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Bone Substitutes and Biologic Markers

With the possible exception of implant fixtures (and their prosthetic attachments), no area in periodontics has proliferated so rapidly as periodontal regeneration materials. Today commercial preparations are marketed almost as soon as the first piece of research is published. Some pan out and some are gone as fast as last week's average movie. Now, with the advent of ridge augmentation to receive implants and sinus lifts, grafting materials are being designed for specific applications. Some are engineered to maximize the space for bone ingrowth while others provide a scaffold and readily available inorganic components of bone that migrating reparative cells can utilize. Biologic modifiers are being introduced to increase the likelihood of regeneration. In addition, some manufacturers have begun to individually test donor materials, such as allografts from tissue banks, to determine the graft's ability to induce bone formation in lab animals in areas which would not normally form bone. This increases the likelihood that the graft will actually induce surrounding tissues to form new bone. Inconsistent induction potential in commercially available allogenic grafting materials may be partly responsible for the variability in study results on osseous grafts. Continuing refinements such as these will ultimately improve the predictability of results.

The search for the "perfect" grafting material has focused on bone and bone substitutes, and more recently had added biologic modifiers; that is, substances which influence the activity of the cells responsible for new periodontal ligament formation. Autogenous bone grafts are the "gold standard" for comparing the success of other graft materials. The table below shows the three categories of non-autogenous materials now being used in periodontics, with major examples of each within the category. It is obvious that the choice of material, or combination or materials, is becoming increasingly complex. We want to inform you of these materials so you may share the wide variety of possibilities with your patients.

For periodontal defects bone substitutes are either specialized forms of DFDBA (decalcified freeze dried bone allograft), other animal forms (xenografts) or synthetic substitutes. The specialized forms of DFDBA presently marketed for periodontal defects are Grafton gel and Regeneration Technologies Regenafil paste. Both materials have excellent retention within the surgically debrided defect, more than conventional materials. Grafton uses glycerol, a water soluble base, as a vehicle to carry DFDBA and is about 50% DFDBA after placement.

Bone Substitutes

For Periodontal Defects-Bone Substitutes    For Periodontal Defects-Biologic Modifiers    For Ridge Augmentation- Bone Substitutes
Regenafil (RTI), Grafton gel   Emdogain (enamel matrix derivative)   DFDBA, FDBA (bone allografts)
Bio-Oss, Osteograf-N (bovine bone skeleton)   Pep-Gen (cell binding peptide)   Regenaform, Regenafil, Grafton Putty, Flex
Perioglass, Biogran (synthetic mineral sources)   PDGF (Platelet derived growth factor)   Bio-Oss Cortical Block

Grafton uses a random lot testing to insure that the DFDBA incorporated is osteoinductive. Regenafil (RTI) is 80% bone by volume after implantation as its vehicle is a gelatin which results in less water absorption during the grafting process. Regenafil comes refrigerated, needs to be warmed prior to placement and solidifies as it cools. The liquid-solid temperature range is very narrow. Above 102-103 degrees it is a liquid/gel and at body temperature it is a solid. RTI tests each batch of materials for its osteoblastic induction potential. On an induction scale of 1-4, all RTI materials must be at least a 2.

The currently available animal derived periodontal defect grafting materials are Bio-Oss, Osteograf-N, Interpore 200 and Biocoral. Biocoral is calcium carbonate derived from natural coral, is resorbable and biocompatible. Bio-Oss is bovine bone from which all the organic material has been extracted, yielding a microporous structure very similar to autogenous bone in its chemical composition and microstructure. Osteograf-N is also a bovine bone, but with a crystalline structure rather than a microporous structure. Synthetic bone substitutes include bioactive glasses (Perioglass and Biogran) and a porous methylmethacrylate (HTR). HTR has been shown to increase bone apposition only when in close contact to adjoining bone, such as along an extraction socket wall. The bioactive glasses are particulate materials, slowly resorb and when mixed with fluids in a periodontal defect form an adherent surface layer of silicon, calcium, flouride and sodium which binds the graft to bone. They obliterate defects well, are not inductive of bone formation, but conduct mineralization by promoting absorption and concentration of proteins used by osteoblasts to form the extracellular matrix of bone.

The key characteristics being sought in these materials are the ability to adhere to the defect, encourage clot formation and rapid vascularization, and provide a physical scaffold along with the minerals needed for bone formation. In the case of DFDBA and autogenous bone, components of the graft act to induce osteoblastic transformation and proliferation. It is the nature of these inducing agents within bone grafts that have led researchers to search for the biologic modifiers in grafts that encourage defect repair. The three most common biologic modifiers today are Emdogain, Pep-Gen and PDGF.

Emdogain is an enamel matrix, protein-rich gel extracted from pig tooth buds. Enamel matrix protein is secreted by Hertwig's epithelial root sheath and is responsible for initiating the original formation of acellular cementum on the developing tooth root. In periodontal defects the rationale for its use suggests that host PDL cells/fibroblasts will be transformed into cementoblasts and begin forming new attachments of connective tissue to the root surface. These enamel matrix proteins when suspended in a thickening agent (propylene glycol alginate - PGA) are retained on root surfaces for up to two weeks. The enamel matrix derivative has also been demonstrated by Gestrelius et al to retard downgrowth of epithelium. In the ten clinical studies of this material published since 1997, including two human histological cases reported, attachment level gains have been compatible to guided tissue regeneration membranes. By comparison of similar studies Emdogain appears to produce results similar to DFDBA. Autogenous bone remains the "gold standard" for regeneration studies.

Pep-Gen is a synthetic amino acid sequence identical to that found in the non-allogenic portion of the collagen molecule. The material is combined with an anorganic microporous bovine bone. The portion of collagen protein incorporated in the graft is thought to be responsible for binding fibroblasts and osteoblasts in the material matrix. Yukna, in a histologic study of four human specimens, showed two of the four specimens had new periodontal attachment over previously diseased root surfaces. In the only clinical study to date, Yukna et al found greater defect fill in Pep-Gen treated defects but no greater gain in attachment levels compared to DFDBA.

The most recent biologic modifier is platelet derived growth factor (PDGF). Since this material is derived from the patient's own platelet rich plasma it is not a commercial preparation. Marx et al have described this process. One hundred and fifty milliliters of whole blood is drawn into a citrated container. The platelet rich plasma is separated using a platelet separator, like a centrifuge, and it is added to autogenous or allogenic bovine bone. After placement of the graft material-enriched PDGF, a coat of PRP plasma is placed over the graft area and the flaps closed.

In Marx's study of mandibular defects, both the amount and rate of bone formation were increased. This could be particularly significant for patients whose bone formation is reduced such as the elderly, those with diabetes or osteoporosis. Platelet rich plasma is high in concentration of three growth factors: PDGF (platelet derived growth factor), TGF-B (transforming growth factor beta) and IGF (insulin-like growth factor). The spin down process of platelets increases the concentration by 300%. PRP/PDGF is just beginning to receive clinical utilization.

When you suggest the possibility of osseous reconstruction to your patients, be it for periodontal defects or pre-implant osseous reconstruction, rest assured that we will make our best effort to choose the grafting approach most suited to your patients total needs. If you have questions about the use of any of these materials please contact our office.
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What's New

Education:
Dr. Rosen has completed training with Dr. Pat Allen in root coverage with Alloderm.

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Dr. Rosen has trained with Dr. Steven Wallace in doing sinus grafts.

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