Hyaluronic acid – the biological power in dentistry

EXCLUSIVE DISTRIBUTORS
Germany / Europe / CIS:
Middle East Region:
Naturelize GmbH
www.naturelize.com
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Elaf Medical Supplies Co.
www.elaf-me.com
[email protected]
Japan:
Asia-Pacific Region:
PRSS Japan. Co.,Ltd
www.prss-i.com
[email protected]
Skin M.D. Pte Ltd
www.skin-md.net
[email protected]
MANUFACTURER
BioScience GmbH
Rheinstraße 96
56235 Ransbach-Baumbach | Germany
www.bio-science.org
[email protected]
Hyaluronic acid – the biological power in dentistry
CONTENTS
I
II Hyaluronic acid:
natural wound healing
Hyaluronic acid:
supporting tissue retention
III HYADENT for targeted
tissue regeneration
IV HYADENT products
V-2 in GTR/GBR
V-3 in sinus elevation
V-4in ridge/socket preservation
V-5in open healing of an implant
VI HYADENT: use in
periodontal therapy
and indications
VII HYADENT in
esthetic reconstruction
V
HYADENT: use in wound
healing and implantology
VIII HYADENT as a
preventive treatment
V-1 in apicoectomy
IX
Benefits of HYADENT
HYALURONIC ACID: natural
wound healing
Hyaluronic acid is an important component of the
human organism and is involved in almost all regenerative processes which take place in the human
body. The HYADENT product family is based on
this natural, endogenous substance and has been
developed with the aim of achieving natural wound
healing. As a biologically inert product of non-animal origin, HYADENT opens up entirely novel wound
treatment options.
What happens during wound healing?
Modern wound treatment is primarily directed at the
wound stage and wound type. Wound healing is a
complex process and occurs in four physiological
stages:
1: Homeostasis
2: Inflammatory phase (exudation phase)
3: Proliferative phase
(granulation, angiogenesis, epithelialization)
4:Remodeling phase (scar formation)
1: Homeostasis
Following injury, platelets aggregated to form a fibrin clot for primary wound closure.
2: Inflammatory phase
Inflammation and exudation are the key features of this phase. Macrophages and neutrophils
migrate into the fibrin plug. This is followed by the production of inflammatory cytokines and
growth factors. These in turn stimulate migration of fibroblasts into the wound area. Hyaluronic
acid promotes and at the same time regulates the inflammatory process, as it has an antioxidative effect and reduces the activity of pro-inflammatory proteases, thus allowing a stable
matrix to be formed. This mechanism is disrupted in chronic wounds, so that inflammation
persists and wound healing is disrupted. Formation of pro-inflammatory cytokines (TNF-alpha,
IL-1 beta, and IL-8) is inhibited. Hyaluronic acid has an anti-oxidative effect and reduces the
activity of pro-inflammatory proteases.
3: Proliferative phase
The granulation tissue, which is rich in hyaluronic acid, forms a hydrated matrix which facilitates
receptor-mediated (CD44) cellular migration. Cell mitosis, cell proliferation, and angiogenesis
are supported by low molecular weight hyaluronic acid polymers. Granulation tissue largely
consists of fibroblasts which have migrated into the tissue, newly formed capillaries, collagen,
fibronectin, and hyaluronic acid. High concentrations of hyaluronic acid are found in the basal
layers of the epidermis. This encourages the proliferation and migration of basal keratinocytes (via the CD44 cell surface receptor). Regulation of keratinocyte proliferation also occurs.
Epithelialization is both stimulated and regulated.
HYALURONIC ACID:
supporting tissue retention
Hyaluronic acid is a natural polysaccharide and a
member of the glycosaminoglycan family. The
molecule consists of a repeating sequence of a
disaccharide composed of D-glucuronic acid and
N-acetylglucosamine.
Most somatic cells, especially connective tissue
cells, are able to produce hyaluronic acid. It is formed at the cell membrane and excreted directly into
the extracellular matrix.
Hyaluronic acid is a major component of the extracellular matrix in almost all tissues. As such, its primary role is to bind water to permit the transportation of key metabolites and maintain tissue structure.
Hyaluronic acid activates metalloproteinase inhibitors, thus suppressing tissue breakdown. A similar
effect is produced by the inhibition of inflammatory
cytokines (e.g. TNF). Hyaluronic acid can thus visibly
contribute to tissue retention.
