Hyaluronic acid ndash the biological power in dentistry

CONTENTS I Hyaluronic acid natural wound healing

II Hyaluronic acid supporting tissue retention

III HYADENT for targeted tissue regeneration

IV HYADENT products and indications

V HYADENT use in wound healing and implantology

V-1 in apicoectomy

V-2 in GTRGBR

V-3 in sinus elevation

V-4 in ridgesocket preservation

V-5 in open healing of an implant

VI HYADENT use in periodontal therapy

VII HYADENT in esthetic reconstruction

VIII HYADENT as a preventive treatment

IX Benefits of HYADENT

Hyaluronic acid is an important component of the human organism and is involved in almost all rege-nerative 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-ani-mal 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)

HYALURONIC ACID supporting tissue retention

Hyaluronic acid is a natural polysaccharide and amember 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 for-med at the cell membrane and excreted directly into the extracellular matrix

Hyaluronic acid is a major component of the extra-cellular matrix in almost all tissues As such its pri-mary role is to bind water to permit the transporta-tion of key metabolites and maintain tissue structure

Hyaluronic acid activates metalloproteinase inhibi-tors thus suppressing tissue breakdown A similar effect is produced by the inhibition of inflammatory cytokines (eg TNF) Hyaluronic acid can thus visibly contribute to tissue retention

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 anti-oxidative 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 keratinocy-tes (via the CD44 cell surface receptor) Regulation of keratinocyte proliferation also occurs Epithelialization is both stimulated and regulated

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 ndash scar formation ndash 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

HYALURONIC ACID natural wound healing

I II

HYADENT for targeted tissue regeneration

III IV

We have now found a way of utilizing the mechanism of ac-tion 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

ndash What objective is the application of the hyaluronic acid product intended to achieve (Effect)

ndash Over what time frame are the effects of hyaluronic acid required (Resorption period)

III

HYADENT products and indications

For a detailed overview of HYADENT indications see also chapter IX

Effect Shields the wound area from penetration of bacteria and connective tissue

Papilla reconstruction

Resorption period 16 ndash21 days

CROSS-LINKED HYALURONIC ACID

Effect Speeds up wound healing after surgical procedures

Supplements and enhances periodontal surgical treatment

Reduces scar tissue

Activates bone regeneration material to accelerate osteogenesis and prevents displacement of the granules

Optimizes procedures for ridgesocket preservation

Resorption period 6 ndash11 hours

NON CROSS-LINKED HYALURONIC ACID

To support and accelerate wound healing HYA-DENT 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 04 x 18 mm) Angulation of the cannula per-mits 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

After surgical extraction of a tooth apicoectomy is the second most common oral surgical procedure A good prognosis ndash 85 success rate over 3 to 6 years ndash makes this procedure where the correct indi-cations for its use are present an excellent option forretaining natural teeth 1)

The modified viscosity and short resorption time (6ndash12 hours) ensures complete absorption by the surrounding tissue Appropriate and correctly exe-cuted suturing technique can prevent the gel from being rinsed away by saliva

HYADENT use in wound healing and implantology

V

1 Applying HYADENT prior to wound closure

2 Applying HYADENT for open healing of an implant

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 HYADENT1048579

6 Covering the wound area with HYADENT barrier gel

USE IN APICOECTOMY

1) Maienfisch A Langzeiterfahrungen mit der Wurzelspitzenresektion Med Diss Zuumlrich (1980)

5

6

3

V-1

1

2

1

2

4

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 manyindications 1)

HYADENT Hyaluronic acid increases osteoblast formation thereby reducing the time required for new bone formation by means of osseointegrati-on stimulating effects 2) The use of HYADENT in sinus elevation surgery ndash nowadays a standard procedure ndash offers numerous benefits for both surgeon and patient

V-2

Application of HYADENT barrier gel to augmented bone

1 Extraoral enrichment of the granules

2 Granules ready to use

3 Application of the gel barrier

USE IN SINUS LIFTS

1) Weigel PH Fuller GM LeBoeuf RD A model for the role of hyaluronic acid and fibrin in the earlyevents during the inflammatory response and wound healing J Theor Biol 119 219-234 (1986)

3

V-3

1

2

2) 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 204211 (2007)

3) Source Dental Clinics Journal Of General Dentistry ldquoHyaluronic acid biological effects and clinical applicationsrdquo Demarosi F Sardella A Lodi G Carrassi A

USE IN GTR GBR

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 riskIn 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 (16ndash21 days for cross-linked hyaluronic acid)

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 possi-ble 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

V-4

Without socket preservation

1 Six weeks post-extraction marked vertical and horizontal resorption

2 Buccal resorption in the alveolar region six weeks post-extraction

3 Moistened collagen sponge

4 After extraction

5 After filling the defect

USE IN RIDGESOCKET PRESERVATION

54

3

V-4

21

The following example illustrates how using HYA-DENT barrier gel can optimize soft tissue manage-ment 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

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

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 implan-tation 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

Using HYADENT barrier gel also significantly reduces scar tissue formation

V-5

1 Initial situation

2 Missing lateral incisor

3 Implantation opening a lateral decompression incision

4 Immediate implant closure using a gingiva former

5 Sutureless wound closure with HYADENT barrier gel

6 Completely filled soft tissue defect

7 3 months post-implantation

8 The papilla has been fully preserved

9 Impression using repositioning technique

10 X-ray shows no loss of bone

11 Clinical crown after insertion

12 Final state1048579

USE IN OPEN HEALING OF AN IMPLANT

4

5

6

7 10

8

9

2

3

1 12

V-5

11

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-inflammato-ries and systemic antibiotics are therefore employed in treating periodontal disease Sub or supragingival application of hyaluronic acid (one of four glycosa-minoglycans in gingival tissue) can also be a suc-cessful additional therapeutic measure for treatingperiodontal disease HYADENTrsquos bacteriostatic properties (especially against Actinobacillus actio-nomyecetemcomitans Prevotella intermedia and Staphylococcus aureus) aid tissue regeneration 2)

In addition periodontal therapy with hyaluronic acid support has been shown to achievean increase in bone level 3)

The angulated cannula makes HYADENT simple and effective to apply In addition to manual supra-gingival and subgingival scaling and root planing of all affected teeth systematic periodontitis treatment involves the sub or supragingival application ofHYADENT HYADENT should then be reapplied 7ndash10 days after initial application As a supplement to mechanical treatment its use leads to a statis-

VI

HYADENT application in the periodontal pocket

1 Initial situation2 Approx 3 weeks after the second injection

VII

1) Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159-164 (2003) 2) 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 3-63) van den Bogaerde L MD DDS Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure

Klinischer Bericht uumlber 19 nacheinander behandelte Laumlsionen Int J Paro amp Rest ZHK 29 3 299-307 (2009)

HYADENT use in periodontal therapy

HYADENT in esthetic reconstruction

Many studies have comprehensively documented the positive clinical outcomes of modern implan-tology The use of modern treatment concepts and improved materials has dramatically expan-ded options for nature-identical esthetic recon-struction 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

HYADENT barrier gel offers dentists a genuine alternative to difficult and lengthy surgical procedures

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 (23G06 x 25 mm) To achieve the desired effect in full the injection may be repeated after about 3 weeksSurgical procedures which result in unwanted scarring are no longer necessary Patients are spared a painful treatment and the limitations it imposes1048579

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 proce-dures come a distinct second

1 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

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

Topical hyaluronic acid therapy is medically useful for accelerating the regeneration of gingiva in the following indications

ndash Professional cleaning Small mechanical soft tissue injuries in the interdental spaces

ndash Gingival retraction To stabilize and accelerate regeneration of the gingiva following exposure of the preparation margin (eg with expasyl)

ndash 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 ndash the most important and most common procedure

Targeted soft tissue regeneration through topical application of HYADENT hyaluronic acid gel is car-ried 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 areable 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

VIII VIII

HYADENT as a preventive treatment

Bleaching Whitening

Most bleaching gels contain hydrogen peroxide or carbamide peroxide (the modes of action of which are almost identical) As well as the desi-red 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 thedentist irritation of the mucosa is very common Recent clinical results call for a reevaluation of this procedure

In addition to the DGZMKrsquos 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 459 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

Here again HYADENT offers a solution with key benefits Specific TISSUE CARE application of HYADENT after bleaching may prevent mucosal irritation

1 2

3 4

TISSUE CARE FOLLOWING BLEACHINGWHITENING TREATMENT (HOME BLEACHING)

1 Bleaching splint

2 Bleaching splint (cross section)

3 Tissue care splint

4 Tissue care splint (cross section)

6

5

1 Filled bleaching splint is applied

2 Bleaching in process

3 Anemic soft tissue following bleaching

4 Tissue care splint is filled with HYADENT

5 Tissue care splint covers anemic papillae

6 Regenerated soft tissue following HYADENT application

4

2

1

3

VIII VIII

TREATMENT PROCEDURE

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 possible1048579

HIGH PRODUCT QUALITY

PRODUCT HYADENT HYADENT barrier gel

PRODUCT TYPESingle1048579use syringe direct application option

Single1048579use syringe direct application option

PACKAGING Sterile blister Sterile blister

UNIT VOLUME 1 x 1 ml 1 x 1 ml

APPLICATION Blunt angulated cannula Blunt straight cannula

DOSAGE FORM

REFERENCES

1 Bartold PM Proteoglycans of the periodontium structure role and function J Periodontal Res 22 431ndash444 (1987)2 Campoccia D Doherty P Radice M Brun P Abatangelo G Williams DF Semi synthetic resorbable materials from hyaluronan esterification Biomaterials 19 2101ndash2127 (1998)3 Chen WY Abatangelo G Functions of hyaluronan in wound repair Wound Repair Regen 7 79ndash89 (1999)4 Engstrom PE Shi XQ Tronje G Larsson A Welander U Frithiof L Engstrom GN The effect of hyaluronan on bone and soft tissue and immune response in wound healing J Periodontol 72 1192ndash1200 (2001)5 Galgut P The role of hyaluronic aciTd in managing inflammation in periodontaI diseases Dental Health 42 3ndash6 6 Hoppe H-D Wund(er)mit tel Hyaluronsaumlure Die Schwester Der Pfleger 45 26ndash31 (2006)7 Hunt DR Jovanovic SA Wikesjo UM Wozney JM Bernard GW Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs A pilot study J Periodontol 72 651ndash658 (2001)8 Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159ndash164 (2003)9 Klinger MM Rahemtulla F Prince CW Lucas LC Lemons JE Proteoglycans at the bone-implant interface Crit Rev Oral Biol Med 9 449ndash463 (1998)10 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 292ndash296 (1991)11 Marinucci L Lilli C Baroni T Becchetti E Belcastro S Balducci C Locci P In vitro comparison of bioabsorbable and non-resorbable membranes in bone regeneration J Periodontol 72 753ndash759 (2001)12 Pilloni A Low molecular weight hyaluronic acid increases osteogenesis in vitro J Dent Res 71 (IADR Abstracts) Abstract 471 (1992)13 Pilloni A Bernard GW The effect of hyaluronan on mouse intramembranous osteogenesis in vitro Cell Tissue Res 294 323ndash333 (1998)14 Pirnazar P Wolinsky L Nachnani S Haake S Pilloni A Bernard GW Bacteriostatic effects of hyaluronic acid J Periodontol 70 370ndash374 (1999)15 Pomowski R Gocke R Jentsch H Treatment of gingivitis with hyaluronan J Dent Res A-453 (2002)16 Prehm P Hyaluronate is synthesized at plasma membranes Biochem J 220 597ndash600 (1984)17 Rabasseda X The therapeutic role of hyaluronic acid Drugs of today Suppl III 1ndash21 (1998)18 Sasaki T Watanabe C Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid Bone 16 9ndash15 (1995)19 Schwartz Z Goldstein M Raviv E Hirsch A Ranly DM Boyan BD Clinical evalu- ation of demineralized bone allograft in a hyaluronic acid carrier for sinus lif t augmentation in humans a computed tomography and histomorphometric study Clin Oral Implants Res 18 204ndash211 (2007)20 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 219ndash224 (1990)21 van den Bogaerde L Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure Klinischer Bericht uumlber 19 nacheinander behandlete Laumlsionen Int J Paro Rest ZHK 29 3 299ndash307 (2009)22 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 219ndash234 (1986)Biol Med 9 449ndash463 (1998)

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 reported1048579

EXTREMELY WELL TOLERATED1048579

Benefits of HYADENT

IXIX

OVERVIEW OF USAGE HYADENT USAGE HYADENT barrier gel USAGE

USE IN GENERAL ORAL SURGERY

Anti1048579inflammatory properties for assisting andaccelerating wound healing X ndash X ndash

Prevention and improved safety followingsurgical procedures as a result of antisepticbacteriostatic effect in the wound area

X ndash X ndash

Increase in production of fibroblasts X ndash X ndash

Increase in production of osteoblasts X ndash X ndash

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 lsquoblack trianglersquoin the interdental area X

Injection of HA preparation into the softtissue (approx 02 ml) ndash treatment may need to be repeated

Barrier effect to shield bone defects in particular following augmentation with bone graft material X

Completely cover the wound area by applying the gel into the wound immediately prior to wound closure (suture)

Improve localization and prevent displacementof augmentation material (granules) X

Application of the gel after enrichment with the augmentation material (eg BioOss)

Support and accelerate wound healing followingimplantology procedures (the clot is stabilizedby the hydrophilic properties of HA resulting infaster complication1048579free tissue regeneration)

X

Application of the gel after enrichment with the augmentation material (eg BioOss) after the defect has been completely covered

Socket Preservation X Application into the extraction alveolus orto moisten a collagen plug or tape

Reducing scar formation in estheticallydemanding areas after implantation X Completely cover the wound area

with HYADENT barrier gel

USE IN PERIODONTAL INDICATIONS

Aiding the regenerative process followingperiodontal procedures by means ofbacteriostatic effect

X Application of the gel into the gingival pocketimmediately following surgical treatment

Increasing bone level following HA1048579assistedperiodontal therapy X Application of the gel into the gingival pocket

immediately following surgical treatment

Significant improvement in SBI (sulcus bleeding index) score X Application of the gel into the gingival pocket

immediately following surgical treatment

Naturelize GmbHwwwnaturelizecomcustomerservicenaturelizecom

PRSS Japan CoLtdwwwprss-icominfoprssjp

Skin MD Pte Ltdwwwskin-mdnetinfoskin-mdnet

Elaf Medical Supplies Cowwwelaf-mecominfoelaf-mecom

Germany Europe CIS

Japan

Middle East Region

Asia-Pacific Region

BioScience GmbHRheinstraszlige 9656235 Ransbach-Baumbach | Germanywwwbio-scienceorginfobio-scienceorg

EXCLUSIVE DISTRIBUTORS

MANUFACTURER

CONTENTS I Hyaluronic acid natural wound healing

II Hyaluronic acid supporting tissue retention

III HYADENT for targeted tissue regeneration

IV HYADENT products and indications

V HYADENT use in wound healing and implantology

V-1 in apicoectomy

V-2 in GTRGBR

V-3 in sinus elevation

V-4 in ridgesocket preservation

V-5 in open healing of an implant

VI HYADENT use in periodontal therapy

VII HYADENT in esthetic reconstruction

VIII HYADENT as a preventive treatment

IX Benefits of HYADENT

Hyaluronic acid is an important component of the human organism and is involved in almost all rege-nerative 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-ani-mal 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)

HYALURONIC ACID supporting tissue retention

Hyaluronic acid is a natural polysaccharide and amember 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 for-med at the cell membrane and excreted directly into the extracellular matrix

Hyaluronic acid is a major component of the extra-cellular matrix in almost all tissues As such its pri-mary role is to bind water to permit the transporta-tion of key metabolites and maintain tissue structure

Hyaluronic acid activates metalloproteinase inhibi-tors thus suppressing tissue breakdown A similar effect is produced by the inhibition of inflammatory cytokines (eg TNF) Hyaluronic acid can thus visibly contribute to tissue retention

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 anti-oxidative 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 keratinocy-tes (via the CD44 cell surface receptor) Regulation of keratinocyte proliferation also occurs Epithelialization is both stimulated and regulated

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 ndash scar formation ndash 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

HYALURONIC ACID natural wound healing

I II

HYADENT for targeted tissue regeneration

III IV

We have now found a way of utilizing the mechanism of ac-tion 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

ndash What objective is the application of the hyaluronic acid product intended to achieve (Effect)

ndash Over what time frame are the effects of hyaluronic acid required (Resorption period)

