GOOD MORNINGGOOD MORNING

Defect angleDefect angleThe defect angle is defined as the angle

between bony wall of the defect & long axis of the tooth. (Cortellini & Tonetti 1999).

The defects with a radiographic angle of 25o or less gained more attachment than defects of 37o or more.

rhBMP-2 rhBMP-2 type I collagen sponge type I collagen sponge : INFUSE® Bone Graft : INFUSE® Bone Graft proteinprotein

Bone formationBone formationWhen graft is placed on recipient bed, osteoblast and stem cells at the surface of bone graft survive the transplantation process are responsible for formation of new osteoid product.However, most of the bone precursor cells comes from recipient bed.

Periosteum EndosteumMarrow of host bone

Graft success depend on the early revascularization. After grafting procedure, blood vessels grow into a graft site at approximately 1mm per day. It will provide nutrition for osteogenic cells. In the initial 3 to7 days, stem cells and osteoblasts produce small amount of osteoid.Production of osteoid will increase as the nutrient & oxygen supply from blood vessels increase.Mineralisation will start, resulting in formation of unorganised woven bone, which later on replaced by lamellar bone.

Woven bone Lamellar bone

Fast growing, at rate of 100 um per day

Slow growing, at rate of 1 to 5 um per day

High cellularity Less cellularity

Less mineralised More mineralised

Weaker and more flexible

Stronger. Also known as load bearing bone

Randomly oriented collagen fibers

Oriented collagen fibers in sheets

Why DFDBA material may vary Why DFDBA material may vary from batch to batch? from batch to batch?

Because Commercial bone banks do not verify the specific amount of BMPs or any level of inductive capacity in any graft material.

Delaying the procurement of donor bone after death, improper storage conditions, or other processing factors may play a significant role in the bioactivity of the final DFDBA preparation.

Studies have determined that the minimal effective amount of BMP necessary to affect bone growth is about 2 ug/40 mg wet weight of explant. The optimal amount is about 10 ug (Sato K, 1983).

Use of DFDBA with barrier Use of DFDBA with barrier membranemembrane

The use of a barrier membrane with the DFDBA graft does not appear to improve the likelihood of a good outcome (Becker W et al, 1996).

There is a possibility that barrier membranes may actually delay initial vascularization of

the grafted sites.

Contents Contents Xenografts

• Anorganic bovine bone• Pepgen P-15• Coralline calcium carbonates

Alloplastic materials• Polymers• Tricalcium phosphate• Hydroxyapatite• Bioglass

Healing of graftsComposite graftsFuture directionsConclusionReferences

Bovine bone

Natural coral

Xenografts/Xenogenic Xenografts/Xenogenic graftsgrafts

A tissue (bone) graft between members of differing (heterograft) species i.e. animal to man. Two available source of Xenografts used as bone replacement grafts in periodontics are:

Advantages:OsteoconductiveReadily available

Disadvantages:

Not acceptable for human use because of their immunogenic properties.

Ex: Bovine spongiform encephalopathy or mad cow disease

Calf bone (Boplant), treated by detergent extraction, sterilized and freeze dried, & has been used for the treatment of osseous defects. Kiel bone is calf or ox bone denatured with 20% hydrogen peroxide, dried with acetone, and sterilized with ethylene oxide. Anorganic bone is ox bone from which the organic material has been extracted by means of ethylenediamine, it is then sterilized by autoclaving.

These materials have been tried and discarded because of their immunogenic properties to humans.

ANORGANIC BOVINE BONE ANORGANIC BOVINE BONE (ABB)(ABB)

Recently, new processing and purification methods have been utilized which make it possible to remove all organic components from a bovine bone source and leaving behind a non-organic bone matrix in an unchanged inorganic form.ABB is hydroxyapatite (HA) skeleton, which retains a high porous structure similar to cancellous bone, that remains after chemical or low heat extraction of the organic component.

Commercially available as

Bio-Oss ® Granules, Bio-Oss ® Collagen, and Bio-Oss ® Blocks.

Endobone®

Ladec®

Bon-Apatite®

OsteoGuide TM (Anorganic Bone Mineral).OsteoGuide Collagen TM (Anorganic Bone Mineral

with Collagen)Osteograf/N.

BioOss®BioOss®Synonyms

Deproteinized bovine bone mineralPorous Bone Mineral.Natural Bone Mineral

Bio-Oss® has a natural mineral structure, with the following positive effect:

This material is screened twice for a total deproteinization process to eliminate any graft rejection elicited by the protein matrix.

