as keloid and
hypertrophic scar formation.
Somatomedins appear to play a significant role in fetal development. Clinical studies indicate
that they are present in amniotic fluid and have receptors in a variety of fetal tissues.
Furthermore, there is a positive correlation between IGF levels in fetal blood and the birth
weight of the baby.
IGF earned its name because of its 50% homology to proinsulin and because it exhibits
insulin-like activity: it can bind to and react with insulin receptors. IGF-I, which is identical
to Somatomedin-C, is known to be a mitogen for bone cells (osteoblasts), smooth muscle
cells, fibroblasts and other cell types. IGF-II, another insulin-like growth factor, is a neutral
somatomedin.
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In July 1997, Celtrix Pharmaceuticals, Inc. initiated a Phase II clinical trial for the treatment
of burns by using SomatoKine, a novel IGF-BP3 complex. The product is designed for use in
regenerating lost muscle, bone and other tissues. SomatoKine targets acute traumatic injuries,
such as severe burns and hip fractures in the elderly. Other potential indications include
severe osteoporosis and protein-wasting diseases associated with cancer and AIDS.
The primary objectives in the burn study are to speed the patients’ recovery time and reduce
their hospital stay. The length of time spent in a burn trauma center is directly related to the
time required for sufficient healthy tissue to be harvested and then grafted at burn sites. With
the trauma of severe burns, key metabolic processes are impaired, and the patient's body is
unable to properly utilize nutrients essential for tissue repair and regeneration. As a result,
graft harvesting is limited, and healing is slow. An associated loss of muscle mass further
reduces the patient's strength and mobility.
Research suggests that low blood levels of IGF-I may contribute significantly to these
problems and that supplementation may restore healthy metabolic processes required for
healing. SomatoKine is the recombinant equivalent of the naturally occurring complex
formed in bloodstream by IGF-I and its major binding protein, BP3.
Celtrix's Phase II clinical feasibility study for burns is being conducted in the United States
and is expected to involve up to 40 severely burned patients, including adults and children.
Participants will be randomized to receive either SomatoKine therapy or a placebo during
standard burn care, and they will be evaluated through two graft cycles. The primary clinical
target is faster healing of the donor site which could shorten the length of hospitalization. The
study is expected to be completed during the first half of 1998.
In January 1997, the FDA gave approval for GeneMedicine Inc. to begin Phase I clinicals of
its IGF-I product. In a series of animal models, GeneMedicine has shown that its IGF-I Gene
Medicine product promotes nerve and muscle growth and provides sustained expression of
the IGF-I protein for several weeks. IGF-I Gene Medicine incorporates the human IGF-I gene
with a proprietary gene delivery system, the polymeric PINC (Protective, Interactive, NonCondensing) system, which enables gene delivery to skeletal muscle. This product is
designed to provide sustained, localized expression of the IGF-I protein after direct
intramuscular injection to repair nerves and restore muscle mass and strength. The company's
non-viral approach to gene therapy is intended to reduce the likelihood of an immunogenic
response and thereby allows for repeat administration over a prolonged period of time.
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7.2.7
Interleukins
Interleukins are monokines that have fibroblastic stimulating activity in vitro. They appear to
have a role in tendon, cartilage and bone remodeling, as they stimulate the production of
synovial cells. Interleukins also have pyrogenic activity and may regulate fibroblast
proliferation and fibrosis in chronic inflammatory states. Interleukin-2 is a 15.5-kilodalton
protein. It is produced by activated T-lymphocytes and is known to enhance the T cellmediated immune response.
7.2.8
Other Growth Factors
Regeneron is a drug-discovery firm engaged in researching protein growth factors, their
receptors and mechanisms of action for the treatment of neurodegenerative disease, nerve
injury and peripheral neuropathy. The U.S. Patent and Trademark Office has granted U.S.
Patent No. 5,521,073 to Regeneron which covers a gene that encodes the human Tie-2 ligand
protein and the method of using that gene to make the Tie-2 ligand protein. The Tie-2 ligand
protein is a growth factor involved in the formation of blood vessels, and its receptor is
present on hemopoietic stem cells.
Regeneron scientists have identified the first member of the second family of growth factors
specific for blood vessels, following exploration of a class of receptors expressed on blood
vessels known as the Tie receptors. Researchers then developed a technology allowing them
to molecularly clone the growth factors that bind to the receptors. Regeneron reported that
evidence demonstrated the vascular endothelial growth factor (VEGF) family and the Tie
growth factors are central to vessel formation and that they work together. Further, the Tie
receptors are expressed on hemopoietic stem cells which are precursors of many different
blood cells, and could be important in regulating blood cell formation in the hemopoiesis
process.
In September 1996, Human Genome Sciences unveiled six new therapeutic proteins, and by
the end of 1997, the company plans to bring one or two of these proteins into clinical trials.
One of the compounds, a keratinocyte growth factor, may be capable of repairing skin as well
as spur hair growth. The other compounds include a macrophage colony inhibition factor and
two myeloid progenitor inhibitory proteins. The macrophage or immune cell inhibitor
regulates the development of cells involved in inflammation and could be used to treat
autoimmune diseases like rheumatoid arthritis and lupus. In addition, this factor may inhibit
tissue destruction due to wounds and other injuries. The progenitor inhibitory proteins seem
to protect bone marrow cells from chemotherapy drugs, without hurting the drugs’
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performance, perhaps allowing for greater doses. Besides these, the company also is
developing a motor neuron growth factor and an antiviral protein.
A major goal of research being done at the University of Texas is to identify factors that
enhance the healing of chronic pressure ulcers. In recent reports, recombinant human growth
hormone (rhGH) when administered systematically improved wound healing and whole body
protein synthesis in severely burned patients and increased plasma pre-albumin and retinolbinding protein concentration in malnourished surgical patients. In addition, it is
hypothesized that rhGH may increase the healing of chronic pressure ulcers in paraplegic
patients.
7.3
Development Status
Studies of growth factors are an outgrowth of cancer research to find the biochemical
mechanism for controlling malignant cell proliferation. Understanding pathogenic
proliferation meant first understanding normal proliferation at the cellular and biochemical
level. New therapies for wound healing, require a deeper understanding of wound healing at
the cellular level.
The same growth factors that stimulate carcinogenic proliferation also trigger wound
inflammation and repair. Availability of the technology to isolate, purify and manufacture
recombinant growth factors, enabling production of large quantities for commercialization,
further promulgated growth factor research. Despite the relationship between normal and
malignant cellular growth, researchers believe that the dosage window for efficacy may not
overlap the dosage window for safety.
When commercialization of growth factors is achieved, it will have a profound clinical
impact for surgical procedures and chronic wounds, ulcers or burns. Although initially they
would be used on the most chronic wounds and ulcers, as product costs decline, they could
be preoperatively on the surgical incisions site to promote rapid wound healing.
7.3.1
Concerns about Growth Factors
There are drawbacks with the current state of growth factor technology that may inhibit broad
usage. First, growth factors are polypeptides, which are inherently chemically unstable. This
is a significant issue for transportation and handling. Second, growth factors also have short
half-lives (most are active for only a few hours), making repeated applications necessary as
well as costly, with unused amounts discarded. Third, the wound environment contains
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significant quantities of proteolytic enzymes, which can degrade growth factors, ultimately
neutralizing their therapeutic effect. Fourth, the dosage level to achieve specific results will
need to be standardized. Both the science of wound healing and diagnostic assessment tools
will also need to be further developed. Accurate assessment of the status of each wound will
be necessary to ensure growth factor therapy will be complementary. Specifically, the early
stages of wounds will need early stage growth factors; and later stage wounds will need end
stage growth factors. Finally, the cost of the growth factors will need to be reduced to capture
wider markets and increase the likelihood of third-party reimbursement.
7.4
Growth Factor Market Potential
Considerable time, effort and money have been devoted to growth factors in hopes that the
technology can yield high returns, both clinically and financially. Growth factor technology
will impact all areas of medicine, with a potential dollar market volume exceeding $4-5
billion. Industry experts predict that the potential market for IGF-I alone is $1 billion in the
United States.
Many believe recombinant growth factors will not be commercially available until 1998. The
commercialization of growth factors could have a profound impact on existing wound care
products such as cleansing agents, debridement agents, wound closure devices and wound
coverings, including biological skin replacements. Cleansing agents could incorporate growth
factors (if biochemically stable for long periods) to promote granulation of the wound bed.
Sutures with growth factors could enhance surgical incision repair, providing earlier closure,
stronger tensile strength and decreased scar formation. In addition, wound dressings could
provide the vehicle for growth factor therapy, providing a stable environment.
Due to the vast applications of growth factors in wound management, the revenue potential
for these unique products is difficult to forecast; however, a conservative projection is that
this market could generate revenues of over $1 billion. Its revenue potential hinges upon the
efficacy of growth factors and their long-term effects, which are being researched in clinical
trials.
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Chapter 8: Instrumented Wound Healing
8.
INSTRUMENTED WOUND HEALING
The methods of improving wound healing can involve instrumented and physical modality
technologies. These products include compression devices, whirlpool, mechanically assisted
devices and hyperbaric oxygen, some of which are in current use or are in the process of
being evaluated. Exhibit 8-1 summarizes the estimated sales of these products for the years
1996 and 2002, and the expected compound annual growth rate (CAGR) from 1997-2002.
8.1
Compression Devices
There are three classifications of compression devices: passive compression bandages, active
sequential/mechanical leg compression devices and dynamic foot compression devices.
Passive dressings are applied to leg and foot ulcerations, while the other two classifications
are used for deep vein thrombosis (DVT). Sequential and dynamic compression pumps are
not used extensively for chronic wounds because their use is reimbursable only when
lymphedema is involved. Most venous ulcers, therefore, are treated with passive compression
bandages such as the Unna boot-type bandaging; this and other devices are described in the
following subsections.
8.1.1
Passive Compression
The most common passive compression devices are elastic stockings, elastic/ace wraps, selfadherent leg dressings and multi-layered bandages. One multi-layered bandage is know as the
Unna boot and consists of several layers of vertical bandage strips covered with various types
of elastic and inelastic wrappings. These bandages are usually made by the clinician and
involve layers of padding, non-elastic or self-adhering wrap, and protective bandaging of
variable elasticity.
The Profore bandage, manufactured by Smith & Nephew, consists of a wound contact layer
and a four-layer bandage system which is used to provide greater pressure at the ankle,
decreasing to the calf. This dressing may be left in place for up to a week after the first few
weeks, when excessive exudate may be present and more frequent changing is required.
There are several products of this type manufactured by Beiersdorf-Jobst, a German company
with a U.S. branch in North Carolina. The UlcerCARE Compression Liner (10 mm Hg) used
in conjunction with the UlcerCARE Therapeutic Stocking with Zipper (30 mm Hg) provides
the clinically recommended level of graduated compression. The Gelocast Unna boot consists
of nonraveling gauze that is impregnated with a zinc oxide formula and may be worn for five
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Exhibit 8-1:
U.S. Market for Instrumented Wound Healing Devices, 1996 and 2002
Physical Modality
1996 Sales
2002 Sales
CAGR
Compression Bandages
$231.0M
$298.0M
5.2%
Sequential Compression
23.0
28.4
4.3
Dynamic Compression
12.0
15.3
5.0
Hyperbaric Oxygen
12.0
5.8
-13.5
Whirlpool
6.0
3.1
-12.4
Lavage
5.6
9.8
11.8
Electrical Stimulation
6.1
11.9
14.3
Electromagnetic Stimulation
4.0
15.1
30.4
Ultraviolet
0.74
Mechanically Assisted Devices
0.57
28.5
118.7
Thermography
0.3
3.7
65.3
Lasers
—
—
—
Ultrasound
—
—
—
$301.3M
$420.4M
Total
0.79
1.3
6.9%
Notes: The growth rates shown in this exhibit are for the years 1997-2002. Ultrasonic
healing devices and lasers for use in wound care are not expected to be available in the
forecast period.
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to seven days. The Compriform is a custom vascular support, and the Fast-Fit is a graduated
compression stocking.
Acme United markets the Setopress, a high compression bandage that provides graduated
compression starting at over 4 mm Hg at the ankle. The correct level of compression is
maintained due to a visual extension guide, in which brown rectangles on the bandage
become squares as the correct extension is reached, thus ensuring optimal compression each
time the bandage is applied. This dressing is manufactured by Seton Healthcare Group in the
United Kingdom.
ConvaTec offers the washable SurePress High Compression Bandage and its SurePress
Absorbent Padding to be worn underneath the bandage. This product is designed to treat a
full range of veno-lymphanic disorders. Another manufacturer in this category, Sigvaris,
offers therapeutic medical compression stockings which vary according to material used and
compression category.
Prizm Medical is focusing on electrotherapy combined with mild passive compression, which
involves blanketing the affected area while increasing blood supply and vascular return.
Electro-Mesh gloves, socks and sleeves are electrodes that facilitate electrotherapy to the
extremities due to their specific configurations for these parts of the body. The
neuromuscular stimulators, the portable Z-Tim II and the wearable Micro-Z, cause
stimulation to the Electro-Mesh electrodes. The Electro-Mesh sock is in clinical trials and has
been effective in the treatment of diabetic foot ulcers. Chronic and acute pain relief and rapid
recovery from soft tissue injuries are conditions being treated by these products.
Other products and competitors in the passive compression market are the T.E.D. Embolism
Stockings and Flex Wrap Cohesive Bandage Roll manufactured by Kendall Healthcare, the
Coban Elastic Wrap Bandage manufactured by 3M, the Sof-Kling manufactured by Johnson
& Johnson, and the Expandover Elastic Adhesive Tape manufactured by Sherwood-Davis &
Geck. Another competitor, Medi USA, L.P., is the U.S. marketing subsidiary of Weihermuller & Voigtmann from Germany.
The total market for passive compression devices was $231 million in 1996: $35 million to
elastic/ace wraps, $15 million to self-adherent leg dressings, $16 million to multi-layered
bandages and $165 million to elastic stockings/T.E.D.s. The total market is expected to grow
to $298 million in the year 2002, representing a 5.2% average annual growth rate.
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8.1.2
Sequential Compression Devices
A mechanical or sequential compression device (SCD), or compression pump, provides
intermittent pneumatic compression which sequentially compresses the leg and thigh in order
to cause more blood to go up the leg. Phlebitis, therefore, can be prevented and the leg
muscle is moved to prevent ulceration. Several companies produce and market SCD devices
which may be employed early in the treatment phase to reduce edema.
