Guided Tissue Regeneration

GUIDED TISSUE REGENERATION
Dr. Rinisha Sinha
MDS Part II Postgraduate Trainee

Contents
• Introduction
• Terminologies
• Methods to assess regeneration
• Biologic rationale of GTR
• Objectives of GTR
• Indications & Contraindications of GTR
• Ideal Barrier membrane
• Functions of Barrier Membrane
• Procedural Guidelines
• Clinical wound healing after GTR
• Various barrier materials for GTR
• GTR in the treatment of Intrabony Defects
• GTR in the treatment of Furcation Defects
• GTR for root coverage procedures
• Localized ridge augmentation with barrier membranes
• Surgical complications with GTR procedures
• Summary & Conclusion.

INTRODUCTION
❖ Periodontal therapy has two major and interrelated goals:
□ Reduction or the elimination of tissue inﬂammation induced
by the bacterial plaque and its byproducts.
□ Correction of the defects and the anatomic problems
caused by the disease process.
❖ Traditional surgical approaches offer limited potential towards
recovering tissues destroyed earlier by the disease phases.
❖ The type of healing that follows the conventional surgical therapy is
described as repair = Connective Tissue Adhesion + Attachment or
Formation of a long Junctional Epithelium.

Since the early 1980s, however, periodontal surgeons
have been approaching this problem, by treatment
modalities grouped under the term Guided Tissue
Regeneration (GTR).

TERMINOLOGIES
❖ 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.
Reference : Glossary of Periodontal Terms; 1992
❖ New Attachment is the embedding of new periodontal ligament ﬁbers
into new cementum and the attachment of the gingival epithelium to
a tooth surface previously denuded by disease.
❖ Reattachment refers to repair in areas of the root not previously
exposed to the pocket, such as after surgical detachment of the
tissues or following traumatic tears in the cementum, tooth fractures,
or the treatment of periapical lesions.

❖ Repair simply restores the continuity of the diseased marginal gingiva
and reestablishes a normal gingival sulcus at the same level on the root
as the base of the pre-existing periodontal pocket.
TERMINOLOGIES
❖ Epithelial adaptation differs from new attachment in that it is the close
adaptation of the gingival epithelium to the tooth surface, with no
gain in the height of gingival ﬁber attachment.
❖ The pocket is not completely obliterated although it may not permit
the penetration of the probe.
❖ These deep sulci lined by long, thin epithelium may be as resistant to
disease as true connective tissue attachments
Reference : (Beaumont RH et al, 1984; Magnusson I et al, 1983)

Regeneration
❖ Regeneration of the periodontium is a continuous
physiological process.
❖ It occurs even during destructive periodontal disease.
❖ It is a part of healing.
❖ However, bacteria and its products that perpetuate the disease
process and are injurious to regenerating cells & tissues, thus
preventing completion of healing process.
❖ By removing bacterial plaque & creating conditions to prevent its
formation, periodontal treatment removes obstacles to
regeneration.

Epithelial Adaptation
❖ Absence of bleeding on
probing, clinically visible
inﬂammation and stainable
plaque on the root surface
when pocket wall is deﬂected
from the tooth may indicate
that “Deep sulcus” persists in
inactive state, causing no
further loss of attachment.
❖ A post therapy depth of 4-5
mm acceptable in these cases.
Reference : Caffesse RG, Ramfjord 1968

Methods to Assess Regeneration
Periodontal
probing
Radiographic
analysis
Direct
measurement
of new bone
Histology

❖ AAP workshop in 1996:
□ Human histological specimens demonstrating formation of new
cementum, periodontal ligament and bone coronal to a notch
indicating the apical extension of the periodontitis affected root
surface.
□ Controlled human clinical trials demonstrating improved clinical
probing attachment and bone.
□ Controlled animal histological studies demonstrating formation of
new cementum, periodontal ligament, and bone.
Methods to Assess Regeneration

Melcher’s theory of
Compartmentalisation (1976)
During healing of pocket, cells invade from four sources:
• epithelium
• Gingival connective tissue
• Alveolar bone
• Periodontal ligament.
Final outcome determined
by cell type which
predominates in healing.

Compartmentalisation
Epithelial cells
Long junctional epithelium
Cells from gingival connective
tissue
fibres parallel to tooth surface ,
remodelling of alveolar bone
and no attachment to
cementum.
Bone cells
Root resorption and ankylosis.
Periodontal cells
new formation of cementum,

Regeneration potential – Bone Cells
❖ :
Researcher Study Conclusion
Lindhe et
al; 1984
monkeys
bone may stimulate the formation of
new connective tissue attachment .
Mandibular and Maxillary incisors
were extracted and reimplanted in
their own sockets under:
Fibrous reunion in
areas where
periodontal
connective tissue
attachment was
retained.
Non-root planed teeth into sockets
normal bone height and reduced bone
height.
Teeth root planed in their coronal
portion, into sockets with normal bone
height and reduced bone height
In areas where
periodontal
was removed ,
epithelium had
always migrated to
the apical extension
of root
instrumentation.
Histologic examination after 6 months

❖
.
Karring et
al 1984
Root of Periodontitis affected
teeth were extracted and
placed in surgically created
sockets in edentulous areas of
dogs.
Periodontal ligament re-
established in apical
of the reimplanted root,
where remnants of pdl
preserved.
Implanted roots covered with
tissue ﬂaps (submerged).
Examined histologically after 3
months.
Coronal portion where root
was scaled and planed,
healing consistently resulted
in ankylosis and root
resorption.
Regeneration potential – Bone Cells
Tissue derived from bone lacks potential for new connective tissue attachment

