REGENERATIVE MATERIALS

Dr. Krishnaraj
Dept Of Periodontics
• Introduction
• Definitions
• Results of conventional procedures
• Concepts of regeneration
• Biology of regeneration
• Osseous grafts and regeneration
• Guided tissue regeneration and periodontal
regeneration
• Resorbable, bioabsorbable and non-
resorbable barrier membranes
• Role of growth factors in periodontal

regeneration

• Tissue engineering

• Summary & Conclusion

• Future directions
INTRODUCTION
 Definitions
• Regeneration: growth and differentiation of new cells

and intercellular substances to form new tissues or parts

• Reproduction or reconstitution of a lost or an injured part

in such a way that the architecture and function of the

lost or injured part is completely restored. (GPT 1992)

• Repair: restoration of the continuity of diseased marginal

gingiva and re-establishment of a normal gingival sulcus

at the same level on the root as the base of the periodontal

pocket.

• New attachment: formation of new cementum with

inserting collagen fibers on a root surface deprived of

periodontal ligament tissue

• Re-attachment: the reunion of surrounding soft tissue and

a root surface with preserved periodontal tissue

 Results of conventional
procedures

• Eliminate the etiologic factors

• Removes the pocket lining/wall

• Accessible for plaque control

 How about this?

• Long JE!!

• Parallel fibers

• Altered root surface!!

• Reduced periodontium
 What next?

• Need for regeneration

• Support
• Function
• Aesthetics
• Better maintenance
 Possible??- Let’s see..

• Melcher hypothesis (1976)

• Epithelial cells

• Gingival connective tissue

• Bone cells

• Periodontal ligament cells

 Regenerative methods

• Earlier regenerative methods

• Bone grafts

• Guided tissue regeneration

• Tissue engineering
 Root surface and its importance

• Altered
• Connects pdl and bone
• Citric acid, tetracycline, fibronectin, growth
factors, EDTA etc..
• Good or bad??
• Role of cementum – is it only attachment??
OSSEOUS GRAFTS
 Osseous grafts

• Graft or substitute?
• Autograft
• Allograft
• Hetero or Xenografts
• Alloplasts.
 Osseous grafts

Ellegaard (1973) and Nielsen (1980):

• Osteoproliferative (osteogenesis)

• Osteoinduction

• Osteoconduction
 Definition and requirements
• Requirements:-
1. Should help in the formation of new bone
2. Be inert and biocompatible
3. Easy to obtain
4. Predictable
5. Cost effective
6. Non toxic
7. No root resorption or ankylosis.
8. Strong and resilient
 Autografts – Gold Standard??
• Intra-oral / Extra –oral.
• I/o – extraction sockets
edentulous ridges
symphysis
ramus
maxillary tuberosity
 Autografts – Gold Standard??
• E/o – iliac crest
femur
calvaria
• Bone swaging
• Osseous coagulum
• Bone blend
• The cells contained in graft start forming new bone.
• The transplanted osteocytes die due to anoxia but
osteoclasts survive and may initiate resorption of graft.
• However, adequate revascularization may ensure
increase osteoblastic population.
• Cortical chips, osseous coagulum and a blend can also
be used.
• Larger particle size of cortical bone may however be
sequestered
 Procedures
• Trephines; available in different sizes
• Olympic ring and significance
• Bone core; compact and cancellous.. Can be
crushed
• Only cancellous can also be used.
• Potential greater for cancellous bone.
 Advantages and Disadvantages
• Better predictability
• No antigenicity

• Time consuming
• Second surgical site
• Insufficient quantity
• Root resorption!
 Risks associated
• Nerve damage.
• Mentalis
• Depressor labii inferioris
• Maxillary sinus
• Inferior alveolar nerve

Is it still the Gold standard?? – Decide..

ALLOGRAFT – BOON OR BANE?
2 TYPES;

• Demineralized freeze dried bone allograft (DFDBA)

and freeze dried bone allograft (FDBA)

• Mellonig (1981) – FDBA is an alternative to

autograft for use in periodontal defects.

• Urist and robinson (1979) - DFDBA

 Why an Allograft?

