GUIDED TISSUE REGENERATION

GUIDED TISSUE REGENERATION

CONTENTS• Introduction• History• The Biologic Concept• Melcher’s Concept• Indications • Contraindications• Design Criteria for GTR devices• Objectives of ideal barrier membrane• Classification• Advantages and disadvantages of non resorbable membrane• Advantages and disadvantages of resorbable membrane

• Factors affecting outcome of GTR• Surgical techniques and approach• Healing of GTR treated bone defects• Guided bone regeneration• Post operative considerations• Types of complications possible• Evaluation of GTR treatment outcome• Current status• Addition of antimicrobial substances.• Microbiota of failing GTR• Conclusion• References.

INTRODUCTION

o In recent times, the use of regenerative procedures aimed at restoring the lost periodontal support has become more common. Indication of applying regenerative periodontal therapy is often based on esthetic considerations besides the fact that function or long term prognosis of the involved teeth may be improved.

o Periodontal regeneration:is defined as a reproduction or reconstruction of a lost or injured part in such a way that the architecture and function of the lost or injured tissues are completely restored.(Glossary of periodontal term 1992)

o GTR procedures were developed to accomplish the objectives of epithelial exclusion via controlled cell/tissue repopulation of the periodontal wound, space maintenance and clot stabilization.

What is GTR?• The 1996 World Workshop in Periodontics defined GTR as

“procedures attempting to regenerate lost periodontal structures through differential tissue responses’’.

• The AAP has defined GTR as “the procedure by which a barrier is utilized to exclude epithelium from the root surfaces”.

• Procedures attempting to regenerate lost periodontal structures through differential tissue responses. (GPT 2001).

o Barriers are employed in the hope of excluding epithelium and connective tissue from the root surface in the belief that they interfere with regeneration.

o This method is derived from the classic studies of

Nyman(1982), Lindhe(1984), Karring(1986) and Gottlow(1986) and is based on the assumption that only the PDL cells have the potential for regeneration of the attachment apparatus of the tooth.

HISTORY• In 1976 – Melcher described the basic concept that led to

development of GTR.

• In 1982 – Nyman et al first described the clinical procedure of GTR using a non absorbable barrier,used in periodontal surgery which allowed regeneration of cementum, periodontal ligament and alveolar bone was a cellulose acetate (paper) laboratory filter (Millipore filter).

 • In 1982 – W.L. Gore and associates, began investigating

materials that would limit the migration of epithelial around dental implants and teeth.

• In 1982 – ePTFE was introduced.

• 1982 era - “Era of tissue integration”

• 1983, era was called “Era of cell separation”

• 1985 - Era of clinically manageable membrane development.

• Gotlow et al. 1986 coined the term Guided Tissue Regeneration and it is also referred to as selective cell repopulation or controlled tissue regeneration.

• 1988 -> the space making property was developed. the central portion of the membrane was stiffened to support the membrane and resist collapse

from the pressure of overlying tissue, while periphery was porous and soft.

THE BIOLOGIC CONCEPT/FOUNDATION OF GTR

oPrinciple of GTR is based on the assumption that only the periodontal ligament cells have the potential for the regeneration of the attachment apparatus of tooth.

o It consists of placing barriers of different types to cover the bone and periodontal ligament thus temporarily separating them from gingival epithelium.

oExcluding the epithelium and the gingival connective tissue from the root surface during the post surgical healing phase - Prevents epithelial migration into the wound. Favours repopulation of the area by cells from the periodontal ligament and bone cells.

oGuided tissue regeneration with the use of barrier membranes works on the principle of cell exclusion.

MELCHER’S CONCEPT/TISSUE COMPARTMENT HYPOTHESIS

Melcher’s hypothesisIn 1976, Melcher suggested in a review paper that the type of cell which repopulates the root surface after periodontal surgery determines the nature of the attachment that will form.

Root surfaces may be repopulated by four different types of cells:1. Epithelial cells.2. Cells derived from the gingival connective tissue3. Cells derived from the bone4. Cells derived from the periodontal ligament

Figure: Schematic diagram depicting the concept of Melchers hypothesis

INDICATIONS2 to 3 walled intrabony defects.Class II furcation defects.Recession defects.Circumferential defectsAlveolar ridge augmentation.Repair of apicoectomy defect.Osseous fill around immediate implant placement sites.Repair of osseous defect associated with failing

implants.Thick gingival biotype.

