Bone Grafting, Naturally TM

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Bone Gra
Bone Grafting, Naturally
TM
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rsion
Bone Grafting, Naturally
Accelerating Innovation in Orthobiologics
TM
Accelerating Innovation in Or
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Bone Grafting, Naturally
TM
Accell Bone Matrix!
Integra DBM: An Expert Approach to DBM Processing
Accell Family of products contain
Accell Bone Matrix (ABM). This
patented, dispersed form of DBM
offers significantly increased surface
area, which provides access to
natural bone proteins.
Integra controls the processing of DBM
and Accell Bone Matrix (ABM) from
start to finish in its state-of-the-art
facility. Each lot is tested in a validated
in vitro assay to ensure
osteoinductive potential. 1
Superior Handling
Safety Through E-Beam Sterilization
Accell Connexus incorporates a
poloxamer Reverse Phase Medium
(RPM), a highly biocompatible carrier.
This unique thermoreversible carrier
allows Accell Connexus to meet
the needs of challenging surgical
applications where robust handling
is essential.
• At room temperature, Accell Connexus is malleable and easily
extruded from the syringe.
• At body temperature, Accell Connexus is more viscous, resists
irrigation and minimizes graft migration.
Integra utilizes electron beam
(e-beam) sterilization to ensure
product sterility. This process has been
shown to preserve the osteoinductive
potential of DBM.1 All products are
e-beam sterilized as the last step in
manufacturing prior to being shipped.
The Accell Advantage — What’s the Difference?
Accell Family of Products combine patented ABM and particulate DBM
Particulate DBM1
Patented ABM1
Standard Process
Accell Process
Ground Cortical Bone
30x
30x
Standard particulate DBM is dense
and requires more time to break
down. Until these dense particles
break down, access to natural bone
proteins is limited.
Combined to Form Accell Family of Products
30x
The combination of ABM and particulate DBM
provides for both immediate and sustained
accessibility to bone proteins which are
important for osteogenesis.2
Accell Bone Matrix (ABM) is an openstructured, dispersed form of DBM,
which provides accessibility to bone
proteins without the need to be
broken down. As a result this creates
a favorable environment for the
formation of bone.
What is Our Patented Accell Bone Matrix?
Particulate DBM is formed
by removing the mineral
component
of
ground
cortical bone.
Particulate DBM
Patented ABM
Accell Bone Matrix is
transformed from particulate
DBM using the patented
Accell Process.
At higher magnification, DBM
can be seen as a dense matrix.
At higher magnification, ABM
can be seen as a white, highly
porous matrix.
Particulate DBM consists
of a highly dense matrix of
Type-I Collagen and naturally
occurring growth factors,
with limited accessibility.
ABM consists of an open pore
structure with high surface
area. The resultant scaffold
provides accessibility to bone
proteins, which creates a
favorable environment for the
formation of bone.
Graphically shown, wavy lines represent Type-I Collagen. The blue and red symbols denote naturally occurring growth factors in bone.
Accell Bone Matrix’s increased
surface area provides access to
natural bone proteins.1
Osteoinductive Potential -- In Vitro Measurement3
Accell Bone Matrix (ABM) vs.
Demineralized Bone Matrix (DBM)
Natural bone protein content of ABM
and particulate DBM was measured in
vitro over time using an Enzyme Linked
Immunosorbent Assay (ELISA). The results
are shown graphically and indicate that
bone protein was detectable in a saline
solution containing ABM at earlier time
points compared to that of particulate DBM.
Bone Protein
The higher surface area and more open pore
structure of ABM provides accessibility to
the bone protein, without the need to be
broken down.