• The demineralization – essential; as bone mineral

blocked the effect of the inductive agent; BMPs.

• Osteoinduction: DFDBA (Urist 1970)

• Osteoconduction: FDBA (Goldberg and Stevenson

1987)
 Rate of bone formation with
DFDBA
 Rapid from day 14 to day 28 and declines
thereafter, esp from day 35 to day 42.
 Low osteogenic index at the beginning but
rapidly increases.
 Whereas the FDBA has osteogenic index at
the start which does not increase post-
grafting.
 Particle Size

 Shapoff 1980 reported that smaller particle size

causes more osteogenesis; but disproved when 44
um failed
 Urist 1967 - 250 – 420 inhibits bone formation, but
larger particles of 1000 – 2000 um do not.
 Mellonig and levy concluded that 250 –750 um is
ideal for periodontal grafting procedures.
 Recent evidence suggests 317 um as an ideal size.
 Pore size is just as crucial as it determines the
neovascularization.

 Pore size of 100 to 200 um is considered optimal

for endothelial and fibroblastic ingrowth (Bhaskar
1971, Hulbert 1970, Topazian 1971).
 Fate of Graft

 Reynolds and Bowers (1996) showed that this the only

graft which, if more residual particles remain post
grafting, results in significantly greater amounts of
new attachment.

 DFDBA may show delayed neovascularization as

compared to autologous bone.
 Antigenicity of FDBA

 Anti – HLA antibodies.

 Friedman (1984); 9 out of 43 patients
 Quattlebaum 1988 – concluded that the FDBA has
markedly reduced antigenicity stating that the freeze
drying procedure may spatially distort the three
dimensional presentation of the HLA antigens on
FDBA affecting immune recognition.
Advantages and Disadvantages

 Commercially available
 Less time consuming
 Predictable and rich source of BMPs

 Suspicion of disease transfer (1 in 8 million).

 Expensive
 Age of donor
 Another disadvantage is that the poor physical
properties of the graft impairing the retention of the
graft in the site.
 Blumenthal 1986 – combined the bone graft with
microfibrillar collagen. This combined graft helped
to;
1. Bind and retain the particles in the defect,
2. Created space between particles – ingrowth
3. Collagen material attached to root.
 Recent evidence indicates that the age of donor is
significant in the transfer of BMPs.
 The graft obtained from donors over the age of 45 years
shows reduced amount of BMPs.
 Jin et al (2003) have shown that gene therapy of bone
morphogenetic protein – 7 demonstrated rapid
chondrogenesis with subsequent osteogenesis,
cementogenesis and predictable bridging of periodontal
defects
 Human tendon collagen dehydrated. When rehydrated

it expands to fill the defect.

 Good replacement for the blood clot.

 Has been an integral part of DFDBA grafts available

ever since..

 Recombinant BMPs (rhBMP-2) can be incorporated

in a variety of graft materials

 Xenografts

 Grafts available free of the organic component

 Kielbone, calfbone used earlier.
 Bovine anorganic cancellous bone (BACB); produced
by a special process which removes the organic part,
retains the inorganic part.
 Another product is the porcine non-antigenic collagen
(PNAC), the collagen of which undergoes prolonged
alkaline treatment, producing a bilayer structure
eliminating any risk of bacterial or viral contamination.
 Telopeptides are split off, the areas most
concerned with the antigenicity of the molecule.
 Specific purification processes remove residual
fat or protein.
 PNAC is produced as a block, which can be
crushed to the desired size or consistency.
 The composite graft of BACB and PNAC
shows no antigenicity (Cohen 1994).
 Earlier xenografts showed rejection ..chemical
detergent extraction
 PepGen – 15
 Contains a synthetic 15-amino acid sequence with steric
similarities to the cell binding sites of Type I collagen.
 Promotes binding of fibroblasts to anorganic bovine
bone mineral.
 Enhanced expression of alkaline phosphatase.
 Increased nucleic acid and protein synthesis.
 Though can be used in combination with
DFDBA,FDBA and Alloplasts, it shows rapid
attachment to xenogeneic grafts.
 Vitronectin and fibronectin
SYNTHETIC BONE SUBSTITUTES
– SAFEST BET?
 Porous hydroxyapatite