4: Remodeling phase
Shrinkage reduces the wound size and accelerates healing. Scar tissue consists of collagen,
elastic fibers, and proteoglycans. Hyaluronic acid plays an important role in regulating scar
formation. In the final phase of wound healing – scar formation – hyaluronic acid is responsible
for ensuring that suppression of collagen production occurs at the right time and for soft scar
formation. In the fetal period, for example, the concentration of hyaluronic acid in wounds is
very high for a prolonged period, as a result of which wound healing always occurs without
scar formation.
I
II
HYADENT for targeted
tissue regeneration
HYADENT products and indications
We have now found a way of utilizing the mechanism of action of hyaluronic acid in dental surgery and have developed
two entirely novel products:
HYADENT: non cross-linked hyaluronic acid
HYADENT barrier gel: cross-linked hyaluronic acid
We have adapted a proven substance, hyaluronic acid, to the
specific practical needs imposed by dentistry, and created
a new mode of application in the form of a viscous gel. Both
of these products can be used to specifically enhance tissue
regeneration.
When should each product be used?
Hyaluronic acid can be metabolized by all somatic cells. This
means that these products are fundamentally suitable for
soft tissue indications, but are also suitable for hard tissue
use. The hyaluronic acid in HYADENT products promotes
the formation of new fibroblast and osteoblasts.
To select the correct product, first-time users should first
clearly identify the indications for use.
– What objective is the application of the hyaluronic acid product intended to achieve? (Effect)
NON CROSS-LINKED HYALURONIC ACID
CROSS-LINKED HYALURONIC ACID
Effect:
● S peeds up wound healing
after surgical procedures
Effect:
● S hields the wound area from penetration
of bacteria and connective tissue
● Supplements and enhances
periodontal surgical treatment
●
Reduces scar tissue
Activates bone regeneration material to
accelerate osteogenesis and prevents
displacement of the granules
●
– Over what time frame are the effects of hyaluronic acid required? (Resorption period)
●
Papilla reconstruction
Resorption period:
16 – 21 days
● Optimizes procedures for
ridge/socket preservation
Resorption period:
6 –11 hours
III
For a detailed overview
of HYADENT indications
see also chapter IX.
IV
HYADENT: use in wound healing
and implantology
To support and accelerate wound healing, HYADENT hyaluronic acid gel is applied directly into the
operation area immediately prior to wound closure.
HYADENT can also help improve wound healing
and esthetic tissue regeneration in implantology
care using gingiva formers.
This makes use of an angulated, blunt cannula
(27G / 0.4 x 18 mm). Angulation of the cannula permits the HYADENT hyaluronic acid gel to be applied
ergonomically between the wound margins.
The suture which is then applied brings the wound
margins into direct contact with the hyaluronic acid
gel, which are then able to resorb it locally.
3
The modified viscosity and short resorption time
(6–12 hours) ensures complete absorption by the
surrounding tissue. Appropriate and correctly executed suturing technique can prevent the gel from
being rinsed away by saliva.
1
4
2
5
USE IN APICOECTOMY
After surgical extraction of a tooth, apicoectomy is the
second most common oral surgical procedure.
A good prognosis – 85% success rate over 3 to 6
years – makes this procedure, where the correct indications for its use are present, an excellent option for
retaining natural teeth. 1)
1
1 Partsch incision
2 Flap mobilization to expose the affected area
3 Exposure of the root tip
4 Curettage of the granulation tissue
5 Filling the bone defect with bone regeneration
material and HYADENT􀀃
6 Covering the wound area with HYADENT barrier gel
6
2
1 Applying HYADENT prior
to wound closure
2 Applying HYADENT for open
healing of an implant
V
1)
Maienfisch A: Langzeiterfahrungen mit der Wurzelspitzenresektion. Med. Diss., Zürich 1980
V-1
USE IN GTR /GBR
USE IN SINUS LIFTS
To improve wound healing in sensitive areas,
HYADENT barrier gel, our cross-linked hyaluronic
acid preparation, should be spread generously over
the augmented area of bone. This aids soft tissue
healing and reduces the risk of infection. HYADENT
barrier gel is thus able to act as a substitute for
standard collagen membranes for many
indications. 1)
HYADENT Hyaluronic acid increases osteoblast
formation, thereby reducing the time required for
new bone formation by means of osseointegration stimulating effects. 2) The use of HYADENT in
sinus elevation surgery – nowadays a standard
procedure – offers numerous benefits for both
surgeon and patient.
