GUIDED

GUIDED TISSUE
TISSUE
REGENERATION
REGENERATION

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• INTRODUCTION
• RATIONALE
• HEALING
• FACTORS AFFECTING OUTCOME
• SPECIFIC MEMBRANES
• SURGICAL PROCEDURE
• GTR IN RECESSION
• FUTURE PERSPECTIVES
• CONCLUSION

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 INTRODUCTION
INTRODUCTION
•DEFINITION
•CRITERIA
•EVALUATION

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 DEFINITION
“procedures attempting to regenerate
lost periodontal structures through
differential tissue responses.
Barriers are employed in the hope of
excluding epithelium and gingival
cornium from the root surface in the
belief that they interfere with
regeneration.”

The 1996 World Workshop in Periodontics

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• goal of periodontal therapy
• Hancock 1989
• biologic principle - guided tissue
regeneration (GTR) was discovered
by Nyman and Karring

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• when is regeneration achieved ???
• exclusion of undesired cells
• migration of desired cells
• BARRIER MEMBRANES

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 FEW
FEW PERTINENT
PERTINENT
TERMS
TERMS
•REPAIR
•REGENERATION
•NEW ATTACHMENT
•RE-ATTACHMENT
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 REPAIR
• 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 preexistent pocket

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 REGENERATION
• 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

GPT 1992

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 NEW ATTACHMENT
• "The reunion of connective tissue
with a root surface that has been
deprived of its periodontal ligament.
This reunion occurs by the formation
of new cementum with inserting
fibers."

American Academy of Periodontology (1986)

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 Reattachment Vs New
attachment
• Fibrous attachment to a root surface
surgically or mechanically deprived of
its periodontal ligament tissue
• Situation where the fibrous attachment
was restored on a root surface
deprived of its CT attachment due to
the progression of periodontitis.

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• New attachment shld be used to
describe the formation of new cementum
with inserting collagen fibers on a root
surface deprived of its periodontal
ligament tissue, whether or not this has
occurred because of periodontal disease
or by mechanical means.”

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• Reattachment - “the reunion of
surrounding soft tissue and a root
surface with preserved periodontal
ligament tissue.”

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Criteria - Regenerative
procedure
• 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.

AAP 1996
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 Reliability of
assessments
• Probing
• Re-entry
• Radiographic analysis
• Histologic methods

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 probing
• Probe
• error - 1.2 mm
• bone probing under LA
• grooved stents

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 radiographic
• Standardized
• minimal 30% bone mineralization
• CADIA

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 Re-entry
• Reliable
• pre-post models
• unnecessary second operation
• does not show type of attachment -
new attachment or long junctional
epithelium

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 Histologic methods
• Determine type of attachment
• need for extraction
• animal studies
• notches

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1> Apical part of calculus
2> Base of pocket
3> Level of the osseous crest

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 RATIONALE
RATIONALE
•Other techniques
•GTR

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 Various techniques
• Open Flap debridement
• Bone grafts
• Root surface biomodification
• Growth factors

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 Open Flap debribement
• Repair
• long junctional epithelium

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• Caton et al 1980
• SRP
• Modified Widman Flap Surgery
• Defect and root debridement
• Implantation of frozen red marrow
and beta tricalcium phosphate

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• Long junctional epithelium
• Epithelial union week
• As resistant to plaque infection as a
normal CT attachment

Magnusson 1983

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 Bone grafts
• Osteogenesis; Osteoconduction;
Osteoinduction
• Induce cells in the bone to produce a
new cementum layer
• result - healing with long junctionl
epithelium rather than CT attachment
-- histologic evidence

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 Root surface
biomodification
• Citric acid
• Histologic evidence - new attachment
• failure in clinical improvement
• EMD
• clinical results
• histologic evidence

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 Growth factors
• PDGF
• IGF
• BMP
• evidence of regeneration
• problem of delivery