CONTRAINDICATIONSo Infection at the site of defecto Poor oral hygieneo Smokingo Tooth Mobility o Defect < 4mmo Width of attached gingiva at defect site ≤1 mm o Thickness of attached gingiva at defect site ≤0.5mmo Furcation with short root trunkso Advanced lesions with little remaining supporto Horizontal bone losso Multiple defectso Any medical condition contraindicating surgery

DESIGN CRITERIA FOR GTR DEVICES

Scantlebury, Gottlow and Hardwilk (1982)• Biocompatibility • Cell exclusion • Space maintenance • Tissue integrity • Ease of use • Biological activity Greenstein & Caton (1993):• Biocompatibility • Cell occlusiveness • Spacemaking • Tissue integration • clinical manageablilty

OBJECTIVES OF AN IDEAL BARRIER MEMBRANE

• It should fulfill occlusive requirements of GTR concept. • It should be biocompatible and/or allow tissue integration.• Non-toxic and non-carcinogenic.• Chemically inert and non-antigenic.• Easily sterilizable.• Easy to handle during surgery.• Sufficiently rigid so as to maintain space between it and root surface.• Supplied in different designs to suit the specific clinical situations• Easily storable and long shelf life.• Easily retrievable in case of complication.• Should not be too expensive.• able in case of complication.

CLASSIFICATION

Classification by Minabe in 1991: Nonabsorbable   

-Polytetrafluoroethylene (e-PTFE) type      -Titanium reinforced polytetrafluoroethylene type  -Rubberdam

Bioabsorbable

Natural

-Collagen type -Synthetic polymer type(lactate-glycol compound) -Connective tissue graft -Durameter -Oxidized cellulose

Synthetic -Alloderm -Polyurethanes -Polylactic acid -Polyglycolic acid

Classification by Gottlow in 1993:

Millipore FilterExpanded polytetrafluoroethylene membrane (e-PTFE)

GORE-TEX Nucleopore membrane.Rubber Dam. Ethyl cellulose. Semi-permeable silicon barrier.

Collagen – Biomend, Periogen, Paroguide, Biostite, Tissue guide.

Polylactic acid Membrane – Guidor, Vicryl, Atrisorb, Resolut, Epiguide, Biofix.

Vicryl Mesh.Cargile Membrane.Oxidised Cellulose Membrane.

First generation membranes: Non-resorbable membranes

Second generation membrane: Resorbable membranes

Third generation membrane: They are the resorbable membrane with added

growth factor incorporated with an aim of improving early bone healing.

Advantages and disadvantages of non-resorbable membranes

Advantages:Excision of

epithelial and gingival CT from PD

defectMaintains space between defect and

barrier allowing entry of cells from PDL and alv

bone.

Helps to stabilize clot which may

enhance regeneration

Space maintainence over an extended time

and can remain in place for longer period.

Disadvantages:

Membrane exposure

Contamination

Infection

Bone loss

Advantages and disadvantages of resorbable membranes

AdvantagesReduce

operatory time More tissue

compatibility Increase

patient acceptance

Elimination of second surgery for

barrier removal

Reduces risk of loss

of regenerated attachment owing to reentry

surgery.

DisadvantagesResorbable

High Cost

Instability of

barrier

Biodegradation

rate cannot

be controll

ed

Lack of stiffness

-collapse

of membra

ne.

Resorbable versus non-resorbable membranes

• AAP paper on regeneration 2005, stated that “there is no difference between resorbable and non-resorbable membranes and that evaluation of both polyactic acid and collagen membranes have reported clinical improvements similar to those achieved with non-resorbable membranes.”

Lindhe (2003), in a review of 21 clinical trials (423 mandibular grade II furcations), concluded:

• There was no significant difference between bioabsorbable and nonabsorbable membranes.

• GTR significantly improved the horizontal CAL results over OFD: 2.5mm versus 1.3mm.

• Complete closure was variable (0-67%).• GTR significantly improved vertical attachment and a

reduction in PD.• CAL-H in maxillary furcation was only 1.6mm, and the

results were variable.

• Parrish et al in 2009 had systematically reviewed on non bioabsorbable versus bioabsorbable membrane assessment of their clinical efficiency in GTR technique and concluded that GTR was confirmed to be superior to OFD.