 Nonporous hydroxyapatite

 Tricalcium phosphate

 HTR polymer

 PLA-PGA

 Bioactive glasses.
 Porous hydroxyapatite

 Uniform pore size, facilitates vascular ingrowth and

subsequent new bone growth.
 250 – 45- um in size.
 Easy to handle.
 Resorbs over a period of 12 months.
 Quite predictable results.
 SEM shows the presence of spreading osteoblasts
and newly formed bone (Krejci 1987).
 Non-porous hydroxyapatite

 Resorbs slowly.
 Does not get replaced by new bone.
 Increased chances of fibrous encapsulation.
 Minimal pore size hence does not facilitate vascular
ingrowth and fibroblast proliferation.
 However, some studies have shown better results
with nonporous hydroxyapatite (Yukna 1989).
 β - Tri Calcium Phosphate

 Calcium : phosphate = 1.5, β - whitlockite

 Thought to stimulate bone formation
 Proved superior to hydroxyapatite in numerous
studies (Fetner 1994)
 But lesser than bioactive glass (Wilson and Low
1992).
 Excellent property..
 HTR POLYMER- or is it?

 Non resorbable, microporous biocompatible

composite of poly-methylmethacrylate (PMMA)
and polyhydroxyethylmethacrylate (PHEMA).
 550- 880 um with a pore size of 50 – 300 um form
the core of the material.
 No inflamm reaction.
 The beads are then coated with Ca(OH)2/CaCO3,
which comes in contact and forms new bone
 HTR POLYMER – contd..
 Provided in a fine, granular form.
 Stahl et al (1990) reported bone in-fills of upto
60%
 Limited handling characteristics
 Bio-Active Glasses

 Used widely in treatment of periodontal defects

develop a layer of hydroxy–carbonate –apatite on

their surface following exposure to body fluids.

 Incorporates collagen fibers into it.

 SiO2 – CaO – Na2O – P2O5

 Bio Glasses..contd

 Flexural strength, fracture toughness less than

bone. Elastic modulus is more than bone

 Hench and Wilson 1984, Hench and West

1996.
 Theory of Bioactivity
 Bioactive index

 Highly bioactive glasses show both osteoproduction

and osteoconduction, while low bioactive glasses
show only osteoconduction.

 Osteoproduction – defined as the process in which the

bio-active surface is colonized by osteogenic stem
cells from the adjacent bone.
 Wilson 1994 showed that highly bioactive
45S5 Bioglass produced more bone than
autogenous bone.
 Two classes of bioactive materials; Classes A
and B.
 Class A – osteoproduction and Class B –
osteoconduction.
 Class A = produces both extra and
intracellular responses.
 Class B = produces only extracellular
response.
 Class A
 Release soluble silicon in the form of silicic acid
due to surface ion exchange with H+ and H3O+ on
contact with body fluids.

 The conc of silicon in solution keeps on increasing

and is finally precipitated forming complex silicate
phases
 Class A
 Intracellular response is by the release of
silicon
 Extracellular effect is by the chemabsorption
of of bone growth promoting factors such as
TGF-β on their surface.
 Class B
 Very low or zero ion exchange
 Release very low amounts or zero amounts of
silicon.
 Role of Silicon

 The released silicon is chemically combined with

glycosaminoglycan – protein complexes, which
surround collagen and elastic fibrils and cover the
surface of cells (Carlisle 1986).