III

HYADENT products and indications

For a detailed overview of HYADENT indications see also chapter IX

Effect Shields the wound area from penetration of bacteria and connective tissue

Papilla reconstruction

Resorption period 16 ndash21 days

CROSS-LINKED HYALURONIC ACID

Effect Speeds up wound healing after surgical procedures

Supplements and enhances periodontal surgical treatment

Reduces scar tissue

Activates bone regeneration material to accelerate osteogenesis and prevents displacement of the granules

Optimizes procedures for ridgesocket preservation

Resorption period 6 ndash11 hours

NON CROSS-LINKED HYALURONIC ACID

To support and accelerate wound healing HYA-DENT 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 04 x 18 mm) Angulation of the cannula per-mits 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

After surgical extraction of a tooth apicoectomy is the second most common oral surgical procedure A good prognosis ndash 85 success rate over 3 to 6 years ndash makes this procedure where the correct indi-cations for its use are present an excellent option forretaining natural teeth 1)

The modified viscosity and short resorption time (6ndash12 hours) ensures complete absorption by the surrounding tissue Appropriate and correctly exe-cuted suturing technique can prevent the gel from being rinsed away by saliva

HYADENT use in wound healing and implantology

V

1 Applying HYADENT prior to wound closure

2 Applying HYADENT for open healing of an implant

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 HYADENT1048579

6 Covering the wound area with HYADENT barrier gel

USE IN APICOECTOMY

1) Maienfisch A Langzeiterfahrungen mit der Wurzelspitzenresektion Med Diss Zuumlrich (1980)

5

6

3

V-1

1

2

1

2

4

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 manyindications 1)

HYADENT Hyaluronic acid increases osteoblast formation thereby reducing the time required for new bone formation by means of osseointegrati-on stimulating effects 2) The use of HYADENT in sinus elevation surgery ndash nowadays a standard procedure ndash offers numerous benefits for both surgeon and patient

V-2

Application of HYADENT barrier gel to augmented bone

1 Extraoral enrichment of the granules

2 Granules ready to use

3 Application of the gel barrier

USE IN SINUS LIFTS

1) Weigel PH Fuller GM LeBoeuf RD A model for the role of hyaluronic acid and fibrin in the earlyevents during the inflammatory response and wound healing J Theor Biol 119 219-234 (1986)

3

V-3

1

2

2) 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 204211 (2007)

3) Source Dental Clinics Journal Of General Dentistry ldquoHyaluronic acid biological effects and clinical applicationsrdquo Demarosi F Sardella A Lodi G Carrassi A

USE IN GTR GBR

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 riskIn 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 (16ndash21 days for cross-linked hyaluronic acid)

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 possi-ble 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

V-4

Without socket preservation

1 Six weeks post-extraction marked vertical and horizontal resorption

2 Buccal resorption in the alveolar region six weeks post-extraction

3 Moistened collagen sponge

4 After extraction

5 After filling the defect

USE IN RIDGESOCKET PRESERVATION

54

3

V-4

21

The following example illustrates how using HYA-DENT barrier gel can optimize soft tissue manage-ment 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

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

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 implan-tation 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

Using HYADENT barrier gel also significantly reduces scar tissue formation

V-5

1 Initial situation

2 Missing lateral incisor

3 Implantation opening a lateral decompression incision

4 Immediate implant closure using a gingiva former

5 Sutureless wound closure with HYADENT barrier gel

6 Completely filled soft tissue defect

7 3 months post-implantation

8 The papilla has been fully preserved

9 Impression using repositioning technique

10 X-ray shows no loss of bone

11 Clinical crown after insertion

12 Final state1048579

USE IN OPEN HEALING OF AN IMPLANT

4

5

6

7 10

8

9

2

3

1 12

V-5

11

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-inflammato-ries and systemic antibiotics are therefore employed in treating periodontal disease Sub or supragingival application of hyaluronic acid (one of four glycosa-minoglycans in gingival tissue) can also be a suc-cessful additional therapeutic measure for treatingperiodontal disease HYADENTrsquos bacteriostatic properties (especially against Actinobacillus actio-nomyecetemcomitans Prevotella intermedia and Staphylococcus aureus) aid tissue regeneration 2)

In addition periodontal therapy with hyaluronic acid support has been shown to achievean increase in bone level 3)

The angulated cannula makes HYADENT simple and effective to apply In addition to manual supra-gingival and subgingival scaling and root planing of all affected teeth systematic periodontitis treatment involves the sub or supragingival application ofHYADENT HYADENT should then be reapplied 7ndash10 days after initial application As a supplement to mechanical treatment its use leads to a statis-

VI

HYADENT application in the periodontal pocket

1 Initial situation2 Approx 3 weeks after the second injection

VII

1) Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159-164 (2003) 2) 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 3-63) van den Bogaerde L MD DDS Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure

Klinischer Bericht uumlber 19 nacheinander behandelte Laumlsionen Int J Paro amp Rest ZHK 29 3 299-307 (2009)

HYADENT use in periodontal therapy

HYADENT in esthetic reconstruction

Many studies have comprehensively documented the positive clinical outcomes of modern implan-tology The use of modern treatment concepts and improved materials has dramatically expan-ded options for nature-identical esthetic recon-struction 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

HYADENT barrier gel offers dentists a genuine alternative to difficult and lengthy surgical procedures

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 (23G06 x 25 mm) To achieve the desired effect in full the injection may be repeated after about 3 weeksSurgical procedures which result in unwanted scarring are no longer necessary Patients are spared a painful treatment and the limitations it imposes1048579

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 proce-dures come a distinct second

1 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

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

Topical hyaluronic acid therapy is medically useful for accelerating the regeneration of gingiva in the following indications

ndash Professional cleaning Small mechanical soft tissue injuries in the interdental spaces

ndash Gingival retraction To stabilize and accelerate regeneration of the gingiva following exposure of the preparation margin (eg with expasyl)

ndash 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 ndash the most important and most common procedure

Targeted soft tissue regeneration through topical application of HYADENT hyaluronic acid gel is car-ried 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 areable 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

VIII VIII

HYADENT as a preventive treatment

Bleaching Whitening

Most bleaching gels contain hydrogen peroxide or carbamide peroxide (the modes of action of which are almost identical) As well as the desi-red 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 thedentist irritation of the mucosa is very common Recent clinical results call for a reevaluation of this procedure

In addition to the DGZMKrsquos 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 459 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

Here again HYADENT offers a solution with key benefits Specific TISSUE CARE application of HYADENT after bleaching may prevent mucosal irritation

1 2

3 4

TISSUE CARE FOLLOWING BLEACHINGWHITENING TREATMENT (HOME BLEACHING)

1 Bleaching splint

2 Bleaching splint (cross section)

3 Tissue care splint

4 Tissue care splint (cross section)

6

5

1 Filled bleaching splint is applied

2 Bleaching in process

3 Anemic soft tissue following bleaching

4 Tissue care splint is filled with HYADENT

5 Tissue care splint covers anemic papillae

6 Regenerated soft tissue following HYADENT application

4

2

1

3

VIII VIII

TREATMENT PROCEDURE

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 possible1048579

HIGH PRODUCT QUALITY

PRODUCT HYADENT HYADENT barrier gel

PRODUCT TYPESingle1048579use syringe direct application option

Single1048579use syringe direct application option

PACKAGING Sterile blister Sterile blister

UNIT VOLUME 1 x 1 ml 1 x 1 ml

APPLICATION Blunt angulated cannula Blunt straight cannula

DOSAGE FORM

REFERENCES

1 Bartold PM Proteoglycans of the periodontium structure role and function J Periodontal Res 22 431ndash444 (1987)2 Campoccia D Doherty P Radice M Brun P Abatangelo G Williams DF Semi synthetic resorbable materials from hyaluronan esterification Biomaterials 19 2101ndash2127 (1998)3 Chen WY Abatangelo G Functions of hyaluronan in wound repair Wound Repair Regen 7 79ndash89 (1999)4 Engstrom PE Shi XQ Tronje G Larsson A Welander U Frithiof L Engstrom GN The effect of hyaluronan on bone and soft tissue and immune response in wound healing J Periodontol 72 1192ndash1200 (2001)5 Galgut P The role of hyaluronic aciTd in managing inflammation in periodontaI diseases Dental Health 42 3ndash6 6 Hoppe H-D Wund(er)mit tel Hyaluronsaumlure Die Schwester Der Pfleger 45 26ndash31 (2006)7 Hunt DR Jovanovic SA Wikesjo UM Wozney JM Bernard GW Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs A pilot study J Periodontol 72 651ndash658 (2001)8 Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159ndash164 (2003)9 Klinger MM Rahemtulla F Prince CW Lucas LC Lemons JE Proteoglycans at the bone-implant interface Crit Rev Oral Biol Med 9 449ndash463 (1998)10 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 292ndash296 (1991)11 Marinucci L Lilli C Baroni T Becchetti E Belcastro S Balducci C Locci P In vitro comparison of bioabsorbable and non-resorbable membranes in bone regeneration J Periodontol 72 753ndash759 (2001)12 Pilloni A Low molecular weight hyaluronic acid increases osteogenesis in vitro J Dent Res 71 (IADR Abstracts) Abstract 471 (1992)13 Pilloni A Bernard GW The effect of hyaluronan on mouse intramembranous osteogenesis in vitro Cell Tissue Res 294 323ndash333 (1998)14 Pirnazar P Wolinsky L Nachnani S Haake S Pilloni A Bernard GW Bacteriostatic effects of hyaluronic acid J Periodontol 70 370ndash374 (1999)15 Pomowski R Gocke R Jentsch H Treatment of gingivitis with hyaluronan J Dent Res A-453 (2002)16 Prehm P Hyaluronate is synthesized at plasma membranes Biochem J 220 597ndash600 (1984)17 Rabasseda X The therapeutic role of hyaluronic acid Drugs of today Suppl III 1ndash21 (1998)18 Sasaki T Watanabe C Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid Bone 16 9ndash15 (1995)19 Schwartz Z Goldstein M Raviv E Hirsch A Ranly DM Boyan BD Clinical evalu- ation of demineralized bone allograft in a hyaluronic acid carrier for sinus lif t augmentation in humans a computed tomography and histomorphometric study Clin Oral Implants Res 18 204ndash211 (2007)20 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 219ndash224 (1990)21 van den Bogaerde L Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure Klinischer Bericht uumlber 19 nacheinander behandlete Laumlsionen Int J Paro Rest ZHK 29 3 299ndash307 (2009)22 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 219ndash234 (1986)Biol Med 9 449ndash463 (1998)

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 reported1048579

EXTREMELY WELL TOLERATED1048579

Benefits of HYADENT

IXIX

OVERVIEW OF USAGE HYADENT USAGE HYADENT barrier gel USAGE

USE IN GENERAL ORAL SURGERY

Anti1048579inflammatory properties for assisting andaccelerating wound healing X ndash X ndash

Prevention and improved safety followingsurgical procedures as a result of antisepticbacteriostatic effect in the wound area

X ndash X ndash

Increase in production of fibroblasts X ndash X ndash

Increase in production of osteoblasts X ndash X ndash

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 lsquoblack trianglersquoin the interdental area X

Injection of HA preparation into the softtissue (approx 02 ml) ndash treatment may need to be repeated

Barrier effect to shield bone defects in particular following augmentation with bone graft material X

Completely cover the wound area by applying the gel into the wound immediately prior to wound closure (suture)

Improve localization and prevent displacementof augmentation material (granules) X

Application of the gel after enrichment with the augmentation material (eg BioOss)

Support and accelerate wound healing followingimplantology procedures (the clot is stabilizedby the hydrophilic properties of HA resulting infaster complication1048579free tissue regeneration)

X

Application of the gel after enrichment with the augmentation material (eg BioOss) after the defect has been completely covered

Socket Preservation X Application into the extraction alveolus orto moisten a collagen plug or tape

Reducing scar formation in estheticallydemanding areas after implantation X Completely cover the wound area

with HYADENT barrier gel

USE IN PERIODONTAL INDICATIONS

Aiding the regenerative process followingperiodontal procedures by means ofbacteriostatic effect

X Application of the gel into the gingival pocketimmediately following surgical treatment

Increasing bone level following HA1048579assistedperiodontal therapy X Application of the gel into the gingival pocket

immediately following surgical treatment

Significant improvement in SBI (sulcus bleeding index) score X Application of the gel into the gingival pocket

immediately following surgical treatment

Naturelize GmbHwwwnaturelizecomcustomerservicenaturelizecom

PRSS Japan CoLtdwwwprss-icominfoprssjp

Skin MD Pte Ltdwwwskin-mdnetinfoskin-mdnet

Elaf Medical Supplies Cowwwelaf-mecominfoelaf-mecom

Germany Europe CIS

Japan

Middle East Region

Asia-Pacific Region

BioScience GmbHRheinstraszlige 9656235 Ransbach-Baumbach | Germanywwwbio-scienceorginfobio-scienceorg

EXCLUSIVE DISTRIBUTORS

MANUFACTURER

Hyaluronic acid is an important component of the human organism and is involved in almost all rege-nerative 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-ani-mal 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)

HYALURONIC ACID supporting tissue retention

Hyaluronic acid is a natural polysaccharide and amember 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 for-med at the cell membrane and excreted directly into the extracellular matrix

Hyaluronic acid is a major component of the extra-cellular matrix in almost all tissues As such its pri-mary role is to bind water to permit the transporta-tion of key metabolites and maintain tissue structure

Hyaluronic acid activates metalloproteinase inhibi-tors thus suppressing tissue breakdown A similar effect is produced by the inhibition of inflammatory cytokines (eg TNF) Hyaluronic acid can thus visibly contribute to tissue retention

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 anti-oxidative 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 keratinocy-tes (via the CD44 cell surface receptor) Regulation of keratinocyte proliferation also occurs Epithelialization is both stimulated and regulated

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 ndash scar formation ndash 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

HYALURONIC ACID natural wound healing

I II

HYADENT for targeted tissue regeneration

III IV

We have now found a way of utilizing the mechanism of ac-tion 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

ndash What objective is the application of the hyaluronic acid product intended to achieve (Effect)

ndash Over what time frame are the effects of hyaluronic acid required (Resorption period)

III

HYADENT products and indications

For a detailed overview of HYADENT indications see also chapter IX

Effect Shields the wound area from penetration of bacteria and connective tissue

Papilla reconstruction

Resorption period 16 ndash21 days

CROSS-LINKED HYALURONIC ACID

Effect Speeds up wound healing after surgical procedures

Supplements and enhances periodontal surgical treatment

Reduces scar tissue

Activates bone regeneration material to accelerate osteogenesis and prevents displacement of the granules

Optimizes procedures for ridgesocket preservation

Resorption period 6 ndash11 hours

NON CROSS-LINKED HYALURONIC ACID

To support and accelerate wound healing HYA-DENT 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 04 x 18 mm) Angulation of the cannula per-mits 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

After surgical extraction of a tooth apicoectomy is the second most common oral surgical procedure A good prognosis ndash 85 success rate over 3 to 6 years ndash makes this procedure where the correct indi-cations for its use are present an excellent option forretaining natural teeth 1)

The modified viscosity and short resorption time (6ndash12 hours) ensures complete absorption by the surrounding tissue Appropriate and correctly exe-cuted suturing technique can prevent the gel from being rinsed away by saliva

HYADENT use in wound healing and implantology

V

1 Applying HYADENT prior to wound closure

2 Applying HYADENT for open healing of an implant

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 HYADENT1048579

6 Covering the wound area with HYADENT barrier gel

USE IN APICOECTOMY

1) Maienfisch A Langzeiterfahrungen mit der Wurzelspitzenresektion Med Diss Zuumlrich (1980)

5

6

3

V-1

1

2

1

2

4

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 manyindications 1)

HYADENT Hyaluronic acid increases osteoblast formation thereby reducing the time required for new bone formation by means of osseointegrati-on stimulating effects 2) The use of HYADENT in sinus elevation surgery ndash nowadays a standard procedure ndash offers numerous benefits for both surgeon and patient

V-2

Application of HYADENT barrier gel to augmented bone

1 Extraoral enrichment of the granules

2 Granules ready to use

3 Application of the gel barrier

USE IN SINUS LIFTS

1) Weigel PH Fuller GM LeBoeuf RD A model for the role of hyaluronic acid and fibrin in the earlyevents during the inflammatory response and wound healing J Theor Biol 119 219-234 (1986)