BioOss®BioOss® Bovine-derived hydroxypatite bone grafts increase the available

surface area that can act as an osteoconductive scaffold due to their porosity and have a mineral content comparable to that of human bone, allowing them to integrate with host bone.

Because this mineral is prepared under a low heat extraction process, its porosity shape remains intact, thus contributing for the initial blood clot stability at the surgical site. The graft becomes revitalized due to ingrowth of blood vessels and osteoblasts, provides a good guide-rail function for the bone.

New bone is laid down directly on the surface of Bio-Oss particles.

Remodeling to lamellar bone occurs after approximately 6 months.Gradual replacements of Bio-Oss by host bone will occur as the particles are resorbed.It could serve as a solid lattice support to an occlusive membrane in GTR applications. Consequently, the predictability of the regenerated osseous volume is improved.It is biocompatible, amalgamate, and incorporates well within the newly formed regenerated hard tissue, with almost no clinical postoperative complications. Clinically the presence of ABB particles does not interfere with the wound healing process.

Chemically and physically, the particles are identical to human mineral matrix, and are very similar in size to that of human cancellous bone.

Human cancellous bone (SEM 50x)

BioOss (SEM 50x)

Schmitt and Buck (1997) compared porous bone mineral (ABB) and bioactive glass ceramics (BGC) in a critically sized defects in rabbits. ABB sites were more radio opaque & showed more new bone formation than BGC.Nevins & Schenk et al (1998) compared ABB & DFDBAResults : Pocket Depth Reduction ….. 3.0mm vs 2 mm CAL gain …………………3.5 mm vs 2.6mm Bone fill ………………….. 55.8% vs 46.8%

Lekovic 2002 compared PRP/ABB/GTR versus a combination of PRP/ABB. The results suggested that GTR adds no clinical benefit to PRP/ABB.

The possible reason suggested by the author was, Once the PRP preparation is coagulated, it assumes a

sticky consistency due to its high fibrin content. It adheres to the root surface and so may impede the

apical migration of epithelial cells and connective tissue cells from the flap.

It is reasonable to assume that PRP may, in that sense exert a GTR effect in the treated defects.

PepGen P-15 is a composite of anorganic bovine-derived bone material (ABM) that mimics the inorganic component of autogenous bone and a synthetic peptide (P-15) that mimics the organic component (Type-I collagen) of autogenous bone.

Pepgen P-15 contains only about

200 nanograms of P-15 in 1 gm of

hydroxyapatite.

PepGen P-15

It is available as:

PepGen P-15 Particulate

PepGen P-15 Flow

PepGen P-15 Putty

The particle size ranges between 0.25–0.42

mm.

How Does PepGen P-15 How Does PepGen P-15 Particulate Mimic Particulate Mimic

Autogenous Bone?Autogenous Bone?

Inorganic ComponentInorganic ComponentMorphologically, the inorganic component of autogenous bone consists primarily of a microporous calcium phosphate mineral (hydroxylapatite).

Inorganic component of Pepgen P-15 is made up of Anorganic Bovine derived natural form of hydroxylapatite which provides:

A substrate for the synthetic peptide A natural hydroxylapatite skeleton that is similar to that of human bone & appears to behave more physiologically during wound healing.A natural scaffold for cell tracking and bone repair (osteoconduction) .Contains essential bone regeneration minerals (notably calcium).

Organic ComponentOrganic ComponentThe organic component of autogenous bone is

primarily Type-I collagen, which consists of three strands of 1300 amino acids that are helically intertwined.

Collagen performs many different functions; Facilitate cell attachment. Most cells (with the

exception of blood cells) must attach to a substrate in order to function in a normal manner.

Collagen provides anchors for cells. Once the cells attach to collagen, they use the collagen fibers as tracks on which to move. So Type-I collagen is responsible for the cascade of events (migration, binding, proliferation and differentiation) that leads to bone formation.

A short (766-GTPGPQGIAGQRGVV-780) sequence of collagen – forming the major component of the organic components of bone has been identified as a cell binding domain for mesenchymal progenitor cells.

The binding of osteoblast progenitor cells at this domain initiates their proliferation and differentiation.

Cell surface receptor contacts P15 binding domain in

human collagen I initiating the natural osteogenic

differentiation process.

The peptide, P-15, is a synthetic tissue engineered linear polypeptide with a 15 amino acid sequence identical to the sequence contained in residues 766-780 of the alpha-1 chain of Type-I collagen.