Regeneration potential - Gingival
connective tissue cells
❖
.
❖
.
Nyman et
al 1980
Root of Periodontitis affected
teeth were extracted and
placed in bone concavities
prepared on the buccal aspect
of the jaws and subsequently
covered by tissue ﬂaps.
Areas with periodontal ligament in
apical portion of roots, where pdl
was previously preserved.
coronally , previously exposed
roots,no signs of new connective
tissue attachment seen.
Partly facing bone and partly
the gingival connective tissue.
Connective tissue with ﬁbres
oriented parallel to root surface
and without attachment root
surface seen.
Histologic examination after
3 months. Root resorption occurred at
majority of surfaces
Gingival connective tissue lacks cells to produce new connective tissue attachment

Regeneration potential - PDL cells
Karring et al;
1985
Healthy and Periodontitis –
involved roots were retained in
their sockets and then
submerged.
Signiﬁcant amounts of new
connective tissue attachment
was observed.
New attachment occurs only on
roots with non-impaired PDL.
Never seen on extracted and
reimplanted teeth with impaired
PDL.
Root resorption observed
occasionally even in the apical
portion of extracted and
reimplanted roots.
Due to retained PDL being
injured and allowing bone and
connective tissue to come in
contact with root surface.
Also damage of PDL prevented
its proliferation in the coronal
direction.

Regeneration potential – Periodontal Ligament
Busser et al 1990, Titanium dental implants Distinct layer of cementum
Warrer et al placed in contact with with inserting collagen ﬁbres
1993: retained root tips, whose formed on the surface of
pdl cells served as a implant.
source for cells which Fibres oriented
could repopulate the perpendicularly and inserted
implant surface during into opposite bone.
healing. Control implants placed
Microscopic analysis done without contact with retained
roots healed with
characteristic features of
osseointegration.

Role of PDL in Regeneration
❖ PDL contains cells with potential to form new connective
tissue attachment.
❖ The apical migration of epithelium reduces the coronal gain
of attachment, evidently by preventing periodontal ligament
cells from repopulating the root surface.
❖ Downgrowth of epithelium (long junctional epithelium) into
the periodontal lesion has most likely occurred to a varying
extent during healing following most ﬂap and grafting
procedures applied in regenerative periodontal therapy, which
may explain the varying results reported.

IDEAL OUTCOME
❖ Aim of the periodontal therapy or the Ideal outcome
of therapy is New Attachment with Bone
Regeneration.

BIOLOGIC RATIONALE OF GTR
New attachment will occur only if periodontal ligament cells
repopulate the root surface during healing, as progenitor cells
for the formation of new attachment, are residing in the
periodontal ligament.
Since gingival epithelium is the fastest tissue to proliferate,
followed by gingival connective tissue, it follows then by
placing a barrier to exclude the epithelium and connective
tissue selectively and allowing periodontal ligament cells to
repopulate the root, new attachment would be obtained.
❖This view was conﬁrmed in a study in monkeys in which both
gingival connective tissue and gingival epithelium were
prevented from contacting the root surface during healing by
the use of a barrier membrane.
Reference : Gottlow et al. 1984

So what is GTR……?
❖ 1996 World Workshop in Periodontics deﬁned
❖ Guided Tissue Regeneration as “procedures attempting to
regenerate lost periodontal structures through differential tissue
responses. Barriers are employed in the hope of excluding
epithelium & gingival corium from the root surface in the belief
that they interfere with regeneration.”
❖ Guided tissue regeneration is the method for the prevention
of epithelial migration along the cemental wall of the
pocket.

Objectives of GTR
Giving preference to cells that
repopulate the wound and
have the potential to
regenerate tissue.
Excluding cells that may
negatively interfere with tissue
regeneration.
Creating suﬃcient space to
allow formation of desired
tissue.
To protect and stabilize blood
clot.

Indications of GTR
❖ Patient selection is extremely important.
□ Favorable results are observed in healthy, non-smoking patients who
demonstrate good plaque control & compliance with other oral
hygiene recommendations.
❖ Speciﬁc defects that show optimal regenerative healing
with GTR includes:
□ Narrow 2 wall or 3 wall infrabony defects with atleast 4mm of
attachment loss and a 4mm infrabony component.
□ Circumferential defects.
□ Class II furcation defects accompanied by a medium to long root
trunk. Reference: Wang HL, MacNeil RL; 1998

❖ GTR is also beneficial if the following non-osseous conditions
co-exists with these types of bone defects:
□ Presence of 1 mm or more of keratinized gingiva.
□ 1 mm or more of flap thickness.
□ Absence of co-factors such as occlusal trauma & endodontic
infection.
❖ Even in these selected situations, however the results can be
inconsistent, especially when considering the class II furcal
defects.
❖ Other potential indications of GTR includes:
□ Augmentation of ridge deficiencies
□ Coverage of root recession
Indications of GTR

(Wang HL, MacNeil RL, 1998 & Gray JL, Hancock EB, 1998)
❖ GTR is generally not recommended for patients with
poor oral hygiene and in the treatment of following
clinical situations:
□ Generalized horizontal bone loss.
□ Class II furcations on the mesial and distal of maxillary
molars.
□ Class III furcation defects.
□ Premolar furcations.
□ Advanced defects with minimal amount of
remaining periodontium.
Contraindications of GTR

Ideal Barrier Membrane
Should be biocompatible & should not elicit an immune response
Should act as a barrier to exclude undesirable cell types from entering the secluded
space adjacent to the root surface.
It is also considered an advantage if the material allows the passage of nutrients and
gases.
Tissue integration is another important property of a barrier material.
It is also essential that the barrier material is capable of creating and maintaining a
space adjacent to the root surface.
Should be provided in conﬁgurations which are easy to trim and to place.