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Healing
Healing

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• Development
• Neural crest cells – ectomesenchymal
cells
• Cementoblasts, P.dl lig., fibroblasts,
osteoblasts
• Epithelial cells -

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• Regeneration
• P.dl lig. Fibroblasts, Paravascular and
endosteal fibroblasts

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 Wound healing
• 1> inflammation - early; late
• 2> granulation tissue formation
• 3> matrix formation and remodelling

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• Flap - tooth surface
• wound closure clotting blood
• seconds - plasma proteins - fibrinogen
fibrin clot
1 hour

• early inflammatory phase (neutrophils)

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• 6 hours - neutrophils - decontaminate-
phagocytosis
• 3 days - late phase of inflammation
(macrophages)
• remove RBC’s, neutrophils, residual
tissue debris
• release growth factors

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• Fibroblast proliferation
• matrix production
• smooth muscle cell proliferation
• endothelial cell proliferation
• angiogensis

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• Macrophage - key role - transition of
inflammation to granulation tissue
formation
• 5-7 days - granulation tissue
formation 7 days

• granulation phase Matrix

formation phase

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• Matrix formation phase
• collagen adhesion
• differentiation of cementoblasts-
3 wks
• resorptive activity

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RATIONALE
RATIONALE FOR
FOR THE
THE
USE
USE OF
OF GTR
GTR

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Biologic principles relating
to new attachment
• Melcher (1976)
• periodontium into four compartments

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• The periodontal membrane was
considered the primary source of
cells necessary for periodontal
regeneration
• The endosteum of bone was also
considered to be a source of
undifferentiated cells.

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• Karring et al (1980) devitalized
periodontitis affected roots and
transplanted them into surgically
created bony defects.

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• The diseased portion of the root
underwent resorption and ankylosis.
• The portion of the root with retained
periodontal ligament showed evidence
of reattachment to the root surface.

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• In another study (Karring et al 1983), a
similar experiment was performed but
incisions were made over the roots,
thereby allowing epithelium to proliferate
along the connective tissue.
• When epithelium was present along the
root surface, ankylosis and root resorption
did not occur.

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• From this study it was hypothesized
that epithelium may act as a
protective barrier and thus prevent
root resorption and ankylosis

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• Nyman and coworkers (1982) created
fenestration defects over the labial
surfaces of monkey canines.
• They removed 2 to 3 mm of bone and
periodontal ligament, thus creating a
fenestration defect over the root.
• The cementum was removed from the
root surface.

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• Millipore filters (Bedford, MA) were
placed over the defects to prevent
gingival connective tissue from
contacting the defects.

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• Biopsy specimens of the experimental
areas revealed new attachment
consisting of new cementum with
inserting fibers and restitution of
the alveolar bone.

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• The conclusions from this study
indicated that the periodontal
membrane may be a very important
source of progenitor cells if new
attachment is to occur.

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• Lindhe et al 1984
• monkeys
• presence of bone stimulates
formation new CT attachment

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• fibrous reunion - P.dl lig CT retained
• Establishment of CT attachment is
irrespective of presence or absence
of bone

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• Studies by Iglhaut et al (1988)
indicated that alveolar bone may also
play a significant role in the
regenerative process.

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• Melcher et al (1986) presented
results from an in vitro study that
suggested the progeny of bone cells
may be able to produce cementum
like substance

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• Results from the above studies
present strong evidence for the
importance of the periodontal
membrane and endosteum in the
regenerative process.

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• Nyman et al (1982)
• indicated that if gingival epithelium
and connective tissue are excluded
from the healing process, new
attachment could occur.

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• Gottlow et al (1984) and Caffesse et al
(1988) used the principles of guided tissue
regeneration (GTR) to treat extensive
defects in experimental animals.
• Gottlow and coworkers removed 50% to
75% of the alveolar bone from monkey
teeth.

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• Periodontitis was then allowed to develop.
• After 3 months the osseous defects
were treated by flap debridement alone
or with Millipore or
polytetrafluoroethylene (PTFE) membrane
placement and flap debridement.