The primary benefits for patient and surgeon:
Stabilization of bone granules
Precise application of bone granules (bone graft material) is
made much easier with HYADENT, as the viscous gel structure
of the preparation prevents subsequent displacement.
Formation of a protective barrier
This beneficial effect arises as a result of the high viscosity of
HYADENT barrier gel, which directly covers the wound like a
biological membrane. This minimizes the risk of bacterial or
microbial contamination (assuming correct surgical technique).
1
Reduced infection risk
In conjunction with the anti-inflammatory effect exerted by
the cross-linked preparation 3), the bacteriostatic and antiseptic
properties lead to improved protection of the wound area
throughout the resorption period (16–21 days for cross-linked
hyaluronic acid).
2
3
1 Extraoral enrichment
of the granules
2 Granules ready to use
Application of HYADENT barrier gel
to augmented bone
3 Application of the gel barrier
2) Sasaki
1)
V-2
Weigel PH, Fuller GM, LeBoeuf RD: A model for the role of hyaluronic acid and fibrin in the early
events during the inflammatory response and wound healing. J Theor Biol 119, 219-234 (1986))
T, Watanabe C: Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid. Bone 16, 9-15 (1995)
Schwartz Z, Goldstein M, Raviv E, Hirsch A, Ranly DM, Boyan BD: Clinical evaluation of demineralized bone allograft in a hyaluronic acid carrier for sinus lift
augmentation in humans: a computed tomography and histomorphometric study. Clin Oral Implants Res 18, 204.211 (2007))
3) Source:
Dental Clinics, Journal Of General Dentistry, “Hyaluronic acid: biological effects and clinical applications” Demarosi F, Sardella A, Lodi G, Carrassi A.
V-3
3
USE IN RIDGE /SOCKET PRESERVATION
Implant dentistry is today expected to do far more
than just meet a need for a fixed prosthesis. Patients
want a reconstruction which is as natural as possible, both functionally and esthetically, down to the
tiniest detail. This essentially means that, in order
to meet these expectations, dentists are frequently
having to get to grips with the presenting situation
at a significantly earlier stage.
Because of recent advances in dentistry and the
development of novel products, this is now feasible
with a high degree of predictability.
In order to achieve the best possible esthetic result
over the course of the planned restorative treatment
and to minimize bone loss, augmentation using
bone regeneration material is frequently carried out
immediately after tooth extraction.
HYADENT is able to help accelerate wound healing
and thus provide rapid protection of the affected
area. Controlled, successful wound healing avoids
problems during two-stage implantation.
Without socket preservation:
1 Six weeks post-extraction, marked vertical
and horizontal resorption
3 Moistened collagen sponge
4 After extraction
2 Buccal resorption in the alveolar region
six weeks post-extraction
1
V-4
2
5 After filling the defect
4
5
V-4
USE IN OPEN HEALING OF AN IMPLANT
2
The following example illustrates how using HYADENT barrier gel can optimize soft tissue management in open post-implantation healing (with no
surgical suture). Open healing of a dental implant
in the front teeth area is a strong case for an ideal,
natural looking esthetic. Unfortunately, this treatment
option is frequently undermined by a failure to meet
patient-related requirements.
3
4
5
7
10
This case is an impressive illustration of the novel
soft tissue management options that HYADENT
barrier gel is able to offer. The risk of major marginal
bone loss and of infection immediately after implantation is significantly reduced.
8
The absence of the characteristic suture-related
retraction around the papilla also has a major effect
on the success of the prosthesis.
The factors from which the dentist is able to benefit
by using HYADENT barrier gel mean that the risk of
infection is minimized and conditions required for
optimal natural esthetics are guaranteed.
6
9
11
1
V-5
Using HYADENT barrier gel also significantly
reduces scar tissue formation.
12
1 Initial situation
7 3 months post-implantation
2 Missing lateral incisor
8 The papilla has been fully preserved
3 Implantation, opening a lateral decompression incision
9 Impression using repositioning technique
4 Immediate implant closure using a gingiva former
10 X-ray shows no loss of bone
5 Sutureless wound closure with HYADENT barrier gel
11 Clinical crown after insertion
6 Completely filled soft tissue defect
12 Final state􀀃
V-5
HYADENT in esthetic reconstruction
HYADENT: use in periodontal
therapy
A key facet of systematic periodontal therapy is
effective removal of supra and subgingival plaque.