Should be nontoxic, non-carcinogenic.
Should be sterile or have the ability to be sterilized easily.
Should have easy handling characteristics during surgery.
Should have long shelf life and be easily stored.
Should preferably be bioresorbable.
Should be retrievable in case of complications
Should be inexpensive.

FUNCTIONS OF A MEMBRANE
❖ Cell occlusive: To predictably isolate and protect the
defect space.
❖ Space making: To create and maintain space in
which clot can form and regeneration can occur.
❖ Epithelial inhibition: To prevent deep pocketing
and interference with regeneration beneath the
material.
❖ Clot stabilization: To enhance healing through
incorporation of material with the surrounding tissues.

PROCEDURAL GUIDELINES
Patient selection
Defects selection
Anesthesia
Incision and ﬂap reﬂection
Wound debridement and root planing
Membrane placement
Wound closure
Periodontal dressing
Post-operative care

Factors adversely affecting the clinical
outcomes after GTR therapy
 Barrier - Independent
Factors
 ✔ Poor plaque control
 ✔ Smoking
 ✔ Occlusal Trauma
 ✔ Mechanical habits
 ✔ Gingival tissue
 ✔ Surgical technique
 ✔ Post-surgical factors
 Barrier -
dependent Factors
 ✔ Inadequate root-barrier
adaptation
 ✔ Nonsterile technique
 ✔ Instability of barrier
 ✔ Premature exposure of
the barrier

Clinical wound healing:
❖ Four clinical patterns of GTR healing have been
identiﬁed.
□ Rapid
□ Typical
□ Delayed
□ Adverse

Barrier Materials For GTR
❖ First Generation (Non-resorbable):
Millipore® ﬁlter
Expanded polytetraﬂuroethylene (e-PTFE) (Gore-Tex®)
e-PTFE + Titanium reinforced (Ti reinforced Gore-
Tex®)
Non porous e-PTFE (TefGen-FD®)
Rubber dam
Composition non absorbable device

❖ Second Generation (Bio-resorbable)
NATURAL
✔ Collagen (Biomed,
Bioguide, Paroguide,
Tissue guide)
✔ Oxidized Cellulose
✔ Connective tissue grafts
✔ Duramater, Cargile
Membrane, Laminnar
SYNTHETIC
✔ Polylactic acid
(Atrisorb, Guidour,
Resolut)
✔ Polyglactin 910 (Vicryl
mesh)
✔ PLA + PGA

❖ Third Generation (Bio-resorbable with growth
factors)
Being developed

Non-resorbable Barriers
❖ General considerations:
Maintain structural integrity.
Stability provides operator with complete control at the
time of application.
Requires second surgical for removal.
Tissue integration function can be accomplished.

❖ Millipore® filter:
□ It was first ever GTR membrane to be used.
□ It is bacterial filter produced from cellulose acetate.
□ Nyman et al, 1982 were the first ones to use a
barrier for regenerative surgery.
□ Gottlow et al. 1984, Magnusson et al. 1985 also used
Milipore® filter for GTR.
□ Although this type of membrane served its purpose, it
was not ideal for clinical application.

❖ Expanded polytetraﬂuroethylene (e-PTFE):
□ The basic molecule of this material consists of a carbon-
carbon bond with four attached ﬂuorine atoms to form a
polymer.
□ It is inert, does not result in any tissue reaction when
implanted in the body and allows tissue ingrowth.
□ To date, Gore-Tex® Membrane (W.L Gore and
Associates, Flagstaff, AHZ) has been most widely
used material.

□ It consists of an open microstructure collar and an
occlusive apron.
□ Collar: 1.0mm thick, porous (100-300um)
□ Apron: 0.15mm thick; 30% porous
□ The collar allows a space for clot formation and early
collagen penetration. The clot and immature collagen ﬁbrils
may stop epithelial proliferation by contact inhibition (Winter
1974).
□ The occlusive apron prevents gingival epithelium and

□ Gore-Tex® is available in various shapes.
Transgingival
Conﬁgurations
Submerged
Conﬁgurations

Goretex
Treatment of furcation invasion defects with nonresorbable membranes.
(A) A nonresorbable ePTFE membrane (GORE-TEX) is adapted to cover a
furcation defect.
(B) A second surgical procedure is performed 6 weeks after the initial
surgery to remove the nonresorbable membrane. Note the presence of a
mature granulation tissue.

❖ e-PTFE + Titanium Reinforced:
□ Titanium is set between two layers of E-PTFE to improve
surface and mechanical properties.
□ The rigidity of this material supports improves space
provision and maintenance.
❖ The biological potential of e-PTFE has been
demonstrated in various animal studies, and human
studies where clinically relevant bone and cementum
regeneration was evident.

□ Gore-Tex®, titanium reinforced is also available in
various shapes.
Transgingival
Conﬁgurations
Submerged
Conﬁgurations

❖ Non porous e-PTFE (TefGen-FD):
□ Shows limited tissue integration.
□ This high density non porous e-PTFE is a relatively
closed structure.
□Although the membrane is usually
removed after 21 days, it can remain
in place for 9 months without any
adverse reactions.
□ Has shown successful regeneration.

❖ Rubber Dam:
□ Sterilized rubber dam was used by Cortellini et al,
1994, however it has not been approved by the U.S.
FDA for GTR.
❖ Diadvantages:
□ Little rigidity to assure space maintenance.
□ Tedious to manipulate.
□ Exhibits no tissue integration.

