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 chondroblast 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.

The osteoinductive capacity of differently HCI-decalcified bone alloimplants

“…Inside the different residual matrices, new trabecular bone, limited by a thin cortex and containing bone marrow, was present. This histologic pattern has also been previously reported (Urist 1965, van de Putte & Vrist 1965, Koskinen et al 1972, Chalmers et al 1975, van der Steenhoven & Spector 1983. Qualitative examination of the samples did not elicit any obvious difference in the amount of induced bone, except in the AAA group where it tended to be lower.…”

“…Several studies have shown that an excellent osteoinductive response was obtained with HC1-decalcified cortical bone, either at 4°C (Urist 1965, Van de Putte & Urist 1965, Koskinen et al 1972, Oikarinen & Korhonen 1979, Glowacki et al 1981, Van der Steenhoven & Spector 1983) or at ambient temperature (Narang et al 1971, Chalmers et al 1975, Tuli & Singh 1978, Gupta & Tuli 1982, Einhorn et al 1984.…”

Augmentation of osseous phenotypes in vivo with a synthetic peptide

“…An enhanced bone repair would be suggestive of an augmentation of endogenous BMP-2 since BMPs are also known to be upregulated during bone repair. [13][14][15] B2A2-K-NS resulted in marked closure of the bone defect, whereas leaving the defect untreated or treated only with carrier was ineffective in supporting full closure of the defect. The defects treated with B2A2-K-NS were at least as effective, if not better, than autograft.…”

“…12 BMPs and their receptors are known to be upregulated during bone repair, [13][14][15] and are widely thought to mediate bone repair.…”

Graft perforations favor osteoinduction

“…This statement is supported by two observations. First, comparison of the rate of bone formation with that of others who did not use ethylene oxide sterilization in their solid (Tuli and Singh 1978, Vandersteenhoven and Spector 1983, Bemick et al 1989 or powdered (Reddi 1985) implants, shows ethylene oxide sterilized Gendler matrix to form new bone at least as rapidly, if not more rapidly, than the others. Secondly, a major factor in reported suppression of osteoinduction is the presence of highly inflammatory ethylene oxide residues in the matrix.…”