Plaque reduction alone is effective in treating
periodontitis in the majority of patients. 1)
A number of scientific studies have shown that
periodontal pathogenic microorganisms cannot
be adequately eliminated using purely mechanical
methods. Additional materials such as disinfectant
agents, antiseptics, non-steroidal anti-inflammatories, and systemic antibiotics are therefore employed
in treating periodontal disease. Sub or supragingival
application of hyaluronic acid (one of four glycosaminoglycans in gingival tissue) can also be a successful additional therapeutic measure for treating
periodontal disease. HYADENT’s bacteriostatic
properties (especially against Actinobacillus actionomyecetemcomitans, Prevotella intermedia and
Staphylococcus aureus) aid tissue regeneration. 2)
tically significant reduction in the sulcus bleeding
score and a reduction in redness and swelling. This
effect is primarily ascribed to the hyaluronic acid, as
it regulates water content in the connective tissue
extracellular matrix and the passage of substances
into the interstitium.
Many studies have comprehensively documented
the positive clinical outcomes of modern implantology. The use of modern treatment concepts
and improved materials has dramatically expanded options for nature-identical esthetic reconstruction of the soft tissues. Patients who have
lost their natural teeth as a result of an accident
or unforeseeable circumstances are increasingly
inclined to reclaim this natural feeling by making
use of fixed dental prostheses. This raises patient
expectations and consequently the demands
made on the dentists who treat them.
The uncomplicated nature of and low-risk involved
in applying HYADENT is a clear argument for its use
in the initial treatment of periodontal disease.
HYADENT barrier gel offers dentists a genuine
alternative to difficult and lengthy surgical
procedures.
In addition, periodontal therapy with hyaluronic
acid support has been shown to achieve
an increase in bone level. 3)
The angulated cannula makes HYADENT simple
and effective to apply. In addition to manual supragingival and subgingival scaling and root planing of
all affected teeth, systematic periodontitis treatment
involves the sub or supragingival application of
HYADENT. HYADENT should then be reapplied
7–10 days after initial application. As a supplement
to mechanical treatment, its use leads to a statis-
2)
VI
1
HYADENT application in the
periodontal pocket
1) Jentsch H, Pomowski R, Kundt G, Gocke R: Treatment of gingivitis with hyaluronan. J Clin Periodontol 30, 159-164 (2003)
Pirnazar P, Wolinsky L, Nachnani S, Haake S, Pilloni A, Bernard GW: Bacteriostatic effects of hyaluronic acid. J Priodontol 70, 370-374 (1999)
Galgut P: The role of hyaluronic acid in managing inflammation in periodontal diseases, Dental Health 42, 3-6
3) van den Bogaerde L, MD, DDS: Behandlung von intraossären Parodontaldefekten mit veresterter Hyaluronsäure:
Klinischer Bericht über 19 nacheinander behandelte Läsionen. Int J Paro & Rest ZHK, 29 3, 299-307 (2009)
The primary benefits for patient and surgeon:
Shorter, simpler procedure under local anesthetic
Our cross-linked hyaluronic acid-based HYADENT barrier gel is
injected directly into the papilla using a sharp needle (23G /0.6
x 25 mm). To achieve the desired effect in full, the injection may
be repeated after about 3 weeks.
Surgical procedures which result in unwanted scarring are no
longer necessary. Patients are spared a painful treatment and
the limitations it imposes.􀀃
Treatment with a higher success rate
By using HYADENT barrier gel, dentists can take advantage of
a highly effective treatment modality which guarantees a high
success rate. In terms of the relationship between the effort
involved and the likelihood of success, standard surgical procedures come a distinct second.
2
1 Initial situation
2 Approx. 3 weeks after the
second injection
VII
HYADENT as a preventive treatment
TISSUE CARE FOLLOWING BLEACHING/ WHITENING TREATMENT (HOME BLEACHING)
1
Topical hyaluronic acid therapy is medically useful
for accelerating the regeneration of gingiva in the
following indications:
– Professional cleaning:
Small mechanical soft tissue injuries in the
interdental spaces
– Gingival retraction:
To stabilize and accelerate regeneration of the gingiva following exposure of the preparation margin (e.g. with expasyl)
– Bleaching / Whitening:
Strongly caustic bleaching gels coming into con
tact with the oral mucosa, especially the papillae
Below, we illustrate the use of HYADENT following
bleaching – the most important and most common
procedure.