❖ Composition non absorbable device:
□ It is made out of nylon fabric mechanically bonded
onto a semipermeable silicon membrane and
coated with collagen peptides (Biobrane®).
□ The disadvantage lies in the fact, that it has limited
space making abilities.

Resorbable Barriers
❖ General considerations:
□ Do not require additional surgery for removal, which
reduce patient discomfort, chairside time and related
cost.
□ Limited control over length of application because the
disintegration process starts upon placement in the
tissues and the ability of each individual patient to
degrade a particular biomaterial may vary signiﬁcantly
particularly for materials requiring enzymatic degradation

❖ Collagen: (Pitaru 1987)
□ The properties of collagen that makes it useful as a barrier
material (Wang HL & MacNeil RL, 1998)
□ Natural component of periodontal tissues, well tolerated
□ Weak immunogenic, favorable response
□ Malleable – can be formed shaped & manipulated
□ Possess haemostatic properties through its ability to aggregate
platelets
□ Supports cell proliferation via lattice structure & cell binding
domains
□ Facilitates early wound stabilization & maturation
□ Chemotatic for ﬁbroblasts
Resorbable Barriers

❖ Collagen:
□ It was ﬁrst used by Pitaru in 1987.
□ The collagen found in GTR barriers can be various
subtypes (usually type I collagen is predominant) & can
be derived from various animal sources (bovine vs
porcine; tendon vs dermis).
□ They are made by using extrusion-coagulation and air
drying to from sheets of material from dilute (< 1%)
collagen solutions.
□ Most barriers are cross linked to extend the
absorption time and to reduce antigenicity, the
Resorbable Barriers

❖ The various commercially available collagen
barriers are:
Resorbable Barriers

❖ Collagen:
□ Type I collagen barriers for GTR have shown results
comparable with those reported with traditional
membranes (like e-PTFE).
□ Van Swol et al, 1993 compared GTR with collagen & open
ﬂap debridement for treating class II furcation defects.
GTR showed greater reduction in horizontal furcation
measurements & greater vertical bone ﬁll than
debridement alone, after 3 months.
□ Yukna & Yukan, 1996 showed greater improvement in
Resorbable Barriers

Biomend &
Biomend
Extend
Bio - Guide
Membrane

❖ Collagen:
□ When a collagen membrane is implanted in the human
body it is resorbed by the enzymatic activity of
macrophages and polymorphonuclear leukocytes
(Tatakis et al, 1999).
□ Complications such as early degradation, epithelial
downgrowth along the material and premature loss of
material were reported following the use of collagen
membranes.
□ The varying results are probably due to the differences
in the properties of the material and the handling at the
Resorbable Barriers

❖ Polylactic Acid & Polyglycolic Acid Polymers:
□ They are synthesized by copolymerization of different
forms of polylactic acid (PLA), polyglygolic acid (PGA), or
mixtures of PLA & PGA.
□ Barrier degradation occurs by hydrolysis of the ester
bonds, a process that requires 30 to 60 plus days
depending on the polymeric composition of the material.
□ Most studies indicate that polymer barriers when used in
GTR therapy, provide results comparable to other
materials including e PTFE
Resorbable Barriers

❖ Polylactic Acid & Polyglycolic Acid
Polymers:
Membrane FDA Company Components
Guidor Yes Butler Co, Chicago, IL PLA & acetyltri-
butyl acetate
Vicryl Yes Ethicon Lab, New Brunswick,
NJ
PLA/PGA
Atrisorb Yes Atrix Lab, Fort Colins, CO PLA/PGA
Resolut Yes W.L, Gore, Flagstaff, AZ PLA/PGA
Epigude Yes THM Biomedical, Duluth, MN PLA (D, L forms)
Bioﬁx No Bioscience LTD, Tempere,
Finland
PGA
Resorbable Barriers

1)Guidor –
• Hydrophobic barrier made from PLA combined with a citric acid
ester softening agent.
• Bilayered – external layer (facing the gingival tissues) has large
(400 to 500/ cm2
) rectangular perforations; internal layer (facing
the root) has smaller (4000 to 5000/ cm2
) circular perforations.
• Designed to resist degradation for upto 3 months, whereby it is
gradually replaced by new periodontal attachment.
• Clinical studies have indicated favorable results, in treatment of
furcation defects, gingival recession, & ridge augmentation.
Resorbable Barriers

2) Vicryl –
• The mesh (polyglactin 910) is made from same copolymer
of glycolide & lactide used in vicryl sutures and is available
as a woven or knitted mesh.
• The knitted mesh has a larger pore size.
• Thought to degrade over a period of 3 to 12 weeks.
• Studies indicate that Vicryl mesh & e-PTFE are equally
effective as GTR barrier materials. (Sander 1995)
Resorbable Barriers

3) Atrisorb –
• Consists of polymer of poly (D,L-lactide) (PLA), dissolved in N-
methyl-2-pyrrolidone (NMP).
• It is prepared as a solution that coagulates or sets to a firm
consistency on contact with water or other aqueous solution.
• This principle is used in forming a barrier that is partially
coagulated to a semirigid state in a chairside mixing kit.
• The barrier is trimmed to the required dimensions, and is flexible
enough to adapt to the defect, yet rigid enough to support the
overlying tissues. The barrier solidifies completely within the fluid
environment of the pocket.
Resorbable Barriers

❖ A newer generation ATRISORB® product, known as
ATRISORB FREE FLOW BARRIER, has recently been
introduced for GTR procedures.
❖ With this material, it is not necessary to fabricate a
GTR membrane. It is applied as a viscous gel over
bone graft replacement material as a direct in situ
technique.
❖ The synthetic barrier then hardens into a biodegradable
semisolid material when sprayed with sterile water or
saline. This free ﬂow technique creates a more intimate
Resorbable Barriers