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• Membranes were placed
supragingivally and glued to the
clinical crowns.
• Biopsy specimens of the treated
sites demonstrated that significant
new attachment had occurred at the
test sites.

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• For test sites, the amount of new
bone ranged from 20% to 100% of
the exposed roots.
• The greatest amount of new
attachment occurred at sites treated
with PTFE membranes.

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• All these studies provided the basis
for the clinical application of the
treatment principle termed “Guided
Tissue Regeneration”

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FACTORS
FACTORS AFFECTING
AFFECTING
OUTCOME
OUTCOME
o DEFECT ANATOMY
o DEBRIBEMENT AND APPROXIMATION
o MATERIAL REQUIREMENTS

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 DEFECT ANATOMY:
• An intrabony defect results when the
junctional epithelium is apical to the
alveolar crest
• GOLDMAN AND COHEN

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• Thick cortical bone
• mesial interproximal location
between the maxillary and
mandibular second molars

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• When furcations are treated with
new attachment procedures
– root trunk length
– interradicular loss of attachment
– root proximity
– buccolingual attachment loss
– depth of a vertical component

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 FLAP DEBRIDEMENT AND
INTERPROXIMAL
DENUDATION
• many reports on the successful
treatment of intrabony defects
• Most reports indicate that the greatest
amount of bone fill occurs in combination
two- and three walled defects and three-
walled intrabony defects.
• One-walled or hemiseptal defects usually
have the least amount of bone fill.

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• Prichard 1957
• three-wall intrabony defects
• By excising the gingival flap margin, -
epithelium was delayed from reaching
the root surface, thereby allowing
time for clot organization

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• Polson and Heijl 1978
• two- and three-walled intrabony
defects with open flap curettage

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• New attachment can be accurately
measured and evaluated clinically,
but, according to Gara and Adams,
absolute proof of new attachment
can only be demonstrated from
histologic sections.

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• From animal and limited human biopsy
specimens of intrabony defects
treated by debridement - healing
– new bone formation
– long junctional epithelium
– (Caton et al 1980; Stahl et al 1982).

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Materials
Materials Used
Used For
For
Guided
Guided Tissue
Tissue
Regeneration
Regeneration

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 MATERIAL
REQUIREMENTS
• should be sterile
• biocompatible
• resorb slowly
• create sufficient space for cell
repopulation
• should be relatively easy to place
surgically

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 DESIGN CRITERIA
• Biocompatibility
• cell exclusion
• space maintenance
• tissue integration
• ease of use
• biological activity

Scantlebury; Gottlow; Hardwick

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 Membrane Permeability
• Exchange of critical fluid substances
• Not a prerequisite for GBR
Schmid et al. 1994
• Prevention of oxygen – intermediate
cartilage formation
Sandberg et al. 1993

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 SPECIFIC
SPECIFIC
MEMBRANES
MEMBRANES
• Absorbable
•Non-absorbable

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 Non- Absorbable
• First approved devices
• maintain structural integrity
• second surgical procedure

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• Polytetrafluoroethylene
• Expanded Polytetrafluoroethylene

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• Polytetrafluoroethylene -
fluorocarbon polymer
• exceptional inertness
• solid PTFE - non porous
• does not allow tissue ingrowth
• does not elicit foreign-body reaction

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• Expanded Polytetrafluoroethylene -
PTFE subjected to tensile stress
during manufacture, resulting in
differences in physical structure
• has a porous microstructure of solid
nodes and fibrils

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• The periodontal material is
commercially available in various sizes
and shapes to accommodate defect
morphology and location.
• The material is provided in a sterile
envelope, is biocompatible, and is
nonresorbable.