P-15 represents approximately 1.5% of the size of the alpha-1 chain or 0.5% of a type I collagen molecule.

Recombinant P15 binding domain on PepGen P 15 substrate simulate

a collagenous biomimetic environment for the cells.

Cell surface integrin receptor contacts PepGen P15 particle and the

natural osteogenic differentiation process is triggered in the same way.

The combination of P-15 and ABM provides a unique 3 dimensional habitat for cells that allows natural bone healing.

Two-dimensional “classical” defect healing

Three-dimensional, multifocal defect healing after filling the defect with

PepGen P-15

PepGen P-15 FLOWPepGen P-15 FLOW PepGen P-15 FLOW is composed of PepGen P-15 particulate suspended in inert biocompatible hydrogen.When introduced to a site, the unique expansive quality allows for complete osseous fill, ensuring intimate contact between PepGen P-15 FLOW and all irregularities within the defect.The natural spacing allows for vascularization and cellular transport throughout the entire grafted site.Available in 0.5cc and 1cc sizes.The particles measure 250 – 420 microns (40-60 mesh) each.

Pepgen P-15 PuttyPepgen P-15 PuttyPutty = Porous particulate + carrier gel

Carrier Gel:

Sodium hyaluronate carrier which is a safe, natural substance found in the human body’s joints, skin and ocular fluids.The carrier contains the particles in a cohesive moldable form and provides effective particle spacing in a 3-D osteoconductive scaffold for cellular and tissue ingrowth.

Due to PepGen P-15 PUTTY’s high molecular weight, it is not readily displaced and yields minimal expansion in biological fluids.Allows the clinician to mold the graft material to the dimensions that meet each procedure’s needs.Improving the handling characteristics of the PepGen P-15 particles at the graft site, preventing particle migration and over packing.

Hanks et al 2004 compared for cell viability and apoptosis of ABB & ABB/P-15. They determined that the P-15 peptide when complexed with ABM, can facilitate a role in enhancing viable cell attachment and survival in anchorage-dependent pre-osteoblasts and fibroblasts. Yukna et al, 2000 used Bio-Oss membrane + PepGen P-15, and concluded that this combination seems to enhance the bone regenerative results of the matrix alone in periodontal defects.

Smiler, 2006 compared ABM plus demineralized freeze dried bone allograft (DFDBA) to ABM + P-15 plus DFDBA for augmentation of maxillary sinuses. Four months after surgery, bone cores were obtained during osteotomies for placement of dental implants.The combination of ABM + P-15 plus DFDBA showed 45% vital bone at 4 months, whereas ABM + DFDBA showed only 13%.

Neiva et al, 2008 compared the effects of a Putty-Form Hydroxyapatite Matrix Combined With the Synthetic Cell-Binding Peptide P-15 on Alveolar Ridge Preservation.Mean bone density was significantly superior in the test group (2.08 ± 0.65) compared to the control group (3.33 ± 0.65).Although complete bone fill, represented by the presence of a flat and continuous ridge surface, was observed in all test sites 4 months following exodontia.59% of the control sites had a residual socket.

i-FACTOR™ i-FACTOR™ i-FACTOR™ bone graft is the bone graft substitute

that uses a unique anorganic bone mineral (ABM) and small peptide, P-15™, that acts as an attachment factor for specific integrins in osteogenic cells.  This novel mechanism of action enhances the natural bone healing process resulting in safe, predictable bone formation.

Coralline calcium Coralline calcium carbonatecarbonate

The use of coral skeleton as a bone graft substitute was proposed by Holmes 1979.

Depending on the pre-treatment procedure, the natural coral turns into

Non-resorbable porous hydroxyapatite (e.g. ProOsteon, Interpore-200).

Resorbable calcium carbonate Biocoral (Inoteb, Saint Gonnery, France).

Biocoral (Inoteb, Saint Gonnery, France) is calcium carbonate obtained from a natural coral, genus Porites, and is composed primarily of aragonite (>98% CaCO3).

Its pore size of 100 to 200 um is similar to the porosity of

spongy bone (Guillemen G, 1987).

The porosity, at greater than 45%, provides a large surface area

for resorption and replacement by bone (Yukna RA, 1993).

Biocoral - granules Biocoral - spheresBiocoral - blocks

Biocoral has a high osteoconductive potential because no fibrous encapsulation has been reported (Yukna RA, 1993).

Coralline calcium carbonate produces comparable results to other bone replacement grafts with significant gain in clinical attachment, reduction of probing depth and defect fill (Kim CK et al, 1996; Gao TJ et al, 1997; Mora F, 1995).

