Histological investigation of bone induction by demineralized allogeneic bone matrix: A natural biomaterial for osseous reconstruction

Abstract
The objective of the study was to delineate the histological sequence of events associated with bone formation induced in extraosseous sites by implants of demineralized allogeneic bone matrix (DABM) in order to provide a more complete basis for the clinical use of the natural biomaterial for osseous reconstruction. The rat was the experimental animal model. Implants were prepared by demineralization of diaphyseal cortical rat bone in 0.6N HCl for 18–24 h. A total of 104 specimens, 4 mm square, were implanted both subcutaneously and intramuscularly in 26 rats for periods of 3 days to 22 weeks. Histological evaluation revealed a sequence of events that at 3 days displayed an inflammatory response to surgical trauma and after 6 weeks exhibited the formation of a mature lamellar ossicle with central marrow which was maintained through 22 weeks. Resorption of the DABM, first evident at 1 week, was accompanied by the appearance of chondroblasts in vascular canals and in crevices in the implant. Osteoblastic activity, initially seen at 2 weeks, appeared to be associated with capillary and blood vessel formation around the implant and within enlarged resorptive cavities within the specimens. Calcification occurred in the cartilaginous matrix and osteoid and within the implanted matrix. The osteoinductive process comprises (1) the inflammation / granulation / scar formation processes elicited by implantation of a material, (2) the resorptive response elicited by DABM, and (3) the process of induction of nonosseous mesenchymal cells to differentiate to chondroblasts and osteoblasts. The results of the present study support previous investigations demonstrating the bone‐inducing property of DABM and provide further evidence for the potential value of this natural biomaterial for use in osseous reconstruction.