Beiersdorf-Jobst offers the Jobst Extremity Pump System 7500 (SCD) with pneumatic
sleeves. The device consists of three independent chambers with sequential inflation, distally
to proximally, to eliminate excess fluid from the extremity. Physiological pressure on the
tissue and venous systems are corrected to help reduce edema and venous hypertension.
Another product, the Comprilan low-stretch compression bandage, is made of 100% cotton
and is recommended for wear between pumping sessions for as long as 10 days. It exerts low
pressure when the patient is immobile and provides high resistance to the muscle when the
patient is active.
Primarily used for patients with DVT, the products are prescribed by physicians and used by
nurses in wound care clinics, long-term care facilities and in home care. Employing both hose
and wraps together, the leg or thigh is completely covered, therefore, the product cannot be
used on patients with casts, pins or high temperatures. In addition, since the wraps are heavy,
motion is limited. The wrapping and unwrapping is also labor intensive, and it is difficult to
monitor the extremity for color and temperature.
The compression pump market totaled approximately $23 million in 1996 and is expected to
grow at an average annual rate of 4.3%, to reach $28.4 million by the year 2002. Kendall
Healthcare is a leader in this market (48% market share), with their SCD Sequel
Compression System. The product is manufactured by Novamedix Ltd. Other competitors are
HNE (formerly Huntleigh), Venodyne, Beiersdorf-Jobst, and several other small companies.
8.1.3
Dynamic Compression Devices
Dynamic compression devices, also known as foot compression devices, are used primarily
for DVT and have been in the marketplace for about five years. Using a surge technique to
apply pressure intermittently to the venous plexuses, the blood is moved up the leg from the
foot in order to mimic walking. While some patients find the device disturbing at first, after
the initial onset of therapy, they tend to find this device less confining.
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This newer technology is more cost effective than other types of compression devices, and
the wrap is placed around the foot, giving access and visibility to the toes and leg. It can be
used on legs with casts, pins and traction.
The 1996 market for dynamic compression devices is estimated at $12 million, and is
expected to grow at an average rate of 5% to approximately $15.3 million in the year 2002.
The primary competitors in this market are Nutech (a division of Kinetic Concepts) and
Novamedix (A-V Impulse System; Kendall distributes the product in the United States).
8.2
Whirlpool Therapy Devices
Whirlpool therapy has been used in extensively in the past; however, it is no longer popular
for the treatment of chronic wounds. Although whirlpool therapy is not thought to enhance
the healing of wounds, it is sometimes used to cleanse and debride wounds. There is active
concern, however, that wounds could be contaminated by fecal or other contamination in the
tanks. The treatment, when it is used, takes place in a physical therapy department of an acute
care facility, physical therapy office or long-term care facility.
One advancement in the field is the Banks Hydro-Therapy Chair, offered by Keith Products.
The product was patented in March 1995 and can be used at home. The Bank Hydro-Therapy
Chair is a combined lift chair and whirlpool device which is designed for patients with open
wounds or injuries on the lower half of their bodies, such as bed sores or open abscesses. The
device is a chair that fits in a bathtub and uses an air blower motor to create a whirlpool
which helps to clean and soothe wounds. There are adjustable settings so the patient can be
elevated to protect wounds from being irritated against surfaces. The chair costs $1,100 and
can be rented for $25 to $50 a week, depending on the geographic location.
The companies presently supplying hydrotherapy tanks are Arjo, Burch Manufacturing,
Ferno-Washington, Fox Pool, Grand Traverse Technologies, Lumex, Samadhi Tank and
Whitehall Manufacturing.
The 1996 U.S. market for these products was estimated at $6 million, with an expected
average annual decrease of 12.4%. By the year 2002, the market is forecast to decline
to $3.1 million.
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8.3
Lavage Devices
Pulsed lavage devices have been on the market for more than 10 years. These Class I devices
have been used by operating rooms and emergency departments for the irrigation of
traumatic wounds. Several have already received 510(k) clearance.
These portable, disposable, hand-held lavage products are also known as focused or "local"
hydrotherapy devices. A pulsed lavage irrigator for hydrotherapy, which includes a
disposable section with a nozzle and hose, can be saved for repeated use on one patient.
These units are used by nurses and physical therapists as a bedside or home care alternative
to total immersion hydrotherapy. These products avoid the cytotoxic agents which are
frequently used in immersion hydrotherapy, such as disinfectants and/or bacteriostatic agents.
Although used in the alternate and home environments, they must still be used by skilled
healthcare workers and are not yet available for self-care. One such product is the Surgi-Lav
by Stryker, Inc., which employs controlled pressure that does not cause trauma at the cellular
level.
Lavage hydrotherapy continues to increase in popularity. At the 1996 Symposium for
Advanced Wound Care, Diane Morgan, BSN, RNC presented the results of a study which
demonstrated the efficacy of hydrotherapy/hydrodebridement in the home environment to
remove necrotic tissue from the wound bed. With the bio-burden on the wound decreased, the
treatment stimulated circulation and healing.
A complete line of pulsed lavage irrigation systems is manufactured by Davol, which is a
subsidiary of C.R. Bard. The Simpulse PLUS System is nitrogen/compressed and airpowered irrigator and has a VariCare retractable splash shield wound tip with suction tubing
and dual spike adapter. The Simpulse SOLO System is a battery-powered irrigator, and the
Simpulse VariCare System is battery-powered with three-speed variable control and
continuous variable control.
Zimmer manufactures the lightweight and mobile Pulsavac III Wound Debridement System,
which ranges from a gentle lavage to a forceful debridement of up to 60 pounds per square
inch (PSI) for bone cleaning. The Pulsavac is a handgun set with tips and is designed for
single use, so there is no risk of cross contamination. The company also sells the Var-A-Pulse
Wound Debridement System, which is more portable and has six variable pressure settings
capable of handling a variety of wound cleaning applications. With batteries in the handgun,
there is also a speed dial at its base which enables quick and easy pressure adjustment. The
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Var-A-Pulse requires a standard irrigation source and suction source, and the entire unit is
disposable. Selected manufacturers of pulsed lavage systems are presented in Exhibit 8-2.
The current market for lavage products is estimated at $5.6 million, and will continue to grow
as more units are used in the home and in long-term care. Also, as simpler and less expensive
units are designed specifically for wound care use, it is expected that the need for whirlpool
therapy will continue to decrease as lavage hydrotherapy increases. Thus, the market is
expected to increase at an average annual rate of 11.8% to $9.8 million in the year 2002.
8.4
Electrical Stimulation Products
High-volt stimulating devices with settings for pulse frequency and polarity are used for
electrostimulation. The amplitude is set to a level that produces a constant number of pulses,
and a monophasic-pulsed current with a low charge of about 10-15 micro ohms per phase.
This creates a comfortable tingling sensation for the wound care patient.
An electrode is placed on top of or inside gauze which has been fluffed and placed on the
wound. An alligator clip is attached to the electrode, and the gauze is moistened in order to
create a pathway for the flow of current. Each treatment lasts for approximately 30-60
minutes, and the clinician may choose to move the electrode to other places on the wound.
Treatment usually consists of one hour per day, five to seven days a week.
The Agency for Health Care Policy and Research (AHCPR) guidelines recognize
electrotherapy as the only useful physical modality for wound care patients, and all other
physical modalities are considered experimental. Electrostimulation therapy for chronic
wounds is reimbursable under Medicare and private payers as therapy for edema or pain, but
not for wound care. This therapy, therefore, is considered an off-label product in wound
management.
No electrical stimulation device is approved for use in chronic wounds at this time; however,
many physical therapists are using the products with some success. Their involvement is
necessary in order to set polarity, waveform, and length of exposure. So far, the devices are
used in physical therapy departments, and they are not generally used by nurses or
physicians. The potential exists, however, to make these devices more portable and more
user-friendly so that patients should eventually be able to apply their own therapy at home.
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Exhibit 8-2:
Selected Manufacturers of Pulsed Lavage Systems
Baxter Healthcare
Bedcolab
Cabot Medical
Circon
Davol/C.R. Bard
Ethicare Products
Meditron Devices/BEI Medical Systems
Micro-Aire Surgical Instruments
Palisades Dental
Stryker
Tava Surgical Instruments
Valley Forge Scientific
Howmedica/Pfizer
Zimmer/Bristol-Myers Squibb
Note: The typical price for lavage units = $1,895 to $2,250.
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Other difficulties with electrical stimulation for wound management is that some research
studies have indicated success for patient populations and/or healthcare facilities, while other
studies have resulted in negative outcomes. There can also be problems with reimbursement
which is usually billed under pain management for edema of the extremity, and not
specifically for wound healing.
Staodyn has developed a proprietary pulsed technology which has not yet been approved by
the FDA after seven years. Furthermore, the FDA is requiring more clinical studies for
another Staodyn product, Dermapulse, a wound healing bandage. The company does not
have the $l million required to accomplish the studies, but the product is being sold in
Germany and may be released in England, Canada and France in 1997.
The current market for these products is estimated at $6.1 million, with the average rental
cost of $170 per patient for an average of two months of use. The market is expected to grow
at an average an rate of 14.3% to $11.9 million in the year 2002. Equipment rental is
common in the United States, and the products are usually rented to the attending physician
or therapist. Manufacturers, manufacturer dealers and/or manufacturer's distributors are the
typical suppliers of these physical modality products. Durable medical equipment (DME)
rental companies are used to a lesser extent; approximately 5% in the United States.
8.5
Electromagnetic Stimulation Devices
Unlike electrical stimulation devices, the removal of compression or other dressings is not
necessary with electromagnetic stimulation, and the devices are used in a physician's office,
wound care clinic or physical therapy department. There is even one product, made by
Electropharmacology, Inc., which is portable and can be used in a long-term care facility or
at home. Staodyn has a device for outpatient and home use, but the size of the unit and
requirement for professional administration may limit its penetration in the home or at wound
centers. The product is currently only sold internationally.
The Smart Magnatherm (Magnatherm 1000), made by International Medical Electronics
(IME), is an electromagnetic stimulation device that has been on the market since 1970. FDA
approval was not necessary in 1970; however, the product was later approved by the FDA for
producing heat in 1973. The heat causes a reduction or elimination of inflammation, exudate
and debris in cells. The metabolic rate and blood flow are also increased, which further
stimulates healing. Furthermore, oxygenation is increased, and cells are theoretically
re-polarized by putting negative ions into the body. The Magnatherm 1000 is a
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hospital/ physician's office unit, and the Magnatherm SSP is a mobile/portable unit which
was developed in 1974 and cleared by the FDA in 1996. With approximately 10,000 units
currently in use, many of these are found in Army, Navy and veteran administration
hospitals.
The market for electromagnetic devices is estimated at $4 million in 1996. Each 15-minute
treatment costs $14, and each patient averages 30 minutes of treatment, three times a week,
for approximately eight weeks. The machines are placed on consignment, not sold to physical
therapy departments. Although several are on the market with 510(k) approval for pain and
edema, none have been approved for chronic wound healing.
8.6
Ultraviolet Wound Healing Devices
Ultraviolet (UV) light has been used for the purification of air against such airborne
organisms such as tuberculosis. Hand-held devices for the application of UV to wounds have
been in existence for more than a decade; however, little research has been done concerning
the use of UV on chronic wounds. Even though some physical therapists use UV-C to treat
infected chronic wounds to retard or kill bacteria or viruses, the drying effects of UV on the
healing wound bed prevent widespread use.
There are a limited number of companies involved in this market. Birtcher manufactured a
device but discontinued the line when it merged with ConMed. Only two companies are
currently involved in the manufacture and distribution of a UV device for wound care:
Medfaxx and American Ultraviolet Company. The units are manufactured by American
Ultraviolet Company and marketed by Medfaxx. Although the device is being marketed for
the treatment of infected wounds, it has not received FDA approval for the treatment of
chronic wounds.
The market for ultraviolet light therapy is small, and was estimated at $740,000 in 1996. The
market is projected to grow at a modest average annual rate of 1.3% to $790,000 in the
year 2002.
8.7
Hyperbaric Oxygen Chambers
Hyperbaric oxygen therapy is a primary therapy for air or gas embolism, decompression
sickness and carbon monoxide poisoning. It is also an important adjunctive therapy for
wounds, including radiation tissue damage, compromised skin grafts, necrotizing soft tissue
and non-healing wounds. Hyperbaric oxygen decreases the amount of edema, and also
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reduces the progression of infection by increasing phagocytic capabilities. In addition, this
therapy also increases revascularization which brings more nutrients to the cells. Epithelialization and wound tensile strength are also increased.
Hyperbaric oxygen therapy is administered in an air-filled, multi-place (multiple patient)
chamber in which patients breathe 100% oxygen at greater than one atmosphere of pressure
using a mask or hood. This increases the level of oxygen delivered to the tissues and
augments wound healing and repair. The Institute for Exercise and Environmental Medicine
at Presbyterian Hospital in Dallas, Texas, enables complex medical care to be provided for
more than one patient at one time, thus increasing efficiency. Selected manufacturers of
hyperbaric oxygen chambers are presented in Exhibit 8-3.
The chambers are large and unwieldy, therefore limiting their usefulness to specialty clinics
such as wound centers or special care delivery organizations. Unless significant new research
emerges, the use of hyperbaric oxygen therapy for the treatment of chronic wounds is not
likely to increase.
The hyperbaric oxygen market in 1996 totaled approximately $12 million. The chambers are
expensive, and treatment costs average $1,500-$2,000 per patient, fueling a decrease in the
market to $5.8 million by the year 2002.
8.8
Mechanically Assisted Wound Healing Devices
Two new devices have been developed for use in wounds where the available skin is
inadequate to cover the wound. Each product has a slightly different mechanism, but each is
considered a mechanically assisted wound healing device.
In 1995, Kinetic Concepts introduced the V.A.C. device in the United States after receiving
FDA approval. The product, initially launched in Europe in 1994, is a device consisting of a
pressure-distributing wound packing, which applies a continuous negative pressure of 50-175
Hg. The device is placed in the wound, and the wound is sealed with an adhesive occlusive
dressing.
The device has been used at the Bowman Gray School of Medicine at Wake Forest
University. V.A.C. was used to treat 150 wounds in 106 patients with a variety of pressure
ulcers, statis ulcers, dehisced incisions and other chronic, non-responsive wounds. All of the
patients improved with the treatment and did not show any significant wound or systemic
complications. This device can be rearranged and reapplied by nursing personnel.
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Exhibit 8-3:
Selected Manufacturers of Hyperbaric Oxygen Chambers
Canty Associates
GWR Medical
Marine Dynamics
Perry Baromedical
Reimers Engineering
Reneau
Sechrist Industries
Stephenson Industries
Note: The typical price for hyperbaric chambers = $15,000 to $1,000,000.