Accell combines the
virtues of ABM and DBM
in one powerful product
ABM
DBM
This analysis shows that while ABM provided
early accessibility of natural bone protein,
particulate DBM provides for accessibility of
natural bone protein at later time points.1
Time
Accell Process
Osteoinductive Assay
Osteoinductive
DBM
Accell Connexus
Lot Division
®
Incorporates
- Accell Technology
- Integra Processed DBM
- 30% Poloxamer Reverse Phase Medium Carrier (RPM)
Extraction
Benefits
- Validated Osteoinductive Potential
- Poloxamer Reverse Phase Medium
- Thickens at body temperature
- Resists irrigation allowing for better graft containment
- Is inert, biocompatible and safe.4
- Moldable and easy to pack into virtually any size or shape defect
- Ready to use
Case Studies
• Knee: Total knee replacement 5
• Foot & Ankle:
- Subtalar arthrodesis 6
- Hindfoot and ankle nonunions 7
Accell TBM
Final Formulation
Research studies, in animals, have
demonstrated poloxamer had a superior
Concentrated
ability to deliver native
human
DBM protein
8
to tissue.
Final Product Configuration
®
E-Beam Sterilization
Incorporates
- Accell Technology
- Integra Processed DBM
- Matrix formulation through lyophilization
Benefits
- Validated Osteoinductive Potential
- Available in different sizes
- Easily cut to fit any size or shape defect
- Osteoconductive framework
- Ready to use
Case Studies
• Spine: Laminectomy and spinal fusion
• Spine: Posterolateral Spinal Fusion 10
• Trauma: Humeral nonunion 11
• Hip: Total hip revision 12
• Knee: Total knee revision 13
• Foot & Ankle: Tibial osteotomy 14
9
In a clinical study, “Accell Total Bone
Matrix® combined with local autograft
demonstrated a higher fusion rate
than local autograft alone based on CT
scans on patients who had undergone
instrumented posterolateral fusion.” 10
Accell. A Technological Leap. A New Standard.
Bone HealingFactors
Process
The Critical Role of BMPs and Growth
in Bone Formation and Healing
B
Bone F
Bone FractureBone Fracture
Bone Fracture
Bone Fracture
Release
G
Release of Growth
Factors
Release
ofRelease
GrowthofFa
Release of Growth Factors
Release of Growth Factors
Bone contains natural BMPs and growth factors which have been shown to be a critical
component in bone formation and healing. 15, 16, 17, 18
The body’s natural response to traumatic injury is to initiate healing through a
complex and highly regulated series of events:
• Stem cell and osteoblast recruitment (chemotaxis)
• Blood vessel establishment (angiogenesis)
• Cell replication (mitogenesis)
• Stem cell differentiation into osteoblasts (osteoinduction)
B
B
GROWTH
GROWTH FACTORS
GROWTH FACTORS B
GROWTH FACTORS
BMP-2
BMP-2
IGF-1
BMP-2
IGF-1
BMP-4
BMP-4
VEGF
GROWTH FACTORS
BMP-2 BMP-4
IGF-1
VEGF
BMP-7
TGF-ß
BMP-7
BMP-4
VEGF
BMP-2
IGF-1
TGF-ß
BMP-7
TGF-ß
BMP-7
BMP-4
VEGF
TGF-ß
BMP-7
Bone Healing Mechanism
Fr
Fractur
Fracture Repair
Fracture Repair
Fracture Repair
Fracture Repair
The Accell Advantage
• Skeletally mature sheep model.1
• Cylindrical 5mm metatarsal defect created in tibial diaphysis.
• Results after 4 weeks.
IGFVEG
TGFBMP
BMP
BMP
Control - Empty
1st Generation DBM
Accell
Minimal bone regeneration observed at 4
weeks. Healing limited to area adjacent to
host bone.1
Bone regeneration occurs throughout
the defect, caused by the presence of
DBM particles. The inert carrier has been
metabolized.1
(DynaGraft® II)
Significantly more bone formation is evident
immediately adjacent to the bone repair
surfaces and within the interior of the defect.1
Note: Sections stained for quantitative assessment of bone healing.