3

V-3

1

2

2) 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 204211 (2007)

3) Source Dental Clinics Journal Of General Dentistry ldquoHyaluronic acid biological effects and clinical applicationsrdquo Demarosi F Sardella A Lodi G Carrassi A

USE IN GTR GBR

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 riskIn 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 (16ndash21 days for cross-linked hyaluronic acid)

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 possi-ble 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

V-4

Without socket preservation

1 Six weeks post-extraction marked vertical and horizontal resorption

2 Buccal resorption in the alveolar region six weeks post-extraction

3 Moistened collagen sponge

4 After extraction

5 After filling the defect

USE IN RIDGESOCKET PRESERVATION

54

3

V-4

21

The following example illustrates how using HYA-DENT barrier gel can optimize soft tissue manage-ment 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

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

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 implan-tation 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

Using HYADENT barrier gel also significantly reduces scar tissue formation

V-5

1 Initial situation

2 Missing lateral incisor

3 Implantation opening a lateral decompression incision

4 Immediate implant closure using a gingiva former

5 Sutureless wound closure with HYADENT barrier gel

6 Completely filled soft tissue defect

7 3 months post-implantation

8 The papilla has been fully preserved

9 Impression using repositioning technique

10 X-ray shows no loss of bone

11 Clinical crown after insertion

12 Final state1048579

USE IN OPEN HEALING OF AN IMPLANT

4

5

6

7 10

8

9

2

3

1 12

V-5

11

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-inflammato-ries and systemic antibiotics are therefore employed in treating periodontal disease Sub or supragingival application of hyaluronic acid (one of four glycosa-minoglycans in gingival tissue) can also be a suc-cessful additional therapeutic measure for treatingperiodontal disease HYADENTrsquos bacteriostatic properties (especially against Actinobacillus actio-nomyecetemcomitans Prevotella intermedia and Staphylococcus aureus) aid tissue regeneration 2)

In addition periodontal therapy with hyaluronic acid support has been shown to achievean increase in bone level 3)

The angulated cannula makes HYADENT simple and effective to apply In addition to manual supra-gingival and subgingival scaling and root planing of all affected teeth systematic periodontitis treatment involves the sub or supragingival application ofHYADENT HYADENT should then be reapplied 7ndash10 days after initial application As a supplement to mechanical treatment its use leads to a statis-

VI

HYADENT application in the periodontal pocket

1 Initial situation2 Approx 3 weeks after the second injection

VII

1) Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159-164 (2003) 2) 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 3-63) van den Bogaerde L MD DDS Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure

Klinischer Bericht uumlber 19 nacheinander behandelte Laumlsionen Int J Paro amp Rest ZHK 29 3 299-307 (2009)

HYADENT use in periodontal therapy

HYADENT in esthetic reconstruction

Many studies have comprehensively documented the positive clinical outcomes of modern implan-tology The use of modern treatment concepts and improved materials has dramatically expan-ded options for nature-identical esthetic recon-struction 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

HYADENT barrier gel offers dentists a genuine alternative to difficult and lengthy surgical procedures

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 (23G06 x 25 mm) To achieve the desired effect in full the injection may be repeated after about 3 weeksSurgical procedures which result in unwanted scarring are no longer necessary Patients are spared a painful treatment and the limitations it imposes1048579

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 proce-dures come a distinct second

1 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

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

Topical hyaluronic acid therapy is medically useful for accelerating the regeneration of gingiva in the following indications

ndash Professional cleaning Small mechanical soft tissue injuries in the interdental spaces

ndash Gingival retraction To stabilize and accelerate regeneration of the gingiva following exposure of the preparation margin (eg with expasyl)

ndash 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 ndash the most important and most common procedure

Targeted soft tissue regeneration through topical application of HYADENT hyaluronic acid gel is car-ried 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 areable 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

VIII VIII

HYADENT as a preventive treatment

Bleaching Whitening

Most bleaching gels contain hydrogen peroxide or carbamide peroxide (the modes of action of which are almost identical) As well as the desi-red 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 thedentist irritation of the mucosa is very common Recent clinical results call for a reevaluation of this procedure

In addition to the DGZMKrsquos 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 459 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

Here again HYADENT offers a solution with key benefits Specific TISSUE CARE application of HYADENT after bleaching may prevent mucosal irritation

1 2

3 4

TISSUE CARE FOLLOWING BLEACHINGWHITENING TREATMENT (HOME BLEACHING)

1 Bleaching splint

2 Bleaching splint (cross section)

3 Tissue care splint

4 Tissue care splint (cross section)

6

5

1 Filled bleaching splint is applied

2 Bleaching in process

3 Anemic soft tissue following bleaching

4 Tissue care splint is filled with HYADENT

5 Tissue care splint covers anemic papillae

6 Regenerated soft tissue following HYADENT application

4

2

1

3

VIII VIII

TREATMENT PROCEDURE

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 possible1048579

HIGH PRODUCT QUALITY

PRODUCT HYADENT HYADENT barrier gel

PRODUCT TYPESingle1048579use syringe direct application option

Single1048579use syringe direct application option

PACKAGING Sterile blister Sterile blister

UNIT VOLUME 1 x 1 ml 1 x 1 ml

APPLICATION Blunt angulated cannula Blunt straight cannula

DOSAGE FORM

REFERENCES

1 Bartold PM Proteoglycans of the periodontium structure role and function J Periodontal Res 22 431ndash444 (1987)2 Campoccia D Doherty P Radice M Brun P Abatangelo G Williams DF Semi synthetic resorbable materials from hyaluronan esterification Biomaterials 19 2101ndash2127 (1998)3 Chen WY Abatangelo G Functions of hyaluronan in wound repair Wound Repair Regen 7 79ndash89 (1999)4 Engstrom PE Shi XQ Tronje G Larsson A Welander U Frithiof L Engstrom GN The effect of hyaluronan on bone and soft tissue and immune response in wound healing J Periodontol 72 1192ndash1200 (2001)5 Galgut P The role of hyaluronic aciTd in managing inflammation in periodontaI diseases Dental Health 42 3ndash6 6 Hoppe H-D Wund(er)mit tel Hyaluronsaumlure Die Schwester Der Pfleger 45 26ndash31 (2006)7 Hunt DR Jovanovic SA Wikesjo UM Wozney JM Bernard GW Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs A pilot study J Periodontol 72 651ndash658 (2001)8 Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159ndash164 (2003)9 Klinger MM Rahemtulla F Prince CW Lucas LC Lemons JE Proteoglycans at the bone-implant interface Crit Rev Oral Biol Med 9 449ndash463 (1998)10 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 292ndash296 (1991)11 Marinucci L Lilli C Baroni T Becchetti E Belcastro S Balducci C Locci P In vitro comparison of bioabsorbable and non-resorbable membranes in bone regeneration J Periodontol 72 753ndash759 (2001)12 Pilloni A Low molecular weight hyaluronic acid increases osteogenesis in vitro J Dent Res 71 (IADR Abstracts) Abstract 471 (1992)13 Pilloni A Bernard GW The effect of hyaluronan on mouse intramembranous osteogenesis in vitro Cell Tissue Res 294 323ndash333 (1998)14 Pirnazar P Wolinsky L Nachnani S Haake S Pilloni A Bernard GW Bacteriostatic effects of hyaluronic acid J Periodontol 70 370ndash374 (1999)15 Pomowski R Gocke R Jentsch H Treatment of gingivitis with hyaluronan J Dent Res A-453 (2002)16 Prehm P Hyaluronate is synthesized at plasma membranes Biochem J 220 597ndash600 (1984)17 Rabasseda X The therapeutic role of hyaluronic acid Drugs of today Suppl III 1ndash21 (1998)18 Sasaki T Watanabe C Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid Bone 16 9ndash15 (1995)19 Schwartz Z Goldstein M Raviv E Hirsch A Ranly DM Boyan BD Clinical evalu- ation of demineralized bone allograft in a hyaluronic acid carrier for sinus lif t augmentation in humans a computed tomography and histomorphometric study Clin Oral Implants Res 18 204ndash211 (2007)20 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 219ndash224 (1990)21 van den Bogaerde L Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure Klinischer Bericht uumlber 19 nacheinander behandlete Laumlsionen Int J Paro Rest ZHK 29 3 299ndash307 (2009)22 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 219ndash234 (1986)Biol Med 9 449ndash463 (1998)

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 reported1048579

EXTREMELY WELL TOLERATED1048579

Benefits of HYADENT

IXIX

OVERVIEW OF USAGE HYADENT USAGE HYADENT barrier gel USAGE

USE IN GENERAL ORAL SURGERY

Anti1048579inflammatory properties for assisting andaccelerating wound healing X ndash X ndash

Prevention and improved safety followingsurgical procedures as a result of antisepticbacteriostatic effect in the wound area

X ndash X ndash

Increase in production of fibroblasts X ndash X ndash

Increase in production of osteoblasts X ndash X ndash

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 lsquoblack trianglersquoin the interdental area X

Injection of HA preparation into the softtissue (approx 02 ml) ndash treatment may need to be repeated

Barrier effect to shield bone defects in particular following augmentation with bone graft material X

Completely cover the wound area by applying the gel into the wound immediately prior to wound closure (suture)

Improve localization and prevent displacementof augmentation material (granules) X

Application of the gel after enrichment with the augmentation material (eg BioOss)

Support and accelerate wound healing followingimplantology procedures (the clot is stabilizedby the hydrophilic properties of HA resulting infaster complication1048579free tissue regeneration)

X

Application of the gel after enrichment with the augmentation material (eg BioOss) after the defect has been completely covered

Socket Preservation X Application into the extraction alveolus orto moisten a collagen plug or tape

Reducing scar formation in estheticallydemanding areas after implantation X Completely cover the wound area

with HYADENT barrier gel

USE IN PERIODONTAL INDICATIONS

Aiding the regenerative process followingperiodontal procedures by means ofbacteriostatic effect

X Application of the gel into the gingival pocketimmediately following surgical treatment

Increasing bone level following HA1048579assistedperiodontal therapy X Application of the gel into the gingival pocket

immediately following surgical treatment

Significant improvement in SBI (sulcus bleeding index) score X Application of the gel into the gingival pocket

immediately following surgical treatment

Naturelize GmbHwwwnaturelizecomcustomerservicenaturelizecom

PRSS Japan CoLtdwwwprss-icominfoprssjp

Skin MD Pte Ltdwwwskin-mdnetinfoskin-mdnet

Elaf Medical Supplies Cowwwelaf-mecominfoelaf-mecom

Germany Europe CIS

Japan

Middle East Region

Asia-Pacific Region

BioScience GmbHRheinstraszlige 9656235 Ransbach-Baumbach | Germanywwwbio-scienceorginfobio-scienceorg

EXCLUSIVE DISTRIBUTORS

MANUFACTURER

HYADENT for targeted tissue regeneration

III IV

We have now found a way of utilizing the mechanism of ac-tion 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

ndash What objective is the application of the hyaluronic acid product intended to achieve (Effect)

ndash Over what time frame are the effects of hyaluronic acid required (Resorption period)

III

HYADENT products and indications

For a detailed overview of HYADENT indications see also chapter IX

Effect Shields the wound area from penetration of bacteria and connective tissue

Papilla reconstruction

Resorption period 16 ndash21 days

CROSS-LINKED HYALURONIC ACID

Effect Speeds up wound healing after surgical procedures

Supplements and enhances periodontal surgical treatment

Reduces scar tissue

Activates bone regeneration material to accelerate osteogenesis and prevents displacement of the granules

Optimizes procedures for ridgesocket preservation

Resorption period 6 ndash11 hours

NON CROSS-LINKED HYALURONIC ACID

To support and accelerate wound healing HYA-DENT 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 04 x 18 mm) Angulation of the cannula per-mits 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

After surgical extraction of a tooth apicoectomy is the second most common oral surgical procedure A good prognosis ndash 85 success rate over 3 to 6 years ndash makes this procedure where the correct indi-cations for its use are present an excellent option forretaining natural teeth 1)

The modified viscosity and short resorption time (6ndash12 hours) ensures complete absorption by the surrounding tissue Appropriate and correctly exe-cuted suturing technique can prevent the gel from being rinsed away by saliva

HYADENT use in wound healing and implantology

V

1 Applying HYADENT prior to wound closure

2 Applying HYADENT for open healing of an implant

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 HYADENT1048579

6 Covering the wound area with HYADENT barrier gel

USE IN APICOECTOMY

1) Maienfisch A Langzeiterfahrungen mit der Wurzelspitzenresektion Med Diss Zuumlrich (1980)

5

6

3

V-1

1

2

1

2

4

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 manyindications 1)

HYADENT Hyaluronic acid increases osteoblast formation thereby reducing the time required for new bone formation by means of osseointegrati-on stimulating effects 2) The use of HYADENT in sinus elevation surgery ndash nowadays a standard procedure ndash offers numerous benefits for both surgeon and patient

V-2

Application of HYADENT barrier gel to augmented bone

1 Extraoral enrichment of the granules

2 Granules ready to use

3 Application of the gel barrier

USE IN SINUS LIFTS

1) Weigel PH Fuller GM LeBoeuf RD A model for the role of hyaluronic acid and fibrin in the earlyevents during the inflammatory response and wound healing J Theor Biol 119 219-234 (1986)

3

V-3

1

2

2) 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 204211 (2007)

3) Source Dental Clinics Journal Of General Dentistry ldquoHyaluronic acid biological effects and clinical applicationsrdquo Demarosi F Sardella A Lodi G Carrassi A

USE IN GTR GBR

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 riskIn 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 (16ndash21 days for cross-linked hyaluronic acid)

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 possi-ble 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

V-4

Without socket preservation

1 Six weeks post-extraction marked vertical and horizontal resorption

2 Buccal resorption in the alveolar region six weeks post-extraction

3 Moistened collagen sponge

4 After extraction

5 After filling the defect

USE IN RIDGESOCKET PRESERVATION

54

3

V-4

21

The following example illustrates how using HYA-DENT barrier gel can optimize soft tissue manage-ment 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

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

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 implan-tation 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

Using HYADENT barrier gel also significantly reduces scar tissue formation

V-5

1 Initial situation

2 Missing lateral incisor

3 Implantation opening a lateral decompression incision

4 Immediate implant closure using a gingiva former

5 Sutureless wound closure with HYADENT barrier gel

6 Completely filled soft tissue defect

7 3 months post-implantation

8 The papilla has been fully preserved

9 Impression using repositioning technique

10 X-ray shows no loss of bone

11 Clinical crown after insertion

12 Final state1048579

USE IN OPEN HEALING OF AN IMPLANT

4

5

6

7 10

8

9

2

3

1 12

V-5

11

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-inflammato-ries and systemic antibiotics are therefore employed in treating periodontal disease Sub or supragingival application of hyaluronic acid (one of four glycosa-minoglycans in gingival tissue) can also be a suc-cessful additional therapeutic measure for treatingperiodontal disease HYADENTrsquos bacteriostatic properties (especially against Actinobacillus actio-nomyecetemcomitans Prevotella intermedia and Staphylococcus aureus) aid tissue regeneration 2)

In addition periodontal therapy with hyaluronic acid support has been shown to achievean increase in bone level 3)

The angulated cannula makes HYADENT simple and effective to apply In addition to manual supra-gingival and subgingival scaling and root planing of all affected teeth systematic periodontitis treatment involves the sub or supragingival application ofHYADENT HYADENT should then be reapplied 7ndash10 days after initial application As a supplement to mechanical treatment its use leads to a statis-

VI

HYADENT application in the periodontal pocket

1 Initial situation2 Approx 3 weeks after the second injection

VII

1) Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159-164 (2003) 2) 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 3-63) van den Bogaerde L MD DDS Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure

Klinischer Bericht uumlber 19 nacheinander behandelte Laumlsionen Int J Paro amp Rest ZHK 29 3 299-307 (2009)

HYADENT use in periodontal therapy

HYADENT in esthetic reconstruction

Many studies have comprehensively documented the positive clinical outcomes of modern implan-tology The use of modern treatment concepts and improved materials has dramatically expan-ded options for nature-identical esthetic recon-struction 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

HYADENT barrier gel offers dentists a genuine alternative to difficult and lengthy surgical procedures