Highly porous calcium phosphate ceramics can also be obtained from porous-apatite of lime-encrusted ocean algae (Frios®, Algipore®). The manufacturing process retains the pure mineral framework of the algae, leaving an interconnected porous structure and a rough surface. It has been shown that the biomaterial is resorbed slowly and substituted by host bone (Schopper et al., 1999).

ALLOPLASTSALLOPLASTSA synthetic bone graft material, a bone graft substitute.Plaster of paris was one of the materials investigated as a bone substitute, which is a β-hemihydrate form of calcium sulfate. It had inherent difficulties and minimal clinical success. The focus began to shift to calcium phosphate ceramics in 1970s. With the exploration of bioceramics, biocompatible filling material became available. Clinical success was reported in terms of bony defect fill but little clinical evidence of true periodontal regeneration.

Alloplastic materials are available in variety of textures, sizes and shapes. Based on their porosity, they can be classified as

Dense, macroporous Microporous

They can be either crystalline or amorphous. The specific properties of an alloplasts determine which synthetic material is best for a particular application. All of the commercially available alloplasts except POP have a particle size between 300-500μm in a diameter

Types:Types:A wide variety of alloplastic materials have been

suggested for use in periodontal therapy.

Plaster of paris, PolymersCalciumCarbonatesTricalcium phosphateHydroxyapatite• Dense, nonporous, nonresorbable• Porous, nonresorbable (xenograft)• Resorbable, low temperature derivedBioglass.

Some of these materials are resorbable to varying degrees, but most are nonresorbable. Clinical results with alloplastic materials are essentially similar to results obtained with autogenous or allogeneic materials (Yukna RA, 1994).

The choice of material then becomes based more on availability, cost, morbidity, and ease of handling than on clinical superiority.

The 1996 World Workshop in Periodontics concluded that “synthetic graft materials function primarily as defect fillers. If regeneration is the desired outcome then other materials are recommended”.

CartilageCartilage

It has been used for repair studies in monkeys and treatment of periodontal defects in humans (Schaffer EM, 1956; 1957; 1958).

It can serve as scaffolding; when so used, new attachment was obtained in 60 of 70 cases.

However cartilage has received only limited evaluation.

 

ScleraSclera 

Sclera was originally used in periodontal procedures because it is a dense, fibrous connective tissue with poor vascularity and minimal cellularity (Klinsberg J, 1972; 1974).This affords a low incidence of antigenicity (Johson W et al, 1962). Acts as a barrier to apical migration of the JE and protects the blood clot during the initial healing.

Disadvantage : Sometimes invaded by host cells and capillaries and replaced by dense connective tissue cells, it does not appear to induce osteogenesis or cementogenesis.

The available scientific research does not warrant the use of sclera in periodontal therapy.

 

Plaster of ParisPlaster of ParisPOP (Calcium sulphate) is biocompatible and porous, thereby allowing fluid exchange, which prevents flap necrosis.

POP resorbs completely in 1 to 2 weeks.

One report suggested its use in combination with DFDBA and Gore-Tex membrane (Sottosanti , 1992).

One study in surgically created three wall defects in the dogs showed significant regeneration of bone and cementum (Kim CK et al, 1998).

Its usefulness in human cases, however has not been proved.

Polymers (Polymers (HTR HTR polymer)polymer)

BioplantTM Hard Tissue Replacement (HTR) polymer is composed of microporous (300-350 mm) beads of three concentric layers:

Inner of polymethylmethacrylate (PMMA): gives the particle an adequate mechanical resistance (strength).

Middle of polyhydroxylethylmethacrylate (PHEMA): is soft and hydrophilic. Its negative charge favors adhesion with the surrounding tissues and also enhances clotting.

Outer of calcium hydroxide-carbonate layer: bioactive and forms calcium carbonate after its introduction into the osseous bleeding surgical site.

The average pore diameter is 250-500 microns.Its hydrophilicity enhances clotting, and its negative particle surface charge allows it to adhere to bone. It appears to serve as a scaffold for bone formation when in close contact with alveolar bone.

Favorable clinical results have been achieved with HTRTM in the treatment of intrabony and furcation defects (Yukna RA, 1990, 1994).

Histologically, new bone growth has been found deposited on HTRTM particles (Forum SJ, 1996; Yukna RA, 1992). However, improved clinical results with this bone replacement graft have not always been achieved (Shahmiri S et al, 1992).