4) Resolut –
• It is copolymer of PGA & PLA that degrades over 4
weeks to 8 months.
• Studies have shown that the results are comparable with
those obtained with the use e-PTFE barriers.
• Available in various sizes and shapes.
Resorbable Barriers

5) Epi-Guide –
• It is hydrophilic membrane formed from PLA (D,L forms).
• It contains a ﬂexible open cell structure (thought to encourage
the uptake ﬂuid, blood & adherence to tooth surface) and
internal void spaces (thought to help blood clot formation).
• Multicenter trails comparing Epi-Guide with Guidor materials
suggest equivalency in promoting tissue repair & regeneration.
(Vernino 1995)
Resorbable Barriers

ATRISORB
VICRYL BIO-
GUIDE
Resorbable Barriers

RESOLUTION
Resorbable Barriers
Transgingival
Conﬁguration
s
Submerged
Conﬁguration
s

□ The polymers of PLA/PGA are degraded by hydrolysis
and eliminated from the organism through the Krebs
cycle as carbon dioxide and water
(Tatkis et al, 1999).
Resorbable Barriers

Disadvantages of Nonresorbable
Membranes
❖ 2nd surgical intervention is necessary
❖ Surgical trauma to newly formed tissues
❖ Expensive
❖ Recession and Bacterial contamination
❖ Fixation of hard membrane may be diﬃcult and
time consuming.

Advantages of Resorbable
Membranes
❖ Elimination of second surgery for barrier removal:
□ operatory time & thus may reduce total cost.
□ overall treatment morbidity.
□ patient acceptance of GTR procedures.
□ risk of loss of regenerated attachment owing to reentry.
❖ Biologically absorbable material holds potential to:
□ Be more tissue friendly & integrated with the host.
□ Enhances tissue coverage and reduce barrier exposure.
□ Resist or prevent microbial colonization.

Other Resorbable Barriers
❖ Periosteum:
□ As a structure rich in osteoprogenitor cells, the periosteum
has long been viewed as having regenerative potential.
□ Coronally repositioned mucoperiosteal ﬂaps is known to
foster new attachment formation and this phenomenon is
thought to result from a combination of the cellular activity of
the periosteum and a barrier type effect by the repositioned
periosteum
□ (Gantes B et al, 1988).

❖ Connective tissue graft:
□ Lekovic et al, 1991 used connective tissue grafts
including periosteum as barriers in 15 patients with
mandibular class II furcations, and found signiﬁcant
reduction in pocket depth & gain in attachment.
□ Bouchard et al, 1993 compared C.T. grafts without
periosteum to e-PTFE barrier and reported similar
outcomes.
□ However, scientiﬁc data is still less regarding its use.

❖ Freeze Dried Duramater:
□ These are procured from human cadavers are
mainly composed of collagen and have low
immunogenicity.
□ Yukna, 1992 found no signiﬁcant differences between
GTR treatment using freeze dried duramater and e-
PTFE as barrier membranes in treating class II
furcation defects.

❖ Lambone:
□ These are sheets or strips of demineralized laminar or cortical
bone, and have been used as barrier membranes around implants
and periodontal defects.
□ Bone sheets can be purchased in thickness of 20 to 100; 100 to
300; & 300 to 700 um, & require hydration for approximately 10
minutes before clinical use.
□ Yamaoka et al, 1996 found unicortical ileum bone sheets to be as
effective as e-PTFE in human class II furcation defects.

❖ Oxidized cellulose (Surgicel):
□ It is absorbable haemostatic dressing available in the form of
knitted ﬁbrous mesh.
□ When placed in contact with blood, it converts to a gelatinous
mass (blood/membrane continuum), which has been reported to
potentiate osseous and soft tissue regeneration in congenitally
maxillary cleft reconstructive surgery (Skoog T, 1967)
□ Surgicel & Gelfoam (Cellulose) have been proposed and used as
biodegradable barriers in treatment of furcation defects & infrabony
defects (Calgut PN, 1990, 1993)

❖ Alkali Cellulose (Gengiﬂex):
□ It is a similar material that has been used in ﬁlling and
covering extraction sockets after immediate implant
placement
□ (Novaes AB, 1993).
□ Although the use of these haemostatic cellulose products
appears promising, controlled animal and clinical studies are
needed before these materials can be considered as true
GTR barriers.

❖ Calcium sulfate (Capset):
□ It has been used in conjunction with DFDBA for GTR
purposes and case reports indicate some utility (Anson D,
1996; Sottosanti JS, 1993).
□ It is proposed to have following advantages:
• Excellent tissue response
• Low incidence of infection, if exposed
• Good adaptation & adherence to root surfaces including
concavities
• Shorter chairtime, allowing multiple defects with greater
ease.

❖ Cargile membrane:
□ It is derived from ox cecum and has been used in GTR
treatment of natural periodontal defects in beagle dogs
□ (Card SJ, 1989; Kon S, 1991).
□ This material may have limited use in GTR therapy
because it is reported to be diﬃcult to manipulate and
secure into position over periodontal defects.

❖ Pericardium:
□ Pericardium® is obtained from human heart of healthy autopsy
specimens within 24hours of death, composed of Type I human
collagen.
□ It is then rinsed in a sterile physiological saline solution and the
subserous fat is removed along with the vessels and nerves.
□ The remaining ﬁbrous membrane is stabilized and crosslinked with
the help of glutaraldehyde (2%).
□ After removal of the remaining glutaraldehyde by repeated
washing in sterile physiological saline solution, the tissue is
freeze dried ﬂat and subsequently wrapped in plastic bags.