 Potent mitogen for osteoblasts (Keeting 1992),

increases the mitotic rate of osteoblasts by 3 fold.
 Role of Silicon..contd
• Enhances the rate and amount of release of alkaline
phosphatase from these cells.
• Enhances the release of osteocalcin (Possibly an
autocrine response).
• Accelerates the precipitation of amorphous calcium
phosphate within the pores of the silica gel
layer..heterogenous nucleation mechanism
 Role of Silicon..contd
• Class A glasses show development of
cyrystalline hydroxy-carbonite-apatite layer
within a few hours whereas Class B glasses
may take weeks.
 Bioglass Reaction Layers

Silica Rich Layer

Bulk Bioglass Bulk Bioglass

Collagen & Proteins

HCA HCA
Silica Rich Layer Silica Rich Layer
Bulk Bioglass Bulk Bioglass
 Anti-Microbial Results
• Staphylococcus aureus - 105 reduction
• Pseudomonas aeruginosa - 104 reduction
• Aspergillus niger - 105 reduction
• Candida albicans - 106 reduction
• Escherichia coli - 104 reduction

• effects remain from 2 to 5 days in culture

• Procedure
– Solid Bioglass
samples cultured with
dilute Type I bone
collagen in TRIS
buffer - 37oC
• Results - 24 hours
– Calcium phosphate
nodules formation
– Proteins observed
attached to surface
In Vitro Development of Bonding
Surface Layer
• Results - 7 days
– Calcium phosphate
nodules cover entire
surface
– Calcification of
entrapped collagen
fibers observed
– Large increase in
surface area
 BioGlass and Hemostasis
• PerioGlas has been shown to be hemostatic,
decreasing clotting time in lab tests by 25% when
compared to controls. (Lee and White 2003)
• While the actual origin of this affect has not yet
being ascertained, two potential causes are the
development of a positive surface charge that
forms on the Bioglass after implantation and the
release of calcium ions during material dissolution
Advantages - Ease of Use

Mixed with blood Mixed with cortico-cancellous chips

 Summary

• Particles bind to collagen  release of silicon 

laid down  prevents epithelial downgrowth 

faster rate of bone and cementum formation.

Cementum Stimulants – Emdogain
DEVELOPMENT REVISITED!!
• Dental papilla
• Dental follicle, HERS
• Disruption..
• Cementogenesis???
• Concept of enamel matrix proteins
• Role of enamel matrix proteins
 EMDs..contd
• Amelogenins = 90%
• Proline rich non-amelogenins , tuft proteins,
tuftelin, serum proteins and atleast one
salivary protein = 10%.
• DNA Sequencing = ameloblastin
(Krebsbach 1996) and amelin (Cerny 1996).
 EMDs..contd
• 3 vehicles were tested for EMD , PGA,
Hydroxyethyl cellulose and dextran and
Hammarstrom (1997) showed that PGA in
combination with the amelogenin fraction resulted
in significant regeneration.
• PGA also shows antibacterial action against
P.Gingivalis
 Mode of Action

• The EMD in PGA adsorbs to hydroxyapatite and

forms spherical insoluble complexes and remains for

2 weeks.

• It promotes the repopulation of root surface by

fibroblast-like cells.

• Forms mineral nodules on root surface.

 Availability
• Powder form or gel form
• Comes with EDTA as a root conditioner prior to
application
• Can itself be used as root conditioner.
• Variety of clinical applications..
• The AEFC formed helps in formation of new pdl
and alv bone.
 Composite Grafts

• β -TCP + HA

• FDBA + DFDBA

• Allograft + Autograft

• Glasses + autograft
 Summary of Osseous Grafts

• Predictability

• Limitations – handling & retention

- resorption

- regeneration
GUIDED TISSUE
REGENERATION
- Current Concepts
 Introduction

• Importance of selective cell repopulation

• Need for excluding gingival epi and conn tissue

cells.

• Nyman 1982

• Act as barrier..also called barrier membranes

• Principles of GTR

• Indications and contra-indications of GTR.

• Clinical procedure

• Pros and cons of resorbable and absorbable

membranes

• Non-resorbable membranes.
• AAP 1992- term used to define procedures wherein

regeneration of lost periodontal structures is sought

via selective cell and tissue repopulation of the

periodontal wound

• 1996 WWP – procedures attempting to regenerate

lost periodontal structures through differential tissue

responses.
• Type of periodontal tissue formed is determined

by the cells attached to the root surface.

