Lecture Topic: ALLOGRAFT IN MAXILLOFACIAL SURGERY

In 1965 Marshall Urist first described the osteoinductive potential of demineralized bone after intramuscular implantation in animal experiments. After an implantation period between 4 and 16 weeks he observed heterotopic ossicle formation, including central bone marrow formation in 50% to 98% of the animals. Several years later the same group showed that chemically altered and decalcified bone matrix yields a higher amount of new bone formation than exclusively demineralized bone. The product of their extraction and alteration procedures was called bone matrix gelatin.

Further investigations revealed that osteinductivity of bone implants could be destroyed either by extraction with 4 mol/L guanidine hydrochloride (GuHCl) and 6 to 8 mol/L urea, respectively or by incubation in neutral phosphate buffer. Explanation for these findings were that 1) GuHCl or urea extracted osteoinductive bone matrix-derived proteins (Bone Morphogenetic Protein, BMPs) which were responsible for induction of new bone formation by diffusion from the bone matrix, and 2) neutral-buffered solutions activated endogenous enzymes in bone matrix, which degraded and metabolized BMPs.

Because alloplastic bone replacement materials and conventionally prepared bone allografts (frozen, freeze dried etc.) only have an osteoconductive effect and autogeneic bone grafts often cause postoperative complaints at the donor sites. we have been looking for an allogeneic bone graft that has osteoinductive as well as osteoconductive characteristics in clinical situations, where a recipient bed with strong regenerative capacity exists.

Depending on the purpose, bone can either totally decalcified or only surface-demineralized. In addition, HCl also extracts acid soluble matrix proteins. The purpose of decalcification is to enable BMPs to defuse in the recipient bed after implantation and to facilitate osteoinduction and resorption by macrophages and osteoclasts.

AAA bone can be prepared by surface demineralization. AAA bone is partly or completely demineralized to expose the organic bone matrix to the recipient bed. The superficial removal of the mineral content of bone is necessary to make possible the diffusion of the osteinductive proteins (BMPs) and their possible cofactors bound tightly to the collagen polypeptide structure of the bone matrix. Sequential extraction Implantation of these semipurified proteins as AAA bone, induces ossicle formation. Human AAA bone contains all inductive factors necessary for the transformation of migratory mesenchymal cells into chondroblasts and osteoblasts.

There are reports that indicate that allogeneic demineralized bone metrix or allogeneic AAA bone matrix induce heterotopic osteogenesis in nonhuman primates. Contrary to these observations, other investigators deny de novo bone formation in heterotopic sites after implantation of allogeneic demineralized bone.

We can conclude that human AAA bone is osteoinductive in contrast to lyophilized or untreated human bone. Human AAA bone includes all morphogens and cofactors necessary for the cascade to induce new bone formation. Through its partial demineralization, human AAA bone has more distinct osteoinductive properties than untreated or lyophilized human bone grafts. Human AAA bone also is safer with regard to the transmission of infectious diseases, including HIV, because its preparation destroys microorganisms within the bone matrix.

Lyophilized and sterilized human AAA bone can be stored at room temperature in a container for several years without loosing its properties.

When different sized particles were evaluated, it was found that the smaller particles induced more bone formation than the larger particles. Demineralized powder provides the maximum surface area necessary for interaction with recipient target cells and best results for bone induction. However it fails to provide the immediate support often needed in skeletal reconstructive procedures. In cystic lesions of the jaws, the ABI grafted into a well-defined defect with bony or periosteal margins. Therefore the powder form of ABI is highly suitable. Furthermore, the soft consistency of the powder enables the operator to overcome the irregularity of the defect and "stuff" it meticulously in order to prevent the postoperative volume changes at the surgical site.

Larger bony defects may fill in from the periphery over a period of many months. Incomplete osteogenesis, mainly in the maxilla, may be seen and such defects may fill with scar tissue partially or completely. There is little cancellous bone in maxilla that can contribute to endosteal osteogenesis and the likelihood of complete bony repair may be reduced in large cavities when both cortical plates are perforated.

Grafting of large defects of the jaws can be accomplished by autogeneous bone, allogeneic bone, xenogeneic bone, lyophilized cartilage and by alloplastic bone substitutes. Clinical studies using allogeneic bone implants(ABI) in the treatment of craniofacial deformities report varying degrees of success. These studies suggest that use of ABI may enhance bone repair in relatively small bony defects.

Autogeneous bone is considered the best material for bone grafting. However donor site morbidity continues to be a major factor when obtaining a bone graft and it is an added surgical morbidity regardless of the site. Therefore the alternatives to autogeneous bone, such as allogeneic bone, xenogeneic bone, lyophilized cartilage or alloplastic bone substitute are increasingly considered.

ABI is considered a powerful inducer of new bone formation. Osteoinduction occurs when BMP are activated. The process of extraskeletel osteoinduction such as in a soft tissue, where no bone exist, can be explained by the fact that BMP is an osteinductive stimulus and host mesenchymal cells are consistently induced to differentiate into cartilage and ultimately bone.

Reconstruction of the severely atropic maxilla and mandible or defects secondary to tumor resection or trauma remains a major challenge for oral and maxillofacial surgeons. The goal of reconstructive procedures is anatomically to restore skeletal and soft tissue anatomy and to provide the patient with an aesthetically acceptable and functional prosthesis.

The most common allogeneic bone preparation currently in use is freeze-dried banked bone. It is readily available in large quantities but revascularization takes longer than in the case of autogeneous bone, and the graft heals by resorption and osteoinduction. In addition, freeze dried allografts have no osteoinductive potential.

AAA bone has been used with mixed results in human beings. An alternative allograft is fresh frozen bone (FFB). It is harvested aseptically from live donors or cadaver donors and then frozen. These allografts can be used for patients of mandibular atropy, jaw defects secondary to either tumor resection or trauma etc. At the time of replacement, FFB has characteristics similar to those of autogeneous bone. The most important advantage of FFB is that osteoinductive proteins are not destroyed in the preparation.

References:

	Norbert K, Jurgen R, Thomas K, Brend P, Walter S,: Osteoinductive, Morphologic, and Biomechanical Properties of Autolyzed Antigen-Extracted, Allogeneic Human Bone: Int J Oral and Maxillofacial Surg: 1993: 1346-1357:
	Marx RE: Tissue Banking Safety: caveats and precautions for the oral and maxillofacial surgeon: 1993: J Oral & Maxillofacial Surg: 1993 Dec;51; 1371-9
	Perrott DH, Smith RA, Kaban LB: The use of fresh frozen allogeneic bone for maxillary and mandibular reconstruction: Int J Oral and Maxillofacial Surg: 1992 Oct; 260-5
	Marx RE, Kline SN, Johnson RP, Malinin TI, Matthews JG, Gambil V; The use of freeze-dried allogeneic bone in oral and maxillofacial surgery; Int J Oral and Maxillofacial Surg; 1981 Apr; 264-74;
	Marshall R Urist; Chemosterilized Antigen-extracted Surface-demineralized Autolyzed Allogeneic (AAA) bone for Arthrodesis; 193-201;
	Lipa Bodner; Osseous regeneration in the jaws using demineralized allogeneic bone implants; J of Cranio-Maxillofacial Surg; 1998; 116-120
	David H, Perrott, Richard AS, Leonard BK, The use of fresh frozen allogeneic bone for maxillary and mandibular reconstruction; Int J Oral Maxillofacial Surg; 1992; 260-265;

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