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 (23G06 x 25 mm) To achieve the desired effect in full the injection may be repeated after about 3 weeksSurgical procedures which result in unwanted scarring are no longer necessary Patients are spared a painful treatment and the limitations it imposes1048579

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 proce-dures come a distinct second

1 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

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

Topical hyaluronic acid therapy is medically useful for accelerating the regeneration of gingiva in the following indications

ndash Professional cleaning Small mechanical soft tissue injuries in the interdental spaces

ndash Gingival retraction To stabilize and accelerate regeneration of the gingiva following exposure of the preparation margin (eg with expasyl)

ndash 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 ndash the most important and most common procedure

Targeted soft tissue regeneration through topical application of HYADENT hyaluronic acid gel is car-ried 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 areable 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

VIII VIII

HYADENT as a preventive treatment

Bleaching Whitening

Most bleaching gels contain hydrogen peroxide or carbamide peroxide (the modes of action of which are almost identical) As well as the desi-red 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 thedentist irritation of the mucosa is very common Recent clinical results call for a reevaluation of this procedure

In addition to the DGZMKrsquos 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 459 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

Here again HYADENT offers a solution with key benefits Specific TISSUE CARE application of HYADENT after bleaching may prevent mucosal irritation

1 2

3 4

TISSUE CARE FOLLOWING BLEACHINGWHITENING TREATMENT (HOME BLEACHING)

1 Bleaching splint

2 Bleaching splint (cross section)

3 Tissue care splint

4 Tissue care splint (cross section)

6

5

1 Filled bleaching splint is applied

2 Bleaching in process

3 Anemic soft tissue following bleaching

4 Tissue care splint is filled with HYADENT

5 Tissue care splint covers anemic papillae

6 Regenerated soft tissue following HYADENT application

4

2

1

3

VIII VIII

TREATMENT PROCEDURE

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 possible1048579

HIGH PRODUCT QUALITY

PRODUCT HYADENT HYADENT barrier gel

PRODUCT TYPESingle1048579use syringe direct application option

Single1048579use syringe direct application option

PACKAGING Sterile blister Sterile blister

UNIT VOLUME 1 x 1 ml 1 x 1 ml

APPLICATION Blunt angulated cannula Blunt straight cannula

DOSAGE FORM

REFERENCES

1 Bartold PM Proteoglycans of the periodontium structure role and function J Periodontal Res 22 431ndash444 (1987)2 Campoccia D Doherty P Radice M Brun P Abatangelo G Williams DF Semi synthetic resorbable materials from hyaluronan esterification Biomaterials 19 2101ndash2127 (1998)3 Chen WY Abatangelo G Functions of hyaluronan in wound repair Wound Repair Regen 7 79ndash89 (1999)4 Engstrom PE Shi XQ Tronje G Larsson A Welander U Frithiof L Engstrom GN The effect of hyaluronan on bone and soft tissue and immune response in wound healing J Periodontol 72 1192ndash1200 (2001)5 Galgut P The role of hyaluronic aciTd in managing inflammation in periodontaI diseases Dental Health 42 3ndash6 6 Hoppe H-D Wund(er)mit tel Hyaluronsaumlure Die Schwester Der Pfleger 45 26ndash31 (2006)7 Hunt DR Jovanovic SA Wikesjo UM Wozney JM Bernard GW Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs A pilot study J Periodontol 72 651ndash658 (2001)8 Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159ndash164 (2003)9 Klinger MM Rahemtulla F Prince CW Lucas LC Lemons JE Proteoglycans at the bone-implant interface Crit Rev Oral Biol Med 9 449ndash463 (1998)10 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 292ndash296 (1991)11 Marinucci L Lilli C Baroni T Becchetti E Belcastro S Balducci C Locci P In vitro comparison of bioabsorbable and non-resorbable membranes in bone regeneration J Periodontol 72 753ndash759 (2001)12 Pilloni A Low molecular weight hyaluronic acid increases osteogenesis in vitro J Dent Res 71 (IADR Abstracts) Abstract 471 (1992)13 Pilloni A Bernard GW The effect of hyaluronan on mouse intramembranous osteogenesis in vitro Cell Tissue Res 294 323ndash333 (1998)14 Pirnazar P Wolinsky L Nachnani S Haake S Pilloni A Bernard GW Bacteriostatic effects of hyaluronic acid J Periodontol 70 370ndash374 (1999)15 Pomowski R Gocke R Jentsch H Treatment of gingivitis with hyaluronan J Dent Res A-453 (2002)16 Prehm P Hyaluronate is synthesized at plasma membranes Biochem J 220 597ndash600 (1984)17 Rabasseda X The therapeutic role of hyaluronic acid Drugs of today Suppl III 1ndash21 (1998)18 Sasaki T Watanabe C Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid Bone 16 9ndash15 (1995)19 Schwartz Z Goldstein M Raviv E Hirsch A Ranly DM Boyan BD Clinical evalu- ation of demineralized bone allograft in a hyaluronic acid carrier for sinus lif t augmentation in humans a computed tomography and histomorphometric study Clin Oral Implants Res 18 204ndash211 (2007)20 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 219ndash224 (1990)21 van den Bogaerde L Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure Klinischer Bericht uumlber 19 nacheinander behandlete Laumlsionen Int J Paro Rest ZHK 29 3 299ndash307 (2009)22 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 219ndash234 (1986)Biol Med 9 449ndash463 (1998)

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 reported1048579

EXTREMELY WELL TOLERATED1048579

Benefits of HYADENT

IXIX

OVERVIEW OF USAGE HYADENT USAGE HYADENT barrier gel USAGE

USE IN GENERAL ORAL SURGERY

Anti1048579inflammatory properties for assisting andaccelerating wound healing X ndash X ndash

Prevention and improved safety followingsurgical procedures as a result of antisepticbacteriostatic effect in the wound area

X ndash X ndash

Increase in production of fibroblasts X ndash X ndash

Increase in production of osteoblasts X ndash X ndash

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 lsquoblack trianglersquoin the interdental area X

Injection of HA preparation into the softtissue (approx 02 ml) ndash treatment may need to be repeated

Barrier effect to shield bone defects in particular following augmentation with bone graft material X

Completely cover the wound area by applying the gel into the wound immediately prior to wound closure (suture)

Improve localization and prevent displacementof augmentation material (granules) X

Application of the gel after enrichment with the augmentation material (eg BioOss)

Support and accelerate wound healing followingimplantology procedures (the clot is stabilizedby the hydrophilic properties of HA resulting infaster complication1048579free tissue regeneration)

X

Application of the gel after enrichment with the augmentation material (eg BioOss) after the defect has been completely covered

Socket Preservation X Application into the extraction alveolus orto moisten a collagen plug or tape

Reducing scar formation in estheticallydemanding areas after implantation X Completely cover the wound area

with HYADENT barrier gel

USE IN PERIODONTAL INDICATIONS

Aiding the regenerative process followingperiodontal procedures by means ofbacteriostatic effect

X Application of the gel into the gingival pocketimmediately following surgical treatment

Increasing bone level following HA1048579assistedperiodontal therapy X Application of the gel into the gingival pocket

immediately following surgical treatment

Significant improvement in SBI (sulcus bleeding index) score X Application of the gel into the gingival pocket

immediately following surgical treatment

Naturelize GmbHwwwnaturelizecomcustomerservicenaturelizecom

PRSS Japan CoLtdwwwprss-icominfoprssjp

Skin MD Pte Ltdwwwskin-mdnetinfoskin-mdnet

Elaf Medical Supplies Cowwwelaf-mecominfoelaf-mecom

Germany Europe CIS

Japan

Middle East Region

Asia-Pacific Region

BioScience GmbHRheinstraszlige 9656235 Ransbach-Baumbach | Germanywwwbio-scienceorginfobio-scienceorg

EXCLUSIVE DISTRIBUTORS

MANUFACTURER

To support and accelerate wound healing HYA-DENT 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 04 x 18 mm) Angulation of the cannula per-mits 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

After surgical extraction of a tooth apicoectomy is the second most common oral surgical procedure A good prognosis ndash 85 success rate over 3 to 6 years ndash makes this procedure where the correct indi-cations for its use are present an excellent option forretaining natural teeth 1)

The modified viscosity and short resorption time (6ndash12 hours) ensures complete absorption by the surrounding tissue Appropriate and correctly exe-cuted suturing technique can prevent the gel from being rinsed away by saliva

HYADENT use in wound healing and implantology

V

1 Applying HYADENT prior to wound closure

2 Applying HYADENT for open healing of an implant

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 HYADENT1048579

6 Covering the wound area with HYADENT barrier gel

USE IN APICOECTOMY

1) Maienfisch A Langzeiterfahrungen mit der Wurzelspitzenresektion Med Diss Zuumlrich (1980)

5

6

3

V-1

1

2

1

2

4

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 manyindications 1)

HYADENT Hyaluronic acid increases osteoblast formation thereby reducing the time required for new bone formation by means of osseointegrati-on stimulating effects 2) The use of HYADENT in sinus elevation surgery ndash nowadays a standard procedure ndash offers numerous benefits for both surgeon and patient

V-2

Application of HYADENT barrier gel to augmented bone

1 Extraoral enrichment of the granules

2 Granules ready to use

3 Application of the gel barrier

USE IN SINUS LIFTS

1) Weigel PH Fuller GM LeBoeuf RD A model for the role of hyaluronic acid and fibrin in the earlyevents during the inflammatory response and wound healing J Theor Biol 119 219-234 (1986)

3

V-3

1

2

2) 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 204211 (2007)

3) Source Dental Clinics Journal Of General Dentistry ldquoHyaluronic acid biological effects and clinical applicationsrdquo Demarosi F Sardella A Lodi G Carrassi A

USE IN GTR GBR

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 riskIn 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 (16ndash21 days for cross-linked hyaluronic acid)

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 possi-ble 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

V-4

Without socket preservation

1 Six weeks post-extraction marked vertical and horizontal resorption

2 Buccal resorption in the alveolar region six weeks post-extraction

3 Moistened collagen sponge

4 After extraction

5 After filling the defect

USE IN RIDGESOCKET PRESERVATION

54

3

V-4

21

The following example illustrates how using HYA-DENT barrier gel can optimize soft tissue manage-ment 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

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

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 implan-tation 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

Using HYADENT barrier gel also significantly reduces scar tissue formation

V-5

1 Initial situation

2 Missing lateral incisor

3 Implantation opening a lateral decompression incision

4 Immediate implant closure using a gingiva former

5 Sutureless wound closure with HYADENT barrier gel

6 Completely filled soft tissue defect

7 3 months post-implantation

8 The papilla has been fully preserved

9 Impression using repositioning technique

10 X-ray shows no loss of bone

11 Clinical crown after insertion

12 Final state1048579

USE IN OPEN HEALING OF AN IMPLANT

4

5

6

7 10

8

9

2

3

1 12

V-5

11

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-inflammato-ries and systemic antibiotics are therefore employed in treating periodontal disease Sub or supragingival application of hyaluronic acid (one of four glycosa-minoglycans in gingival tissue) can also be a suc-cessful additional therapeutic measure for treatingperiodontal disease HYADENTrsquos bacteriostatic properties (especially against Actinobacillus actio-nomyecetemcomitans Prevotella intermedia and Staphylococcus aureus) aid tissue regeneration 2)

In addition periodontal therapy with hyaluronic acid support has been shown to achievean increase in bone level 3)

The angulated cannula makes HYADENT simple and effective to apply In addition to manual supra-gingival and subgingival scaling and root planing of all affected teeth systematic periodontitis treatment involves the sub or supragingival application ofHYADENT HYADENT should then be reapplied 7ndash10 days after initial application As a supplement to mechanical treatment its use leads to a statis-

VI

HYADENT application in the periodontal pocket

1 Initial situation2 Approx 3 weeks after the second injection

VII

1) Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159-164 (2003) 2) 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 3-63) van den Bogaerde L MD DDS Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure

Klinischer Bericht uumlber 19 nacheinander behandelte Laumlsionen Int J Paro amp Rest ZHK 29 3 299-307 (2009)

HYADENT use in periodontal therapy

HYADENT in esthetic reconstruction

Many studies have comprehensively documented the positive clinical outcomes of modern implan-tology The use of modern treatment concepts and improved materials has dramatically expan-ded options for nature-identical esthetic recon-struction 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

HYADENT barrier gel offers dentists a genuine alternative to difficult and lengthy surgical procedures

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 (23G06 x 25 mm) To achieve the desired effect in full the injection may be repeated after about 3 weeksSurgical procedures which result in unwanted scarring are no longer necessary Patients are spared a painful treatment and the limitations it imposes1048579

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 proce-dures come a distinct second

1 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

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

Topical hyaluronic acid therapy is medically useful for accelerating the regeneration of gingiva in the following indications

ndash Professional cleaning Small mechanical soft tissue injuries in the interdental spaces

ndash Gingival retraction To stabilize and accelerate regeneration of the gingiva following exposure of the preparation margin (eg with expasyl)

ndash 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 ndash the most important and most common procedure

Targeted soft tissue regeneration through topical application of HYADENT hyaluronic acid gel is car-ried 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 areable 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

VIII VIII

HYADENT as a preventive treatment

Bleaching Whitening

Most bleaching gels contain hydrogen peroxide or carbamide peroxide (the modes of action of which are almost identical) As well as the desi-red 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 thedentist irritation of the mucosa is very common Recent clinical results call for a reevaluation of this procedure

In addition to the DGZMKrsquos 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 459 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

Here again HYADENT offers a solution with key benefits Specific TISSUE CARE application of HYADENT after bleaching may prevent mucosal irritation

1 2

3 4

TISSUE CARE FOLLOWING BLEACHINGWHITENING TREATMENT (HOME BLEACHING)

1 Bleaching splint

2 Bleaching splint (cross section)

3 Tissue care splint

4 Tissue care splint (cross section)

6

5

1 Filled bleaching splint is applied

2 Bleaching in process

3 Anemic soft tissue following bleaching

4 Tissue care splint is filled with HYADENT

5 Tissue care splint covers anemic papillae

6 Regenerated soft tissue following HYADENT application

4

2

1

3

VIII VIII

TREATMENT PROCEDURE

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 possible1048579

HIGH PRODUCT QUALITY

PRODUCT HYADENT HYADENT barrier gel

PRODUCT TYPESingle1048579use syringe direct application option

Single1048579use syringe direct application option

PACKAGING Sterile blister Sterile blister

UNIT VOLUME 1 x 1 ml 1 x 1 ml

APPLICATION Blunt angulated cannula Blunt straight cannula

DOSAGE FORM

REFERENCES

1 Bartold PM Proteoglycans of the periodontium structure role and function J Periodontal Res 22 431ndash444 (1987)2 Campoccia D Doherty P Radice M Brun P Abatangelo G Williams DF Semi synthetic resorbable materials from hyaluronan esterification Biomaterials 19 2101ndash2127 (1998)3 Chen WY Abatangelo G Functions of hyaluronan in wound repair Wound Repair Regen 7 79ndash89 (1999)4 Engstrom PE Shi XQ Tronje G Larsson A Welander U Frithiof L Engstrom GN The effect of hyaluronan on bone and soft tissue and immune response in wound healing J Periodontol 72 1192ndash1200 (2001)5 Galgut P The role of hyaluronic aciTd in managing inflammation in periodontaI diseases Dental Health 42 3ndash6 6 Hoppe H-D Wund(er)mit tel Hyaluronsaumlure Die Schwester Der Pfleger 45 26ndash31 (2006)7 Hunt DR Jovanovic SA Wikesjo UM Wozney JM Bernard GW Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs A pilot study J Periodontol 72 651ndash658 (2001)8 Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159ndash164 (2003)9 Klinger MM Rahemtulla F Prince CW Lucas LC Lemons JE Proteoglycans at the bone-implant interface Crit Rev Oral Biol Med 9 449ndash463 (1998)10 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 292ndash296 (1991)11 Marinucci L Lilli C Baroni T Becchetti E Belcastro S Balducci C Locci P In vitro comparison of bioabsorbable and non-resorbable membranes in bone regeneration J Periodontol 72 753ndash759 (2001)12 Pilloni A Low molecular weight hyaluronic acid increases osteogenesis in vitro J Dent Res 71 (IADR Abstracts) Abstract 471 (1992)13 Pilloni A Bernard GW The effect of hyaluronan on mouse intramembranous osteogenesis in vitro Cell Tissue Res 294 323ndash333 (1998)14 Pirnazar P Wolinsky L Nachnani S Haake S Pilloni A Bernard GW Bacteriostatic effects of hyaluronic acid J Periodontol 70 370ndash374 (1999)15 Pomowski R Gocke R Jentsch H Treatment of gingivitis with hyaluronan J Dent Res A-453 (2002)16 Prehm P Hyaluronate is synthesized at plasma membranes Biochem J 220 597ndash600 (1984)17 Rabasseda X The therapeutic role of hyaluronic acid Drugs of today Suppl III 1ndash21 (1998)18 Sasaki T Watanabe C Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid Bone 16 9ndash15 (1995)19 Schwartz Z Goldstein M Raviv E Hirsch A Ranly DM Boyan BD Clinical evalu- ation of demineralized bone allograft in a hyaluronic acid carrier for sinus lif t augmentation in humans a computed tomography and histomorphometric study Clin Oral Implants Res 18 204ndash211 (2007)20 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 219ndash224 (1990)21 van den Bogaerde L Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure Klinischer Bericht uumlber 19 nacheinander behandlete Laumlsionen Int J Paro Rest ZHK 29 3 299ndash307 (2009)22 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 219ndash234 (1986)Biol Med 9 449ndash463 (1998)