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z

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• Gore Tex ePTFE periodontal device
features two structural designs to
address specific needs.
• Open microstructure collar corresponding
to the coronal aspect of the device to
promote CT ingrowth and support wound
stability and inhibit epithelial apical
migration

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• This part of the device is 1 mm thick
and 90% porous (100-300 m between
nodes)
• Remainder device - partially occlusive
• stable; provides space for
regeneration; serves as a barrier for
gingival flap invasion

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• 0.15 mm thick
• 30% porous <8 m between nodes

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• Show evidence of regeneration
• minor complications
– pain
– purulence
– swelling
– tissue sloughing

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• Modifications:
• Titanium reinforcements
• improved mechanical strength
• improved space provision and
maintenance

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• Rubber dam
• little rigidity
• tediuos manipulation
• no tissue integration
• resin ionomer barrier
• difficult to fabricate
• unknown tissue integration properties

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 Absorbable
• No additional surgery
• no control over length of application
• varying disintegration rates
• should maintain their in vivo
structure for atleast 4 weeks
Minabe

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• Absorbable

natural synthetic

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 natural
• Collagen
• Exogenous collagen exhibits
– hemostatic activity
– able to attract and activate neutrophils
and fibroblasts
– interacts with various cells during tissue
remodeling and wound healing

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• Implanted collagen devices -
degraded - enzymatic activity of
infiltrating macrophages and
Polymorphonuclear leukocytes

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• Bovine collagen mem. - 8 wks
• Rat tail collagen mem. - 4 wks

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• BIOMEND - type I collagen - bovine
deep flexor tendon
• semi occlusive
• pore size - 0.004m
• absorbed in 4-8 wks

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• Hemostatic collagen barriers
• AVITENE
• COLLISTAT
• resorb faster
• limited regeneration

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• Indian brand names -
• Bioguide
• Healiguide
• Surgicel

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• Dura mater
• cargile membranes
• oxidised cellulose
• laminar bone

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 synthetic

• Organic aliphatic thermoplastic

polymers
• poly  hydroxy acids -
– polylactic acid
– polyglycolic acid
– polyglycolide-lactide

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• Degradation - hydrolysis
• CO2 and water - citric acid (Kreb’s cycle)
• degradation rate - dependent
– pH
– mechanical strain
– enzymes
– bacteria

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• Polyglycolic acid - fastest
degradation
• polylactide - most stable
• polyglycolic:polylactide copolymer
50:50 - 1wk

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• A double layered absorbable device
GUIDOR matrix barrier made of
polylactic and citric acid ester was
the first to gain FDA approval

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• External layer - rectangular
perforations
• limited gingival recession
• internal layer - bar - seal b/w barrier
and tooth
• biodegradable suture

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• Device is completely absorbed within
6-12 months

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• RESOLUT
• composite consisting of occlusive
mem. Of glycolide and lactide
copolymer
• porous web structure of bonded
polyglycolide fiber

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• Supplied with polycaprolate coated
polyglycolic acid suture
• as effective as non-absorbable
devices
• retains its structure for four weeks
• absorbs completely within 5-6 months

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• Polyglactin 910
• copolymer of glycolide and lactide
90/10 molar ratio
• VICRYL periodontal mesh
• polyglactin 910 sutures

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• Lose integrity within 2 wks
• resorb within 4 or more wks
• Modified polyglactin 910 mem. Coated
with bovine type I and type III
collagen
• resorbs 30-90 days

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• Chair side mem.
• ATRISORB
• polymer - flowable formulation - 37%
• solvent - 63%
• 0.9% saline - 4-6 minutes
• desired shape and size is cut and trimmed

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• 600-750 m thick
• completely absorbed - 6-12 months

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• Polyurethanes
• organic polymers containing urethane
grp -NH-CO-O-
• degrade by hydrolysis; enzymes and
oxidative degradation

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• Not suitable for GTR
• more inflammation
• more recession
• swelled more

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 Generations of GTR
• I - non absorbable
• II - absorbable
• III - incorporated adhesion factors
and growth factors

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 SURGICAL
SURGICAL
PROCEDURE
PROCEDURE

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•mucoperiosteal flap with vertical
incisions, extending a minimum of
two teeth anteriorly and one tooth
distally to the tooth being treated

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• Debride the osseous defect and
thoroughly plane the roots

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• Trim the membrane - approximate size of
the area being treated.
• The apical border of the material should
extend 3 to 4 mm apical to the margin of
the defect and laterally 2 to 3 mm beyond
the defect; the occlusal border of the
membrane should be placed 2 mm apical to
the CEJ.