❖ Pericardium:
□ Sterilization is performed by gamma-radiation or by
means of ethylene oxide in peel-stabilization packs.
□ Available in four sizes, 1x1 cm, 2x2cm,
2x4cm and 3x3 cm.
□ It however carries the risk of antigenic
reaction or disease transfer

❖ Emdogain
□ Not all cells involved in periodontal regeneration respond to
EMD in a comparable manner.
□ Attachment rate, growth factor production, proliferation and
metabolism of human PDL cells were all signiﬁcantly increased in
presence of EMD (Lyngstadaas et al, 2001).
□ Furthermore it has been shown that EMD also seems to exhibit a
cytostatic effect upon cultured epithelial cells (Gestrelius et al,
1997; Kawase et al, 2000).
□ This may explain EMDs “Biological Guided Tissue Regeneration”
effect observed in vivo, analogous to mechanical barriers.

Other Barriers
❖ Alloderm:
□ Alloderm is a dermal graft harvested from Cadavers and
processed to remove the epidermal and dermal cells.
□ The ﬁnal product after processing is an acellular, non-
immunogenic connective tissue matrix, complete with a basement
membrane complex and retained vascular channels.
□ It has been widely used for root coverage procedures as an
alternative to SCTG & to increase the width of attached gingiva.

Other Barriers
❖ Alloderm:
□ Tal (1999) suggested that acellular dermal matrix graft may also act
as a barrier equivalent to selective repopulation membrane placed
between the gingival connective tissue on one side and the
exposed bone, periodontal ligament and root surface on the other,
thus encouraging periodontal guide tissue regeneration.

GTR in Intrabony Defects
❖ Early evidence that GTR treatment of deep intrabony defects may
produce clinical improvements in terms of clinical attachment gain
was presented in several case reports (Nyman et al. 1982, Gottlow
et al. 1986 Becker et al. 1988, Schallhorn & McClain 1988,
Cortellini et al. 1990).
❖ Cortellini & Tonetti, 2000 in a review (which included a number of
recent studies) , reported a total of 1283 intrabony defects treated with
GTR. The weighted mean of the reported results indicated a mean
gain in clinical attachment of 3.8 ± 1.7 mm, which was signiﬁcantly
larger than the ones obtained from conventional ﬂap surgery

❖ A recent review (Lang 2000) on conventional ﬂap surgery reported a
weighted mean of the clinical attachment gain as 1.172 defects in 40
studies.
❖ In the same review article (Cortellini & Tonetti, 2000) it was shown
that application of non-resorbable or bioresorbable barriers
membranes consistently and predictably resulted in the same clinical
improvements in the intrabony defects.
❖ Also, it was shown that shallow pockets were consistently found
(weighted mean of residual pocket depth being 3.4±1.2 mm) at the
end of 1 year, after the use of GTR.

❖ In some of the investigations, changes in bone levels
were also reported (Becker et al. 1988, Handelsman et
al. 1991, Kersten et al. 1992, Cortellini et al. 1993,
Selvig et al 1993).
❖ Bone gains in these studies ranged between 1.1 and 4.3
mm and correlated with the reported gains in clinical
attachment.

❖ Combination Treatment in Intrabony Defects:
□ Schallhorn & McClain suggested that the use of combination
therapy of bone grafting & barrier membrane may result in an
improved clinical outcomes.
□ However four studies (Chen CC et al, 1995; Kilic A et al, 1997;
Kim C et al, 1996 & Mellado JR et al, 1995) evaluating the added
beneﬁt of bone grafts & substitutes used in combination with
barrier membranes failed to demonstrate an additive effect.

Factors affecting clinical outcomes
of GTR in intrabony defects
❖ A series of factors associated with the clinical outcomes were
identiﬁed using multivariate approaches (Tonetti et al. 1993,
1995,1996, Cortellini et al 1994, Machtei et al 1994). These
studies have evaluated three types of factors associated with
the observed variability of the results:
□ Patient factors
□ Defect factors
□ Factors associated with the GTR technique and the
healing period.

Factors affecting clinical outcomes of GTR in intrabony
defects
❖ Patient
Factors:

of GTR in intrabony defects
❖ Defect
factors:
Shallo
w
(≤ 3
mm)
Defect
Anatomy
Gingival
thickness (≥ 1
mm)
1,2 or 3 wall
defect
WIDE (≥ 37
degrees) NARROW (≤ 25
degrees)
Deep
(> 3
mm)
Deep
(> 3
mm)
Shallow
(≤ 3
mm)
Increasing
Predictability

Factors affecting clinical outcomes of GTR in
intrabony defects
❖ Technical considerations:
□ Successful GTR requires careful ﬂap design, correct
placement of the material, good closure of the wound
and optimal postoperative plaque control.
□ Membrane exposure is reported to be a major
complication of GTR with a prevalence in the range of
50 to 100%. Many studies have shown that the exposed
membranes are contaminated with bacteria.