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The second product, Proxiderm, has been developed by Progressive Surgical Products for the
healing of chronic ulcerative wounds. By using Proxiderm over a period of days to a few
weeks, it is possible to heal open chronic wounds that have refused to heal for as long as nine
years. The process involves a more active approach to the treatment of ulcerative wounds, as
opposed to the passive approach of natural methods or growth factors. The method recruits
healthy skin to the wound and covers the wound with full-thickness healthy skin.
Proxiderm consists of two tissue hooks which move along a path inside a frame of plastic
material. The hooks are inserted into viable tissue adjacent to the wound margins and apply a
sustained, constant force of 460 grams to the wound edges. Multiple devices are used
depending upon the length and contour of the wound. The shape of the devices varies from
slightly curved for relatively flat surfaces, to right-angled for lesions near the borders of the
foot. The device accommodates curved surfaces such as the heel and borders of the foot, and
the underside of the device is padded to avoid pressure effects on the wound.
Over a period of time, usually four to 10 days, these two tissue hooks near the opposing
wound margins slowly approach each other and follow the contour of the body part being
treated. As these tissue hooks approach each other, there is a continuous process of tissue
approximation supplemented by increased skin growth and tissue expansion. The constant
force that is applied by the device to the wound edges encourages angiogenesis and tissue
generation, as well as epidermal multiplication. The low-grade force and gradual closure of
the chronic wound reduces the risk of ischemia and diminishes the risk of entrapment of
contaminated material and subsequent sepsis. The wound closes in a minimally stressed
environment resulting in a sutureless closure of the ulcerative wound.
This product has been on the market since 1996, and it is approved for pressure ulcers. The
device is used with local anesthesia, and the procedure can be performed at a skilled
nursing home.
The sales of these novel devices were estimated at $570,000 in 1996. This market has
excellent potential and is expected to grow to $28.5 million by the year 2002.
8.9
Thermography
Thermography systems can be liquid crystal or infrared, and the infrared devices’ average
price in the United States ranges between $22,400 and $60,000. Liquid-crystal thermography
devices average between $4,000 to $8,500. Even though few thermographic devices were
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used in the United States prior to 1997, there were some that had FDA approval. Selected
manufacturers of thermography systems in the United States are presented in Exhibit 8-4.
Ashwin Systems International is one of the medical thermography systems selling to private
physicians and research clinics in the United States. Although their product, the Teletherm
Mark/1026, was cleared by the FDA in 1987 as a Class I device, the company believes the
technology is underutilized. The company’s product is used by hospitals in Japan for the
profiling of wounds, which involves evaluating the physiological condition and changes that
have occurred to wounds. The product is also well received in Eastern Europe.
With proper positioning and marketing for the diagnosis of chronic wounds, a device like
Ashwin's infrared system could reach a level of $3.7 million by the year 2002 (74,000
patients at $50 per image). Ideally, home health care nurses could transmit images via
computer file transfer over the Internet. The standard procedure would involve a nurse to take
the image and a physician to interpret it. The delivery site for contact thermography could be
a physician's office, long-term care facility, clinic or a home. Use in an acute care setting is
unlikely; however, managed care organizations could be shown that use of thermography
reduces costs due to more exact diagnosis and more precise prescription of treatment
protocols.
8.10
Emerging Technologies
Two promising instrumented technologies that have great potential in the wound treatment
market are ultrasonic devices and laser-based devices. Both technologies are not expected on
the U.S. market until after the forecast period; however, growth of these markets once
products become available is expected to be rapid. The following subsections describe these
technologies.
8.10.1
Ultrasonic Wound Healing Devices
Ultrasound is the high-frequency mechanical vibration created by the conversion of electrical
energy to a sound wave, that is beyond the range of human hearing. When these ultrasonic
waves are transmitted through a conductive medium such as water or gel, they can be applied
to soft tissue and serve as a source of absorbable energy. Thus, the absorption by various
components of tissue can initiate a variety of physiologic effects classified as either thermal
or non-thermal. Wound healing is primarily a non-thermal response.
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Exhibit 8-4:
Selected Manufacturers of Thermography Systems
Liquid Crystal Devices
Infrared Devices
Biosynergy
Canadian Medical Products
Clark Research & Development
Davis Liquid Crystals
Flexi Therm
Hallcrest Products
Medical Products of America
Seven C’s
Trademark
Ashwin Systems
Bales Scientific
Dorex
Flir Systems
Inframetrics
Temptek
Texas Medical Instruments
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A clinical study, which investigated ultrasonic therapy in wound healing, was conducted by
Drs. Young and Dyson of Guy's Hospital in London, England. The researchers concluded
that ultrasound can affect an early phase of the wound repair process, such as the
inflammatory phase. During the early phase of inflammation, the wound and/or intact tissue
surrounding the wound contains a component receptive to ultrasound. This component, the
macrophage, is present in large numbers in the wound bed and contains factors which
stimulate blood vessel formation.
A hand-held ultrasonic healing device is currently being developed by Exogen, which will be
similar to the company's current device being used to heal fresh fractured bone. The product,
however, is being designed for use by the patient at home, eliminating the need for a licensed
caregiver. The hand-held device is also intended to be used by physical therapists and will be
used in acute care hospitals, long-term care facilities and outpatient clinics.
The hand-held ultrasonic healing device is expected on the market after the year 2002. The
device is estimated to gain significant momentum following its release, with sales of
$46 million expected by the year 2006.
8.10.2
Laser-Based Wound Healing Devices
Lasers stimulate wound healing by increasing leukocyte phagocytosis and collagen
production. Laser welding of tissues is also possible at low radiances, circumventing the need
for sutures. Low-level lasers are being extensively researched in Russia and Israel, and one
American company, The Chattanooga Group, offers low-level lasers for export.
Low-intensity lasers are used in Europe; however, these products are not being used in the
United States for the treatment of chronic wounds. These devices have 1-150 mW of power;
a 632.8 nm to 950 nm wavelength; gallium, aluminum and arsenide (GaAIA) diode lasers;
and some devices use a pulsing action to enhance their therapeutic effect. Lasermedics has a
laser product for use in treating carpal tunnel syndrome, and more than 2,000 units are used
in the United Kingdom by physiotherapists who treat sports injuries.
Industry experts predict that a laser device for use in wound care will be approved by the
FDA by the year 2006. The market potential for this type of device could be as high as
$40-$45 million.
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Chapter 9: Pressure Relief and Pressure Reduction Equipment
9.
PRESSURE RELIEF AND PRESSURE REDUCTION EQUIPMENT
Specialty beds, mattress replacements and overlays are the primary products currently
available for pressure relief and pressure reduction. Suppliers in these markets offer low,
medium and high-tech products, and purchasers are understandably confused in making the
difficult decisions concerning the correct support surfaces for patients. Additionally, specialty
bed, mattress replacement and overlay manufacturers are aggressively marketing their
products, and are in continual debate over the best product for treatment and prevention of
pressure ulcers. For the consumer, the appropriate use must be balanced with the costs
involved. Costs, ease of use, reduced hospital waste/disposal and reduced labor-intensity are
issues to be considered when deciding hospital purchases and/or rental agreements.
Pressure ulcers, either as a primary diagnosis or noted as a secondary diagnosis upon hospital
admission, will continue to justify third-party reimbursement for treatment for specialty beds
and other pressure relief equipment. However, third-party payers do not reimburse for the
costs associated with prophylactic use of pressure ulcer equipment. The end result in such
cases is the at-risk patient develops pressure ulcers while hospitalized, and the hospital then
must bear the cost for healing. As a result, hospitals are focusing on using pressure relief
equipment to reduce the incidence of hospital acquired pressure ulcers as well as the
associated costs and morbidity.
The increasing incidence of pressure ulcers and the lack of reimbursement for hospitalacquired pressure ulcers forces a more stringent physical assessment of the patient’s skin by
both nurses and physicians, for all patients admitted to hospitals. The focus is to catch and
document pre-existing ulcerations so that they become reimbursable to hospitals and to
identify at-risk patients so that aggressive preventative therapy can be implemented before
patients develop pressure ulcers. Hospitals can no longer afford the exorbitant costs for
pressure ulcer treatment, particularly the costs associated with pressure ulcer litigation, which
can reach as high as $4 million.
An extensive investigation by the Agency for Health Care Policy and Research (AHCPR) has
provided guidelines for clinicians to assess at-risk patients, adequately identify pressure ulcer
stages and implement preventive skin care programs and early treatment procedures. This
agency also provides guidelines instructing clinicians on the proper use of mechanical
loading and support devices. The AHCPR published their guidelines for the treatment of
stage II, III and IV pressure ulcers in December 1994. These established protocols and
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procedures for pressure ulcer prevention and treatment include requirements for continuous
repositioning of patients every two hours, and caregivers frequently find this schedule
difficult to maintain. The requirement for repositioning patients has drawn an influx of highend products designed to assist in turning patients, thus helping manufacturers increase sales
and diversify their product lines.
9.1
Developmental Considerations
A number of factors contribute to ulceration: nutritional status, level of continence, physical
condition, mental awareness, level of activity/immobility and patient exposure to shear and
friction forces. The primary factor in tissue damage is continuous, unrelieved pressure.
Without the relief of localized pressure, no healing is possible and all other treatment
procedures will be rendered ineffective.
The mattress and bed can help prevent ulcerations or can significantly affect the ongoing
treatment of ulcerations and wounds. Historically, the purchasing of mattresses and beds was
relegated to purchasing agents or to housekeeping services. With a more detailed clinical
understanding of mattress and bed effects, hospitals now recognize that mattress selection
must be made with a clinical focus on therapy and treatment. Mattresses that are at the lower
end of the cost spectrum typically are not as clinically effective as more advanced models.
Many support surfaces are available, each with advantages and drawbacks; all claim to
relieve or reduce the external forces contributing to the development of pressure ulcers.
These forces, pressure and shear, must be considered in choosing the best patient support
surface.
9.1.1
Pressure
Historically, pressure-relieving product purchases have been made by comparing the
interface pressures of products. In today's market this is still a major factor; however,
clinicians are becoming more experienced purchasers, interpreting interface pressure
cautiously, because of the difficulty of obtaining measurements on patient populations in a
controlled environment. Interface pressure is not the perfect predictor of product
performance; rather, it is an assessment tool for defining the lowest peak pressure points and
best pressure distribution of the tissue for each product. Various types of patients, such as
burn, comatose or wound care patients, will require lower interface pressures at specific
pressure points because internal pressures are often three to five times greater than the
pressures at the skin surface.
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Pressure on the recumbent body is a vertical force caused by the patient’s weight being
pulled by gravity onto the support surface. This weight causes pressure to be applied to the
body tissue, compressing it between the support surface and the patient’s bony prominences.
The most common bony prominences that contact the support surface during recumbency are
the sacrum, heels, trochanters, scapulae, elbows, and head. Breakdown at the coccyx or
ischial tuberosities is usually caused during sitting. Pressure shuts off capillary bloodflow,
causing tissue damage from lack of oxygen.
Although it is often accepted that capillary occlusion occurs above 32 mm Hg , this can be
misleading when one considers the multidimensional nature of tissue breakdown. In addition,
patients with compromised nutrition and health can have capillary pressures significantly
lower than 32 mm Hg.
9.1.2
Shear
Shear is the horizontal force perpendicular to pressure. It is caused by a combination of
friction and movement: friction occurs because the skin is grabbed by the sheet or support
surface, and then movement of the patient or support surface causes the bony prominence to
literally move across the tissue as the skin is held in place. Shear significantly increases the
effect of pressure in reducing blood flow through the capillaries. Prolonged shear is the
primary reason why the tissue of the heel often breaks down on support surfaces which
deliver interface pressures below capillary closure.
Shear is introduced on a support surface in several ways, including patient movement, nurse
movement of the patient and bed movement. Each of these factors is discussed below.
9.1.2.1 Patient Movement
When the patient turns over, the sacrum and other bony prominence move against the support
surface. This is a relatively short stroke of movement, meaning the skin is being moved a
short distance against the support surface. A more severe situation occurs when the patient
pulls his heels up, causing the skin to be dragged a long distance on the bed surface. The
result is friction on the heels, with secondary shear effects.
9.1.2.2 Nurse Movement of Patient
When a nurse turns a patient, it is important that the patient is lifted, then turned, to avoid the
shearing effect which occurs on the sacrum and other bony prominences. Another instance
that produces shear against bony prominences is when the nurse finds the patient near the
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foot of the bed, and the patient is pulled up the bed. In this case, the movement has an
additional negative effect because the stroke of shear is extremely long.
9.1.2.3 Bed Movement
This movement may be the least recognized source of shear. When the head of the bed is
raised, the movement drives the patient toward the foot of the bed, shearing the bony
prominences that are in contact with the bed surface. This can be particularly destructive at
the heel which tends to dig into the support surface. The greater the distance between the bed
frame and the patient’s hips, the longer the driving or shearing effect. This driving force is
noticeable especially when using overlays, which distance the hips further from the bed
frame.
9.1.3
Support Surface Requirements
There are some basic requirements for any support surface when relief is sought from the
forces of pressure and shear. There are seven basic requirements for a support surface to
prevent pressure and shear. The surface must:
•
conform to bony prominences without resistance;
•
not have significant memory;
•
allow patient immersion;
•
not bottom out;
•
relieve shear caused by patient movement;
•
prevent skin maceration; and,
•
provide patient comfort.
The first requirement to conform to bony prominences is important because most tissue
breakdown occurs over these structures. The highest interface pressures occur on the thinnest
patients or on patients with muscle atrophy caused by lack of movement and whose bony
prominences are not well padded by tissue. To relieve pressure, a surface must conform to a
bony prominence without resistance. Many materials provide surface tension or resistance
because the materials used cannot conform. This tension is often called hammocking because
the surface material, like a tight sheet, acts as a hammock to prevent conformation to a bony
prominence. The resulting pressure can cause capillary closure over that bony prominence.
There are two ways to eliminate this surface tension or resistance. The first is to have no
surface material present at all, such as floating in a pool of water. The second way is to keep
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the surface material very flexible and loose, or even wrinkled. This technique causes some
consternation among caregivers because it runs counter to conventional hospital bed-making
wisdom where the tighter sheet is preferred. Traditionally, caregivers assumed that wrinkles
in the bed sheets could cause pressure ulcers. This can be true if the wrinkle in the sheet is
over a conventional hospital mattress that pushes the wrinkle into the patient’s skin. This
issue is moot if the wrinkle is over a fluid medium such as air, water or a viscous fluid. In
this case, the wrinkle is absorbed into the fluid, leaving barely a pattern on the patient’s skin.