• PDL cells primarily important (Gottlow 1984)

 INDICATIONS

• PATIENT SELECTION

• SMOKING

• NARROW 2 OR 3 WALL DEFECTS

• CLASS II FURCATION WITH MEDIUM TO

LONG ROOT TRUNK

• RIDGE AUGMENTATION
 INDICATIONS-contd..
• ROOT COVERAGE

• REPAIR OF APICOECTOMY DEFECTS

• AILING/FAILING IMPLANTS
 CONTRAINDICATIONS

• GENERALIZED HORIZONTAL BONE LOSS

• CLASS III FURCATION, MESIAL AND DISTAL

FURCATION

• ADVANCED DEFECTS WITH MINIMAL

PERIODONTIUM
CONTRAINDICATIONS-contd..

• MULTIPLE ADJACENT DEFECTS

• INADEQUATE ATTACHED GINGIVA

• ADVANCED MOBILITY OF TEETH

FACTORS AFFECTING
OUTCOME OF GTR
PROCEDURES
(Causes of Failure)
 Barrier-Independent Factors

• Poor plaque control

• Smoking

• Occlusal trauma

• Sub optimal tissue health (I.e. Inflammation persists)

• Mechanical habits (e.g.. Aggressive tooth brushing)

 Barrier-Independent Factors-
contd..
Overlying gingival tissue
– Inadequate zone of keratinized tissues.
– Inadequate tissue thickness
surgical technique
- improper incision
- Traumatic flap elevation and management
- Excessive surgical time
- Inadequate closure or suturing
 Barrier-Independent Factors-
contd..
• Post surgical factors
- premature tissue challenge
* Plaque recolonization
* Mechanical insult
- Loss of wound stability (loose sutures,
loss of fibrin clot).
 Barrier – Dependent Factors
• Inadequate root adaptation (absence of barrier
effect)
• Non sterile technique
• Instability (movement) of barrier against root.
• Premature exposure of barrier to oral environment
and microbes.
• Premature loss or degradation of barrier.
 Nonresorbable membranes

• Preoperative considerations; 3 factors

- adequate gingiva to cover the barrier.

- cervical enamel projections, narrow furcal

openings.

- surgical access.
 Nonresorbable membranes

• Predictability
- degree of destruction
- compliance
- technique sensitive, requiring excellent
surgical skills
 Nonresorbable membranes
• PTFE (Teflon, dense or full body PTFE)
• e-PTFE (expanded PTFE).
• Older ones; millipore filters, ultrathin
semipermeable silicone barrier.
• Sterilized rubber dam.
• e- PTFE considered gold standard, but now we are
moving back to the full bodied, dense PTFE.
 E-PTFE

• Concept of e-PTFE, microporosities

• Prob assoc with e-PTFE (Fleszor 1990)

• Importance of primary closure.

• Titanium reinforcement
 Barrier placement

• Trimmed with scissors

• 3mm overlap of bone in all directions.

• Remove sharp corners to prevent flap perforation

• Interproximal barriers require special handling as

they need to be folded and passed in the
interproximal area.
 Membrane stabilization
• Titanium screws (can give ‘tent effect’).
• Bone tacks
• Sutures; e-PTFE sutures are of choice,
biocompatible,
strong
does not wick.
Sling sutures are reliable
Interproximal membranes need not be sutured.
Postoperative care
 Resorbable membranes
• Desirable properties of resorbable
membranes
1. Nontoxic,nonantigenic.
2. Acceptable handling props;
- malleable
- preserves and maintains space.
- conforms to defect shape.
- ability to customize for unique situations
Desirable properties of resorbable
membranes – contd..
3. Adherence to or ability to approximate root

surfaces.

4. Promotes tissue coverage and reduces barrier

exposure rates.

5. Promotes flap attachment after surgery.

Desirable properties of resorbable
membranes
6. Resists bacterial seeding and contamination.

7. Promotes selective cell repopulation.

8. Absorbs/resorbs at a rate parallel to regenerative

tissue formation.
 Collagen Membranes

• Initially used as a gel or matrix to fill or cover

periodontal defects.

• 1987, Yaffe and Shoshan, application of collagen

prevented epi downgrowth.