FACTORS AFFECTING THE OUTCOMES OF GTR

Barrier independent factors • Patient factors • Defect factors • Surgical technique

Patient factors

Defect factors Type of defect:- Intrabony defects or class II furcations.

Morphology of defect:- Deeper defect shows more gain in CAL as compared to wider defects which show less gain in CAL (Garrett et al 88; Tonetti et al 93,96).

Defects deeper than 3 mm - greater probing attachment

gains than defects of 3 mm or less (Cortellini P 1998).

• Root canal treatment (Cortellini & Tonetti 2000)

• Tooth mobility with < 1mm horizontally have been positively related to PDL regeneration.(Cortellini et al 2001; Trejo & Weltman 2004)

• Gingival thickness <1mm exhibited more post operative recession(Anderegg et al 95) and severity of flap dehiscence. (Anderegg et al 91)

• Number of residual bony walls was related to the outcomes of various regenerative approaches (Goldman & Cohen 1958, Schallhorn et al. 1970).

Surgical technique – Improper incision placement.– Traumatic flap elevation.– Excessive surgical time.– Inadequate closure or suturing.– Bacterial contamination: Colonization may occur on the

coronal part of membrane.

• Administration of systemic antibiotics has shown no improvement after GTR therapy (Slots 94) as they are ineffective in prevention of plaque biofilm. (Frandsen et al 94)

Barrier dependent factors • Inadequate root barrier adaptation.• Non-sterile technique• Instability of barrier against root.• Premature exposure of barrier to oral

environment and microbes.• Premature loss or degradation of barrier.

The primary factors affecting the clinical outcomes of periodontal surgery have been classified by Kornman and Robertson (2000) as:

• 1) Bacterial contamination • 2) Innate wound-healing potential • 3) Local site characteristics and • 4) Surgical procedure

Cortelini and Tonetti in 2000 gave the following factors:

PASS principleHom-LayWang and Boyapati in 2006 have

suggested 4 factors that play a critical role in regeneration -

• P- Primary wound coverage (passive flap tension)• A- Angiogenesis• S- Space maintenance • S- Stability

SURGICAL TECHNIQUE AND APPROACHES.

Conventional approach• access flap or modified Widman flap • Full-thickness flaps are elevated to try to preserve the marginal and

interdental tissues to the maximum possible extent. • Vertical releasing incisions• Coronal displacement of the flap

• In 1995 and 1999, Cortillini and Tonetti have described flap techniques for the preservation of the interdental papillae. These techniques i.e. the modified papilla preservation flap and the simplified papilla preservation flap can be used with better prognosis while attempting GTR procedure.

Modified papilla preservation techniqueThe rationale for developing this technique was

to achieve and maintain primary closure of the flap in the interdental space over the membrane.

Interdental tissue maintenance• Interproximal tissue maintenance is a technique proposed

by Murphy to be used in combination with nonresorbable barrier membranes and grafting material.

Free gingival graft at membrane removal• The use of free gingival grafts has been proposed to

afford better coverage and protection of the regenerated interproximal tissues after membranes removal when the occurrence of a dehiscence of the gingival flap does not allow a primary coverage of the interdental area .

• In a randomized controlled clinical study of 45 patients

significantly greater amounts of probing attachment were gained with the modified papilla preservation technique, in comparison with either conventional guided tissue regeneration or access flap surgery

• The sites accessed with the modified papilla preservation technique showed primary closure of the flap in 73% of

the cases. (Cortellini et 1995)

• Thorough pre-surgical preparation of the patient consisting of SRP, oral hygiene instructions and oral hygiene maintenance monitoring must be done.

• Raise a muco-periosteal flap with crevicular and vertical incisions, extending a minimum of 2 teeth mesially and 1 tooth distally to the tooth being treated.

• Debride the osseous defect and thoroughly plane the roots.

• Trim the membrane with sharp scissors to the approximate size of the area being treated.

• The apical border of the material should extend 3-4mm apical to the margin of the defect and laterally 2-3mm beyond the defect.

• The occlusal border of the membrane should be placed 2mm apical to the CEJ.

• Suture the membrane tightly around the tooth with a sling suture.

• Suture the flap back in its original position or slightly coronal to it, using independent sutures interdentally and in the vertical incisions.

• The flap should cover the membrane completely.

• Periodontal dressing is optional.

• Antibiotic therapy given for a week.