Reflection Logo Version
Lot Division
Bone Grafting, Naturally
TM
Extraction
Description
Final Formulation
Accell
Connexus
Reverse
(white) Logo Version
®
0.5 cc syringe 1 cc syringe
2.5 cc syringe
5 cc syringe
10 cc syringe
Concentrated
DBM
Catalog Number
02-3000-005
02-3000-010
02-3000-025
02-3000-050
02-3000-100
Bone Grafting, Naturally
TM
Final Product Configuration
Accell TBM
Description
®
E-Beam Sterilization
5 x 2 x 0.5 cm strip
5 x 5 x 0.5 cm square
7 x 0.6 cm round
Catalog Number
02-4000-520
02-4000-550
02-4000-760
Contact Integra Customer Service
(800) 550-7155 or (949) 595-8710
www.IntegraOrthoBiologics.com
References
Accelerating Innovation in Orthobiologics
Accelerating Innovation in Orthobiologics
Accelerating Innovation in Orthobiologics™
Accelerating Innovation in Orthobiologics™
1 Data on file
2 Lian J and Stein G, The Cells of Bone, (1999) Dynamics of Bone and Cartilage Metabolism (Ed Seibel J)
3 R&D Systems, Inc.: Quantikine(R) - BMP-2 Immunoassay, For the quantitative determination of bone morphogenetic protein 2 (BMP-2) concentrations in bone tissue extracts and cell culture supernates.
4 Li C, et al: Disposition of poloxamer 407 in rats following a single intraperitoneal injection assessed using a simplified calorimetric assay. J Pharm Biomed Anal 1996;14:659-665.
5 Keppler L: The use of Accell Connexus® in a right total knee replacement with allograft reconstruction of extensor mechanism. Case Study, 2006.
6 Keppler L: The use of Accell Connexus® in a subtalar arthrodesis of the left foot. Case Study, 2006.
7 Rodriguez ER, et al: Use of high concentrate demineralized bone matrix in ankle and hindfoot orthopedic
procedures.
The Podiatry
Institute Update
2005, Chapter
45, pages
234-237. in Orthobiologics™
™
Accelerating
Innovation
Accelerating
Innovation
in Orthobiologics
8 Clokie ML, Urist MR: Bone morphogenetic protein excipients: Comparative observations on poloxamer. Plastic & Reconstructive Surgery 2000; 105(2): 628-637.
9 Keppler L: The use of Accell TBM® in a decompressive laminectomy at L4 and L4-L5 with spinal fusion at L4-L5 to treat hemangioma with an L4 fracture. Case Study, 2006.
10 Isaza J, et al: Fusion success with Accell Total Bone Matrix and autograft: 1 year post-surgical fusion rates in posterolateral spinal fusion. Retrospective study, 2007.
11 Tom JA, et al: Humeral non-unions treated successfully with internal fixation and demineralized bone matrix. Case Study, 2006.
12 Johanson NA, Cerynik DL: Filling acetabular defects with preformed demineralized bone matrix in revision total hip arthroplasty. Case Study, 2006.
13 Bezwada HP, et al: Distal femoral allograft reconstruction for massive osteolytic bone loss in revision total knee arthroplasty. Case Study, 2006.
14 Keppler L: The use of Accell DBM 100™ and Accell TBM® in a proximal tibial osteotomy for left medial joint osteoarthritis. Case Study, 2006.
15 Wozney J.: Overview of bone morphogenetic proteins. Spine 27(16S), 2002
16 Cheng H, et al: Osteogenic activity of the fourteen types of human bone morphogenetic protiens (BMPs). J Bone and Joint Surgery 2003; 85-A(8): 1544-1552
17 Urist ML: Bone: Formation by autoinduction. Science 1965;150:893-899.
18 Blum B, et al: Measurement of bone morphogenetic proteins and other growth factors in demineralized bone matrix. Orthopedics, January 2004 (Supplement): 161-165.
*The Accell products are protected by one or more of the following U.S. Patent Nos 7,241,813, 7,205,337, 7,132,110, 6,309,659, 6,623,748 and other patents pending in the U.S. and other countries.
The Accell© family of products are manufactured by IsoTis OrthoBiologics, Inc., a subsidiary of Integra LifeSciences Corporation. Accell, DynaGraft, Accell Connexus and Accell TBM are registered trademarks
of IsoTis OrthoBiologics Inc., Accell 100 is a trademark of IsoTis OrthoBiologics Inc., the Integra Wave logo is a trademark of Integra LifeSciences Corporation. Copyright © 2008 by Integra LifeSciences
Corporation • Integra OrthoBiologics • 2 Goodyear, Irvine, CA 92618 • (949) 595-8710 • NS1977-04/09