If the sheet is not kept loose or wrinkled over a properly designed support surface, then the
surface tension or hammocking created may prevent the surface from conforming to a bony
prominence.
The support surface also must not have significant memory. Memory is the “desire” of a
surface, when compressed, to return to its original shape. Compressing a foam cushion causes
fatigue to the hand because of the foam’s desire to return to its original shape. These memory
forces prevent the surface from evenly distributing pressure over the entire body. In
comparison, if properly designed, surfaces using a fluid medium, such as air, water or a
viscous fluid, can flow to equalize pressure and reduce the forces of memory.
The support surface must allow patient immersion, and the greater this immersion, the lower
the peak interface pressures. If a person weighs 150 pounds and all body weight is put on a
surface area of five square inches at the sacrum, the pressure per square inch (psi) would be
150/5, or 30 psi. Double the surface area to 10 square inches, and the average psi is lowered
to 15. By increasing the surface area, peak pressures are decreased. To maximize the surface
area, there must be maximum immersion into the support surface without resistance. A
surface delivering six inches of immersion will provide lower peak interface pressures than a
surface that provides only one or two inches of immersion.
In addition, the support surface must not bottom out. This action occurs when a bony
prominence has pushed down the support surface so that the patient’s body is resting on the
hard surface below. If the support surface is not thick enough, or does not provide enough
support when the head of the bed is raised, bottoming out may occur at the sacrum or other
bony prominences. This situation can be dangerous as pressures can quickly move to 100 mm
Hg or more and can cause skin breakdown within hours. Much attention has been devoted to
whether a given support surface has a few millimeters more or less pressure than another
support surface. These differences are minor when compared to the dangers of a surface
bottoming out. Clinicians must be particularly alert to this issue.
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The support surface must relieve the shear forces caused by patient movement. This is
particularly important for patients with skin flaps; shear can lead to flap failure. As the
patient moves, the ideal surface moves with the patient’s body. The shear forces are then
absorbed into the support surface. Relieving shear forces is further complicated by the length
of stroke present when the patient moves his heels or when the head of the bed is raised. The
majority of support surfaces do not accommodate for such a long stroke of movement.
One answer to long shear forces is to introduce a lubricated slip layer over the support
surface at the patient’s heels and scapulae. This slip layer slides to absorb shear forces;
however, it is best not to use a slip layer under the sacrum. This allows the pelvis to remain in
place when the head of the bed is raised.
The support surface should prevent skin maceration. Wet or macerated skin is more
susceptible to breakdown than dry skin. Preventing excessive wetness and maceration is as
important as preventing the adverse effects of pressure and shear. Wetness comes from two
major sources: urine and perspiration. Urine must be drained away or absorbed into an
incontinence pad; evaporation alone will not suffice. Even with enhanced airflow, urine may
dry and crystallize on the skin, causing tissue irritation. When using incontinence pads on a
pressure relieving surface, care must be taken to keep the pad loose to prevent the pad from
causing increased surface tension or hammocking.
Accumulation of perspiration can be avoided by laying the patient on a breathable surface
which permits vapor transmission and allows moisture to dissipate from the skin. Coverings
for support systems should have pores large enough to allow vapor transmission, yet small
enough to prevent the transmission of bacteria. Vinyl or other relatively impervious
membranes are usually poor choices for coverings because they encourage sweating and
potential skin maceration.
Lastly, the support surface must provide patient comfort. Comfort itself does not directly
affect wound healing. If patients can be kept more comfortable, however, the more accepting
they will be of the support surface. Thus, excessive noise, heat or instability should be
avoided with any support surface in order to maximize patient acceptance.
9.1.4
Pressure Relief versus Pressure Reduction
Support surfaces used in wound care can be categorized as either pressure-relieving or
pressure-reducing devices. Pressure-relieving devices can provide interface pressure below
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capillary closure. These devices are used for patients who are incapacitated and are unable to
self turn in bed. Specialty beds are such devices. Pressure-reduction devices, on the other
hand, reduce pressure but do not consistently keep the skin and tissue below capillary closing
pressure. Mattress overlays and mattress replacements are usually considered pressurereduction devices.
9.2
Specialty Beds
Most specialty beds are used for treating patients as a result of a condition, as opposed to
preventive treatment applications. This is primarily due to the cost of specialty beds and the
lack of third-party reimbursement for preventative skin care. Specialty beds are used in
conjunction with wound care management of burns, Stage III and IV pressure ulcers, venous
and arterial ulcers, reconstructive skin grafts and flaps. They relieve and minimize external
pressure on the skin and bony prominences as well as provide for rotation capabilities. These
features for rotation increase the likelihood that patients will be repositioned when necessary,
as many clinicians are able to turn the patient without assistance. The two most common
types of specialty beds are air-fluidized and low-air-loss beds. These beds are used for a
majority of wound care management conditions, although they can also be used in other
applications.
9.2.1
Air-Fluidized Beds
Air-fluidized beds consist of 1,800 to 2,000 pounds of silicone-coated beads placed within a
mattress enclosure and activated by low-pressure, heated airflow. A filtered sheet of woven
polyester covers the mattress and provides an optimal healing environment by allowing
airflow from the mattress to gravitate upward toward the patient’s skin and bodily
fluids/exudate to be absorbed by the filtered sheet. Air-fluidized beds are used primarily in
the acute care hospitals, with only a small portion of alternate site locations using this bed.
These beds are expensive to purchase or rent. Air-fluidized beds have gradually declined in
the marketplace as a result of the market introduction of the low airloss bed.
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9.2.2
Low Airloss Beds
The low airloss bed consists of air distributed through a cushion structure. Some of the air
within the cushion is able to slowly escape and then be refilled. This bed has become the
preferred choice over the air-fluidized bed, because it allows for easier patient transfer both
in and out of bed, and the bed itself can be raised or lowered. The head of the bed can also be
raised, allowing patients to sit up without being propped up by pillows. The beds are
primarily used in acute care hospitals; however, a growing number are being utilized in
nursing homes and in home healthcare settings. This type of bed is expensive, and most are
rented rather than purchased. They are commonly used for patients with severe burns and
pressure ulcers, as well as for the relief of pain.
9.3
Mattress Replacements
The mattress replacement is a concept introduced in 1983 by an orthopedic technician,
replacing the hospital standard mattress with a specialty mattress that had a foam core and
foam cubes, which could be removed beneath bony prominences for pressure reduction.
Today’s mattress replacements incorporate various technologies for pressure reduction,
including air floatation and alternating air as well as the traditional static technologies. Air
floatation mattresses consist of interconnected fabric pillows which can be variably inflated,
while alternating air mattresses have interconnecting air cells which cyclically inflate and
deflate to produce high and low pressure intervals.
Mattress replacements often provide less than the accepted pressure relief for sacrum, heel
and trochanter. Thus, mattress replacements are an alternative to expensive specialty beds for
at-risk patients with Stage I and II dermal ulcers, but the patient must still be aggressively
turned and their skin vigilantly monitored. Even with these reservations, mattress
replacements do perform better than standard hospital bed mattresses, and cost much less
than the daily rate for a specialty bed.
9.4
Mattress Overlays
Many hospital patients request mattress overlays because they experienced an uncomfortable
hospital mattress during a former hospitalization. Nurses, too, tend toward indiscriminate use
of two-inch overlays believing they aid in relieving pressure and provide for additional
mattress comfort. Although these overlays provide patient comfort, they should not be
utilized for therapeutic purposes. Their primary use is as a preventative device; however,
only three- to four-inch foam overlays should be considered for extended use.
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Overlays are placed over the mattress, reducing the need for specialty beds and mattress
replacements. Overlays have been used indiscriminately in the past, and their predominant
usage has increased hospital waste costs. An overlay is usually a single-patient item that is
purchased and can be taken home with the patient.
The foam mattress overlay is made of convoluted foam in various thicknesses. Foam
overlays eventually become dense through the compression of the foam under the body's
weight, negating their benefits. Specialty foam overlays were developed to address the
drawbacks of convoluted foam products as well as reduce the amount of body heat retention
and perspiration, which were common by-products of standard foam overlays.
Another type of overlay uses air to cushion the patient, and the technologies are similar as
those used in specialty beds and mattress replacements: static, air floatation, low airloss and
alternating air. All types of air-mattress overlays are rented or purchased for hospital and
nursing home care as well as for home healthcare.
Gel overlays are infrequently used as mattress overlays, because they are expensive,
cumbersome, and heavy to lift. Many of the gel products are used as overlays on smaller
surfaces, such as wheelchair seats.
9.5
Market Analyses
Due to changes in Medicare reimbursement for the home care market in 1996, the
manufacturers in pressure-relief and pressure-reduction products have had to review their
product and marketing strategies. Specifically, Group 2 reimbursement was changed to add
non-airloss forms of air floatation devices, which allowed these manufacturers to be
reimbursed at high rates. However, for manufacturers of low airloss products, this meant
more competition in the home market and loss of reimbursement for pressure ulcer treatment.
In some cases, this change caused low airloss manufacturers’ sales to significantly decrease.
However, for some low-air loss manufacturers, the home market continued to grow due to the
introduction of new products and marketing strategies which were specifically targeted at the
home care environment. Regardless, in order to effectively compete in this market, all
manufacturers will need to focus on clinical research to justify higher Medicare
reimbursement rates.
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9.5.1
Specialty Bed Market Analysis
For the purpose of market segmentation, specialty beds are defined as full-framed beds with
mattresses, usually with some advanced technology such as the low airloss and air fluidized
systems. Although acute care settings have purchased most pressure relieving equipment in
the past, much of the durable equipment is now rented. Suppliers may sell direct to the
consumer (as is the case with some large suppliers), or sell through distributive dealer
networks.
In 1996, the market for specialty beds was estimated at $520 million. Pricing has become a
significant factor in the use of these beds. Suppliers of specialty beds must not only compete
with other suppliers in the market, but also with alternative products such as overlays and
hospital mattress replacements. This direct and indirect competition is keeping rental prices
for specialty beds lower than anticipated. A few suppliers in the specialty bed arena have
developed their own overlays and mattress products so as to continue an upward revenue
incline and compete with a much broader product mix. This is especially favorable in the
current marketplace of national accounts and long-term contracts. In addition, major
manufacturers, such as Hill-Rom, are actively marketing to alternate sites, which is helping to
offset pricing pressures. Overall, this market is projected to increase at a modest 2.6%,
reaching $610 million by 2002. This market is represented in Exhibit 9-1.
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Exhibit 9-1:
U.S. Specialty Bed Market Forecast, 1996-2002
Year
Sales
1996
$520.1M
1997
536.0
3.1%
1998
551.5
2.9
1999
567.2
2.8
2000
582.4
2.7
2001
596.7
2.5
2002
610.8
2.4
CAGR 1997-2002
Growth
—
2.6%
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9.5.2
Specialty Bed Competitive Analysis
Hill-Rom offers a complete line of specialty beds, including the Clinitron At-Home, an air
fluidized therapy system specifically for home use. Other air fluidized beds include the
Clinitron Elexis, Clinitron Up-Lift and Clinitron II. The company’s line of beds includes the
Clinitron Rite Hite which is targeted at the long-term care market. Hill-Rom also offers low
airloss beds, such as the Clensicair and Flexicair beds, as well as lateral rotation therapy.
Kinetic Concepts Inc. (KCI) also manufacturers an extensive line of specialty beds, including
TriaDyne, which is designed for severely injured patients in the acute care environment. This
bed features the company’s Kinetic Therapy technology which rotates the patient laterally, at
least 40 degrees to each side. The company also manufacturers bed products for the extended
and home care environments, such as the HomeKair DMS. As shown in Exhibit 9-2, other
manufacturers in the specialty bed market include Cardio Systems and Gaymar.
The two market leaders, Hill-Rom and KCI, have products in all three pressure relief and
reduction segments: beds, mattress replacements and overlays. This broad product line has
made them more competitive throughout all the segments in this market.
Hill-Rom is the leader with 67% of the market due to its broad product line at competitive
prices and effective, direct marketing which actively targets the alternate site environments.
Kinetic Concepts must rely on their independent dealers to market its products; however, the
company increased its sales in 1996 due to the success of the TriaDyne specialty bed which
was introduced in May 1995. In addition, KCI acquired H.F. Systems in February 1997,
which will enhance its product line and geographic reach, especially in California where H.F.
Systems is based. Exhibit 9-3 presents the market shares of the manufacturers in the specialty
bed market.
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Exhibit 9-2:
Selected Manufacturers of Specialty Beds
Manufacturer
Product
Cardio Systems
Model 600 ICU Bed
Gaymar
Clini-Care
Hill-Rom
Clinitron II, Clinitron At-Home, Clinitron Elexis, Clinitron
Up-Lift, Clinitron Rite Hite, Efica CC, Pulmonex,
Clensicair Flexicair MC3, Flexicair Eclipse and Flexicair II
Kinetic Concepts Inc.
TriaDyne, TheraPulse, FirstStep Plus, KinAir III,
DynaPulse and HomeKair DMS
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Exhibit 9-3:
1996 Specialty Bed Market, Share by Supplier
Supplier
Sales
Market Share
Hill-Rom
$346.8M
67%
Other*
Total
163.2
31
10.1
2
$520.1M
100%
*Other includes Cardio Systems and Gaymar.
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9.5.3
Mattress Replacement Market Analysis
Mattress replacements have experienced higher growth than other segments in this market
because the powered devices are a cost-effective alternative for specialty beds. In addition,
these products generally require less nursing time than overlays because the patient does not
have to be turned as much to prevent bottoming out on the support surface. Manufacturers are
aggressively marketing these products, which is helping to fuel a 5.7% annual increase in
sales, from $135 million in 1996 to $187 million in 2002. The market forecast for mattress
replacements is presented in Exhibit 9-4.
9.5.4
Mattress Replacement Competitive Analysis
There are more than 20 companies in the mattress replacement market, and many of these
companies have strong ties in the mattress overlay and specialty bed segments. These
manufacturers have recognized the steady erosion of their existing product segments and
have offered mattress replacements to broaden their product line and maintain market share
and dollar volume. Bio Clinic has products in both the mattress replacement and overlay
segments, and products in the mattress replacement segment include Orthoderm HC, which is
a low airloss mattress designed for the home market. Exhibit 9-5 presents selected
manufacturers of mattress replacements.
B.G. Industries was the first company to introduce mattress replacements, and the company’s
current products, including Maxifloat series, Maxiflex and Model 200 Mattresses, are
considered high quality products by many clinicians. B.G. Industries specializes in marketing
to hospitals and nursing homes.