Overall, clinical defect fill and resolution can be achieved supporting its use as a biocompatible, osteophilic, and osteoconductive alloplastic bone substitute (Ashman A et al, 1994; Froum SJ, 1996).

POLYLACTIC ACID (PLA) AND POLYLACTIC ACID (PLA) AND POLYGLYCOLIC ACID (PGA):POLYGLYCOLIC ACID (PGA):

Fisiograft: It is a totally synthetic Co-polymer based on polylactic and polyglycolic acid completely risk free from cross contamination.The relatively small molecular weight of the Fisiograft compared to its large surface area permits it to be rapidly dissolved with total absorption not exceeding eight months.This copolymer has a spongy open-cell structure enabling it to be colonized by the osteoblasts.It is available in sponge, powder and gel form and can be used in dentistry as a filler.

Fisisograft - Sponge

Fisiograft - Powder

Fisiograft - GelFisiograft - Test

BioceramicsBioceramicsBioceramic alloplasts are comprised primarily of calcium phosphate, with the proportion of calcium and phosphate similar to bone. Show excellent tissue biocompatibility and are osteoconductive.Two types:

Hydroxyapatite (HA) has a calcium-to-phosphate ratio of 1.67, similar to that found in bone mineral. HA is generally non-resorbable.Tricalcium phosphate (TCP), with a calcium-to-phosphate ratio of 1.5, is mineralogically B-whitlockite. TCP is atleast partially resorbable.

Tricalcium phosphateTricalcium phosphateTricalcium phosphate is a porous form of calcium phosphate, the most commonly used form of which is ß-tricalcium phosphate.

It serves as a biological filler which is partially resorbable and allows bone replacement.

Conversion of the graft is pivotal to periodontal regeneration; first, serving as a scaffold for bone formation, and then permitting replacement with bone (Hashimoto-Uoshima et al, 1995; Shetty , 1991).

TCP + Naphthalene ………………. Composite cools

Naphthalene evaporates

High Temperature

Porous form of calcium phosphate

Has gained clinical acceptance, but the results are not predictable. Allogeneic grafts appear to outperform tricalcium phosphate (Strub JR et al, 1990). The tricalcium phosphate particles generally become encapsulated by fibrous connective tissue and do not stimulate bone growth (Baldock et al, 1985). However, some bone deposition has been reported with tricalcium phosphate grafts (Amler, 1987; Baldock et al, 1985; Strub et al, 1990; Stahl , 1986).

Tricalcium phosphateTricalcium phosphateCommercially available as Synthograft®, OsSatura®, Bioresorb®

Tricalcium phosphateTricalcium phosphateVitosss®, Chronos®, Ceross®, Cerasorbs®

Vitoss

Vitoss Vitoss

HydroxyapatiteHydroxyapatiteHydroxyapatite, Ca10 (PO4)6 (OH)12, is the primary

mineral component of bone. Synthetic hydroxyapatites have been marketed in a variety of forms, primarily as a

a dense or solid nonresorbable– E.g. Periograf, Calcite, Osteograf D,porous nonresorbable- E.g. Interpore 200 and a resorbable (non-ceramic, porous) form – E.g. Osteograf L/D.

Hydroxyapatite resorbability is determined by the temperature at which it is processed, and this resorbabiltiy is desirable, if it has to replaced by bone.

When prepared at high temperature (sintered),

hydroxyapatite is nonresorbable, nonporous,

dense, and has a larger crystal size (Klein et al, 1983).

DENSE HYDROXYAPATITEDENSE HYDROXYAPATITEDense hydroxyapatite grafts are osteophillic, osteoconductive Act primarily as inert biocompatible fillers. They have produced clinical defect fill greater than flap debridement alone in the treatment of intrabony defects (Rabalais et al, 1981). Histologically, new attachment is not achieved (Froum et al, 1982). They yield similar defect fill as other bone replacement grafts and the clinical improvement is more stable than with debridement alone.

Porous hydroxyapatitePorous hydroxyapatiteObtained by the hydrothermal conversion of the calcium carbonate exoskeleton of the natural coral genus Porites into the hydroxyapatite. It has a pore size of 190 to 200 µm, which allows fibrovascular ingrowth & subsequent bone formation, (West et al, 1985) into the pores and ultimately within the lesion itself (Kenny et al, 1986). Commercially available as Interpore 200® (Irvine, CA).

Clinical defect fill, probing depth reduction, and attachment gain have been reported (Kenny EB et al, 1985). Kenney et al (1986) provided histological evidence suggesting that porous hydroxyapatite supports bone formation, but no evidence of a new connective tissue attachment or cementum was noted.