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 reported1048579

EXTREMELY WELL TOLERATED1048579

Benefits of HYADENT

IXIX

OVERVIEW OF USAGE HYADENT USAGE HYADENT barrier gel USAGE

USE IN GENERAL ORAL SURGERY

Anti1048579inflammatory properties for assisting andaccelerating wound healing X ndash X ndash

Prevention and improved safety followingsurgical procedures as a result of antisepticbacteriostatic effect in the wound area

X ndash X ndash

Increase in production of fibroblasts X ndash X ndash

Increase in production of osteoblasts X ndash X ndash

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 lsquoblack trianglersquoin the interdental area X

Injection of HA preparation into the softtissue (approx 02 ml) ndash treatment may need to be repeated

Barrier effect to shield bone defects in particular following augmentation with bone graft material X

Completely cover the wound area by applying the gel into the wound immediately prior to wound closure (suture)

Improve localization and prevent displacementof augmentation material (granules) X

Application of the gel after enrichment with the augmentation material (eg BioOss)

Support and accelerate wound healing followingimplantology procedures (the clot is stabilizedby the hydrophilic properties of HA resulting infaster complication1048579free tissue regeneration)

X

Application of the gel after enrichment with the augmentation material (eg BioOss) after the defect has been completely covered

Socket Preservation X Application into the extraction alveolus orto moisten a collagen plug or tape

Reducing scar formation in estheticallydemanding areas after implantation X Completely cover the wound area

with HYADENT barrier gel

USE IN PERIODONTAL INDICATIONS

Aiding the regenerative process followingperiodontal procedures by means ofbacteriostatic effect

X Application of the gel into the gingival pocketimmediately following surgical treatment

Increasing bone level following HA1048579assistedperiodontal therapy X Application of the gel into the gingival pocket

immediately following surgical treatment

Significant improvement in SBI (sulcus bleeding index) score X Application of the gel into the gingival pocket

immediately following surgical treatment

Naturelize GmbHwwwnaturelizecomcustomerservicenaturelizecom

PRSS Japan CoLtdwwwprss-icominfoprssjp

Skin MD Pte Ltdwwwskin-mdnetinfoskin-mdnet

Elaf Medical Supplies Cowwwelaf-mecominfoelaf-mecom

Germany Europe CIS

Japan

Middle East Region

Asia-Pacific Region

BioScience GmbHRheinstraszlige 9656235 Ransbach-Baumbach | Germanywwwbio-scienceorginfobio-scienceorg

EXCLUSIVE DISTRIBUTORS

MANUFACTURER

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 manyindications 1)

HYADENT Hyaluronic acid increases osteoblast formation thereby reducing the time required for new bone formation by means of osseointegrati-on stimulating effects 2) The use of HYADENT in sinus elevation surgery ndash nowadays a standard procedure ndash offers numerous benefits for both surgeon and patient

V-2

Application of HYADENT barrier gel to augmented bone

1 Extraoral enrichment of the granules

2 Granules ready to use

3 Application of the gel barrier

USE IN SINUS LIFTS

1) Weigel PH Fuller GM LeBoeuf RD A model for the role of hyaluronic acid and fibrin in the earlyevents during the inflammatory response and wound healing J Theor Biol 119 219-234 (1986)

3

V-3

1

2

2) 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 204211 (2007)

3) Source Dental Clinics Journal Of General Dentistry ldquoHyaluronic acid biological effects and clinical applicationsrdquo Demarosi F Sardella A Lodi G Carrassi A

USE IN GTR GBR

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 riskIn 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 (16ndash21 days for cross-linked hyaluronic acid)

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 possi-ble 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

V-4

Without socket preservation

1 Six weeks post-extraction marked vertical and horizontal resorption

2 Buccal resorption in the alveolar region six weeks post-extraction

3 Moistened collagen sponge

4 After extraction

5 After filling the defect

USE IN RIDGESOCKET PRESERVATION

54

3

V-4

21

The following example illustrates how using HYA-DENT barrier gel can optimize soft tissue manage-ment 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

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

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 implan-tation 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

Using HYADENT barrier gel also significantly reduces scar tissue formation

V-5

1 Initial situation

2 Missing lateral incisor

3 Implantation opening a lateral decompression incision

4 Immediate implant closure using a gingiva former

5 Sutureless wound closure with HYADENT barrier gel

6 Completely filled soft tissue defect

7 3 months post-implantation

8 The papilla has been fully preserved

9 Impression using repositioning technique

10 X-ray shows no loss of bone

11 Clinical crown after insertion

12 Final state1048579

USE IN OPEN HEALING OF AN IMPLANT

4

5

6

7 10

8

9

2

3

1 12

V-5

11

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-inflammato-ries and systemic antibiotics are therefore employed in treating periodontal disease Sub or supragingival application of hyaluronic acid (one of four glycosa-minoglycans in gingival tissue) can also be a suc-cessful additional therapeutic measure for treatingperiodontal disease HYADENTrsquos bacteriostatic properties (especially against Actinobacillus actio-nomyecetemcomitans Prevotella intermedia and Staphylococcus aureus) aid tissue regeneration 2)

In addition periodontal therapy with hyaluronic acid support has been shown to achievean increase in bone level 3)

The angulated cannula makes HYADENT simple and effective to apply In addition to manual supra-gingival and subgingival scaling and root planing of all affected teeth systematic periodontitis treatment involves the sub or supragingival application ofHYADENT HYADENT should then be reapplied 7ndash10 days after initial application As a supplement to mechanical treatment its use leads to a statis-

VI

HYADENT application in the periodontal pocket

1 Initial situation2 Approx 3 weeks after the second injection

VII

1) Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159-164 (2003) 2) 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 3-63) van den Bogaerde L MD DDS Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure

Klinischer Bericht uumlber 19 nacheinander behandelte Laumlsionen Int J Paro amp Rest ZHK 29 3 299-307 (2009)

HYADENT use in periodontal therapy

HYADENT in esthetic reconstruction

Many studies have comprehensively documented the positive clinical outcomes of modern implan-tology The use of modern treatment concepts and improved materials has dramatically expan-ded options for nature-identical esthetic recon-struction 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

HYADENT barrier gel offers dentists a genuine alternative to difficult and lengthy surgical procedures

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 (23G06 x 25 mm) To achieve the desired effect in full the injection may be repeated after about 3 weeksSurgical procedures which result in unwanted scarring are no longer necessary Patients are spared a painful treatment and the limitations it imposes1048579

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 proce-dures come a distinct second

1 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

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

Topical hyaluronic acid therapy is medically useful for accelerating the regeneration of gingiva in the following indications

ndash Professional cleaning Small mechanical soft tissue injuries in the interdental spaces

ndash Gingival retraction To stabilize and accelerate regeneration of the gingiva following exposure of the preparation margin (eg with expasyl)

ndash 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 ndash the most important and most common procedure

Targeted soft tissue regeneration through topical application of HYADENT hyaluronic acid gel is car-ried 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 areable 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

VIII VIII

HYADENT as a preventive treatment

Bleaching Whitening

Most bleaching gels contain hydrogen peroxide or carbamide peroxide (the modes of action of which are almost identical) As well as the desi-red 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 thedentist irritation of the mucosa is very common Recent clinical results call for a reevaluation of this procedure

In addition to the DGZMKrsquos 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 459 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

Here again HYADENT offers a solution with key benefits Specific TISSUE CARE application of HYADENT after bleaching may prevent mucosal irritation

1 2

3 4

TISSUE CARE FOLLOWING BLEACHINGWHITENING TREATMENT (HOME BLEACHING)

1 Bleaching splint

2 Bleaching splint (cross section)

3 Tissue care splint

4 Tissue care splint (cross section)

6

5

1 Filled bleaching splint is applied

2 Bleaching in process

3 Anemic soft tissue following bleaching

4 Tissue care splint is filled with HYADENT

5 Tissue care splint covers anemic papillae

6 Regenerated soft tissue following HYADENT application

4

2

1

3

VIII VIII

TREATMENT PROCEDURE

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 possible1048579

HIGH PRODUCT QUALITY

PRODUCT HYADENT HYADENT barrier gel

PRODUCT TYPESingle1048579use syringe direct application option

Single1048579use syringe direct application option

PACKAGING Sterile blister Sterile blister

UNIT VOLUME 1 x 1 ml 1 x 1 ml

APPLICATION Blunt angulated cannula Blunt straight cannula

DOSAGE FORM

REFERENCES

1 Bartold PM Proteoglycans of the periodontium structure role and function J Periodontal Res 22 431ndash444 (1987)2 Campoccia D Doherty P Radice M Brun P Abatangelo G Williams DF Semi synthetic resorbable materials from hyaluronan esterification Biomaterials 19 2101ndash2127 (1998)3 Chen WY Abatangelo G Functions of hyaluronan in wound repair Wound Repair Regen 7 79ndash89 (1999)4 Engstrom PE Shi XQ Tronje G Larsson A Welander U Frithiof L Engstrom GN The effect of hyaluronan on bone and soft tissue and immune response in wound healing J Periodontol 72 1192ndash1200 (2001)5 Galgut P The role of hyaluronic aciTd in managing inflammation in periodontaI diseases Dental Health 42 3ndash6 6 Hoppe H-D Wund(er)mit tel Hyaluronsaumlure Die Schwester Der Pfleger 45 26ndash31 (2006)7 Hunt DR Jovanovic SA Wikesjo UM Wozney JM Bernard GW Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs A pilot study J Periodontol 72 651ndash658 (2001)8 Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159ndash164 (2003)9 Klinger MM Rahemtulla F Prince CW Lucas LC Lemons JE Proteoglycans at the bone-implant interface Crit Rev Oral Biol Med 9 449ndash463 (1998)10 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 292ndash296 (1991)11 Marinucci L Lilli C Baroni T Becchetti E Belcastro S Balducci C Locci P In vitro comparison of bioabsorbable and non-resorbable membranes in bone regeneration J Periodontol 72 753ndash759 (2001)12 Pilloni A Low molecular weight hyaluronic acid increases osteogenesis in vitro J Dent Res 71 (IADR Abstracts) Abstract 471 (1992)13 Pilloni A Bernard GW The effect of hyaluronan on mouse intramembranous osteogenesis in vitro Cell Tissue Res 294 323ndash333 (1998)14 Pirnazar P Wolinsky L Nachnani S Haake S Pilloni A Bernard GW Bacteriostatic effects of hyaluronic acid J Periodontol 70 370ndash374 (1999)15 Pomowski R Gocke R Jentsch H Treatment of gingivitis with hyaluronan J Dent Res A-453 (2002)16 Prehm P Hyaluronate is synthesized at plasma membranes Biochem J 220 597ndash600 (1984)17 Rabasseda X The therapeutic role of hyaluronic acid Drugs of today Suppl III 1ndash21 (1998)18 Sasaki T Watanabe C Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid Bone 16 9ndash15 (1995)19 Schwartz Z Goldstein M Raviv E Hirsch A Ranly DM Boyan BD Clinical evalu- ation of demineralized bone allograft in a hyaluronic acid carrier for sinus lif t augmentation in humans a computed tomography and histomorphometric study Clin Oral Implants Res 18 204ndash211 (2007)20 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 219ndash224 (1990)21 van den Bogaerde L Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure Klinischer Bericht uumlber 19 nacheinander behandlete Laumlsionen Int J Paro Rest ZHK 29 3 299ndash307 (2009)22 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 219ndash234 (1986)Biol Med 9 449ndash463 (1998)

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 reported1048579

EXTREMELY WELL TOLERATED1048579

Benefits of HYADENT

IXIX

OVERVIEW OF USAGE HYADENT USAGE HYADENT barrier gel USAGE

USE IN GENERAL ORAL SURGERY

Anti1048579inflammatory properties for assisting andaccelerating wound healing X ndash X ndash

Prevention and improved safety followingsurgical procedures as a result of antisepticbacteriostatic effect in the wound area

X ndash X ndash

Increase in production of fibroblasts X ndash X ndash

Increase in production of osteoblasts X ndash X ndash

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 lsquoblack trianglersquoin the interdental area X

Injection of HA preparation into the softtissue (approx 02 ml) ndash treatment may need to be repeated

Barrier effect to shield bone defects in particular following augmentation with bone graft material X

Completely cover the wound area by applying the gel into the wound immediately prior to wound closure (suture)

Improve localization and prevent displacementof augmentation material (granules) X

Application of the gel after enrichment with the augmentation material (eg BioOss)

Support and accelerate wound healing followingimplantology procedures (the clot is stabilizedby the hydrophilic properties of HA resulting infaster complication1048579free tissue regeneration)

X

Application of the gel after enrichment with the augmentation material (eg BioOss) after the defect has been completely covered

Socket Preservation X Application into the extraction alveolus orto moisten a collagen plug or tape

Reducing scar formation in estheticallydemanding areas after implantation X Completely cover the wound area

with HYADENT barrier gel

USE IN PERIODONTAL INDICATIONS

Aiding the regenerative process followingperiodontal procedures by means ofbacteriostatic effect

X Application of the gel into the gingival pocketimmediately following surgical treatment

Increasing bone level following HA1048579assistedperiodontal therapy X Application of the gel into the gingival pocket

immediately following surgical treatment

Significant improvement in SBI (sulcus bleeding index) score X Application of the gel into the gingival pocket

immediately following surgical treatment

Naturelize GmbHwwwnaturelizecomcustomerservicenaturelizecom

PRSS Japan CoLtdwwwprss-icominfoprssjp

Skin MD Pte Ltdwwwskin-mdnetinfoskin-mdnet

Elaf Medical Supplies Cowwwelaf-mecominfoelaf-mecom

Germany Europe CIS

Japan

Middle East Region

Asia-Pacific Region

BioScience GmbHRheinstraszlige 9656235 Ransbach-Baumbach | Germanywwwbio-scienceorginfobio-scienceorg

EXCLUSIVE DISTRIBUTORS

MANUFACTURER

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 possi-ble 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

V-4

Without socket preservation

1 Six weeks post-extraction marked vertical and horizontal resorption

2 Buccal resorption in the alveolar region six weeks post-extraction

3 Moistened collagen sponge

4 After extraction

5 After filling the defect

USE IN RIDGESOCKET PRESERVATION

54

3

V-4

21

The following example illustrates how using HYA-DENT barrier gel can optimize soft tissue manage-ment 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

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

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 implan-tation 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

Using HYADENT barrier gel also significantly reduces scar tissue formation

V-5

1 Initial situation

2 Missing lateral incisor

3 Implantation opening a lateral decompression incision

4 Immediate implant closure using a gingiva former

5 Sutureless wound closure with HYADENT barrier gel

6 Completely filled soft tissue defect

7 3 months post-implantation

8 The papilla has been fully preserved

9 Impression using repositioning technique

10 X-ray shows no loss of bone

11 Clinical crown after insertion

12 Final state1048579

USE IN OPEN HEALING OF AN IMPLANT

4

5

6

7 10

8

9

2

3

1 12

V-5

11

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-inflammato-ries and systemic antibiotics are therefore employed in treating periodontal disease Sub or supragingival application of hyaluronic acid (one of four glycosa-minoglycans in gingival tissue) can also be a suc-cessful additional therapeutic measure for treatingperiodontal disease HYADENTrsquos bacteriostatic properties (especially against Actinobacillus actio-nomyecetemcomitans Prevotella intermedia and Staphylococcus aureus) aid tissue regeneration 2)