• After 4-6 weeks, the margin of the membrane becomes exposed.

• The membrane is removed with a gentle tug.

• If it cannot be removed easily, the tissues are anaesthetised and the material is removed surgically using a miniflap.

• The results obtained with the GTR technique are enhanced when the technique is combined with bone grafts placed in the defects.

• The area should be scaled every 3 months for about 9 months.

• By the 9th month, there should be radiographic evidence of bone formation.

• Second surgery is not needed with resorbable membranes.

HEALING OF GTR TREATED BONE DEFECTS

• Following initial organization of the blood clot, protected by the membrane, regeneration was initiated by deposition of woven bone along new vascular structures originating from the bony walls

• The primary spongiosa was characterized by blood vessels originating from marrow spaces.

• The network of woven bone was reinforced by concentrically deposited parallel-fibered lamellar bone, which resulted in the development of a new cortical structure at the periphery of the defects

• The onset of bone remodeling with the formation of secondary osteons could be observed in the newly formed bone close to the defect margins

• The duration of the maturation process exceeded 4 months in the large defects .

(Schenk et al 1994)

GUIDED BONE REGENERATION• In GBR, the osseous defects are covered with a barrier membrane, which is

adapted closely to the surrounding bone surface

• Nonosseous cells (epithelial cells and fibroblasts) are inhibited and space is preserved between the bone surface and membrane.

• Osteoblasts derived from the periosteum and bone are selectively induced on the osseous defect area, facilitating new bone formation

• GBR is for the regeneration of supporting bone.

• Because of less membrane exposure, the chance of infection is decreased making bone regeneration highly predictable.

GBR – The Principle• The GBR biological rationale advocated the mechanical

exclusion of undesirable soft tissues for growing into the osseous defect, thereby allowing only osteogenic cell populations derived from the parent bone to repopulate the osseous wound space (Dahlin et al. 1988; Hammerle et al. 1995).

POSTOPERATIVE CONSIDERATIONS• CHX mouthwash should be used for 10 days.

• If the material becomes exposed, CHX should be used until removal.

• Tetracycline 250 mg daily or doxycycline 100 mg twice daily should be used for 7 to 10 days.

• Periodontal dressing may or may not be used depending on the clinician.

• Gentle brushing is recommended for the first 6 weeks.

• Flossing at the treated site is to be avoided while the material is in place.

• The patient should be seen biweekly if there is no membrane exposure and weekly if exposure is present.

• Do not attempt to cover previously exposed material.

• The material should be removed immediately if any complication develop.

• Avoid deep mechanical instrumentation and probing of the site for 6 to 9 months.

TYPES OF COMPLICATIONS POSSIBLE• Membrane exposure - the most common complication with prevalence 70- 80%

(Murphy 1995) & 50% -80% (Becker et al 1988, Cortellini et al 1993).

• Prevalence of membrane exposure has been highly reduced with the use of access flaps (MPPT, SPPT, interproximal tissue maintenance)

• Other complications Pain Swelling Abscess formation Apical perforation of the flap. Purulence Sloughing Perforation Bacterial contamination Root resorption and ankylosis

Evidence based

Non-resorbable membranes:• ePTFE membrane plus DFDBA versus allograft alone in

intrabony defects - no significant differences between groups.

• ePTFE membranes in mandibular Class II furcation defects - significant clinical improvement. However, only one study reported complete clinical closures (Pontoriero et al 1988).

• furcation defects with a combination of GTR barriers and bone

grafts appears to produce greater clinical improvements than GTR alone (Evans et al 1996).

Bioabsorbable Membranes:• Evaluations of both PLA and collagen membranes have reported

clinical improvements similar to those achieved with nonresorbable membranes.

• Addition of bone grafts with collagen membranes appears to improve the clinical results in furcation, but not intrabony, defects.

• PLA, PGA or combination of PLA and PGA - comparable clinical results to ePTFE.

• PLA/PGA copolymer to a type I collagen membrane in the treatment of intrabony defects has reported similar clinical improvements.

Furcation defects: • Most favorable results - Class II mandibular furcations.• Less favorable results - mandibular and maxillary Class III defects

and maxillary Class II defects. • Pontoriero et al. 1987 - showed complete defect closure in 67% of

Class II defects and 25% of Class III defects in the group receiving ePTFE membrane.