Interpore 200®

Resorbable, particulate Resorbable, particulate material material

Processed at a low temperature.This resorbable form is a non-sintered (nonceramic) precipitate with particles measuring 300 to 400 µm. It has been proposed that non-sintered hydroxyapatite resorbs acting as a mineral reservoir inducing bone formation via osteoconductive mechanisms (Ricci et al, 1992; Wagner, 1989).Its reported advantage is the slow resorption rate, allowing it to act as a mineral reservoir at the same time acting as a scaffold for bone replacement (Ricci et al, 1992; Wagner , 1989).

Commercially available as,OsteoGraf LD®, (CeraMed Dental ), OsteoGen® (Impladent);

The material has also been used for endosseous implants and for sinus augmentation (Vlassis JM et al, 1990).

MODIFICATIONS OF MODIFICATIONS OF HYDROXYAPATITEHYDROXYAPATITE

Silicate Substitution to Porous Hydroxyapatite Bone Graft Substitutes (Hing et al. 2005): The substitution of silicon into the apatite lattice

of porous HA scaffolds had a profound affect on the progression of osseointegration.

Small additions promoted the rapid apposition of immature woven bone.

Increasing the amount of silicon to = 0.8wt% appeared to restore/promote the apposition of more mature lamellar bone at earlier time points.

OSTIMSOSTIMS

It is a nanocrystalline-precipitated hydroxyapatite that still contains about 40% of water.

It has a viscous, fluid-like consistence and can therefore be directly injected into a defect.

Bovine BMP product bound to synthetic microgranular hydroxyapatite (BMPb-HA) ) is available for bone grafting procedure.(Gen-ProTM, Baumer, Mogi Mirin, SP, Brazil)Ramalho, 2004 conducted study using BMPb-HA in the treatment of critical size bone defects in the rat skull and found that it leads to the formation of numerous agglomerates of hydroxyapatite particles, which promote a foreign body-type granulomatous reaction that markedly inhibits new bone formation. These findings suggest that this type of synthetic hydroxyapatite ceramic does not represent a good carrier for BMP-induced bone formation.

BMPb-HABMPb-HA

BIOACTIVE GLASSESBIOACTIVE GLASSESThere are two forms of bioactive glass currently available :

• PerioGlass® (Block Drug Co.) • BiogranTM (Orthovita)

Hench et al, 1980 developed this glass.The first studies on bioactive glass and the possibility of its application as a bone filling material were published in the 1970’s and 1980’s. Bioactive glasses - bond to bone through the development of a surface layer of carbonated hydroxyapatite (Hench et al, 1973, 1975).

Composed of elements naturally occuring in bone, like silicon dioxide (46 mole %), sodium oxide (24.4 mole %), calcium oxide (26 mole %), and phosphorous pentoxide (6 mole %).

When exposed to tissue fluids, bioactive glasses are covered by a double layer composed of silica gel and a calcium-phosphorous rich (apatite) layer. The calcium phosphate-rich layer promotes adsorption and concentration of proteins utilized by osteoblasts to form a mineralized extracellular matrix (El-Ghannam A et al, 1997).

It has been theorized that these bioactive properties guide and promote osteogenesis (Schepers et al, 1991, 1993), allowing rapid formation of bone (Hench et al, 1995).

Commercially available as Perioglas®, Biogran®.

PerioGlass®PerioGlass®

Particle size ranging from 90 to 710 µm, which facilitates manageability and packing into osseous defects. In surgically created defects in nonhuman primates, 68% defect repair was achieved as new attachment (Fetner , 1996). Compared to tricalcium phosphate, hydroxyapatite and unimplanted controls, Fetner et al showed that PerioGlass produced significantly greater bone and cementum repair.Observations of the material suggest good manageability, hemostatic properties.Possibility that PerioGlass® not only is osteoconductive, but may also act as a barrier retarding epithelial downgrowth !!

Bioactive glass (Mechanism of Action)

Inhibition Of Long Juctional Epithelium:Henrique et al (2005) tested bioactive glass showed

an inhibitory property on the apical migration of the junctional epithelium. It was observed that in the sites treated with the bioactive glass, the junctional epithelium migrated apically to the level of the particles most coronally located inside the defect, not surpassing this point.