In addition periodontal therapy with hyaluronic acid support has been shown to achievean increase in bone level 3)

The angulated cannula makes HYADENT simple and effective to apply In addition to manual supra-gingival and subgingival scaling and root planing of all affected teeth systematic periodontitis treatment involves the sub or supragingival application ofHYADENT HYADENT should then be reapplied 7ndash10 days after initial application As a supplement to mechanical treatment its use leads to a statis-

VI

HYADENT application in the periodontal pocket

1 Initial situation2 Approx 3 weeks after the second injection

VII

1) Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159-164 (2003) 2) 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 3-63) van den Bogaerde L MD DDS Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure

Klinischer Bericht uumlber 19 nacheinander behandelte Laumlsionen Int J Paro amp Rest ZHK 29 3 299-307 (2009)

HYADENT use in periodontal therapy

HYADENT in esthetic reconstruction

Many studies have comprehensively documented the positive clinical outcomes of modern implan-tology The use of modern treatment concepts and improved materials has dramatically expan-ded options for nature-identical esthetic recon-struction 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

HYADENT barrier gel offers dentists a genuine alternative to difficult and lengthy surgical procedures

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 (23G06 x 25 mm) To achieve the desired effect in full the injection may be repeated after about 3 weeksSurgical procedures which result in unwanted scarring are no longer necessary Patients are spared a painful treatment and the limitations it imposes1048579

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 proce-dures come a distinct second

1 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

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

Topical hyaluronic acid therapy is medically useful for accelerating the regeneration of gingiva in the following indications

ndash Professional cleaning Small mechanical soft tissue injuries in the interdental spaces

ndash Gingival retraction To stabilize and accelerate regeneration of the gingiva following exposure of the preparation margin (eg with expasyl)

ndash 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 ndash the most important and most common procedure

Targeted soft tissue regeneration through topical application of HYADENT hyaluronic acid gel is car-ried 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 areable 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

VIII VIII

HYADENT as a preventive treatment

Bleaching Whitening

Most bleaching gels contain hydrogen peroxide or carbamide peroxide (the modes of action of which are almost identical) As well as the desi-red 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 thedentist irritation of the mucosa is very common Recent clinical results call for a reevaluation of this procedure

In addition to the DGZMKrsquos 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 459 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

Here again HYADENT offers a solution with key benefits Specific TISSUE CARE application of HYADENT after bleaching may prevent mucosal irritation

1 2

3 4

TISSUE CARE FOLLOWING BLEACHINGWHITENING TREATMENT (HOME BLEACHING)

1 Bleaching splint

2 Bleaching splint (cross section)

3 Tissue care splint

4 Tissue care splint (cross section)

6

5

1 Filled bleaching splint is applied

2 Bleaching in process

3 Anemic soft tissue following bleaching

4 Tissue care splint is filled with HYADENT

5 Tissue care splint covers anemic papillae

6 Regenerated soft tissue following HYADENT application

4

2

1

3

VIII VIII

TREATMENT PROCEDURE

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 possible1048579

HIGH PRODUCT QUALITY

PRODUCT HYADENT HYADENT barrier gel

PRODUCT TYPESingle1048579use syringe direct application option

Single1048579use syringe direct application option

PACKAGING Sterile blister Sterile blister

UNIT VOLUME 1 x 1 ml 1 x 1 ml

APPLICATION Blunt angulated cannula Blunt straight cannula

DOSAGE FORM

REFERENCES

1 Bartold PM Proteoglycans of the periodontium structure role and function J Periodontal Res 22 431ndash444 (1987)2 Campoccia D Doherty P Radice M Brun P Abatangelo G Williams DF Semi synthetic resorbable materials from hyaluronan esterification Biomaterials 19 2101ndash2127 (1998)3 Chen WY Abatangelo G Functions of hyaluronan in wound repair Wound Repair Regen 7 79ndash89 (1999)4 Engstrom PE Shi XQ Tronje G Larsson A Welander U Frithiof L Engstrom GN The effect of hyaluronan on bone and soft tissue and immune response in wound healing J Periodontol 72 1192ndash1200 (2001)5 Galgut P The role of hyaluronic aciTd in managing inflammation in periodontaI diseases Dental Health 42 3ndash6 6 Hoppe H-D Wund(er)mit tel Hyaluronsaumlure Die Schwester Der Pfleger 45 26ndash31 (2006)7 Hunt DR Jovanovic SA Wikesjo UM Wozney JM Bernard GW Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs A pilot study J Periodontol 72 651ndash658 (2001)8 Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159ndash164 (2003)9 Klinger MM Rahemtulla F Prince CW Lucas LC Lemons JE Proteoglycans at the bone-implant interface Crit Rev Oral Biol Med 9 449ndash463 (1998)10 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 292ndash296 (1991)11 Marinucci L Lilli C Baroni T Becchetti E Belcastro S Balducci C Locci P In vitro comparison of bioabsorbable and non-resorbable membranes in bone regeneration J Periodontol 72 753ndash759 (2001)12 Pilloni A Low molecular weight hyaluronic acid increases osteogenesis in vitro J Dent Res 71 (IADR Abstracts) Abstract 471 (1992)13 Pilloni A Bernard GW The effect of hyaluronan on mouse intramembranous osteogenesis in vitro Cell Tissue Res 294 323ndash333 (1998)14 Pirnazar P Wolinsky L Nachnani S Haake S Pilloni A Bernard GW Bacteriostatic effects of hyaluronic acid J Periodontol 70 370ndash374 (1999)15 Pomowski R Gocke R Jentsch H Treatment of gingivitis with hyaluronan J Dent Res A-453 (2002)16 Prehm P Hyaluronate is synthesized at plasma membranes Biochem J 220 597ndash600 (1984)17 Rabasseda X The therapeutic role of hyaluronic acid Drugs of today Suppl III 1ndash21 (1998)18 Sasaki T Watanabe C Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid Bone 16 9ndash15 (1995)19 Schwartz Z Goldstein M Raviv E Hirsch A Ranly DM Boyan BD Clinical evalu- ation of demineralized bone allograft in a hyaluronic acid carrier for sinus lif t augmentation in humans a computed tomography and histomorphometric study Clin Oral Implants Res 18 204ndash211 (2007)20 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 219ndash224 (1990)21 van den Bogaerde L Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure Klinischer Bericht uumlber 19 nacheinander behandlete Laumlsionen Int J Paro Rest ZHK 29 3 299ndash307 (2009)22 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 219ndash234 (1986)Biol Med 9 449ndash463 (1998)

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 reported1048579

EXTREMELY WELL TOLERATED1048579

Benefits of HYADENT

IXIX

OVERVIEW OF USAGE HYADENT USAGE HYADENT barrier gel USAGE

USE IN GENERAL ORAL SURGERY

Anti1048579inflammatory properties for assisting andaccelerating wound healing X ndash X ndash

Prevention and improved safety followingsurgical procedures as a result of antisepticbacteriostatic effect in the wound area

X ndash X ndash

Increase in production of fibroblasts X ndash X ndash

Increase in production of osteoblasts X ndash X ndash

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 lsquoblack trianglersquoin the interdental area X

Injection of HA preparation into the softtissue (approx 02 ml) ndash treatment may need to be repeated

Barrier effect to shield bone defects in particular following augmentation with bone graft material X

Completely cover the wound area by applying the gel into the wound immediately prior to wound closure (suture)

Improve localization and prevent displacementof augmentation material (granules) X

Application of the gel after enrichment with the augmentation material (eg BioOss)

Support and accelerate wound healing followingimplantology procedures (the clot is stabilizedby the hydrophilic properties of HA resulting infaster complication1048579free tissue regeneration)

X

Application of the gel after enrichment with the augmentation material (eg BioOss) after the defect has been completely covered

Socket Preservation X Application into the extraction alveolus orto moisten a collagen plug or tape

Reducing scar formation in estheticallydemanding areas after implantation X Completely cover the wound area

with HYADENT barrier gel

USE IN PERIODONTAL INDICATIONS

Aiding the regenerative process followingperiodontal procedures by means ofbacteriostatic effect

X Application of the gel into the gingival pocketimmediately following surgical treatment

Increasing bone level following HA1048579assistedperiodontal therapy X Application of the gel into the gingival pocket

immediately following surgical treatment

Significant improvement in SBI (sulcus bleeding index) score X Application of the gel into the gingival pocket

immediately following surgical treatment

Naturelize GmbHwwwnaturelizecomcustomerservicenaturelizecom

PRSS Japan CoLtdwwwprss-icominfoprssjp

Skin MD Pte Ltdwwwskin-mdnetinfoskin-mdnet

Elaf Medical Supplies Cowwwelaf-mecominfoelaf-mecom

Germany Europe CIS

Japan

Middle East Region

Asia-Pacific Region

BioScience GmbHRheinstraszlige 9656235 Ransbach-Baumbach | Germanywwwbio-scienceorginfobio-scienceorg

EXCLUSIVE DISTRIBUTORS

MANUFACTURER

The following example illustrates how using HYA-DENT barrier gel can optimize soft tissue manage-ment 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

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

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 implan-tation 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

Using HYADENT barrier gel also significantly reduces scar tissue formation

V-5

1 Initial situation

2 Missing lateral incisor

3 Implantation opening a lateral decompression incision

4 Immediate implant closure using a gingiva former

5 Sutureless wound closure with HYADENT barrier gel

6 Completely filled soft tissue defect

7 3 months post-implantation

8 The papilla has been fully preserved

9 Impression using repositioning technique

10 X-ray shows no loss of bone

11 Clinical crown after insertion

12 Final state1048579

USE IN OPEN HEALING OF AN IMPLANT

4

5

6

7 10

8

9

2

3

1 12

V-5

11

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-inflammato-ries and systemic antibiotics are therefore employed in treating periodontal disease Sub or supragingival application of hyaluronic acid (one of four glycosa-minoglycans in gingival tissue) can also be a suc-cessful additional therapeutic measure for treatingperiodontal disease HYADENTrsquos bacteriostatic properties (especially against Actinobacillus actio-nomyecetemcomitans Prevotella intermedia and Staphylococcus aureus) aid tissue regeneration 2)

In addition periodontal therapy with hyaluronic acid support has been shown to achievean increase in bone level 3)

The angulated cannula makes HYADENT simple and effective to apply In addition to manual supra-gingival and subgingival scaling and root planing of all affected teeth systematic periodontitis treatment involves the sub or supragingival application ofHYADENT HYADENT should then be reapplied 7ndash10 days after initial application As a supplement to mechanical treatment its use leads to a statis-

VI

HYADENT application in the periodontal pocket

1 Initial situation2 Approx 3 weeks after the second injection

VII

1) Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159-164 (2003) 2) 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 3-63) van den Bogaerde L MD DDS Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure

Klinischer Bericht uumlber 19 nacheinander behandelte Laumlsionen Int J Paro amp Rest ZHK 29 3 299-307 (2009)

HYADENT use in periodontal therapy

HYADENT in esthetic reconstruction

Many studies have comprehensively documented the positive clinical outcomes of modern implan-tology The use of modern treatment concepts and improved materials has dramatically expan-ded options for nature-identical esthetic recon-struction 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

HYADENT barrier gel offers dentists a genuine alternative to difficult and lengthy surgical procedures

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 (23G06 x 25 mm) To achieve the desired effect in full the injection may be repeated after about 3 weeksSurgical procedures which result in unwanted scarring are no longer necessary Patients are spared a painful treatment and the limitations it imposes1048579

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 proce-dures come a distinct second

1 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

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

Topical hyaluronic acid therapy is medically useful for accelerating the regeneration of gingiva in the following indications

ndash Professional cleaning Small mechanical soft tissue injuries in the interdental spaces

ndash Gingival retraction To stabilize and accelerate regeneration of the gingiva following exposure of the preparation margin (eg with expasyl)

ndash 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 ndash the most important and most common procedure

Targeted soft tissue regeneration through topical application of HYADENT hyaluronic acid gel is car-ried 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 areable 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

VIII VIII

HYADENT as a preventive treatment

Bleaching Whitening

Most bleaching gels contain hydrogen peroxide or carbamide peroxide (the modes of action of which are almost identical) As well as the desi-red 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 thedentist irritation of the mucosa is very common Recent clinical results call for a reevaluation of this procedure

In addition to the DGZMKrsquos 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 459 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

Here again HYADENT offers a solution with key benefits Specific TISSUE CARE application of HYADENT after bleaching may prevent mucosal irritation

1 2

3 4

TISSUE CARE FOLLOWING BLEACHINGWHITENING TREATMENT (HOME BLEACHING)

1 Bleaching splint

2 Bleaching splint (cross section)

3 Tissue care splint

4 Tissue care splint (cross section)

6

5

1 Filled bleaching splint is applied

2 Bleaching in process

3 Anemic soft tissue following bleaching

4 Tissue care splint is filled with HYADENT

5 Tissue care splint covers anemic papillae

6 Regenerated soft tissue following HYADENT application

4

2

1

3

VIII VIII

TREATMENT PROCEDURE

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 possible1048579

HIGH PRODUCT QUALITY

PRODUCT HYADENT HYADENT barrier gel

PRODUCT TYPESingle1048579use syringe direct application option

Single1048579use syringe direct application option

PACKAGING Sterile blister Sterile blister

UNIT VOLUME 1 x 1 ml 1 x 1 ml

APPLICATION Blunt angulated cannula Blunt straight cannula

DOSAGE FORM

REFERENCES

1 Bartold PM Proteoglycans of the periodontium structure role and function J Periodontal Res 22 431ndash444 (1987)2 Campoccia D Doherty P Radice M Brun P Abatangelo G Williams DF Semi synthetic resorbable materials from hyaluronan esterification Biomaterials 19 2101ndash2127 (1998)3 Chen WY Abatangelo G Functions of hyaluronan in wound repair Wound Repair Regen 7 79ndash89 (1999)4 Engstrom PE Shi XQ Tronje G Larsson A Welander U Frithiof L Engstrom GN The effect of hyaluronan on bone and soft tissue and immune response in wound healing J Periodontol 72 1192ndash1200 (2001)5 Galgut P The role of hyaluronic aciTd in managing inflammation in periodontaI diseases Dental Health 42 3ndash6 6 Hoppe H-D Wund(er)mit tel Hyaluronsaumlure Die Schwester Der Pfleger 45 26ndash31 (2006)7 Hunt DR Jovanovic SA Wikesjo UM Wozney JM Bernard GW Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs A pilot study J Periodontol 72 651ndash658 (2001)8 Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159ndash164 (2003)9 Klinger MM Rahemtulla F Prince CW Lucas LC Lemons JE Proteoglycans at the bone-implant interface Crit Rev Oral Biol Med 9 449ndash463 (1998)10 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 292ndash296 (1991)11 Marinucci L Lilli C Baroni T Becchetti E Belcastro S Balducci C Locci P In vitro comparison of bioabsorbable and non-resorbable membranes in bone regeneration J Periodontol 72 753ndash759 (2001)12 Pilloni A Low molecular weight hyaluronic acid increases osteogenesis in vitro J Dent Res 71 (IADR Abstracts) Abstract 471 (1992)13 Pilloni A Bernard GW The effect of hyaluronan on mouse intramembranous osteogenesis in vitro Cell Tissue Res 294 323ndash333 (1998)14 Pirnazar P Wolinsky L Nachnani S Haake S Pilloni A Bernard GW Bacteriostatic effects of hyaluronic acid J Periodontol 70 370ndash374 (1999)15 Pomowski R Gocke R Jentsch H Treatment of gingivitis with hyaluronan J Dent Res A-453 (2002)16 Prehm P Hyaluronate is synthesized at plasma membranes Biochem J 220 597ndash600 (1984)17 Rabasseda X The therapeutic role of hyaluronic acid Drugs of today Suppl III 1ndash21 (1998)18 Sasaki T Watanabe C Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid Bone 16 9ndash15 (1995)19 Schwartz Z Goldstein M Raviv E Hirsch A Ranly DM Boyan BD Clinical evalu- ation of demineralized bone allograft in a hyaluronic acid carrier for sinus lif t augmentation in humans a computed tomography and histomorphometric study Clin Oral Implants Res 18 204ndash211 (2007)20 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 219ndash224 (1990)21 van den Bogaerde L Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure Klinischer Bericht uumlber 19 nacheinander behandlete Laumlsionen Int J Paro Rest ZHK 29 3 299ndash307 (2009)22 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 219ndash234 (1986)Biol Med 9 449ndash463 (1998)