• Most favorable results - combination of GTR and bone grafts.• ePTFE+bone graft – significant results• Polymeric or cellulose barrier + bone grafts - no difference• Mandibular and maxillary buccal Class II furcation defects.

A systematic review of GTR for periodontal furcation defects by Jepsen in 2002 -GTR was consistently more effective than OFD in reducing open horizontal furcation depths, horizontal and vertical attachment levels and pocket depths for mandibular or maxillary class II furcation defects.

In another systematic review by Gunsolley et al, the

treatment of furcation defects, GTR procedures compared to OFD controls result in significantly more favourable gains in VPAL, reductions in VPD and improvements in HOPA measurements.

Evidence of application of GTR in Intrabony defects

• Nickles et al 2009 evaluated 10-year results after open flap debridement (OFD) and guided tissue regeneration (GTR) therapy of infrabony defects in a randomized controlled clinical trial and concluded that ten years after OFD and GTR in infrabony defects 35 of 41 teeth were still in place. The study failed to show statistically significant attachment gain differences between both groups after 120 months.

• Nygaard-ostby et al 2010 in a 10-year randomized-controlled trial evaluated the stability of treatment outcomes following the implantation of autogenous bone graft with or without guided tissue regeneration (GTR) in the treatment of deep intra-bony periodontal defects. The authors concluded that statistically significant differences were found with the adjunct use of GTR to an autogenous bone graft at 10 years.

• Stavropoulos and Karring in 2010 presented the 6-year results of a randomized-controlled clinical trial evaluating GTR combined with or without deproteinized bovine bone mineral (DBBM) (Bio-oss) in intrabony defects. Statistically significant clinical improvements were observed and these improvements can be preserved on a long term basis.

• Two meta-analyses by Laurell et al in 1998 and Cortilinni et al in 2000 have reported greater benefits to GTR than found in the present systematic review. These reviews indicated a difference in attachment gain between GTR and OFD of 2.7mm and 1.6mm difference respectively.

• In a systematic review by Needleman et al in 2002, results indicated that for attachment change, the mean difference between GTR and OFD was 1.11mm. Overall, GTR was more effective than OFD in improving attachment levels.

In another systematic review by Gunsolley et al, the conclusions drawn were:

• In the treatment of intrabony defects, GTR procedures compared to OFD controls result in significantly more favourable gains in CAL and PD.

• Meta-analysis did not show any significant superior results among the barrier types evaluated.

• The use of specialized flap techniques may enhance the clinical outcomes, but insufficient data is present.

In a chocrane based review by Needleman et al published in 2005 it was concluded that 11 out of 16 studies showed greater attachment gain for GTR than for OFD. There is little benefit of a combination therapy of bone grafts + GTR over GTR alone. Choice of flap may be important.

Evidence of application of GTR in recession defects

• Pini prato et al 1992 – First described in a comparative clinical study GTR vs mucogingival technique.

• Zucchelli et al 1998 – conducted a mucogingival and GTR study and concluded that the mucogingival bilaminar technique is at least as effective as GTR procedures in the treatment of gingival recessions and recession depth is not the parameter which influences the selection of the surgical procedure.

• Wang et al 2001 compared GTR and sub epithelial connective tissue graft – no difference in improvements was found between both the groups.

• Chambrone et al 2010 – With respect to gingival recession and keratinized tissue changes, there was a statistically significantly greater reduction in gingival recession and greater gain in the width of keratinized tissue for subepithelial connective tissue grafts compared to GTR bioabsorbable membrane sites. Concluded that GTR may be used as root-coverage procedures for the treatment of recession-type defects but better results are seen with the use of SECTG.

• Danesh-Meyer et al (2001) had reviewed the value of GTR in the management of gingival recession defects. The authors concluded that GTR does not appear to offer a significant advantage over mucogingival procedures. They recognized difficulties associated with GTR including primary wound closure, secondary membrane exposure, space maintenance and unacceptable foreign body reaction.

• Al Hamdan et al 2003 had done a meta analysis to determine whether guided tissue regeneration based root coverage (GTRC) provides significantly improved clinical outcomes compared to conventional periodontal plastic surgical approaches for the treatment of marginal tissue recession. The meta analysis concluded that guided tissue regeneration based root coverage can be used successfully to repair gingival recession defects.

Combination therapy• Karring and Cortellini 1999 indicated that an added benefit may be obtained by

the use of grafting materials in combination with barrier membranes.