Mechanism involved in this phenomenon:The calcium phosphate layer formed on surface of silica is composed of hydroxycarbonate apatite that is chemically and structurally equivalent to bone mineral composition. The osteogenic cells and collagen fibers colonize the surface of the bioactive glass, are incorporated into this layer. The collagen that attaches to the bioactive glass surface and is embedded into the hydroxycarbonate apatite extends apically to the junctional epithelium, thus inhibiting apical migration (Wilson, 1992).

Ossteostimulation (Schepers and Ducheyne, 1997):It is a property shown by bioactive glass.In simple terms, it is "controlled induction". It can be defined as the capacity of an osseoconductive material to stimulate new bone deposition on its surface. The term "osteoinductive" is applied to materials with the affinity to induce new bone formation, regardless of where it is implicated in the body. PerioGlass is not osteoinductive, as it does not stimulate bone formation in a non-osseous site.

BiogranBiogranTMTM

Narrower range of particle sizes of the purportedly critical 300 to 355 µm size range which has been reported to be advantageous for guiding osteogenesis (Sigurdsson et al, 1996).

Formation of hollow calcium phosphate growth chambers occurs with this particle size because phagocytosing cells can penetrate the outer silica gel layer by means of small cracks in the calcium-phosphorous layer and partially resorb the gel.

This resorption leads to the formation of protective pouches where osteoprogenitor cells can adhere, differentiate and proliferate.

PerioGlass® has a particle size ranging from 90 to 710 um, which facilitates manageability and packing into osseous defects. BiogranTM has a narrower range of particle sizes of the purportedly critical 300 to 355 um size range which has been reported to be advantageous for guiding osteogenesis (Sigurdsson TJ et al, 1996).

It is argued that the more uniform sized BiogranTM would have a clinical advantage over the PerioGlass® preparation, which has multiple particle sizes, however there has been no comparison.

Unigraft – Unigraft – 200-420200-420 µm µm

Showed that bioglass resulted in greater clinical improvements than surgical debridement alone (Froum et al 1998).

Other controlled studies – failed to demonstrate statistically significant better clinical results than surgery alone or DFDBA grafting (Zamet et al 1997).

No histological evidence that bioglass may promote true periodontal regeneration (Nevins et al 2000).

However, animal study has suggested that bioglass favors new cementum formation & inhibit epithelial downgrowth (Karatzas et al 1999)

Morphological and Biological Morphological and Biological Implications Implications

The morphology of bone replacement grafts has been postulated to contribute to their osteoconductive capacity mainly due to:

influence of particle size and shape on the resorption and replacement phenomenon &influence of interparticulate space on infiltration of vascular cellular elements and bone formation.

Particles too large in size will resorb at a slower rate and offer an overall reduced surface area.Particles too small in size may induce inflammation, be readily resorbed or phagocytosed and result in an interparticulate space of a reduced dimension that would not be conducive to cellular migration and ingrowth. Trabeculae of bone vary in size from 20 to over 100 um. Compact bone has Haversian systems or osteons of size between 50 to 250 um.

Thus, to support trabecular bone ingrowth, the pores of the bone grafts would need to be at least 40 to 100 um, and to support osteonal bone ingrowth, pores of at least 100 um would appear necessary (Klawitter JJ et al, 1971). Particle sizes of about 380 um in diameter would yield this minimal dimension (Hirschorn JS, et al, 1971). To date, little or no histological evidence is available to support this claim.

In a small clinical study, Fucini et al (1993) found that there was no difference in defect fill between demineralized freeze-dried bone allograft particles of 250 to 500 µm size compared to those of 850 to 1000 µm.

In vitro analysis of the interparticulate space among bone replacement grafts condensed under a uniform standard force showed that autogenous bone harvested by low- and high-speed rotary instruments, freeze-dried bone allograft (250-710 µm), Bio-Oss(cancellous and cortical), Osteograf LD, PerioGlass and Osteogen yielded a 40 to 100 µm interparticulate space.

Human periodontal ligament fibroblasts were grown on a variety of bone replacement grafts to analyze differences in cell binding and spreading as a function of the bone replacement graft substrata.

Scanning electron microscopy observations demonstrated that adherence dynamics varied among bone replacement grafts, with cell spreading occurring most rapidly on materials derived directly from bone.

Cell spreading was slower on non-osseous hydroxylapatites and other synthetic surfaces, although there was considerable variability within classes of these materials (Moses et al, 1996).