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 reported1048579

EXTREMELY WELL TOLERATED1048579

Benefits of HYADENT

IXIX

OVERVIEW OF USAGE HYADENT USAGE HYADENT barrier gel USAGE

USE IN GENERAL ORAL SURGERY

Anti1048579inflammatory properties for assisting andaccelerating wound healing X ndash X ndash

Prevention and improved safety followingsurgical procedures as a result of antisepticbacteriostatic effect in the wound area

X ndash X ndash

Increase in production of fibroblasts X ndash X ndash

Increase in production of osteoblasts X ndash X ndash

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 lsquoblack trianglersquoin the interdental area X

Injection of HA preparation into the softtissue (approx 02 ml) ndash treatment may need to be repeated

Barrier effect to shield bone defects in particular following augmentation with bone graft material X

Completely cover the wound area by applying the gel into the wound immediately prior to wound closure (suture)

Improve localization and prevent displacementof augmentation material (granules) X

Application of the gel after enrichment with the augmentation material (eg BioOss)

Support and accelerate wound healing followingimplantology procedures (the clot is stabilizedby the hydrophilic properties of HA resulting infaster complication1048579free tissue regeneration)

X

Application of the gel after enrichment with the augmentation material (eg BioOss) after the defect has been completely covered

Socket Preservation X Application into the extraction alveolus orto moisten a collagen plug or tape

Reducing scar formation in estheticallydemanding areas after implantation X Completely cover the wound area

with HYADENT barrier gel

USE IN PERIODONTAL INDICATIONS

Aiding the regenerative process followingperiodontal procedures by means ofbacteriostatic effect

X Application of the gel into the gingival pocketimmediately following surgical treatment

Increasing bone level following HA1048579assistedperiodontal therapy X Application of the gel into the gingival pocket

immediately following surgical treatment

Significant improvement in SBI (sulcus bleeding index) score X Application of the gel into the gingival pocket

immediately following surgical treatment

Naturelize GmbHwwwnaturelizecomcustomerservicenaturelizecom

PRSS Japan CoLtdwwwprss-icominfoprssjp

Skin MD Pte Ltdwwwskin-mdnetinfoskin-mdnet

Elaf Medical Supplies Cowwwelaf-mecominfoelaf-mecom

Germany Europe CIS

Japan

Middle East Region

Asia-Pacific Region

BioScience GmbHRheinstraszlige 9656235 Ransbach-Baumbach | Germanywwwbio-scienceorginfobio-scienceorg

EXCLUSIVE DISTRIBUTORS

MANUFACTURER

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-inflammato-ries and systemic antibiotics are therefore employed in treating periodontal disease Sub or supragingival application of hyaluronic acid (one of four glycosa-minoglycans in gingival tissue) can also be a suc-cessful additional therapeutic measure for treatingperiodontal disease HYADENTrsquos bacteriostatic properties (especially against Actinobacillus actio-nomyecetemcomitans Prevotella intermedia and Staphylococcus aureus) aid tissue regeneration 2)

In addition periodontal therapy with hyaluronic acid support has been shown to achievean increase in bone level 3)

The angulated cannula makes HYADENT simple and effective to apply In addition to manual supra-gingival and subgingival scaling and root planing of all affected teeth systematic periodontitis treatment involves the sub or supragingival application ofHYADENT HYADENT should then be reapplied 7ndash10 days after initial application As a supplement to mechanical treatment its use leads to a statis-

VI

HYADENT application in the periodontal pocket

1 Initial situation2 Approx 3 weeks after the second injection

VII

1) Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159-164 (2003) 2) 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 3-63) van den Bogaerde L MD DDS Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure

Klinischer Bericht uumlber 19 nacheinander behandelte Laumlsionen Int J Paro amp Rest ZHK 29 3 299-307 (2009)

HYADENT use in periodontal therapy

HYADENT in esthetic reconstruction

Many studies have comprehensively documented the positive clinical outcomes of modern implan-tology The use of modern treatment concepts and improved materials has dramatically expan-ded options for nature-identical esthetic recon-struction 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

HYADENT barrier gel offers dentists a genuine alternative to difficult and lengthy surgical procedures

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 (23G06 x 25 mm) To achieve the desired effect in full the injection may be repeated after about 3 weeksSurgical procedures which result in unwanted scarring are no longer necessary Patients are spared a painful treatment and the limitations it imposes1048579

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 proce-dures come a distinct second

1 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

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

Topical hyaluronic acid therapy is medically useful for accelerating the regeneration of gingiva in the following indications

ndash Professional cleaning Small mechanical soft tissue injuries in the interdental spaces

ndash Gingival retraction To stabilize and accelerate regeneration of the gingiva following exposure of the preparation margin (eg with expasyl)

ndash 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 ndash the most important and most common procedure

Targeted soft tissue regeneration through topical application of HYADENT hyaluronic acid gel is car-ried 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 areable 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

VIII VIII

HYADENT as a preventive treatment

Bleaching Whitening

Most bleaching gels contain hydrogen peroxide or carbamide peroxide (the modes of action of which are almost identical) As well as the desi-red 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 thedentist irritation of the mucosa is very common Recent clinical results call for a reevaluation of this procedure

In addition to the DGZMKrsquos 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 459 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

Here again HYADENT offers a solution with key benefits Specific TISSUE CARE application of HYADENT after bleaching may prevent mucosal irritation

1 2

3 4

TISSUE CARE FOLLOWING BLEACHINGWHITENING TREATMENT (HOME BLEACHING)

1 Bleaching splint

2 Bleaching splint (cross section)

3 Tissue care splint

4 Tissue care splint (cross section)

6

5

1 Filled bleaching splint is applied

2 Bleaching in process

3 Anemic soft tissue following bleaching

4 Tissue care splint is filled with HYADENT

5 Tissue care splint covers anemic papillae

6 Regenerated soft tissue following HYADENT application

4

2

1

3

VIII VIII

TREATMENT PROCEDURE

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 possible1048579

HIGH PRODUCT QUALITY

PRODUCT HYADENT HYADENT barrier gel

PRODUCT TYPESingle1048579use syringe direct application option

Single1048579use syringe direct application option

PACKAGING Sterile blister Sterile blister

UNIT VOLUME 1 x 1 ml 1 x 1 ml

APPLICATION Blunt angulated cannula Blunt straight cannula

DOSAGE FORM

REFERENCES

1 Bartold PM Proteoglycans of the periodontium structure role and function J Periodontal Res 22 431ndash444 (1987)2 Campoccia D Doherty P Radice M Brun P Abatangelo G Williams DF Semi synthetic resorbable materials from hyaluronan esterification Biomaterials 19 2101ndash2127 (1998)3 Chen WY Abatangelo G Functions of hyaluronan in wound repair Wound Repair Regen 7 79ndash89 (1999)4 Engstrom PE Shi XQ Tronje G Larsson A Welander U Frithiof L Engstrom GN The effect of hyaluronan on bone and soft tissue and immune response in wound healing J Periodontol 72 1192ndash1200 (2001)5 Galgut P The role of hyaluronic aciTd in managing inflammation in periodontaI diseases Dental Health 42 3ndash6 6 Hoppe H-D Wund(er)mit tel Hyaluronsaumlure Die Schwester Der Pfleger 45 26ndash31 (2006)7 Hunt DR Jovanovic SA Wikesjo UM Wozney JM Bernard GW Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs A pilot study J Periodontol 72 651ndash658 (2001)8 Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159ndash164 (2003)9 Klinger MM Rahemtulla F Prince CW Lucas LC Lemons JE Proteoglycans at the bone-implant interface Crit Rev Oral Biol Med 9 449ndash463 (1998)10 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 292ndash296 (1991)11 Marinucci L Lilli C Baroni T Becchetti E Belcastro S Balducci C Locci P In vitro comparison of bioabsorbable and non-resorbable membranes in bone regeneration J Periodontol 72 753ndash759 (2001)12 Pilloni A Low molecular weight hyaluronic acid increases osteogenesis in vitro J Dent Res 71 (IADR Abstracts) Abstract 471 (1992)13 Pilloni A Bernard GW The effect of hyaluronan on mouse intramembranous osteogenesis in vitro Cell Tissue Res 294 323ndash333 (1998)14 Pirnazar P Wolinsky L Nachnani S Haake S Pilloni A Bernard GW Bacteriostatic effects of hyaluronic acid J Periodontol 70 370ndash374 (1999)15 Pomowski R Gocke R Jentsch H Treatment of gingivitis with hyaluronan J Dent Res A-453 (2002)16 Prehm P Hyaluronate is synthesized at plasma membranes Biochem J 220 597ndash600 (1984)17 Rabasseda X The therapeutic role of hyaluronic acid Drugs of today Suppl III 1ndash21 (1998)18 Sasaki T Watanabe C Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid Bone 16 9ndash15 (1995)19 Schwartz Z Goldstein M Raviv E Hirsch A Ranly DM Boyan BD Clinical evalu- ation of demineralized bone allograft in a hyaluronic acid carrier for sinus lif t augmentation in humans a computed tomography and histomorphometric study Clin Oral Implants Res 18 204ndash211 (2007)20 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 219ndash224 (1990)21 van den Bogaerde L Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure Klinischer Bericht uumlber 19 nacheinander behandlete Laumlsionen Int J Paro Rest ZHK 29 3 299ndash307 (2009)22 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 219ndash234 (1986)Biol Med 9 449ndash463 (1998)

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 reported1048579

EXTREMELY WELL TOLERATED1048579

Benefits of HYADENT

IXIX

OVERVIEW OF USAGE HYADENT USAGE HYADENT barrier gel USAGE

USE IN GENERAL ORAL SURGERY

Anti1048579inflammatory properties for assisting andaccelerating wound healing X ndash X ndash

Prevention and improved safety followingsurgical procedures as a result of antisepticbacteriostatic effect in the wound area

X ndash X ndash

Increase in production of fibroblasts X ndash X ndash

Increase in production of osteoblasts X ndash X ndash

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 lsquoblack trianglersquoin the interdental area X

Injection of HA preparation into the softtissue (approx 02 ml) ndash treatment may need to be repeated

Barrier effect to shield bone defects in particular following augmentation with bone graft material X

Completely cover the wound area by applying the gel into the wound immediately prior to wound closure (suture)

Improve localization and prevent displacementof augmentation material (granules) X

Application of the gel after enrichment with the augmentation material (eg BioOss)

Support and accelerate wound healing followingimplantology procedures (the clot is stabilizedby the hydrophilic properties of HA resulting infaster complication1048579free tissue regeneration)

X

Application of the gel after enrichment with the augmentation material (eg BioOss) after the defect has been completely covered

Socket Preservation X Application into the extraction alveolus orto moisten a collagen plug or tape

Reducing scar formation in estheticallydemanding areas after implantation X Completely cover the wound area

with HYADENT barrier gel

USE IN PERIODONTAL INDICATIONS

Aiding the regenerative process followingperiodontal procedures by means ofbacteriostatic effect

X Application of the gel into the gingival pocketimmediately following surgical treatment

Increasing bone level following HA1048579assistedperiodontal therapy X Application of the gel into the gingival pocket

immediately following surgical treatment

Significant improvement in SBI (sulcus bleeding index) score X Application of the gel into the gingival pocket

immediately following surgical treatment

Naturelize GmbHwwwnaturelizecomcustomerservicenaturelizecom

PRSS Japan CoLtdwwwprss-icominfoprssjp

Skin MD Pte Ltdwwwskin-mdnetinfoskin-mdnet

Elaf Medical Supplies Cowwwelaf-mecominfoelaf-mecom

Germany Europe CIS

Japan

Middle East Region

Asia-Pacific Region

BioScience GmbHRheinstraszlige 9656235 Ransbach-Baumbach | Germanywwwbio-scienceorginfobio-scienceorg

EXCLUSIVE DISTRIBUTORS

MANUFACTURER

Topical hyaluronic acid therapy is medically useful for accelerating the regeneration of gingiva in the following indications

ndash Professional cleaning Small mechanical soft tissue injuries in the interdental spaces

ndash Gingival retraction To stabilize and accelerate regeneration of the gingiva following exposure of the preparation margin (eg with expasyl)

ndash 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 ndash the most important and most common procedure

Targeted soft tissue regeneration through topical application of HYADENT hyaluronic acid gel is car-ried 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 areable 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

VIII VIII

HYADENT as a preventive treatment

Bleaching Whitening

Most bleaching gels contain hydrogen peroxide or carbamide peroxide (the modes of action of which are almost identical) As well as the desi-red 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 thedentist irritation of the mucosa is very common Recent clinical results call for a reevaluation of this procedure

In addition to the DGZMKrsquos 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 459 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

Here again HYADENT offers a solution with key benefits Specific TISSUE CARE application of HYADENT after bleaching may prevent mucosal irritation

1 2

3 4

TISSUE CARE FOLLOWING BLEACHINGWHITENING TREATMENT (HOME BLEACHING)

1 Bleaching splint

2 Bleaching splint (cross section)

3 Tissue care splint

4 Tissue care splint (cross section)

6

5

1 Filled bleaching splint is applied

2 Bleaching in process

3 Anemic soft tissue following bleaching

4 Tissue care splint is filled with HYADENT

5 Tissue care splint covers anemic papillae

6 Regenerated soft tissue following HYADENT application

4

2

1

3

VIII VIII

TREATMENT PROCEDURE

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 possible1048579

HIGH PRODUCT QUALITY

PRODUCT HYADENT HYADENT barrier gel

PRODUCT TYPESingle1048579use syringe direct application option

Single1048579use syringe direct application option

PACKAGING Sterile blister Sterile blister

UNIT VOLUME 1 x 1 ml 1 x 1 ml

APPLICATION Blunt angulated cannula Blunt straight cannula

DOSAGE FORM

REFERENCES

1 Bartold PM Proteoglycans of the periodontium structure role and function J Periodontal Res 22 431ndash444 (1987)2 Campoccia D Doherty P Radice M Brun P Abatangelo G Williams DF Semi synthetic resorbable materials from hyaluronan esterification Biomaterials 19 2101ndash2127 (1998)3 Chen WY Abatangelo G Functions of hyaluronan in wound repair Wound Repair Regen 7 79ndash89 (1999)4 Engstrom PE Shi XQ Tronje G Larsson A Welander U Frithiof L Engstrom GN The effect of hyaluronan on bone and soft tissue and immune response in wound healing J Periodontol 72 1192ndash1200 (2001)5 Galgut P The role of hyaluronic aciTd in managing inflammation in periodontaI diseases Dental Health 42 3ndash6 6 Hoppe H-D Wund(er)mit tel Hyaluronsaumlure Die Schwester Der Pfleger 45 26ndash31 (2006)7 Hunt DR Jovanovic SA Wikesjo UM Wozney JM Bernard GW Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs A pilot study J Periodontol 72 651ndash658 (2001)8 Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159ndash164 (2003)9 Klinger MM Rahemtulla F Prince CW Lucas LC Lemons JE Proteoglycans at the bone-implant interface Crit Rev Oral Biol Med 9 449ndash463 (1998)10 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 292ndash296 (1991)11 Marinucci L Lilli C Baroni T Becchetti E Belcastro S Balducci C Locci P In vitro comparison of bioabsorbable and non-resorbable membranes in bone regeneration J Periodontol 72 753ndash759 (2001)12 Pilloni A Low molecular weight hyaluronic acid increases osteogenesis in vitro J Dent Res 71 (IADR Abstracts) Abstract 471 (1992)13 Pilloni A Bernard GW The effect of hyaluronan on mouse intramembranous osteogenesis in vitro Cell Tissue Res 294 323ndash333 (1998)14 Pirnazar P Wolinsky L Nachnani S Haake S Pilloni A Bernard GW Bacteriostatic effects of hyaluronic acid J Periodontol 70 370ndash374 (1999)15 Pomowski R Gocke R Jentsch H Treatment of gingivitis with hyaluronan J Dent Res A-453 (2002)16 Prehm P Hyaluronate is synthesized at plasma membranes Biochem J 220 597ndash600 (1984)17 Rabasseda X The therapeutic role of hyaluronic acid Drugs of today Suppl III 1ndash21 (1998)18 Sasaki T Watanabe C Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid Bone 16 9ndash15 (1995)19 Schwartz Z Goldstein M Raviv E Hirsch A Ranly DM Boyan BD Clinical evalu- ation of demineralized bone allograft in a hyaluronic acid carrier for sinus lif t augmentation in humans a computed tomography and histomorphometric study Clin Oral Implants Res 18 204ndash211 (2007)20 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 219ndash224 (1990)21 van den Bogaerde L Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure Klinischer Bericht uumlber 19 nacheinander behandlete Laumlsionen Int J Paro Rest ZHK 29 3 299ndash307 (2009)22 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 219ndash234 (1986)Biol Med 9 449ndash463 (1998)

