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Hyaluronic acid the biological power in dentistry

CONTENTS

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-4 ridge/socket preservation
in
V-5 open healing of an implant
in
VI HYADENT: use in
periodontal therapy

and indications

VII HYADENT in
esthetic reconstruction

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: roliferative phase
P

(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.

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:
peeds up wound healing
S
after surgical procedures

Effect:
hields the wound area from penetration
S
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.

The modified viscosity and short resorption time


(612 hours) ensures complete absorption by the
surrounding tissue. Appropriate and correctly executed suturing technique can prevent the gel from
being rinsed away by saliva.

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)

USE IN APICOECTOMY

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

1 Applying HYADENT prior


to wound closure
2 Applying HYADENT for open
healing of an implant

1)

Maienfisch A: Langzeiterfahrungen mit der Wurzelspitzenresektion. Med. Diss., Zrich (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).

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 (1621 days for cross-linked
hyaluronic acid).
2

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

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

5 After filling the defect


4

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.

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.

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

11

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

V-5

Using HYADENT barrier gel also significantly


reduces scar tissue formation.

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. HYADENTs 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
710 days after initial application. As a supplement
to mechanical treatment, its use leads to a statis-

2)

VI

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 intraossren Parodontaldefekten mit veresterter Hyaluronsure:
Klinischer Bericht ber 19 nacheinander behandelte Lsionen. 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.

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.

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 DGZMKs 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.

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 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

VIII

OVERVIEW OF USAGE

HYADENT

HYADENT
barrier gel

USAGE

USAGE

USE IN GENERAL ORAL SURGERY:


Antiinflammatory properties for assisting and
accelerating wound healing

Prevention and improved safety following


surgical procedures as a result of antiseptic,
bacteriostatic effect in the wound area

Increase in production of osteoblasts

REFERENCES:

Increase in production of fibroblasts

Benefits of HYADENT

USE IN IMPLANTOLOGY
Reducing scar formation in esthetically demanding
areas by reducing collagen deposition

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, complicationfree tissue regeneration)

Socket Preservation

Application of the gel after enrichment with


the augmentation material (e.g. BioOss) /
after the defect has been completely covered

Completely cover the wound area by


applying the gel into the wound immediately
prior to wound closure (suture)

Application of the gel after enrichment with


the augmentation material (e.g. BioOss)

Injection of HA preparation into the soft


tissue (approx. 0.2 ml) treatment may
need to be repeated

Application into the extraction alveolus or


to moisten a collagen plug or tape

Reducing scar formation in esthetically


demanding areas after implantation

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

Completely cover the wound area


with HYADENT barrier gel

HYADENT

HYADENT barrier gel

PRODUCT TYPE

USE IN PERIODONTAL INDICATIONS

PRODUCT

Singleuse syringe /
direct application option

Singleuse syringe /
direct application option

PACKAGING

Sterile blister

Sterile blister

Aiding the regenerative process following


periodontal procedures by means of
bacteriostatic effect

Application of the gel into the gingival pocket


immediately following surgical treatment

Increasing bone level following HAassisted


periodontal therapy

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

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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The effect of hyaluronan on bone and soft tissue and immune response in
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45, 2631 (2006)
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J Periodontol 72, 651658 (2001)
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Bacteriostatic effects of hyaluronic acid. J Periodontol 70, 370374 (1999)
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by high-molecular hyaluronic acid. Bone 16, 915 (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, 204211 (2007)
Tammi R, Tammi M, Hakkinen L, Larjava H: Histochemical localization of
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veresterter Hyaluronsure: Klinischer Bericht ber 19 nacheinander
behandlete Lsionen. Int J Paro Rest ZHK 29 3, 299307 (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, 219234 (1986)Biol Med 9, 449463 (1998)

IX

EXCLUSIVE DISTRIBUTORS

Germany / Europe / CIS:

Middle East Region:

Naturelize GmbH
www.naturelize.com
customer.service@naturelize.com

Elaf Medical Supplies Co.


www.elaf-me.com
info@elaf-me.com

Japan:

Asia-Pacific Region:

PRSS Japan. Co.,Ltd


www.prss-i.com
info@prss.jp

Skin M.D. Pte Ltd


www.skin-md.net
info@skin-md.net

MANUFACTURER

BioScience GmbH
Rheinstrae 96
56235 Ransbach-Baumbach | Germany
www.bio-science.org
info@bio-science.org