Creative Bedding Industries offers its ComFORM series, which is made of high-quality,
convoluted foam. The company’s ProFORM series is a line of static mattress replacements,
including the ProFORM Choice, ProFORM Maximum, ProFORM Maxim and ProFORM
Strata.
B.G. Industries is the traditional leader with a 21% market share in 1996 due partly to its
consistent effort to improve its non-powered mattress replacement product line. Bio Clinic,
with a 16% market share, is in a strong second-place position due to a product line which
includes high-end mattress replacements as well as non-powered products.
Creative Bedding Technologies began manufacturing their own product line in 1996 after
providing private label manufacturing for other suppliers. This company offers high-end
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foam mattress replacements which have better conforming characteristics, enabling them to
gain market share in a short amount of time. While Creative Bedding competes at the bottom
end of the market, this company is expected to gain market share in the foam mattress
replacement segment due to its high quality products at a cost-effective price. Other
competitors and their market shares are presented in Exhibit 9-6.
9.5.5
Mattress Overlay Market Analysis
Unit volume will continue to increase in the overlay market with the aging of the American
population and higher acuity of patients. As shown in Exhibit 9-7, the estimated dollar
market for mattress overlays was $210 million in 1996, with an anticipated average annual
growth rate of 4.3%. The dollar growth is attributed to increasing unit volume of static and
dynamic air overlays, as foam products exhibit a slight decline in unit volume. The
competitiveness of this market will keep price increases relatively low.
As competitors such as Crown, which distributes for Roho, work aggressively with managed
care for reimbursement in the home market, the market is projected to begin to experience
upward growth in the future. In addition, because the patient can take the overlay with them
throughout their course of care in various sites, from the hospital to long-term care, the onetime purchase of overlays may begin to be seen as more cost effective than mattress
replacements. Thus, the dollar volume for 2002 is projected to be at $272 million.
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Exhibit 9-4:
U.S. Mattress Replacement Market Forecast, 1996-2002
Year
Sales
1996
$135.0M
1997
142.1
5.3%
1998
149.9
5.5
1999
158.5
5.7
2000
167.8
5.9
2001
177.5
5.8
2002
187.4
5.6
CAGR 1997-2002
Growth
—
5.7%
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Exhibit 9-5:
Selected Manufacturers of Mattress Replacements
Manufacturer
American Health Systems
Product
UltraForm Therapeutic Mattress and UltraForm DPM
B.G. Industries
Maxifloat (LFP, VFP, DFP, EF), Comfort Plus, Maxiflex and Model 200
Mattresses
Bio Clinic
ProAire, Orthoderm, Biotherapy APM and BioMedx
Cardio Systems
Pneu-Care Plus, Pneu-Care Plus Pulse, Pneu-Care Plus Dynamic and
Synergy
Comfortex
DeCube, NewLife, Silhouette
Creative Bedding
Technologies
ComFORM series and ProFORM series
Dermacare
Dermaguard Prism and Dermaguard Spectrum
Gaymar
Top Guard II and SoftMatt (low air loss and alternating pressure mattresse
Hill-Rom
Acucair Matt, Comfortline, Flexicair Eclipse Low Airloss and Simplimatt
Huntleigh
Alpha Active, DFS Homecare and AutoExcel
Invacare
APM Alternating Pressure Mattress and 3500S series
KCI
TheraRest
Lumex
ClassicAir Akrotech 4000 and 4000T, AltaDyne
Mason Medical Products
Phoenix, Falcon and Masonair series
Medline
Nylex II, Q-Star IV and Q-Star Voyager
National Patient Care Systems Alamo HC and Alamo M.R.S.
Pegasus Airwave
Pegasus Airwave Therapeutic System and Renaissance Therapeutic
Mattress Replacement System
Progressive Medical
Base Deep Cell 1000, Base Large Cell 625, Base Large Cell 700
RIK Medical
RIK Fluid Mattress
Span America
Pressure Guard series
Standard Textile
Excel All -in-One and Ultimate All-in-One
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Exhibit 9-6:
1996 Mattress Replacement Market, Share by Supplier
Supplier
Sales
B.G. Industries
$28.8M
Market Share
21%
Bio Clinic
21.4
16
Cardio Systems
14.7
11
Comfortex
12.3
9
8.7
7
49.1
36
RIK Medical
Other*
Total
$135M
100%
*Other includes American Health Systems, Creative Bedding, Dermacare, Gaymar, HillRom, Huntleigh, Invacare, KCI, Lumex, Mason Medical, Medline, National Patient Care,
Pegasus, Progressive Medical, Span America and Standard Textile.
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Exhibit 9-7:
U.S. Mattress Overlay Market Forecast, 1996-2002
Year
Sales
1996
$210M
1997
220
4.7%
1998
230
4.5
1999
240
4.3
2000
250
4.1
2001
260
4.3
2002
272
4.5
CAGR 1997-2002
Growth
4.3%
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9.5.6
Mattress Overlay Competitive Analysis
Bio Clinic’s overlay product line consists of foam overlays in many different widths and
sizes. The company’s foam products include eggcrate convoluted overlays, flat foam
overlays, Bio Gard, Iris, and BodyWrap. Biotherapy, Biotherapy Plus and BioFlote are the
company’s air mattress overlay systems.
The Roho Dry Floatation system is a high-end mattress overlay with 720 soft, low pressure
air cells that are inteconnected at their base by air passages that evenly support and distribute
the patient’s weight. The air cells compress as the body is immersed into the overlay,
transferring air from one cell to the other to conform to the patient’s body. Other competitors
in the overlay market are presented in Exhibit 9-8.
Bio Clinic is the market leader in the overlay market with a 16% market share. This company
offers a broad product line in the overlay and mattress replacement segments, enabling it to
offer a wide variety of products for acute care, nursing homes and home care. The company
makes an extensive line of foam overlays, including its Bio Gard which is used in nursing
homes.
Gaymar is in second place with a 13% share of the overlay market due to its broad overlay
product line, including static air, low airloss and alternating pressure overlays. Gaymar is
expected to gain market share as its products expand beyond overlays. The company
currently offers mattress replacements and has started to build a line of specialty beds, which
will make it more competitive in purchasing contracts with large competitors.
Span America is in third place with 10% of the market. This company readily competes in
the acute care market with its Geo-Matt foam overlay. Roho/Crown offers the Roho Dry
Floatation system, which is now being reimbursed by Medicare under Group 2. This change
in Medicare reimbursement has helped boost Roho/Crown’s market share to 9% in 1996.
Exhibit 9-9 provides the market shares for the leading suppliers.
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Exhibit 9-8:
Selected Manufacturers of Mattress Overlays
Manufacturer
American Health Systems
Product
UltraForm Mattress Overlay
Bio Clinic
Eggcrate convoluted overlays, flat foam overlays, Bio Gard, Iris,
BodyWrap, Biotherapy, Biotherapy Plus, BioFlote
Cardio Systems
Pro 1000 and 2000
EHOB
Waffle overlay
Gaymar
Grant
Sof-Care Plus, PAL, Pillo-Pump with Pillo-Pad and Airflo
Dyna-Care and Dyna Soft
Hill-Rom
Huntleigh
Frameless Zoneaire Sleep Surface System, Acucair
Deltabed, Bubble Pad, Double Bubble Pad and Air-O-Pad
Invacare
MicroAire Pup 3500S
First-Step, K-Soft and TriCell
Lotus Health Care Products
DU-care, Lotus Long Life, Lotus PXM 3666, GL 3666, HM 3666,
MD3677, High Profile Deep-Air-Care
Medline
Aerofoam and Hexaguard
National Patient Care Systems Prevent-A-Care, Apropos and Alamo
Pegasus
Bi-Wave, Bi-Wave Plus and Carelight II
RIK Medical
Roho/Crown
RIK Mattress Overlay
Roho Dry Floatation
Span America
Geo-Matt
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Exhibit 9-9:
1996 Mattress Overlay Market, Share by Supplier
Supplier
Sales
Bio Clinic
$33.5M
Market Share
16%
Gaymar
27.4
13
Span America
19.9
10
Roho/Crown
19.2
9
EHOB
15.8
7
Huntleigh
13.2
6
Other*
81.3
39
Total
$210.3M
100%
*Other includes American Health Systems, Cardio Systems, Grant, Hill-Rom, Invacare, KCI,
Lotus, Medline, National Patient Care, Pegasus and RIK Medical
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Chapter 10: Company Profiles
10.
COMPANY PROFILES
10.1
3M Corporation
3M Corporation was founded more than 90 years ago, and the original company has
expanded into one of the world's major manufacturing companies. The company's businesses
developed from its research and technology in coating and bonding for coated abrasives, the
only product in the early years. Beginning with sandpaper in 1904, the company progressed
to Scotch Transparent Tape in 1930, nonwoven fabric in 1948, Post-it Notes in 1980 and
liquid- crystal display film in the 1990s. The company has operations in 60 countries with
products sold in over 200 countries.
The company consists of two major sectors: the Industrial and Consumer Sector and the Life
Sciences Sector. The first sector consists of industrial markets, automotive and chemical
markets, electro and communications markets, and consumer and office markets. The Life
Sciences Sector is composed of medical markets, pharmaceuticals, dental markets, traffic and
safety markets, diaper closures, commercial graphics markets and advertising markets.
Spanning all disciplines of science, the company operates on more than 30 technology
platforms to create specialty chemicals and polymers, adhesives, nonwoven fibers, films,
optics, filtration and microstructured surfaces.
A broad range of supplies, devices and equipment are included in the medical markets
businesses. Medical supplies include tapes, dressings, surgical drapes and masks, orthopedic
casting materials and electrodes, and biological indicators. Devices and equipment include
sterilization equipment, stethoscopes, blood gas monitors, heart-lung machines and powered
orthopedic instruments. Clinical information systems are also developed by these businesses.
3M has operations in 34 states and more than 60 countries. There are 42 international
companies with manufacturing operations and 22 companies with laboratories. 3M products
are sold in more than 200 countries.
The company employs 39,415 people in the United States and 74,289 worldwide. Total
research and development expenditure for the last five years was $4.3 billion, $947 million in
1996. Worldwide sales were $14.2 billion in 1996, an increase of 5.8% over the previous
year. Net sales in the Life Sciences Sector were $5.2 billion in 1996, an increase of 4.4%
from a total of $5 billion the previous year.
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Sales and profits for the first quarter of 1997 were the highest for any quarter in the history of
3M. The total sales of $3.7 billion reflected an increase of 11% in local currencies and 7.1%
in U.S. dollars.
The 3M Skin Health Program includes the following wound dressings: Tegaderm
transparent dressings, Tegagen alginate dressings, and Tegasorb hydrocolloid dressings.
Tegaderm Transparent Dressing with Absorbent Pad offers a non-adherent, absorbent pad
which absorbs exudate. Tegaderm HP is available in a great variety of shapes and sizes with
a shape suited specifically for the sacral area which is particularly hard to dress. It is a
primary dressing for Stage I and II pressure ulcers with minimal to moderate amounts of
drainage. All of the Tegaderm dressings offer precise and secure dressing placement as the
result of 3M's "picture frame" delivery system which is unique to these dressings.
Tegagen HG and HI alginate dressings are well-suited to be used with the Tegaderm sacral
dressing to treat wounds such as pressure ulcers, arterial and venous ulcers, diabetic ulcers,
donor sites, trauma wounds and cancerous lesions. The wounds can be partial thickness to
full thickness and moderately exudating to heavily exudating. Tegagen HG alginate dressing
contains high-gelling properties which permit gentle removal from fragile tissue. The
Tegagen HI dressing allows a fast, trouble-free dressing change by providing high integrity.
Finally, Tegasorb hydrocolloid dressing is used on partial and full thickness dermal ulcers.
The product enhances healing by providing an optimal moist environment which rapidly
absorbs exudate.
3M products are sold directly to users in the United States and in many other countries
around the world. They are sold through wholesalers, retailers, jobbers, distributors and
dealers in a great variety of trades. There are 286 sales offices and distribution centers; 9
major branch offices and 75 distribution centers are located in the United States.
10.2
Advanced Tissue Sciences, Inc.
Advanced Tissue Sciences is a tissue engineering company which develops and manufactures
human tissue products for transplantation. The company utilizes biocompatible matrices that
are seeded with human cells to produce its products. Advanced Tissue Science’s main
applications of its proprietary core technology include skin tissue, cartilage, cardiovascular
tissues, bone, tendons and ligaments.
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The company is publicly traded and employs approximately 170 people. Revenues in 1996
were $16.9 million compared to $4.8 million in 1995. The company sustained a net loss of
$22.4M in 1996, which was a 3% decrease over the $23.1M loss in 1995.
The company’s skin tissue product, Dermagraft, is engineered human dermal tissue
combined with a synthetic epidermal layer which is designed to treat patients with thirddegree burns on more than 20% of the body’s surface. The product also provides a protective
cover for burn patients to help retain fluids and reduce the risk of infection until a sufficient
amount of the patient's own skin becomes available for grafting. After an expedited review
process, the FDA approved Dermagraft in March 1997.
Dermagraft production begins by culturing human dermal fibroblasts onto a semipermeable
membrane which is bonded to nylon mesh. The nylon mesh provides structure as a threedimensional scaffold for the growth of dermal tissue, and the membrane forms the synthetic
epidermis. As the dermal fibroblasts grow on the mesh, they secrete growth factors and
structural components. The resultant product is then frozen which kills the cells, but leaves
the tissue matrix and cell growth factors intact. Later in the operating room, the surgeon
unfreezes the dermal patch as a temporary skin replacement for the patient’s destroyed
dermis. This product uses living human tissue, namely neonatal foreskin, which does not
elicit an allergic or immune response because the basic component has not developed
antibodies to cause a reaction.
10.3
Bristol-Myers Squibb Company/ConvaTec
Bristol-Myers, a worldwide health and personal care company, was founded in 1887. The
company merged with Squibb in 1989 and consists of three major business groups:
Worldwide Medicines, Nutritionals and Medical Devices, and Worldwide Beauty Care. The
Nutritionals and Medical Devices business groups is composed of Mead Johnson
Nutritionals, Zimmer and ConvaTec.
ConvaTec was founded in 1978, and the division’s initial products were manufactured for the
ostomy market. In 1982, ConvaTec launched a second core business, wound care, by
introducing DuoDerm Hydroactive Dressing. This dressing created a moist environment
while completely excluding air, thus enhancing the wound healing process. ConvaTec added
other dressings to its product line, making it a leader in the occlusive dressing market. In
early 1995, ConvaTec joined forces with Calgon Vestal Laboratories, which broadened the
scope of its wound care product line.