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 reported1048579

EXTREMELY WELL TOLERATED1048579

Benefits of HYADENT

IXIX

OVERVIEW OF USAGE HYADENT USAGE HYADENT barrier gel USAGE

USE IN GENERAL ORAL SURGERY

Anti1048579inflammatory properties for assisting andaccelerating wound healing X ndash X ndash

Prevention and improved safety followingsurgical procedures as a result of antisepticbacteriostatic effect in the wound area

X ndash X ndash

Increase in production of fibroblasts X ndash X ndash

Increase in production of osteoblasts X ndash X ndash

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 lsquoblack trianglersquoin the interdental area X

Injection of HA preparation into the softtissue (approx 02 ml) ndash treatment may need to be repeated

Barrier effect to shield bone defects in particular following augmentation with bone graft material X

Completely cover the wound area by applying the gel into the wound immediately prior to wound closure (suture)

Improve localization and prevent displacementof augmentation material (granules) X

Application of the gel after enrichment with the augmentation material (eg BioOss)

Support and accelerate wound healing followingimplantology procedures (the clot is stabilizedby the hydrophilic properties of HA resulting infaster complication1048579free tissue regeneration)

X

Application of the gel after enrichment with the augmentation material (eg BioOss) after the defect has been completely covered

Socket Preservation X Application into the extraction alveolus orto moisten a collagen plug or tape

Reducing scar formation in estheticallydemanding areas after implantation X Completely cover the wound area

with HYADENT barrier gel

USE IN PERIODONTAL INDICATIONS

Aiding the regenerative process followingperiodontal procedures by means ofbacteriostatic effect

X Application of the gel into the gingival pocketimmediately following surgical treatment

Increasing bone level following HA1048579assistedperiodontal therapy X Application of the gel into the gingival pocket

immediately following surgical treatment

Significant improvement in SBI (sulcus bleeding index) score X Application of the gel into the gingival pocket

immediately following surgical treatment

Naturelize GmbHwwwnaturelizecomcustomerservicenaturelizecom

PRSS Japan CoLtdwwwprss-icominfoprssjp

Skin MD Pte Ltdwwwskin-mdnetinfoskin-mdnet

Elaf Medical Supplies Cowwwelaf-mecominfoelaf-mecom

Germany Europe CIS

Japan

Middle East Region

Asia-Pacific Region

BioScience GmbHRheinstraszlige 9656235 Ransbach-Baumbach | Germanywwwbio-scienceorginfobio-scienceorg

EXCLUSIVE DISTRIBUTORS

MANUFACTURER

6

5

1 Filled bleaching splint is applied

2 Bleaching in process

3 Anemic soft tissue following bleaching

4 Tissue care splint is filled with HYADENT

5 Tissue care splint covers anemic papillae

6 Regenerated soft tissue following HYADENT application

4

2

1

3

VIII VIII

TREATMENT PROCEDURE

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 possible1048579

HIGH PRODUCT QUALITY

PRODUCT HYADENT HYADENT barrier gel

PRODUCT TYPESingle1048579use syringe direct application option

Single1048579use syringe direct application option

PACKAGING Sterile blister Sterile blister

UNIT VOLUME 1 x 1 ml 1 x 1 ml

APPLICATION Blunt angulated cannula Blunt straight cannula

DOSAGE FORM

REFERENCES

1 Bartold PM Proteoglycans of the periodontium structure role and function J Periodontal Res 22 431ndash444 (1987)2 Campoccia D Doherty P Radice M Brun P Abatangelo G Williams DF Semi synthetic resorbable materials from hyaluronan esterification Biomaterials 19 2101ndash2127 (1998)3 Chen WY Abatangelo G Functions of hyaluronan in wound repair Wound Repair Regen 7 79ndash89 (1999)4 Engstrom PE Shi XQ Tronje G Larsson A Welander U Frithiof L Engstrom GN The effect of hyaluronan on bone and soft tissue and immune response in wound healing J Periodontol 72 1192ndash1200 (2001)5 Galgut P The role of hyaluronic aciTd in managing inflammation in periodontaI diseases Dental Health 42 3ndash6 6 Hoppe H-D Wund(er)mit tel Hyaluronsaumlure Die Schwester Der Pfleger 45 26ndash31 (2006)7 Hunt DR Jovanovic SA Wikesjo UM Wozney JM Bernard GW Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs A pilot study J Periodontol 72 651ndash658 (2001)8 Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159ndash164 (2003)9 Klinger MM Rahemtulla F Prince CW Lucas LC Lemons JE Proteoglycans at the bone-implant interface Crit Rev Oral Biol Med 9 449ndash463 (1998)10 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 292ndash296 (1991)11 Marinucci L Lilli C Baroni T Becchetti E Belcastro S Balducci C Locci P In vitro comparison of bioabsorbable and non-resorbable membranes in bone regeneration J Periodontol 72 753ndash759 (2001)12 Pilloni A Low molecular weight hyaluronic acid increases osteogenesis in vitro J Dent Res 71 (IADR Abstracts) Abstract 471 (1992)13 Pilloni A Bernard GW The effect of hyaluronan on mouse intramembranous osteogenesis in vitro Cell Tissue Res 294 323ndash333 (1998)14 Pirnazar P Wolinsky L Nachnani S Haake S Pilloni A Bernard GW Bacteriostatic effects of hyaluronic acid J Periodontol 70 370ndash374 (1999)15 Pomowski R Gocke R Jentsch H Treatment of gingivitis with hyaluronan J Dent Res A-453 (2002)16 Prehm P Hyaluronate is synthesized at plasma membranes Biochem J 220 597ndash600 (1984)17 Rabasseda X The therapeutic role of hyaluronic acid Drugs of today Suppl III 1ndash21 (1998)18 Sasaki T Watanabe C Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid Bone 16 9ndash15 (1995)19 Schwartz Z Goldstein M Raviv E Hirsch A Ranly DM Boyan BD Clinical evalu- ation of demineralized bone allograft in a hyaluronic acid carrier for sinus lif t augmentation in humans a computed tomography and histomorphometric study Clin Oral Implants Res 18 204ndash211 (2007)20 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 219ndash224 (1990)21 van den Bogaerde L Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure Klinischer Bericht uumlber 19 nacheinander behandlete Laumlsionen Int J Paro Rest ZHK 29 3 299ndash307 (2009)22 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 219ndash234 (1986)Biol Med 9 449ndash463 (1998)

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 reported1048579

EXTREMELY WELL TOLERATED1048579

Benefits of HYADENT

IXIX

OVERVIEW OF USAGE HYADENT USAGE HYADENT barrier gel USAGE

USE IN GENERAL ORAL SURGERY

Anti1048579inflammatory properties for assisting andaccelerating wound healing X ndash X ndash

Prevention and improved safety followingsurgical procedures as a result of antisepticbacteriostatic effect in the wound area

X ndash X ndash

Increase in production of fibroblasts X ndash X ndash

Increase in production of osteoblasts X ndash X ndash

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 lsquoblack trianglersquoin the interdental area X

Injection of HA preparation into the softtissue (approx 02 ml) ndash treatment may need to be repeated

Barrier effect to shield bone defects in particular following augmentation with bone graft material X

Completely cover the wound area by applying the gel into the wound immediately prior to wound closure (suture)

Improve localization and prevent displacementof augmentation material (granules) X

Application of the gel after enrichment with the augmentation material (eg BioOss)

Support and accelerate wound healing followingimplantology procedures (the clot is stabilizedby the hydrophilic properties of HA resulting infaster complication1048579free tissue regeneration)

X

Application of the gel after enrichment with the augmentation material (eg BioOss) after the defect has been completely covered

Socket Preservation X Application into the extraction alveolus orto moisten a collagen plug or tape

Reducing scar formation in estheticallydemanding areas after implantation X Completely cover the wound area

with HYADENT barrier gel

USE IN PERIODONTAL INDICATIONS

Aiding the regenerative process followingperiodontal procedures by means ofbacteriostatic effect

X Application of the gel into the gingival pocketimmediately following surgical treatment

Increasing bone level following HA1048579assistedperiodontal therapy X Application of the gel into the gingival pocket

immediately following surgical treatment

Significant improvement in SBI (sulcus bleeding index) score X Application of the gel into the gingival pocket

immediately following surgical treatment

Naturelize GmbHwwwnaturelizecomcustomerservicenaturelizecom

PRSS Japan CoLtdwwwprss-icominfoprssjp

Skin MD Pte Ltdwwwskin-mdnetinfoskin-mdnet

Elaf Medical Supplies Cowwwelaf-mecominfoelaf-mecom

Germany Europe CIS

Japan

Middle East Region

Asia-Pacific Region

BioScience GmbHRheinstraszlige 9656235 Ransbach-Baumbach | Germanywwwbio-scienceorginfobio-scienceorg

EXCLUSIVE DISTRIBUTORS

MANUFACTURER

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 possible1048579

HIGH PRODUCT QUALITY

PRODUCT HYADENT HYADENT barrier gel

PRODUCT TYPESingle1048579use syringe direct application option

Single1048579use syringe direct application option

PACKAGING Sterile blister Sterile blister

UNIT VOLUME 1 x 1 ml 1 x 1 ml

APPLICATION Blunt angulated cannula Blunt straight cannula

DOSAGE FORM

REFERENCES

1 Bartold PM Proteoglycans of the periodontium structure role and function J Periodontal Res 22 431ndash444 (1987)2 Campoccia D Doherty P Radice M Brun P Abatangelo G Williams DF Semi synthetic resorbable materials from hyaluronan esterification Biomaterials 19 2101ndash2127 (1998)3 Chen WY Abatangelo G Functions of hyaluronan in wound repair Wound Repair Regen 7 79ndash89 (1999)4 Engstrom PE Shi XQ Tronje G Larsson A Welander U Frithiof L Engstrom GN The effect of hyaluronan on bone and soft tissue and immune response in wound healing J Periodontol 72 1192ndash1200 (2001)5 Galgut P The role of hyaluronic aciTd in managing inflammation in periodontaI diseases Dental Health 42 3ndash6 6 Hoppe H-D Wund(er)mit tel Hyaluronsaumlure Die Schwester Der Pfleger 45 26ndash31 (2006)7 Hunt DR Jovanovic SA Wikesjo UM Wozney JM Bernard GW Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs A pilot study J Periodontol 72 651ndash658 (2001)8 Jentsch H Pomowski R Kundt G Gocke R Treatment of gingivitis with hyaluronan J Clin Periodontol 30 159ndash164 (2003)9 Klinger MM Rahemtulla F Prince CW Lucas LC Lemons JE Proteoglycans at the bone-implant interface Crit Rev Oral Biol Med 9 449ndash463 (1998)10 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 292ndash296 (1991)11 Marinucci L Lilli C Baroni T Becchetti E Belcastro S Balducci C Locci P In vitro comparison of bioabsorbable and non-resorbable membranes in bone regeneration J Periodontol 72 753ndash759 (2001)12 Pilloni A Low molecular weight hyaluronic acid increases osteogenesis in vitro J Dent Res 71 (IADR Abstracts) Abstract 471 (1992)13 Pilloni A Bernard GW The effect of hyaluronan on mouse intramembranous osteogenesis in vitro Cell Tissue Res 294 323ndash333 (1998)14 Pirnazar P Wolinsky L Nachnani S Haake S Pilloni A Bernard GW Bacteriostatic effects of hyaluronic acid J Periodontol 70 370ndash374 (1999)15 Pomowski R Gocke R Jentsch H Treatment of gingivitis with hyaluronan J Dent Res A-453 (2002)16 Prehm P Hyaluronate is synthesized at plasma membranes Biochem J 220 597ndash600 (1984)17 Rabasseda X The therapeutic role of hyaluronic acid Drugs of today Suppl III 1ndash21 (1998)18 Sasaki T Watanabe C Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid Bone 16 9ndash15 (1995)19 Schwartz Z Goldstein M Raviv E Hirsch A Ranly DM Boyan BD Clinical evalu- ation of demineralized bone allograft in a hyaluronic acid carrier for sinus lif t augmentation in humans a computed tomography and histomorphometric study Clin Oral Implants Res 18 204ndash211 (2007)20 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 219ndash224 (1990)21 van den Bogaerde L Behandlung von intraossaumlren Parodontaldefekten mit veresterter Hyaluronsaumlure Klinischer Bericht uumlber 19 nacheinander behandlete Laumlsionen Int J Paro Rest ZHK 29 3 299ndash307 (2009)22 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 219ndash234 (1986)Biol Med 9 449ndash463 (1998)

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 reported1048579

EXTREMELY WELL TOLERATED1048579

Benefits of HYADENT

IXIX

OVERVIEW OF USAGE HYADENT USAGE HYADENT barrier gel USAGE

USE IN GENERAL ORAL SURGERY

Anti1048579inflammatory properties for assisting andaccelerating wound healing X ndash X ndash

Prevention and improved safety followingsurgical procedures as a result of antisepticbacteriostatic effect in the wound area

X ndash X ndash

Increase in production of fibroblasts X ndash X ndash

Increase in production of osteoblasts X ndash X ndash

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 lsquoblack trianglersquoin the interdental area X

Injection of HA preparation into the softtissue (approx 02 ml) ndash treatment may need to be repeated

Barrier effect to shield bone defects in particular following augmentation with bone graft material X

Completely cover the wound area by applying the gel into the wound immediately prior to wound closure (suture)

Improve localization and prevent displacementof augmentation material (granules) X

Application of the gel after enrichment with the augmentation material (eg BioOss)

Support and accelerate wound healing followingimplantology procedures (the clot is stabilizedby the hydrophilic properties of HA resulting infaster complication1048579free tissue regeneration)

X

Application of the gel after enrichment with the augmentation material (eg BioOss) after the defect has been completely covered

Socket Preservation X Application into the extraction alveolus orto moisten a collagen plug or tape

Reducing scar formation in estheticallydemanding areas after implantation X Completely cover the wound area

with HYADENT barrier gel

USE IN PERIODONTAL INDICATIONS

Aiding the regenerative process followingperiodontal procedures by means ofbacteriostatic effect

X Application of the gel into the gingival pocketimmediately following surgical treatment

Increasing bone level following HA1048579assistedperiodontal therapy X Application of the gel into the gingival pocket

immediately following surgical treatment

Significant improvement in SBI (sulcus bleeding index) score X Application of the gel into the gingival pocket

immediately following surgical treatment

Naturelize GmbHwwwnaturelizecomcustomerservicenaturelizecom

PRSS Japan CoLtdwwwprss-icominfoprssjp

Skin MD Pte Ltdwwwskin-mdnetinfoskin-mdnet

Elaf Medical Supplies Cowwwelaf-mecominfoelaf-mecom

Germany Europe CIS

Japan

Middle East Region

Asia-Pacific Region

BioScience GmbHRheinstraszlige 9656235 Ransbach-Baumbach | Germanywwwbio-scienceorginfobio-scienceorg

EXCLUSIVE DISTRIBUTORS

MANUFACTURER

Naturelize GmbHwwwnaturelizecomcustomerservicenaturelizecom

PRSS Japan CoLtdwwwprss-icominfoprssjp

Skin MD Pte Ltdwwwskin-mdnetinfoskin-mdnet

Elaf Medical Supplies Cowwwelaf-mecominfoelaf-mecom

Germany Europe CIS

Japan

Middle East Region

Asia-Pacific Region

BioScience GmbHRheinstraszlige 9656235 Ransbach-Baumbach | Germanywwwbio-scienceorginfobio-scienceorg

EXCLUSIVE DISTRIBUTORS

MANUFACTURER