2
Bleaching / Whitening
Most bleaching gels contain hydrogen peroxide or carbamide peroxide
(the modes of action of which are almost identical). As well as the desired effect of bleaching the teeth, both substances can also frequently
exert unwanted effects on the mucosal tissue surrounding the teeth.
Despite the care taken and protective measures employed by the
dentist, irritation of the mucosa is very common. Recent clinical results
call for a reevaluation of this procedure.
In addition to the DGZMK’s 2001 statement, a notable review has been
published (Hasson et al., Cochrane Database Syst Rev 2006) which
takes a systematic look at available publications and calls for a critical
reevaluation of our current knowledge. The review found that 45.9% of
8143 participating dentists evaluated mucosal irritation as a side effect
of tooth whitening treatments. An EU recommendation on hydrogen
peroxide-based bleaches and oral hygiene products (Dec. 2007) gives
added urgency to the need to reevaluate this treatment.
3
4
Targeted soft tissue regeneration through topical
application of HYADENT hyaluronic acid gel is carried out in the same way as bleaching using a splint
(figs. 3 and 4). In contrast to a bleaching splint (figs.
1 and 2), the tissue care splint also covers areas of
the gingiva which have come into contact with the
bleaching gel during bleaching. Soft tissues are
able to undergo complete healing.
To achieve rapid and effective regeneration of
affected gingiva, in particular healing of in some
cases anemic papillae, HYADENT hyaluronic acid
gel should be applied, in combination with wearing
a special splint for 6-11 hours (night or day). Wearing
the splint for the recommended period ensures
complete resorption of the hyaluronic acid gel by
the gingiva, facilitating optimum tissue regeneration.
Continued overleaf
Here again, HYADENT offers a solution with key benefits. Specific
TISSUE CARE application of HYADENT after bleaching may prevent
mucosal irritation.
1 Bleaching splint
2 Bleaching splint (cross section)
3 Tissue care splint
4 Tissue care splint (cross section)
VIII
VIII
TREATMENT PROCEDURE
1
4
2
5
4 Tissue care splint is filled
with HYADENT
1 Filled bleaching splint
is applied
2 Bleaching in process
5 Tissue care splint covers
anemic papillae
3 Anemic soft tissue
following bleaching
6 Regenerated soft tissue following
HYADENT application
3
VIII
6
VIII
OVERVIEW OF USAGE
HYADENT
HYADENT
barrier gel
USAGE
USAGE
USE IN GENERAL ORAL SURGERY:
Anti‐inflammatory properties for assisting and
accelerating wound healing
X
–
X
–
Prevention and improved safety following
surgical procedures as a result of antiseptic,
bacteriostatic effect in the wound area
X
–
X
–
Increase in production of fibroblasts
X
–
X
–
Increase in production of osteoblasts
X
–
X
–
USE IN IMPLANTOLOGY
Reducing scar formation in esthetically demanding
areas by reducing collagen deposition
X
Cover the wound area by applying the gel
into the wound immediately prior to wound
closure (suture)
Papilla reconstruction to correct ‘black triangle’
in the interdental area
Barrier effect to shield bone defects, in particular
following augmentation with bone graft material
Improve localization and prevent displacement
of augmentation material (granules)
Support and accelerate wound healing following
implantology procedures (the clot is stabilized
by the hydrophilic properties of HA, resulting in
faster, complication‐free tissue regeneration)
Socket Preservation
X
Application of the gel after enrichment with
the augmentation material (e.g. BioOss)
X
Application of the gel after enrichment with
the augmentation material (e.g. BioOss) /
after the defect has been completely covered
X
Application into the extraction alveolus or
to moisten a collagen plug or tape
Reducing scar formation in esthetically
demanding areas after implantation
X
Injection of HA preparation into the soft
tissue (approx. 0.2 ml) – treatment may
need to be repeated
X
Completely cover the wound area by
applying the gel into the wound immediately
prior to wound closure (suture)
REFERENCES:
HIGH PRODUCT QUALITY
HYADENT is manufactured in Germany under strict