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ConvaTec employs approximately 3,000 people in over 100 countries around the world. The
company offers its products in the United States and Europe as well as Canada, Japan,
Australia, New Zealand, and the major markets of Eastern Europe, Asia, Africa, the Middle
East and Latin America.
Sales for Bristol-Myers Squibb in 1996 were $15.1 billion, a 9% increase from sales of $13.8
billion in 1995. Net income in 1996 was $2.9 billion compared to $1.8 billion in 1995.
Bristol-Myers Squibb employs approximately 51,200 persons worldwide.
ConvaTec has a broad product line which includes cleansers and wound care dressings.
ConvaTec’s SAF-Clens is a dual surface surfactant system for cleansing wounds with
moderate- to high-foaming capabilities, while the company’s alginate dressing, Kaltostat, is
available as a wound dressing or wound packing.
ConvaTec manufacturers several hydrocolloids, including SignaDress for the home care
market. This dressing is easy-to-use because of a “tear drop” in the middle which allows easy
centering of the dressing on the wound. As the dressing absorbs exudate, a bubble is formed
in the tear drop. When the bubble reaches a visible indication line, the dressing is ready to be
changed. Convatec also offers DuoDerm CGF which creates an acidic environment and
promotes an anti-infective environment.
10.4
Cardio Systems
Cardio Systems, a manufacturer of pressure-relief equipment, was founded by Robert Hasty
in 1963. The company was called N&H Instruments, and at that time, it only manufactured
surgical instruments. In 1968, the son of the founder, Charles Hasty, developed a hydraulic,
radiolucent bed for use in intensive care and critical care units. In the 1980s, Cardio Systems
diversified into patient support surface technology. In 1988, the company offered the first
portable low-air loss mattress which could convert any bed into an air support therapy bed.
Cardio Systems has since expanded its pressure-relief product line to include overlays which
provide lateral rotation and other full-framed beds. In 1996, sales for Cardio Systems was
estimated at $80 million.
The company’s product line includes products with its patented micro adjust pressure
profiling (MAPP) which allows control of interface pressure in each individual air sac on a
low-air loss bed. The company’s frameless air support therapy (FAST) is incorporated into a
number of products, including the Synergy mattress replacement with three types of
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therapies: pulsation, low-air loss and lateral rotation. The company has also patented the
Pneu Scale, which is a portable weighing system that allows patients to be weighed without
being transferred.
In 1990, Cardio Systems decided to establish its own offices and service centers with a direct
sales and service force. The company has since expanded to over 50 service centers in the
United States and actively markets its beds, mattress replacement systems and overlays to
hospitals, extended care facilities and home healthcare. In 1996, Cardio Systems began
introducing its products to the European market.
10.5
Carrington Laboratories, Inc.
Carrington Laboratories is a research-based pharmaceutical and medical device company
which develops complex carbohydrate-based therapeutics. The company focuses its research
and development activities in three key areas: wound care and skin conditions, consumer
products and veterinary products.
In 1996, the company posted revenues of $21.3 million, compared to $24.4 in 1995. This
decrease in revenues was due to a reduction in wound care product selling prices, which was
aimed to enhance the company’s competitive position. Carrington has approximately 230
employees.
Carrington Laboratories has a broad product line based on products derived from Aloe vera
plant. Carrasyn hydrogel wound dressing is used for the management of stage I-IV pressure
ulcers, stasis ulcers and first- and second-degree burns. The company also offers other
hydrogel products such as CarraGauze Strips, CarraGauze Pads and Carrasyn Spray Gel. In
January 1996, Carrington launched its new, freeze-dried hydrogel wound dressing called
CarraSorb M. This product is made with an Aloe vera extract containing acemannan which
absorbs wound exudate, up to 20 times its own weight. Indications for CarraSorb include
pressure ulcers, diabetic ulcers, foot ulcers, post-surgical incisions, radiation dermatitis and
abrasions. In November 1996, Carrington launched a new acemannan product called
RadiaCare Gel which is used in radiation therapy for the treatment of radiation induced
dermatitis. The company also introduced its DiaB Gel which is formulated for diabetic and
foot ulcer care.
Carrington Laboratories introduced its new CarraSmart foam dressing in 1996 which is made
up of three layers. The first layer consists of a hydrophilic polyurethane to maintain moisture
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in the wound, while the second layer is a hydrophilic, open-cell foam which also helps to
manage moisture. The last layer is a porous, pressure-sensitive adhesive. CarraSmart is
indicated for venous stasis ulcers, diabetic ulcers, pressure sores, partial-thickness and fullthickness wounds, first- and second-degree burns and donor sites.
In January 1996, Carrington Laboratories introduced its first calcium alginate product,
CarraSorb H. This dressing is made for wounds with heavy exudate, and the corresponding
indications include pressure ulcers, stasis ulcers, diabetic ulcers, arterial and venous ulcers,
foot ulcers, post-surgical incisions, radiation dermatitis, donor sites, trauma wounds, dermal
lesions and abrasions.
Carrington Laboratories is a relatively new participant in the film dressing market with their
Carra Film, launched in early 1996, and CarraSmart Film, introduced in March 1997. Carra
Film is designed to be used with the company’s Carrasyn hydrogel dressing or low exudating
wounds, such as superficial pressure ulcers, skin grafts, donor sites and closed surgical
wounds.
Carrington’s products are offered in 19 countries worldwide. The company markets its
products through a direct sales force and also uses distributors in the United States.
Carrington has distribution agreements with large companies in Central and South America,
Australia, New Zealand, Canada and China.
10.6
Coloplast Corporation
Coloplast Corporation was founded in 1957 by Aage Louis-Hansen after he had entered into
a license agreement to produce the world's first disposable ostomy bag in 1955. The company
is located in Humlebaek, Denmark and has 18 subsidiaries and numerous worldwide
distributors. Production and research facilities are located in Germany, the United States,
Puerto Rico and China, as well as Denmark. Sales subsidiaries were established in Sweden
and Norway in 1981, Belgium in 1982, Germany and the United States in 1983, Spain in
1984, Holland in 1987, and Japan in 1988. The wound and skin care businesses were
established in 1982. Sween Corporation was acquired in 1995, and the merger created a new
organization which included breast and skin care with a joint North American sales division.
The Sween acquisition added a leading manufacturer of a broad range of skin care products
used primarily in hospitals, long-term care facilities, health maintenance organizations and
home care. The extensive Sween product line includes products used both for professional
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and personal care, with specific application for ostomy, incontinence, wound care and
pediatric care. The largest single product in this line is Sween Cream, first introduced in
1987.
The company currently develops, manufactures and markets products for ostomy care,
continence care, wound care, skin and breast care, special dressings and consumer products.
It is a worldwide leader in the production of disposable medical devices to the healthcare
sector. Coloplast is also recognized as a leader in adhesive technology used for wound
dressings, advanced urological collection systems, ostomy applications, and in postmastectomy attachable forms.
Coloplast Group employs 2,588 people. The company reported a net turnover of nearly DKK
2 billion in 1996 with an operating profit of DKK 260 million.. Net turnover is an increase of
17% from the previous year's total of DKK 1.7 billion. The wound care market continues to
grow with sales of the Comfeel wound dressing; however, skin care sales have been
disappointing.
Coloplast wound care products include hydrocolloid and alginate wound dressings for
healing chronic and acute wounds by providing optimal moist wound healing environments
with maximum patient comfort. Alginate products include Comfeel SeaSorb and Comfeel
SeaSorb filler. Comfeel Plus is the company's hydrocolloid product. These products were
launched in 1996 along with Conveen Continence Guard, Conveen EasiCath and the
improved Assura/Alterna program. All the products launched in 1996 had a greater impact in
Europe than expected, although the turnover rate is not expected to increase at the same rate
as when the products were first introduced.
Through its acquisition of Sween, Coloplast acquired Woun’Dress, a natural collagen
hydrogel that provides a moist wound environment and promotes debridement. Other wound
care products include hydrophilic dressings, cleansers, deodorizers and preparations. For
personal care, Sween produces creams, shampoos, cleansers, sanitizers, bodywashes,
powders, and lotions. For incontinent care, the company produces antifungal-antimicrobial
barriers, citric-acid skin paste, and cleansers.
New resources were channeled to servicing key customers as part of a restructuring of the
U.S. sales functions during 1995-1996. United States marketing and service activities were
also merged at this time. Many people were moved to new positions, particularly in the sales
division where districts were reorganized and extensive training took place. With the market
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changing and purchasing concentrations increasing, these changes were required in order to
meet the increasing demands on the sales force. Since U.S. sales had not met expectations,
increased efficiency was an ongoing concern.
Sold through a worldwide net of subsidiaries and distributors, the product lines are directed at
two particular market segments, hospitals and community healthcare, which serve the
following end users: ostomists for colostomy, ileostomy and urostomy; patients with leg
ulcers, pressure sores or surgical wounds; paralyzed or immobilized patients who are
incontinent; people who suffer from light incontinence due to stress or urge incontinence; and
post-mastectomy patients. Consumer products for personal care are marketed through
pharmacists and chemists.
10.7
ConMed Corporation
ConMed Corporation is a leading provider of advanced electrosurgical systems and ECG
electrodes and accessories, as well as being a manufacturer of minimally invasive surgical
instruments and products used for therapy and wound care. Incorporated in 1970, the
company has employed a strategy of acquiring businesses in order to increase its market
share as well as broaden its product offerings. In 1996, the company acquired certain assets
of New Dimensions in Medicine, Inc. For a purchase price of approximately $31.6 million
and the assumption of $3.3 million in liabilities, ConMed gained businesses relating to the
design, manufacture and marketing of a wide range of ECG electrode products, disposable
electrosurgical products and various hydrogel wound care products. By acquiring New
Dimensions in Medicine, a proprietary hydrogel technology, ClearSite, was ConMed's first
expansion into the wound care market.
By the end of December 1996, ConMed had 957 employees and had increased its sales to
$125.6 million from $99.6 million in 1995, an increase of 26.2%. This increase was primarily
attributed to the New Dimensions in Medicine acquisition.
ClearSite dressings consist of a saline based, polymer gel designed to absorb and control
exudate while staying structurally intact. A flexible, continuous protective polyurethane film
covers the gel and allows visualization and moisture vapor transmission. ClearSite is able to
absorb 2-1/2 times its weight. ClearSite wound care products are indicated for use on
superficial and full-thickness wounds, pressure ulcers, first- and second-degree burns and
dermal leg and venous stasis ulcers.
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The wound care technology has resulted in the development of a number of innovative
products for clinical markets. One is an island dressing of ClearSite which has a clean,
breathable, pliable adhesive polyurethane film border. Another is ClearSite HydroGauze, a
gauze-like material that has been impregnated with dehydrated ClearSite which hydrates
upon contact with wound exudate. HydroGauze is used on heavier draining wounds, as well
as being used to pack wounds or cover burns and donor sites.
With a sales force of territory managers located in key metropolitan areas, supervision and
support is provided by regional managers. Direction for sales of the company's products is
provided by home office sales and marketing management. In addition, there are
approximately 20 national and regional hospital distributors and 150 to 250 local distributors.
10.8
C.R. Bard, Inc.
C.R. Bard, Inc. was founded in 1907 by Charles Russell Bard. A silk urethral catheter
imported from France was one of the company's first medical products. The company was
incorporated in 1923 and was distributing urological and surgical products at that time. In
1963, the company became publicly traded and was on the New York Stock Exchange five
years later.
The company presently designs, manufactures, and distributes medical, surgical, diagnostic
and patient care devices. There are three principal product lines: cardiovascular, urological
and surgical. The surgical products include specialty access catheters and ports; implantable
blood vessel replacements; fabrics and meshes for vessel and hernia repair; surgical suction,
irrigation and drainage devices; gastroenterological products; irrigation devices for
orthopedic and laparoscopic procedures; laparoscopic accessories; blood management
devices; and products for wound management and skin care. Approximately 90% of the
company's mostly disposable products are purchased by hospitals, physicians and nursing
homes.
Worldwide sales in 1996 were $1.2 billion, an increase of 5% from 1995 sales of $1.1 billion.
Net income in 1996 was $92.5 million ($1.62 per share), increasing 7% from 1995. The
approximate percentage contribution by each of the three principal product lines is as
follows: 33% cardiovascular, 29% urological and 38% surgical. Surgical product group sales
increased 4% in 1996 to $457.8 million, with international markets increasing slightly more
than in the United States.
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The company's four major wound care products are Biolex wound gel, Biolex wound
cleanser, AlgiDerm calcium alginate dressing and Vigilon primary wound dressing. Biolex
wound gel is clear, non-toxic and non-aerosol. It maintains the slightly acidic, moist
environment in the wound bed which is vital to the synthesis of collagen and the growth of
fibroblasts. It also maintains the pH range which has been shown most favorable for wound
healing. Biolex wound cleanser is a spray with a setting that can help remove slough and
debris from the wound. AlgiDerm is the company’s calcium alginate dressing, while Vigilon
is an inert, cross-linked polyethylene oxide hydrogel sheet.
C.R. Bard distributes its domestic products directly to hospitals and other institutions. The
company also has distribution agreements with numerous hospital and surgical supply
distributors. International practices vary by country but involve either direct distribution or
distributors. Sales to distributors accounted for approximately 8% of the company's sales.
The five largest distributors combined represented approximately 21% of these sales.
10.9
Cryolife, Inc.
Founded in 1984, CryoLife developed a new technology for ultra-low temperature tissue
preservation for subsequent transplantation that allowed long-term storage with little damage
to cells. CryoLife, which went public in 1993, became a leader in the development and
commercialization of techniques for the cryopreservation of tissues. In addition to U.S. and
Canadian tissue sales, CryoLife also distributes stentless pig heart valves in the European
Community.
After initial success with cryopreservation of aortic and pulmonary human heart valves, the
technique was expanded in 1986 to preservation of veins for coronary bypass surgery and
peripheral bypass vascular surgery, and in 1990 to connective tissue for orthopedic surgery.
The successful preservation of aortic and pulmonary heart valves has given patients an
alternative to the use of porcine valves, and replacement of damaged meniscal tissue holds
the promise of a return to normal knee function. After collection, the tissues are disinfected
and frozen until matched with patients. There is early indication of human heart valves have
survived for some 15 years.
In 1996, revenues totaled $37.2 million, compared to $29.2 million in 1995. Net income for
1996 was $3.9 million, which was a 77% increase over $2.2 the previous year. The company
employs approximately 160 people.