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

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• 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.

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• The use of periodontal dressings is
optional, and the patient is placed on
antibiotic therapy for 1 week

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• After 4 to 6 weeks, the margin of
the membrane becomes exposed. The
membrane is removed with a gentle
tug 5 weeks after the operation.
• anesthetized and the material is
surgically removed using a miniflap.

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• Pretreatment
photograph of
mandibular left
posterior teeth
with marked
recession and
tissue
inflammation.

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• Underlying
extensive crestal
bone loss,
dehiscence, and
intrabony osseous
defects.

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• Barrier
membranes over
the bone grafts.

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• Flaps coronally
positioned and
secured over the
barrier membranes

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• Membrane removal
revealing new
alveolar bone.

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GTR
GTR in
in recession
recession

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• Gingival recession is defined as the
displacement of the marginal tissue
apical to the CEJ.
• Mucogingival procedures

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• Pedicle flap
• free gingival graft
• CT graft

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• Guided Tissue Regeneration using an
ePTFE mem. in a deep gingival recession
defect was evaluated at 6 months post-
surgery.
• The histometric analysis revealed 3.7 mm
of a new connective tissue attachment
associated with regeneration of
cementum and alveolar bone.

Cortellini 1993
129
 Factors influencing
periodontal regeneration

• Defect characteristics
• Deeper and Narrower defects
• Ratio between avascular root surface
and residual vascular bed

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• Site-specific anatomy and function
• wound stabilization - mechanical
forces
• tooth location
• vestibular depth
• muscular and frenum insertions

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• Interproximal tissue support
• compromised vascularity and
mechanical stability
• class III and IV - limited P.dl lig.
cells

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• Coronal positioning of the flap
• supports regeneration - controversy

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• Root surface conditioning
• supports new CT attachment
• recession defects - no differences in
soft tissue gains, bone regeneration

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• GTR
• mem -
space for prefrential cells
wound stabilization
74% defects with GTR - new
cementum - collagen

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• Titanium reinforced PTFE membranes
• enhanced strength
• prevent collapse

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Guided
Guided bone
bone
regeneration
regeneration

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• Increasing the rate of bone
formation and for augmenting bone
volume
– Osteoinduction
– Osteoconduction
– Distraction osteogenesis
– Guided Bone Regeneration

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• Biochemical induction of bone
formation by growth factors is still
in an experimental phase
• GBR and Bone grafting - successful
• Dhalin et al. 1988

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 Basic pattern of bone
formation by GBR
• Intermediate CT matrix
• Ossification

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• Cortical bone- circular defects < 200
m – concentric formation of lamellar
bone
• 200 – 500 m – trabecular network

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 Problems encountered
with GBR
1. Collapse of barrier membrane
2. Membrane exposure
3. Incomplete bone regeneration

148
 materials
• PTFE • Polylactic acid
• ePTFE • Polyglycolic acid
• Collagen • Polyorthoester
• Freeze-dried fascia • Polyurethane
lata • Polyhydroxybutyrate
• Freeze-dried dura • Calcium Sulfate
mater • Micro titanium mesh
• Polyglactin 910

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Future
Future Perspectives
Perspectives

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• GTR +
• Growth factors
• adhesion molecules
• antimicrobial agents

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CONCLUSION
CONCLUSION

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• Predictable regeneration
• Future - biological factors
• choice of therapy - evidence based

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THANK
THANK YOU
YOU

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