controls, using a proven process, in conditions of
maximum biological purity. Each production batch
is individually tested for cytotoxicity to ensure that
the product is as pure and efficacious as possible.􀀃
EXTREMELY WELL TOLERATED􀀃
Hyaluronic acid is safe to use. The literature
contains no evidence of any negative effect on
the immune response from topical treatment with
hyaluronic acid. Intolerance of hyaluronic acid has
not been reported.􀀃
DOSAGE FORM
X
USE IN PERIODONTAL INDICATIONS
Benefits of HYADENT
Completely cover the wound area
with HYADENT barrier gel
PRODUCT
HYADENT
HYADENT barrier gel
PRODUCT TYPE
Single‐use syringe /
direct application option
Single‐use syringe /
direct application option
PACKAGING
Sterile blister
Sterile blister
Aiding the regenerative process following
periodontal procedures by means of
bacteriostatic effect
X
Application of the gel into the gingival pocket
immediately following surgical treatment
Increasing bone level following HA‐assisted
periodontal therapy
X
Application of the gel into the gingival pocket
immediately following surgical treatment
UNIT VOLUME
1 x 1 ml
1 x 1 ml
Significant improvement in SBI
(sulcus bleeding index) score
X
Application of the gel into the gingival pocket
immediately following surgical treatment
APPLICATION
Blunt, angulated cannula
Blunt, straight cannula
IX
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
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Galgut P: The role of hyaluronic aciTd in managing inflammation in
periodontaI diseases. Dental Health 42, 3–6
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45, 26–31 (2006)
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reconstruction of advanced alveolar ridge defects in dogs. A pilot study.
J Periodontol 72, 651–658 (2001)
Jentsch H, Pomowski R, Kundt G, Gocke R: Treatment of gingivitis with
hyaluronan. J Clin Periodontol 30, 159–164 (2003)
Klinger MM, Rahemtulla F, Prince CW, Lucas LC, Lemons JE: Proteoglycans
at the bone-implant interface. Crit Rev Oral Biol Med 9, 449–463 (1998)
Longaker MT, Chiu ES, Adzick NS, Stern M, Harrison MR, Stern R: Studies in
fetal wound healing. V. A prolonged presence of hyaluronic acid characterizes fetal wound fluid. Ann Surg 213, 292–296 (1991)
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vitro. J Dent Res 71 (IADR Abstracts), Abstract 471 (1992)
Pilloni A, Bernard GW: The effect of hyaluronan on mouse intramembranous osteogenesis in vitro. Cell Tissue Res 294, 323–333 (1998)
Pirnazar P, Wolinsky L, Nachnani S, Haake S, Pilloni A, Bernard GW:
Bacteriostatic effects of hyaluronic acid. J Periodontol 70, 370–374 (1999)
Pomowski R, Gocke R, Jentsch H: Treatment of gingivitis with hyaluronan.
J Dent Res A-453 (2002)
Prehm P: Hyaluronate is synthesized at plasma membranes. Biochem J 220, 597–600 (1984)
Rabasseda X: The therapeutic role of hyaluronic acid.
Drugs of today Suppl. III, 1–21 (1998)
Sasaki T, Watanabe C: Stimulation of osteoinduction in bone wound healing
by high-molecular hyaluronic acid. Bone 16, 9–15 (1995)
Schwartz Z, Goldstein M, Raviv E, Hirsch A, Ranly DM, Boyan BD: Clinical evaluation of demineralized bone allograft in a hyaluronic acid carrier for sinus lift augmentation in humans: a computed tomography and histomorphometric
study. Clin Oral Implants Res 18, 204–211 (2007)
Tammi R, Tammi M, Hakkinen L, Larjava H: Histochemical localization of
hyaluronate in human oral epithelium using a specific hyaluronate-binding
probe. Arch Oral Biol 35, 219–224 (1990)
van den Bogaerde L: Behandlung von intraossären Parodontaldefekten mit
veresterter Hyaluronsäure: Klinischer Bericht über 19 nacheinander
behandlete Läsionen. Int J Paro Rest ZHK 29 3, 299–307 (2009)
Weigel PH, Fuller GM, LeBoeuf RD: A model for the role of hyaluronic acid and fibrin in the early events during the inflammatory response and wound healing.
J Theor Biol 119, 219–234 (1986)Biol Med 9, 449–463 (1998)
IX
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Denmark
+45 3131 1925
www.puredent.dk
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MANUFATURER
BioScience GmbH
Rheinstraße 96
56235 Ransbach-Baumbach | Germany
www.bio-science.org
[email protected]