Factors affecting clinical outcomes of GTR in intrabony
defects
□ Contamination of exposed non-bioabsorbable as well as
bioabsorbable membranes was associated with lower probing
attachment level gains in intrabony detects (Selvig et al. 1992,
Nowzari & Slots 1994, Nowzari et al. 1995, DeSanctis et al. 1996).
□ Although the use of local or systemic antibiotics may reduce the
bacterial load on exposed membranes, it seems ineffective in
preventing the formation of a microbial bioﬁlm (Frandsen et al.
1994, Nowzari et al. 1995).

intrabony defects
□ Another important issue associated with the clinical results is the
coverage of the regenerated tissue after removal of a non-
bioabsorbable membrane.
□ Incomplete coverage of the regenerated tissue was associated
with reduced attachment and bone gain at 1 year (Tonetti et al.
1993).
□ Recently, the positioning of a saddle-shaped free gingival graft
over the regenerated interproximal tissue was suggested

GTR in Furcation Involvement
❖ According to a review (Sanz M & Giovannoli JL, 2000)
□ Mandibular class II furcation:
• If furcation closure is considered as the main endpoint of GTR
therapy, the results obtained are very limited, since no study
has shown this, even in 50% of the cases.
• If conversion from class II to class I is considered as the main
endpoint, the GTR therapy is again unpredictable. In some
studies, this event occurs in majority of the cases, while in
others, the incidence doesn’t reach even 50% of the cases.

GTR in furcation involvement
• If clinical attachment gain, is taken as the criteria of success,
then expected gains are around 2.0 mm in the vertical direction
and around 2.5 mm in the horizontal direction.
• Considering the standard mode of therapy (open flap
debridement) which according to various studies show 1.0 mm
attachment gain in both horizontal and vertical directions, this
1.0 - 1.5 mm of benefit by GTR is only modest and of doubtful
clinical significance.

• GTR procedures in treatment of furcation defects
demonstrate similar outcomes when different membrane
barrier materials (resorbable vs non-resorbable) are
compared.
• Advantages in patient management would therefore
recommend the use of polylactic acid based resorbable
membranes.

• If the eﬃcacy of root conditioning or systemic antibiotics in
conjunction with GTR in class II mandibular furcation is to be
considered, the conditioning of the root, either by means of
citric acid, tetracycline does not improve the clinical results
compared with placing the membrane alone.
• Clinical attachment gains both vertically & horizontally are of
similar magnitude, showing a limited clinical signiﬁcance of this
approach.

• If the efficacy of bone replacement graft in combination with
GTR is to be considered, the results obtained in controlled
studies demonstrate that the use of bone replacements
with barrier membranes is of limited significant additional
benefit, if any, to the use of membranes alone.
• Although a significant clinical benefit has been reported by
some studies, this is unpredictable and does not

□ Maxillary class II furcation:
• According to various studies, the placement of
barrier in this clinical situation does not add any
beneﬁt when compared to the standard treatment
(open ﬂap debridement).
• The location of the maxillary furcation (buccal,
mesial or lingual) does not change the clinical
outcome.

□ Class III furcation:
• Four investigations on the treatment of mandibular
degree III furcations (Becker et al, 1998; Pontoriero
et al, 1989; Cortellini et al, 1990; Pontoriero and
Lindhe, 1995) indicate that the treatment of such
defects with GTR is unpredictable.

furcation defects
❖ The great variability in the results obtained with GTR in furcation
defects, is probably related to the factors discussed relative to the
intrabony defects.
❖ Regarding defect factors, it was shown that ﬁrst and second
mandibular molars and buccal and lingual furcations respond equally
well to GTR treatment (Pontoriero et al 1988, Machtei et al 1994).
❖ The deeper the baseline horizontal pocket, the greater was the H- CAL
and bone gain. The anatomy of the furcations in terms of height, width,
depth and volume, however, does not correlate with

of GTR in furcation defects
❖ Anderegg et al (1995) demonstrated that sites with a
gingival thickness of > 1 mm exhibited less gingival
recession post surgery than sites with a gingival thickness
of less than 1 mm.
❖ Based on present evidence, it seems that mandibular
degree II furcations in the ﬁrst or second molars, either
buccal or lingual, with deep pockets at baseline and a
gingival thickness of greater than 1 mm may beneﬁt from
GTR treatment.

GTR in Gingival Recession
❖ GTR refers to the placement of a barrier membrane
between surgical ﬂap and root surface to prevent
gingival epithelial and connective tissue from contacting
the root surface.
❖ The membrane may enhance wound stabilization by
absorbing or defeating wound rupturing forces that
otherwise would be transmitted to fragile maturing ﬁbrin
clot on the root surface.

GTR in Gingival Recession
❖ Cortellini et al (1991) showed that recession defects
treated with guided tissue regeneration exhibited a ﬁve
fold increase and new connective tissue attachment
compared to control.
❖ Human histology has demonstrated cementum and bone
regeneration following guided tissue regeneration on root
surface with long-standing history of gingival recession
Cortellini et al (1993).

Factors affecting clinical outcomes of GTR used for
Root Coverage
❖ Deeper and narrower the defect, the greater the
periodontal regeneration.
❖ Stabilizing of fragile attachment between the root and
gingival flap, provided by the fibrin clot in the interface, is
paramount to the outcome of wound healing following
mucogingival flap procedures. Factors such as tooth
location, vestibular depth, and muscular and frenum
insertion may affect wound stabilizing.

Localized ridge augmentation with barrier
membranes
❖ Reconstructive surgery is needed to regenerate defects:
□ extracted teeth with advanced periodontal disease
□ root fracture or a periapical lesion, if endosseous implants are to be
inserted.
❖ The membrane prevents the in growth of competing non- osteogenic
cells from overlying mucosa and allows the ingrowth of angiogenic and
osteogenic cells derived from the marrow space or populate and
regenerate the secluded space with bone.
❖ Barrier membranes can be used either with simultaneous
approach, or staged approach.