• Blumenthal 1993, reported the successful formation

of pdl, cementum and alv bone with collagen

 Collagen Membranes
• Usually type I collagen is preferred derived from
various sources; bovine or porcine, tendon or
dermis.
• Made by extrusion-coagulation and air-drying to
form sheets of material from dilute collagen (1%)
solutions.
• Resorbed within 20-21 days; insufficient callus
formation.
• Need to extend the resorption time
 Cross-Linking
• Increases the resorption time
• Also reduces the antigenicity.
• Physical;
gamma or ultraviolet radiation or
• Chemical;
formaldehyde
processing methods
 Cross-Linking – contd..
• Minabe 1989 increased regeneration with
cross-linked than non-crosslinked collagen.
• Brunel 1996 reported increased bone even
in GBR procedures.
• Helps in preventing the epi. downgrowth
 Important properties of collagen

• Natural component of tissues; well tolerated.

• Weak immunogen; favorable tissue response.

• Malleable – shaped and manipulated.

• Semipermeable to nutrients and gases.

• Possesses hemostatic properties through its ability

to aggregate platelets.
 Important properties of collagen
• Supports cell proliferation via lattice structure and
cell binding domains.
• Facilitates early wound healing and stabilization.
• Substrate for attachment of cells.
• Chemotactic for fibroblasts.
• Promotes cell migration;potential to reduce barrier
exposure.
• Absorbed naturally;replace by host tissues, increases
the bulk of tissue.
 Collagen Resorption
• Starts with action of collagenase, splitting the
molecule at several sites.
• The resultant fragments become temp
sensitive
• Denatures at 37 C to gelatin.
• Gelatinases and other proteinases degrade
gelatin to oligopeptides and amino acids.
 Disadvantages

• Reduced strength

• Reduced space maintaining ability

• Difficult to manipulate in vivo.

• Gets resorbed by 48 days; cannot be used when

large increases in ridge height or width are desired.

• Difficult to suture the membrane.

Recent advances – New Improved!!
• Tendon derived collagen has been
extensively studied and shows the weakest
immunologic reaction.
• Incorporation of antibiotics into collagen
membranes improves the effect;
• Incorporation of tetracycline decreases the
degradation of collagen membrane (Chin Jin
2003)
• Addition of metronidazole and amoxicillin have been

tried out with clinically beneficial results.

• Myrand (1985) found reduced amounts of

P.gingivalis, B. melaninogenicus in sites treated with

collagen membrane impregnated with antibiotics.

 Material Company Source Crosslink Components
name

Biomend Sulzer, CA Bovine tendon Formaldehyde 100% type I

Periogen Collagen Inc,CA Bovine dermis Glutaraldehyde Type I and III

Paroguide Coletica, France Calfskin DPPA 96% type I +

4% chondroitin
sulfate
Biostite Coletica, France Calfskin DPPA Collagen plus
hydroxyapatite
Biogide Geistlich, Porcine dermis DPPA Types I and III
Switzerland
Tissue guide Koken, Japan Bovine HMDIC Atelocollagen
dermis+tendon plus tendon
collagen
SX-COL Dr. Pitaru Rat tail tendon Not treated 100% type I
(Israel)
 Absorbable membranes –Viable
alternative?
• Primarily degradable polymers.

• Synthesized by co polymerization of different forms

of PLA,PGA or mixtures of PLA and PGA.

• PLA increases the strength of the membrane

• PGA improves the handling properties of the

material
 PLA-PGA Polymers
• Degradation of PLA PGA polymers occurs by
hydrolysis of ester bonds,

• Initiation of degradation depends upon.. 30 to 60 days

depending upon the composition of the polymer.