COMPOSITE GRAFTSCOMPOSITE GRAFTSThe concept of composite grafts came into existence with the thought that the graft materials may show some synergy by combining the potential of two materials. The most widely used composite grafts include the combination of

 β -TCP + HAFDBA + DFDBAAllograft + AutograftGlasses + autograftDFDBA + Antibiotics

HEALING OF GRAFTHEALING OF GRAFTThe first wound-healing phase is revascularization. Revascularization is initiated within the first few days following the grafting procedure. Blood vessels originating from the host bone invade the graft. A pore size of 100 to 200 µm is very conducive to vascular invasion. Revascularization is followed by the incorporation of the grafted bone particles by new bone emanating from the host. If the graft material contains vital osteogenic precursor cells that survive the transplantation process, these cells may contribute to new bone formation.

The graft may possess inductive proteins that actively stimulate the host to form new bone (osteoinduction), or the graft may simply act passively as a lattice network over which the new host bone forms (osteoconduction).

As the graft is being incorporated, it is gradually resorbed and replaced by new host bone. This process is sometimes referred to as creeping substitution.

The final phase of healing is bone remodeling.

Resorption, replacement, and remodeling take many years. Large allografts may never be fully resorbed and replaced (Goldberg et al, 1987). Most alloplasts do not undergo resorption, replacement, or remodeling. Formation of new bone, new cementum, and a new periodontal ligament has been reported to occur following most types of autograft and allografts but not alloplasts .(Mellonig JT, 1992).

 

FUTURE DIRECTIONSFUTURE DIRECTIONSAlthough the bone grafts have been shown to be efficacious for the treatment of periodontal osseous lesions the reconstruction appears to be limited to a mean bone fill of approximately 3.0mm irrespective of type of bone graft material. Additional stimuli to enhance the regenerative process are clearly needed.

Also, the development and manufacture of effective, safe and user-friendly bone replacement grafts will increase their use in oral and maxillofacial and periodontal reconstructive therapy.

Other products like polypeptide growth factors; a potential class of natural biologic response modifiers may be future answer.

Factors such as osteogenin or combination of PDGF and IGF may have potential. Other growth factors such as TGF-β and FGF may also have a place.

Autologus PRP to make platelet gel which is rich in growth factors for periodontal regeneration was the first of its kind of treatment modality using the principles of tissue engineering for periodontal regeneration.

Bone grafts/substitutes recombinant growth factors and BMPs for bone, denting periodontal regeneration has been widely studied in the recent

 Anorganic bovine material, natural and converted coral may have potential as carriers for recombinant BMP-2 or other Biological modulators, which may increase their usefulness.

GEM 21 S® (Osteohealth GEM 21 S® (Osteohealth Company)Company)

It is an innovative combination of rhPDGF-BB and β-TCP.McGuire et al, 2006 found comparable clinical outcomes to SCTG, when rhPDGF-BB +β -TCP was used to cover gingival recession.

In a RCT, treatment with rhPDGF-BB stimulated a significant increase in the rate of CAL gain, reduced gingival recession at 3 months post-surgery, and improved bone fill as compared to a beta-TCP bone substitute at 6 months(Nevins M et al, 2005).

CONCLUSIONSCONCLUSIONS

The role of regenerative materials has become quite significant and has become an indispensable part of the periodontist kit. What we need to introspect is the critical evaluation of each available material prior to usage with a thorough knowledge of the composition and procedural requirements of the material. Future research needs to focus on predictability of these materials in the long-term success of periodontal therapy.

References References Periodontal Therapy: Clinical approaches and evidence of success, Vol. 1, Myron Nevins and James Mellonig.Nasr F.H. et al. Bone and bone substitutes, PERIO 2000 1999: 74-86.Textbook of Clinical Periodontology and Implant Dentistry, 4th edition, Jan Lindhe.Carranza, Textbook of Clinical Periodontology, 10th edition.James T, Mellonig. Autogenous and allogenous bone grafts in periodontal therapy, Crit Rev Oral Biol. 1992; 333-352.

 

Annals of Periodontology. Regeneration of periodontium around natural teeth. 1996; 71-112.Biologic and clinical considerations for autografts and allografts in periodontal regeneration therapy. DCNA, 1998, 42(3); 467-490.Bone replacement grafts. DCNA, 1998, 42(3); 491-503.Devices for periodontal regeneration. Periodontology 2000, Vol. 19, 1999, 59-73Biological mediators for periodontal regeneration. Periodontology 2000, VoL. 19, 1999, 40-58Effects of a Putty-Form Hydroxyapatite Matrix Combined With the Synthetic Cell-Binding Peptide P-15 on Alveolar Ridge Preservation. J Periodontol 2008;79:291-299.

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