Indications
❖ Immediate or delayed extraction socket defects.
❖ Bone dehiscence defects in the crestal area of the implant.
❖ Bone fenestration defects in apical area of the implant.
❖ Lateral ridge augmentation.
❖ Vertical ridge augmentation.
❖ Sinus ﬂoor elevation eventually combined with ridge
augmentation procedures.

Other emerging materials
The use of PRP with GTR:
❖The use of PRP enriched with growth factors is considered to be
'new frontier' in today clinical practice.
❖ The use of PRP with GTR improves tissue repair and
regeneration at the wound site.
❖ Growth factors derived from platelets initiate connective tissue
healing bone regeneration and repair, promote development of
new blood vessels and stimulate the wound healing process.

Pep-Gen P-15:
• Pep-Gen P-15 is another material recently
introduced for periodontal regeneration. It is putative
collagen binding peptide that uses a combination of
an anorganic bovine derived hydroxyapatite matrix
and a synthetic 15-amino acid sequence type I
collagen (P-15).
• P-15 is a collagen derived cell binding peptide that is
reported to attract and bind ﬁbroblasts and
osteoblasts and to promote PDL ﬁbroblast
attachment to the anorganic bovine derived

Surgical complications in GTR
❖ Pain:
□ Generally occurs in class II and III furcations.
□ Use of chemical root preparation during
debridement may contribute to postoperative pulpal
inﬂammation.
□ High speed rotary burs in the furca may also result in
pulpal damage.
□ Proper postoperative assessment of pulpal status is
critical.

❖ Swelling:
□ The incidence is greater in mandible than maxilla.
□ The use of methyl prednsilone dramatically
reduces this postoperative swelling.
□ Before administration proper medical history should be
taken, if steroids are to prescribed, as its use should be
kept to the minimum.

❖ Purulence or abscess formation:
□ Purulence occurs only at sites that demonstrate
material exposure and appears to be dependant on
the development of pseudopocket.
□ The psuedopocket is a space that develops lateral
to the membrane during healing as a result of
failure of the membrane to become incorporated
into the most coronal aspect of gingival ﬂap.

Abscess
formation
Pseudopocket lateral to the
membrane

❖ Purulence or abscess formation:
□ Treatment:
• Irrigate with chlorhexidine mouthwash.
• Decide about the membrane removal.
• Culture the site if the membrane is to be left in place for
more than 3 weeks.
• Prescribe systemic antibiotics (Augmentin or cipro) i.e.,
Augmentin 250mg - 3times -10days, Cipro 500mg - 2 times
- 10days
• Recommend home irrigation with chlorhexidine.
• Reassess weekly.

❖ Exophytic tissue:
□ Rapidly growing granulation tissue that grows past the
barrier membranes. It may bleed spontaneously.
□ This is very rare and the reaction usually presents
within the ﬁrst 3 weeks of postoperative
□ healing.
□ The areas are treated by incisional
□ biopsy.

❖ Sloughing:
□ Postoperative reduction or recession of the flap height of greater that
4mm.
□ Very rare condition, generally seen in maxilla, associated with poor
oral hygiene and smoking.
□ Due to the reduced blood supply to the flap, related to improper flap
designs.
□ Treatment consists of supportive care to the patient until
membrane is removed. Removal of the membrane may be
necessary, some clinicians suggest retaining till 6 to 8 weeks
with strict oral hygiene.
□ Few case reports showed significant gains in alveolar bone

❖ Apical perforation of ﬂap:
□ It is an exposure of the membrane through the mucosal ﬂap at the
apical border of the membrane.
□ This occurs where thin alveolar mucosa is laid over sharp
osseous contours.
□ Usually occurs 2-5 weeks postoperatively.
□ Prevention of this complication can be arrived by bending or
contouring the membrane under a gentle tensile force into a
shape that will be passive over the bone defect.
□ Resorbable membranes are less likely to result in this

Apical perforation of the ﬂap

SUMMARY & CONCLUSION
❖ GTR materials, non-resorbable or bioabsorbable, give
similar clinical results.
❖ GTRprocedures have been demonstrated to beclinically
effective in treating infrabony osseous defects, mandibular
buccal or lingual molar Class II furcation defects, recession
defects and preserving alveolar bone in recent extraction
sites.
❖ GTR procedures are not clinically effective in treating Class
II maxillary molar proximal furcation defects or Class III

❖ GTR procedures are technique sensitive and the success of
these procedures is dependent on surgical flap design, root
planing, regenerative material placement, surgical flap
placement and postoperative management of the surgically
treated area.
❖ GTR procedures are adversely affected by poor home oral
hygiene care, poor follow-up professional maintenance care and
smoking.
❖ Few studies have reported the added benefit with the use of bone
grafts & substitutes with GTR in the treatment of mandibular class
II furcation defects, however the results are unpredictable and do

❖ In infrabony defects, there is currently no evidence indicating that
GTR membranes combined with bone grafts will give better
clinical results than when GTR membranes are used alone.
❖ GTR results indicate that periodontal stability is achieved after
ﬁve years in patients with good oral hygiene and patients
receiving effective periodontal supportive maintenance therapy.

References
Regeneration of Periodontal Tissues: Guided Tissue
Regeneration : Cristina C. Villar, DDS, MS, PhD*,
David L. Cochran
Carranza 11th edition
Lindhe 5th edition
Jop 2005 perio regeneration position paper
Clinical concepts for regenrative in furcations sanz m
et al perio 2000 (2015)
Jop 2015 perio regeneration intrabony defects : a
systematic review by Richard t kao et al from AAP
REGENERATION WORKSHOP1999
Devices for periodontal regeneration perio 2000
(1999)
Biodegradable barriers and GTR perio 2000 (1993)

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