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CryoLife is developing two surgical bioadhesives, FibRx and BioGlue. FibRx is an adhesive,
designed to control bleeding, and based on the blood clotting factors fibrinogen and
thrombin. BioGlue, which has a stronger adhesive power than FibRx, is being developed to
replace suturing or stapling in some surgical procedures and is being evaluated for artery
attachment and gluing bone fractures.
CryoLife is also working on the development of technology to bioengineer an animal tissue
to human transplant that would not activate an immune reaction. The SynerGraft program is
attempting to develop a “human” heart valve using a porcine heart valve collagen matrix
which is seeded with autograft human cells.
CryoLife continues to strengthen its position through management’s efforts to increase sales.
CryoLife plans to expand its customer base by making other types of tissues available.
Cryopreserved mitral valves will be made available, in addition to the presently available
aortic and pulmonary heart valves. Because the company is virtually debt free, it has the
financial flexibility to capitalize on new market opportunities. The company’s core business
and its research and development efforts are completely financed by operations.
10.10
Curative Health Services, Inc.
Curative Health Services is a disease management company specializing in chronic wound
care. The company provides a range of service to healthcare providers through a nationwide
network of programs that offer wound care in 109 centers.
Curative is of interest to manufacturers in the wound care product industry because of its
focus as a profitable wound management company incorporating both comprehensive wound
care services and proprietary treatment technologies. The firms’ wound care centers are a
growing network of outpatient treatment centers that represent the core of the company’s
business. These innovative centers are managed by the company on behalf of acute care
hospitals throughout the country. The company is currently expanding its market
opportunities by developing new types of wound care service models for subacute care
facilities and other market niches. Curative is seeking to integrate this range of service by
establishing comprehensive managed care capabilities and by contracting directly with
managed care organizations.
Historically, it has been difficult for patients to receive treatment for wounds unless they
consulted separate medical specialists for each aspect of their treatment. The company’s
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wound care centers develop comprehensive therapeutic protocols which are tailored to the
individualized needs of patients. This includes the use of Procuren solution, a novel therapy
developed by Curative. Procuren is a naturally occurring complex mixture of several growth
factors contained within platelets in a patient’s own blood.
The company applies a case management approach to wound treatment. A customized
database maintains all of the relevant clinical data on patients, and provides clinicians with an
effective means of managing wound patients on an ongoing basis, adjusting their treatment
programs when necessary. This case management approach minimizes waste and saves
money by ensuring that patients do not receive unnecessary treatments. The involved
programs include administration, training for hospital physicians and other clinical personnel,
management of quality assurance programs, and reimbursement and strategic marketing
support.
Revenues in 1996 increased 29% to $67.4 million compared to $52.4 million in 1995. The
net income for 1996 was $10.7 million compared to $4.2 million for 1995. Curative, a
publicly traded company, employs over 400 people.
10.11
Genzyme Tissue Repair
Genzyme Tissue Repair is a division of the Genzyme Corporation, which was formed in
December, 1994, after Genzyme Corporation acquired BioSurface Technology and combined
it with existing Genzyme tissue repair programs. At that time, BioSurface Technology
developed and supplied tissues grown from normal human cells. The division is divided into
three major segments: cartilage repair, skin repair, and other tissue repair technologies for
multiple sclerosis and bone repair. In addition, during the third quarter of 1996, Genzyme
Tissue Repair and Diacrin Inc. announced a joint venture to develop and commercialize
NeuroCell-PD for Parkinson’s disease and NeuroCell-HD for Huntington’s disease. In July
1996, Genzyme Corporation acquired Deknatel Snowden Pencer which manufactures
cardiovascular surgical sutures, chest drainage devices and other surgical products for
operating room and intensive care use.
Service revenues for Genzyme Tissue Repair in 1996 were $7.3 million as compared to $5.2
million in 1995. Genzyme Tissue Repair employs 135 persons, including a 60-person, direct
sales force in the United States.
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The main products in the skin repair segment include the Epicel service (for the treatment of
burns) and the TGF-Beta2 and Vianain debriding product development programs. The Epicel
service was developed at BioSurface and consists of a sheet of proliferative cultured
autologous keratinocytes, ranging from 2 to 8 cell layers thick. The autologous keratinocytes
are harvested from human skin tissue and are processed to isolate specific cell types for
future epidermal autografts. While Genzyme Tissue Repair still continues to develop TGFBeta2 in collaboration with Celtrix to promote wound healing, the company has begun to
explore the possibility of licensing Vianain to a undisclosed third party.
Genzyme Tissue Repair markets its Epicel service in the United States and Europe with its
own direct sales representatives. The company provides a 24-hour customer support service
as well as on-site clinical support and availability to reimbursement specialists. As of 1996,
Genzyme Tissue Repair had treated more than 800 patients with Epicel worldwide.
10.12
Haemacure Corporation
Haemacure Corporation is a research and development company with products that target the
surgical wound care market. The company is developing a fibrin sealant called Hemaseel and
is also researching an artificial collagen which could replace bovine collagen products in the
clinical and consumer markets.
Revenues for 1996 totaled $652,000, compared to $41,000 in 1995. A net loss of $4.5 million
was reported in 1996, compared to a $2.8 million loss in 1995. This increase in net loss was
due to the development of a worldwide clinical program for Hemaseel and to update the
product’s manufacturing processes. The company employs 33 people.
Haemacure has three U.S. patents for the manufacturing of its Hemaseel technology, which is
a human-based, liquid fibrin sealant with hemostatic and adhesive properties. One product in
liquid form, called Hemaseel HMN, is absorbable and contains fibrinogen and thrombin
which has been isolated from human plasma by the company’s patented processes.
Haemacure is also developing a solid fibrin sealant, Hemaseel Dressing. This product is also
absorbable and has been designed to arrest bleeding in emergency and surgical situations.
The company has begun Phase III clinical trials for Hemaseel HMN and Phase I clinical trials
for Hemaseel Dressing. Haemacure plans to be completed with the regulatory process for
both of these products by late 1998 or early 1999.
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Haemacure has a manufacturing agreement with the Central Laboratory of the Swiss Red
Cross, which will manufacture components of the Hemaseel technology. Both parties shared
the costs of improving the manufacturing process, and as a result, the up-scaled
manufacturing processes for fibrinogen and thrombin were finalized at the end of 1996.
Cohesion Corporation, an affiliate of Collagen Corporation, is another strategic partner which
is adding more funding for Haemacure’s product development.
10.13
Hillenbrand Industries/Hill-Rom
Hillenbrand Industries, Inc. is a public company with four diversified and wholly owned
subsidiaries in two industry segments, funeral services and health care. These subsidiaries are
Batesville, Forethought, Medeco and Hill-Rom. The latter two subsidiaries form
Hillenbrand’s health care segment, and Hill-Rom is a leading manufacturer in the pressurerelief market. In 1985, Hillenbrand acquired SSI Medical Services, a specialized therapy bed
company, which was fully integrated in Hill-Rom in 1994.
Hill-Rom manufactures patient care products and is a leading provider of specialized rental
therapy products. The company’s products are designed to manage the complications of
patient immobility, and the products include medical-surgical beds, critical care beds,
stretchers, birthing beds and radiant infant warmers. Hill-Rom also manufacturers patient
room furniture, modular headwall systems, power columns, nurse communication systems
and patient voice-activated systems. In addition, the company rents patient support surfaces
and beds for wound and pulmonary therapy.
Net revenues for 1996 were $1.7 billion, which was an 4% increase compared to $1.6 billion
in 1995. The health care segment had sales revenues of $568 million, compared to $556
million in 1995. Health care rental revenues were $373 million in 1996. Net income was
$140 million in 1996, up from $90 million in 1995. Hillenbrand employs approximately
10,000 persons worldwide.
Hill-Rom has a complete line of pressure-relief products, namely, beds, mattress
replacements and overlays. The company’s extensive line of beds includes the Resident LTC
bed which is targeted at the long-term care market. This product is fully electric and the sleep
surface can be lowered to just over a foot from the floor. In late 1995, Hill-Rom introduced
the Flexicair Eclipse Low Airloss Therapy Unit, which is a portable mattress replacement
designed to prevent and treat pressure ulcers in moderate- to high-risk patients.
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10.14
Integra LifeSciences Corporation
Formed in 1990, Integra LifeSciences Corporation (ILC) is currently engaged in the
development and use of proprietary biomaterials technology which enables the body to create
functional substitutes to replace damaged and diseased body tissues. The company is
focusing this technology on the creation of functional substitutes for dermal skin, articular
cartilage and peripheral nerves. Its product, Integra Artificial Skin, is designed to grow new
skin and permanently replace damaged skin on severe burn victims After receiving PMA
approval from the FDA on March 1, 1996, this artificial skin became the first tissue
regeneration product on the market.
Integra Corporation was founded in 1991 to acquire patent rights for a collagen-based skin
replacement technology from Massachusetts Institute of Technology and to acquire clinical
data on the product from Marion Merrell Dow, Inc. In May 1993, the company acquired
Vitaphore Corporation from Union Carbide Chemical and Plastics Company. Vitaphore is a
developer and manufacturer of collagen-based products involved in hemostasis, infection and
ophthalmic surgery. Its subsidiary, Colla-Tec, Inc., develops and manufactures surgical,
medical and dental collagen-based products based on a proprietary process used to purify
insoluble collagen fibrils from bovine flexor tendon.
Integra LifeSciences purchased Telios Pharmaceuticals in 1995 resulting in further
development of proprietary core technology to apply RGD peptides to promote cell directed
behavior. The RGD peptide products under current development include a cell-adhesive
coating designed to improve the performance of implantable devices and the body's
acceptance of them. ABS LifeSciences, Inc. and Biomat Corporation are two other
companies that are included within Integra LifeSciences.
In 1996, Integra LifeSciences revenues were $13.1 million which included $3.1 million in
sales of Integra Artificial Skin. This was a 29% increase over the 1995 revenues of $10.2
million. Sales of Integra Artificial Skin continued to increase by over $500,000 per month in
both January and February 1997. By the end of January alone, more than 160 patients had
received treatment with the product.
Integra Artificial Skin may be used to stabilize a patient until the silastic film can be replaced
by autograft. The product is a dermal composite which consists of a porous lattice of fibers of
a cross-linked bovine collagen and glycosaminoglycan (GAG), and a synthetic epidermal
layer of polysiloxane polymer (silicone). The GAG that is used is chondroitin-6-sulfate. The
product was originally approved by the FDA to be manufactured in 4" by 10" sheets. The
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company applied to the FDA and was granted a PMA approval supplement to manufacture
additional sizes of 4" x 5" and 8" x 10". This will accommodate physicians' requirement to
use the product in more applications.
By early 1997, more than 300 surgeons had been trained in the United States and Canada, as
well as an additional 300 in Europe and Asia in the use of Integra Artificial Skin. More than
12 national and regional training sessions have been held in Orlando, Phoenix, Dallas,
Chicago, Pittsburgh, Philadelphia, San Francisco, Omaha, Birmingham, and St. Paul.
Furthermore, the company's marketing program recently produced and distributes a
newsletter for clinicians.
The product is manufactured in the United States and has been marketed directly by
experienced area managers in the United States since March 1996. It has been marketed
internationally to such countries as Denmark, Hong Kong, Singapore, Switzerland, Ireland
and parts of Germany since 1995. The managers support the nurses, as well as the physicians
who use the product in the treatment of severe burns. The product is sold only after medical
professionals have been trained in the used of the product. Specialized registered nurses are
employed to provide in-hospital training for operating room and burn unit personnel. The
company also markets the product through individual distributors in some foreign markets.
Integra LifeSciences Corporation manufactures and sells several medical products and
devices which are based on biomaterials. They are used in wound care, surgery, infection
control, ophthalmology, and dentistry. VitaCuff, which is implanted, and BioPatch, which is
topical, are used in percutaneous infection control. Other products include Helistat and
Helitene (surgical hemostasis), Collagen Corneal Shield (ophthalmic treatment), Biomend
(periodontal surgery), and Chronicure (wound dressing). These products are used both
domestically and internationally and are sold either directly or through the previously
described supply and distribution arrangements.
10.15
Invacare Corporation
Invacare Corporation is one of the only companies that designs, manufactures, markets and
distributes products in the following major home health and extended care medical
equipment categories: power and manual wheelchairs, patient aids, home care beds, home
respiratory products, low-air loss therapy products, seating and positioning products and
ambulatory infusion pumps. The company's origins can be traced to Worthington and
Company, founded in 1885 as a producer of vehicles designed for the disabled. By the early
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1970s, this wheelchair company was known as Invacare, a relatively obscure subsidiary of
Technicare Corporation which at the time was a major player in the field of diagnostic
imaging. Technicare was purchased by Johnson & Johnson in 1978, and Johnson and
Johnson then put the Invacare subsidiary up for sale.
The following year, after being purchased by a group of investors which included former
Technicare management, the company began a dramatic turnaround. By 1980, earnings had
increased to $1.4 million from pro-forma earnings of $100,000 in 1979. In 1981, the
company entered its first new market, home care beds, through a small acquisition. Thus
began a series of successful strategic acquisitions which included GSI, Inc. in 1993, a
manufacturer of low-air loss therapy systems for home and institutional use, and Healthtech
Products, Inc. in 1996, a manufacturer of extended care beds and patient furniture. During
1996, the company made a total of five acquisitions costing $24.9 million which extended or
added new product lines while expanding distribution capabilities.
Thus, the company has grown from a small U.S. company with 350 employees and $19
million in annual sales, to an international company of over 24 product lines in more than 80
countries with 4,200 employees and $619 million in sales in 1996. The net sales growth
represents a 22.5% compound average sales growth since 1979. The company's products now
include manual wheelchairs, motorized and lightweight prescription wheelchairs, motorized
scooters, patient aids such as crutches and walkers, home care beds, home respiratory care
products, seating and positioning products, mattress replacements and overlays.
Net sales for the first quarter of 1997 were $151.5 million compared to $134.5 million during
the first quarter of 1996, a 13% increase. Net sales for 1996 were $619.5, up 23% from $504
million in 1995, 11% of this being the net effect of acquisitions and foreign currency
translation. North American sales increased 17% with 9% of this due to acquisitions. Net
income rose to $38.9 million in 1996, 21% over net sales of $32.2 million in 1995.