• Murphy and Gunsolley 2003 examined the effect of the addition of an augmentation material under the physical barrier. Collectively reviewing all barriers - vertical probing attachment level was significantly enhanced by the addition of a particulate bone graft.

• Blumenthal et al in 1990 researched 15 test and 15 control defects with one-year reentry showed a significant improvement in collagen barrier plus DFDBA vs collagen barrier-alone treated sites. Defect fill was 63% versus 31% in favor of the collagen- and DFDBA treated sites.

• Chen et al (1995) in their study performed to evaluate the addition of bone grafts with or without collagen membranes to treat intrabony defects concluded that utilizing 6 to 12 month reentry of eight test and eight control defects showed no difference in CAL gain or defect fill between the test and control groups.

WWP and AAP in 2005 papers on periodontal regeneration in intrabony defects and furcations found the following:

• GTR provided additional benefits over OFD in CAL and PDR in intrabony defects and furcations.

• Bone replacement grafts enhance GTR treatment outcomes in furcations and not in intrabony defects.

• Bioabsorbable and nonabsorbable membranes provide similar outcomes in intrabony defects and CAL-H levels in furcations.

• Only e-ptfe membranes significantly enhanced the vertical probing attachment level in furcations.

• Acc to the participants of the workshop… GTR should be limited to mandibular and maxillary buccal grade II furcation defects.

Evaluation of GTR treatment outcome

Clinical methods– Probing- soft tissue changes (bleeding on probing) pocket depth clinical attachment level Bone levels- re-entry procedures bone sounding Radiographic bone changesHistological methodsRe-entry surgery

CURRENT STATUS/RECENT ADVANCES IN GTR

• Inion GTR membrane - biomedical material of the third generation which combines biodegradability with bioactivity.

• Tetracyclines (Chung et al 1997).

• Membranes containing metronidazole

• Incorporation of CHX into GTR membranes (Chen et al. 2003)

• Combination of growth and differentiation factors like PDGF,emdogain and BMPS.

ADDITION OF ANTI MICROBIAL SUBSTANCES

• Controlling bacterial colonization in the early healing phase and reducing the spread of infection. The addition of antimicrobial substances increase predictability.

• Hung et al (2005) - incorporation of amoxicillin or tetracycline into various GTR membranes may enhance the attachment of periodontal ligament cells in the presence of the oral pathogens S mutans and Aac.

• Cheng et al (2009) - penetration of S mutans and Aac through amoxicillin- or tetracycline loaded ePTFE, glycolide fiber and collagen membrane was delayed and/or reduced.

• Bottino et al (2011) proposed a novel Functionally graded membrane (FGM) designed and fabricated via sequential multilayer electrospinning. Consists of a core layer and two functional surface layers interfacing with bone (n-HA) and epithelial tissues. Incorporation of n-HA to enhance osteoconductive behavior and metronidazole to combat periodontal pathogens.

MICROBIOTA OF FAILING GTR

• Mombelli et al 1997 gram- negative anerobic rods made up 31% of total membrane isolates at 6 weeks post surgery .

• One site yielded high proportions of P.gingivalis, 6 sites demonstrated Prevotella intermedia and 6 sites showed Prevotella melaninogenica.

• Fusobacterium and Capnocytophaga species were also frequent membrane isolates.

• Nowzari & Slots 1995 detected P.gingivalis in 3 periodontal sites that experienced a net loss of clinical attachment after membrane removal.

• A.actinomycetemcomitans was recovered from a periodontal sites that gained as little as 1mm of probing attachment.

• Total microbial counts and percentage of Peptostreptococcus micros, Capnocytophaga species and motile rods on barrier membranes seemed also negatively to affect periodontal regeneration.

CONCLUSION• The principle of GTR lies in the establishment of the cells of periodontal ligament to

selectively repopulated the root surface.

• Clot establishment and stabilization, site selection, epithelial cell exclusion, space provision, neovascularization, and complete gingival coverage are favourable characteristics in any GTR procedure.

• The use of GTR membranes can lead to significant periodontal regeneration and formation of cementum with inserting fibers, although complete regeneration has never been reported.

• It has considerable value as a regenerative procedure, particularly in intrabony, furcation and gingival recession defects.

• In the future, GTR can be combined with the use of biological growth factors that allowed for selectively control the type of cells proliferated from the fibroblast precursor.

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