• Available membranes include; Guidor, Vicryl,

Atrisorb, Resolut and EpiGuide
Membrane Company Components

Guidor Butler Co, Chicago PLA &

acetyltributyl citrate
Vicryl Ethicon Lab, NJ PLA/PGA

Atrisorb Atrix Labs,Collins,CO PLA/PGA

Resolut W.L.Gore, Flagstaff, PLA/PGA

AZ
Epiguide THM Biomedical,MN PLA (D,L forms)

Biofix Bioscience,Finland PGA

 GUIDOR
• Hydrophobic barrier – PLA with citric acid ester
softening agent.
• Bilayered; external layer (facing gingival tissue)
with rectangular perforations (400-500/cm2).
• Internal layer with smaller circular perforations
(4000-5000/cm2).
• Available with attached suture at the collar.
 GUIDOR
• Designed to resist degradation for 3 months.
• Gradually replaced by newly regenerated periodontal
tissue.
• Gottlow –1993- comparable with e-PTFE
• Gottlow 1994 and Rocusso 1996 also used in the
coverage of denuded roots,augmentation of alveolar
ridges and regeneration of implant related osseous
defects.
 VICRYL

• Periodontal mesh (Polyglactin 910), copolymer of

glycolide and lactide used in sutures.

• Available as woven or knitted mesh

• Larger pore size with better handling properties.

• Degrades over 3-12 weeks.

 Supporting Studies

• Moon 1996 – better than flap debridement.

• Caton 1994 – useful in furcations.

• Sander 1995 – comparable to e-PTFE.

• Moon 1997 – composite treatment is not more

effective than vicryl alone.

 ATRISORB
• Polymer of lactic acid, poly (D,L-lactide), dissolved in
N-methyl-2-pyrrolidone (NMP).
• Prepared as a solution that sets to firm consistency on
contact with water or other aqueous solutions.
• Can be trimmed and adapted to the defect.
• Solidifies completely within the fluids of the
periodontal environment, obviating the need for
suturing.
 ATRISORB..contd

• Difficult to use in interproximal defects as the

flexible, semisolid nature makes it difficult to pass
through intact contact point.

• Membrane applied from both sided and bonded in

between in situ.

• Difficult in surgical field.

 Supporting studies

• Polson 1995 – useful in intrabony defects.

• Bogle 1997 – 71% defect regeneration in class II

furcation defects.b

• Garrett 1997 – reduced incidence of postoperative

suppuration and abscess formation

 RESOLUT

• Copolymer of PLA and PGA.

• Degrades over a period of 4 weeks to 8 months.

• Comparable to e-PTFE (Lindhe 1995).

• Useful in class II furcations, 2 wall defects

• Resolut-XT – titanium reinforced, more strength

and structural stability (ridge augmentation).
 Epi-Guide

• Hydrophilic membrane from PLA (L,D forms).

• Flexible open cell structure; thought to encourage

uptake of fluid blood and adherence to tooth
surface.

• Internal void spaces (sponsor blood clot formation.

• Vernino 1995 - effective

 Degradation of PLA-PGA
• Enzymes in Kreb’s cycle
• Whether change in pH occurs is not clear but
insignificant
• PLA degradation: 2 stages;
• 1st; random non-enzymatic cleavage of the
polymer,
• 2nd, loss of mechanical strength and weight
 Degradation of PLA-
PGA..contd

• Degradation releases lactic acid, 

metabolized in liver  CO2 and water

 Material Company Components

Periosteum - Collagen
Connective - Collagen
tissue graft
Freezedried Miami tissue Bank Collagen
duramater
Alloderm Dentsply, CA Acellular dermal matrix

Lambone Pacific coast, LA DFDB sheet/plate

Grafton Osteotech, NJ Allograft gel

Cementum Nishimura (Japan) Cementum particles +

impregnated gelatine gel
gelatin
 Material Company Components

Emdogain Biora Inc, IL Enamel matrix proteins

Surgicel Johnson &Johnson, NJ Oxidized cellulose

Gelform Upjohn Pharma, MI Cellulose

Gengiflex Biofill products, Brazil Alkali cellulose

Capset Lifecore, Brazil POP

Hapset Lifecore, Brazil POP + HA

Cargile memb Ethicon, NJ Cecum of ox

Elastin fibrin Etikpatch, France Elastin, fibrin, type I

matrix collagen and fibronectin
 Advantages of resorbable barriers
over non resorbable barriers
• Elimination of 2nd stage surgery may

1. Reduce operator time

2. Reduce costs

3. Reduce treatment morbidity

4. Inc patient compliance

5. Reduced risk of loss of regenerated attachment

 Advantages of resorbable barriers
over non resorbable barriers – contd..
• Biologically resorbable membranes hold potential
to:
1. More tissue-friendly
2. Integrate with host tissue.
3. Enhance tissue coverage.
4. Reduce barrier exposure.
5. Resist or reduce microbial colonization.
COMBINED REGENERATIVE
PROCEDURES
• Mostly used in resorbable and absorbable
membranes.