Invacare manufactures and distributes a wide range of home care beds which are manual,
semi-electric, and fully-electric beds. Bed accessories include bed side rails, overbed tables,
trapeze bars, traction equipment and mattresses. The Geo-Mattress HC is a therapeutic foam
mattress which provides pressure reduction and comfort. The APM Alternating Pressure
Mattress is a full-depth powered air mattress replacement system which reduces interface
pressure for the treatment of Stage I through Stage IV pressure ulcers. In alternating mode,
the APM's 22 adjacent air cells alternately inflate and deflate at five-minute intervals which
periodically redistribute the pressure against the skin to promote capillary circulation. The
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Turn-Q Plus Mattress is a MicroAIR product which combines the benefits of lateral rotation,
true low-air loss and pressure relief in a single portable system.
The company's low-air loss products include a complete line of mattress overlays and
replacement products which use air flotation to redistribute weight and moisture away from
patients who are immobile. The MicroAIR PUP is an advanced pressure reduction overlay
which uses true low-air loss to arrest skin breakdown before Stage III and IV levels. The
MicroAIR 3500S Portable Low Air Loss Therapy System is a portable unit which provides
the comfort of pressure relief with skin moisture management by using continuous air flow to
remove excess moisture. This product serves as an institutional quality mattress replacement
unit and attaches to any standard medical bed.
Invacare's products are sold primarily to over 10,00 healthcare and medical equipment
provider locations in the United States, Australia, Canada, New Zealand and Europe. The
remainder of its sales are primarily to government agencies and distributors. The products are
sold through a worldwide distribution network by the company's sales force, telemarketers
and some independent manufacturers’ representatives. The company also distributes medical
equipment and related supplies manufactured by others through its extensive dealer network.
In the United States, the company markets primarily to the home medical equipment
providers who in turn sell or rent them directly to the users or to healthcare institutions such
as hospitals and nursing facilities. In the past, the company's primary customers have been
the providers, but Invacare also markets its home healthcare products using the "pull
through" method where medical professionals such as doctors, physical therapists and
occupational therapists refer their patients to the providers for their equipment needs.
The company continues to focus on its home care market while managing the extended and
acute care market with separate sales and distribution. It considers its "one stop shopping"
program a major contributor to superior service and the resultant increase in business. This
program offers the HME provider the broadest range of products and services at the lowest
total cost. The products of this program include HME retail merchandising, a dedicated
territory business manager with specialist support; and account services. The intention is to
increase sales at a rate of 50% more than the overall market growth rate, reaching $1 billion
in sales by 2000.
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10.16
Johnson & Johnson
Johnson & Johnson was founded as a partnership in 1885 between Robert Wood Johnson and
his two brothers, James and Edward, and incorporated under the name Johnson & Johnson
two years later. The company has great historic significance as one of the first companies to
apply the then new theory of antiseptic wound treatment by developing and marketing readymade, ready-to-use surgical dressings.
Johnson & Johnson is divided into three business segments: consumer, pharmaceutical and
professional. The consumer segment includes non prescription drugs, hygienic products,
sanitary protection products, adult incontinence products and first-aid products. The
pharmaceutical segment includes antifungals and biotech products as well as products related
to dermatology, allergies, contraception, gastrointestinal concerns, immunobiology and the
central nervous system. The professional segment includes equipment, devices and other
products related to diagnostics, wound management, eye care, infection prevention and
surgery. The products in the professional segment are used by physicians, dentists, nurses,
therapists, hospitals, diagnostic labs and clinics.. Among the most prominent of the products
are sutures and mechanical wound closure devices, minimally-invasive surgical instruments,
disposable contact lenses and joint replacement devices.
In 1941, Johnson & Johnson formed a separate division for the suture business which became
Ethicon, Inc. in 1949. This division manufactured surgical sutures and other related ethical
surgical products. Ethicon, Inc. became two separate companies in 1992. Ethicon EndoSurgery manufactures and markets endoscopic procedure products and mechanical wound
closure devices, and Ethicon, Inc. has products which include sutures, adhesion prevention
and newly-developed pharmacology products. One of Ethicon’s numerous suture products is
Vicryl Rapide, a faster absorbing skin suture which enhances cost effectiveness.
Worldwide sales have increased for the sixty-fourth consecutive year with record sales of
$21.6 billion in 1996. With a minimal price increase of 1%, sales increased by 14.7%
compared to $18.8 billion in 1995. This breaks down to $10.9 billion domestically and $10.7
internationally. The Professional sector increased 19.8% from $6.7 billion in 1995 to $8.1
billion in 1996. Approximately 54% of this amount was domestic, and 46% was international
sales.
In the first quarter of 1997, the company reported record sales of $5.7 billion and record net
earnings of $909 million. This reflects increases of 7.1% and 15.1% respectively over the
first quarter of the previous year. In the Professional sector, worldwide sales of $2.1 billion
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were reported which represent a 6.9% increase over the first quarter of 1996. Domestic grow
was 11.6% and international growth was 1.6%. Vistakon's disposable contact lenses, Ethicon
Endo Surgery's minimally invasive surgical instruments, Lifescan's blood glucose monitoring
systems and the Cordis interventional cardiology franchise are the major factors influencing
this growth. The company employs 89,300 people worldwide. Distribution is done directly,
through surgical suppliers, and through other dealers.
10.17
Kinetic Concepts, Inc.
Kinetic Concepts, Inc. (KCI) develops and markets therapeutic healing systems which help to
prevent skin breakdown associated with patient immobility. The company markets its
products, including specialty beds and mattress replacements, to the hospital, long-term care
and home care markets. In February 1997, KCI acquired H.F. Systems Inc. which KCI hopes
will strengthen the company’s position in California’s high-growth extended care market.
Revenues for 1996 totaled $269.9 million, an increase of 11% from $243.4 million the
previous year. Net income was nearly $39 million, a 37% increase from $28.4 million in
1995. The strongest growth occurred in the domestic surface and international businesses.
Sales from the specialty surface business in the United States was $181.3 million, which was
an increase of $18.3 million from 1995.
The increase in sales in 1996 was partly due to the success of the TriaDyne specialty bed
which was introduced in May 1995. This bed features the company’s Kinetic Therapy
technology which rotates the patient laterally, at least 40 degrees to each side. Other specialty
beds products include TheraPulse, FirstStep Plus, KinAir III, DynaPulse, HomeKair DMS
and BariKare. Overlay products include K-Soft, First-Step and TriCell; the latter overlay is
a top-of-the-line product designed for the home care market.
10.18
LifeCell Corporation
LifeCell Corporation was formed in 1986 and is developing and commercializing patented
technology for processing and preserving transplantable biological tissue grafts and other
human cell products. Its first product, AlloDerm, is a universal tissue graft used to
permanently graft third-degree burn wounds. AlloDerm is also used as soft tissue
augmentation in plastic and periodontal surgery, as well as guided tissue regeneration in
periodontal surgery.
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LifeCell is a public company and employs 75 people. The company has incurred substantial
losses since it was formed, but industry experts predict that the company should begin to
show a profit in 1998. LifeCell reported product revenues of over $2 million in 1996
compared to approximately $742,00 in 1995.
The company first began shipping AlloDerm, a cryopreserved allograft skin in June 1995 to
be used as a temporary burn dressing. Using donated cadaveric skin grafts, the patented
process removes all cells while preserving the dermal matrix. The cells of these grafts
normally maintain the matrix which are also the targets of the body's immune response. The
end result is a totally intact, acellular matrix. The matrix contains all the facilities for cell
residence and function so that when the nonviable processed matrix is transplanted, the
patient's own cells repopulate it and create a permanently integrated living tissue graft. The
grafts are effective in helping skin heal, promoting the growth of fibroblasts which are the
key maintenance cells of dermis. By using AlloDerm, integrated living tissue grafts can be
formed which are invisible to the immune system.
In September 1996, the FDA has classified AlloDerm as a "banked human tissue" and not a
medical device. A porcine equivalent called XenoDerm is being developed, and a number of
universities and burn centers have shown that XenoDerm decreases wound contraction and
improves cosmesis compared to conventional treatment. By using an immune-deficient
mouse reconstituted with human immune system cells, LifeCell is evaluating the immune
response to XenoDerm. If successful, human clinical applications will then take place.
LifeCell is also developing a composite, bi-layered AlloDerm graft for burn wound treatment
in order to eliminate the need for self-donated skin to graft burn wounds. Also, the National
Science Foundation has provided LifeCell with the funding to develop a composite skin by
combining AlloDerm and the cells of the epidermis. This program focuses on using stem
cells in skin to create the readily available composite skin from AlloDerm and a patient's own
epidermal cells, eliminating patient autograft requirements.
In January 1997, the company announced the award of over $1 million from the U.S. Army
Medical Research and Material Command in order to fund the development of new tissue
transplant products for use in neurological, dermatological and cardiovascular surgery.
Investigation of AlloDerm grafts to repair dura mater and the membrane lining of the brain,
as well as investigation of its use in conjunction with micro-skin grafting to cover large
wound surfaces with small, biopsy-sized skin grafts, will be the focus of this two-year
cooperative agreement.
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LifeCell's aggressive marketing program began during the second half of 1994 when the
company expanded its sales force from two to five people. Numerous quantities of AlloDerm
were shipped at reduced cost or free of charge. By 1996, the company began to set up a
nationwide network of regional distributors to market AlloDerm to the plastic surgery
market. Sun Medical of Dallas, Texas, was the first distributor selected since it carries a
sophisticated line of products used by plastic surgeons. The company's territory was Texas,
Oklahoma, New Mexico and Arkansas.
During the third quarter of 1996, Dentsply International formally launched a promotional
program for AlloDerm in periodontal surgery after it was signed as the exclusive worldwide
distributor of the product. The market for AlloDerm tissue in burn treatment continued to
expand by means of the company's direct sales force with over 60 representatives servicing
the U.S. plastic surgery market. By the second half of 1996, representatives were selling to
the nation's burn units and signing distribution agreements aimed at reaching the nation's
periodontists, plastics surgeons and reconstructive surgeons.
10.19
Mylan Laboratories, Inc./Dow Hickam Pharmaceuticals
Mylan Laboratories is engaged in the development, licensing, manufacturing, and marketing
of generic and proprietary pharmaceutical and wound care products. Dow Hickam
Pharmaceuticals was acquired by Mylan in 1991, and this division specializes in the
manufacturing and marketing of wound care products for hospitals, nursing homes, and home
health care.
Mylan Pharmaceutical’s net sales for fiscal 1997 (ended March 31) were $440.2 million,
compared to $392.9 million for fiscal 1996. Net income for fiscal 1997 was $63.1 million,
compared to $102.3 million during the same period in 1996. This decrease in net income was
partly due to extreme pricing pressure in their generic drug sales.
Dow Hickam has a variety of wound care products, including a debriding agent and
numerous wound dressings. Granulex is a vasodilating, lubricating ointment applied to
wound beds to enhance tissue granulation. However, it also contains trypsin, which results in
a mild debriding action. As a prescription drug, it is marketed as a maintenance debridement
agent, cleansing the wound bed after eschar has been removed. Granulex is unable to debride
thick eschar or hard necrotic tissue; however, it stimulates the blood supply and maintains a
moist environment for optimum healing.
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Dow Hickam offers Flexzan, a ultra-thin, highly conformable foam dressing with an opencell foam and a closed-cell outer surface. This dressing is indicated for skin tears, early-stage
pressure ulcers, and dermatologic and plastic surgery procedures.
The company also offers Hydrocol, a hydrocolloid wound dressing, which is available in
three different types: square shaped with rounded corners, sacral, and a thin construction
product which is semi-transparent. In addition, Dow Hickam markets a biosynthetic dressing
called Biobrane which is a 1/100th of an inch thick, nylon-knit fabric bonded to a siliconeplastic membrane. Collagen peptides are also bonded to the surface.
In 1989, Dow Hickam introduced the first calcium alginate dressing called Sorbsan. Through
sodium ion exchange, this dressing transforms into an absorbent, conformable sodium
alginate gel when the dressing contacts the sodium-rich exudate in the wound bed. Sorbsan is
indicated for all wet wounds, including those that are infected.
The company employs a sales force of approximately 80 people in the United States who sell
to distributors, corporate healthcare providers, plastic surgeons, and dermatologists. While
Dow Hickam has a strong presence in the institutional and alternate care markets, the
company plans to focus their marketing on dermatologists in the future.
10.20
Organogenesis, Inc.
Formed in 1985, Organogenesis, Inc. develops and manufactures medical therapeutics
consisting of living cells and natural connective tissues. These therapeutics are intended to
interact with the body to enhance the natural healing process by promoting the establishment
of new tissues. The company's products are used in wound care, cardiovascular surgery,
general surgery, urology and orthopedics. Apligraf, a full-thickness living skin equivalent
which contains both dermal and epidermal layers, was developed for the treatment of
wounds, including chronic wounds, skin surgery wounds and burns.
Organogenesis employs 124 full-time employees. Total revenues for 1995 were $627,000,
which increased to $7.5 million in 1996, due mainly to support payments of $6.5 million
received from Sandoz Ltd. in order to carry out research and development. Research and
development costs increased from $9.3 million for 1995 to $10.9 million for 1996 due
primarily to personnel additions and activities supporting the lead product, Apligraf. These
activities included expanding Apligraf operations, initiation of the diabetic ulcer pivotal trial
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and supporting the PMA application for the treatment of venous ulcers, which is pending at
the FDA.
The agreement entered into with Sandoz Ltd. grants the company global marketing rights to
Apligraf in exchange for bearing all sales and marketing costs and giving Organogenesis per
unit manufacturing payments as well as royalties on all Apligraf sales. Sandoz also
contributes strong representation in key markets as well as extensive expertise in marketing
breakthrough medical products.
Apligraf is a organotypic tissue product which consists of complex tissue with living cells
organized like native tissue. The upper layer of Apligraf is composed of living human
epidermal cells (keratinocytes), and the lower layer consists of living human dermal cells
(fibroblasts) in an organized dermal matrix. These cells can interact with the wound bed and
directly contribute to the wound healing process.
Among the fundamental raw materials needed to manufacture Apligraf are keratinocytes and
fibroblasts which are derived from donated infant foreskins. The lab separates the different
cell types and keeps them growing so that a dozen donations could provide enough material
to treat the world.
With its proven expertise in organotypic cell culture, Organogenesis has made other tissues
for research purposes, one example being the cornea. Also, the company has several
programs in research and development which are exploring the application of organotypic
cell culture to the development of living tissue for other clinical situations such as in
reconstructive surgery.
Organogenesis has four patents either issued or pending for tissue cryopreservation which
enables the freezing and storage of complex living tissue and its return to ambient
temperature so that tissue viability is maintained. The company is also developing products
used in the treatment of female urinary incontinence and in cardiovascular surgery.
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U.S. Markets for Wound Management Products

Transcription

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