• Similar or greater results.

• Controversial..
 Summary of GTR materials

• Patient selection and compliance

• Criteria for selecting membranes determined by the

type of defect, vascularity and severity of destruction.

In retrospect, are we in the right

direction????
 GROWTH FACTORS –

REGENERATION REVISITED!!
• 6 tissue types must be restored for regeneration; ging
epi, ging conn tissue, pdl, cementum, alv bone and
surrounding vasculature.

• Growth factors – general term used to denote a class

of naturally occurring proteins that function in the
body to promote the mitogenesis (proliferation),
directed migration and matrix synthesis (3M).

• For growth factor to help in regeneration, it must play

a role in mineralized and non mineralized tissues
 Various growth factors and
their origin
Growth Major source at wound site
factor
PDGF Platelets, macrophages,endothelial cells
TGF – B Platelets, macrophages,osteoblasts
EGF/TGF–A Platelets, macrophages,epi cells, eosinophils
IGF-1 Plasma, epi cells, fibroblasts, bone matrix
bFGF Macrophages, endo cells, osteoblasts
 PDGF – The key factor!
• Chemotactic for neutrophils, macrophages
and osteoblasts
• Helps in angiogenesis (neovascularization).
• Substantially increases the mitotic rate of
differentiated osteoblasts.
• Faster mineralization of bone matrix.
• Inc collagen synthesis; helps in pdl
formation.
 PDGF – The key factor!
• Acts synergistically with IGF-1, bFGF,
TGF-B.
• Helps in re-epithelialization.
• Induces receptor on the surfaces of these
cells and stimulates the cell by signal
transduction.
• Depending on enviroment, it can also
stimulate bone resorption (Cochran 1991)
 IGF-1
• Present in plasma
• Helps in bone mineralization and collagen
synthesis.
• Acts synergistically with PDGF.
• Also acts on endothelial cells.
• bFGF helps in soft tissue matrix formation. Known
to form periodontal ligament consistently.
 Platelet Rich Plasma

• Nomenclature..concentration

• Growth factor enhancement for regeneration.

• Extensive research

• Realize the synergistic role of growth factors.

• No one factor is individually responsible..

 Platelet Rich Plasma – clinical
application
• Can be used with bone grafts, under a
membrane or as a membrane per se..
• Availability..
• Techniques of procurement..
• Safety..
• Storage..
• Thrombin..
 Platelet Rich Plasma-Studies
• Ratio of mixing
• Lynch et al 1991, Rutherford 1992, Lynch
1989, Niekrash 1992, Terranova 1986,
Robert Marx 1998, Lekovic 2002,2003,
Camargo 2002, Shanaman 1995, Cortellini
2002, Moon Cho 1996, etc…
 SUMMARY
&
CONCLUSION
 REFERENCES
• Clinical Periodontology – Carranza 6th, 8th and 9 th
edition.
• Clinical Periodontology and Implant Dentistry – Jan
Lindhe
• Outline of periodontics – Manson and Eley 4th
Edition
• Periodontal Regeneration – Alan Polson
• Connective tissues of the periodontium – Perio
2000;1999.
• DCNA 1988: Advances in Periodontics – II
• European Workshop – Regenerative Materials.
 REFERENCES – contd..
• Tissue engineering – Samuel Lynch
• Enamel matrix, Cementum and Regenration; JCP
1997 – Hammarstrom
• Role of PGA – JCP 1997.
• Collagen binding peptide (P-15) in bone grafts; JP
• Comparison of FDBA and DFDBA; JCP 1989
• Collagen Membranes: A Review; JP
• Gene therapy for BMPs in periodontal defects; JP
2003;1:
 COMBINATION OF THERAPIES

DEFINITELY IS MORE PREDICTABLE!!