Carriers May Change Osteoinductivity of Human Demineralized Bone in the Athymic Mouse

Objectives: Demineralized freeze-dried bone allograft (DFDBA) is an effective osteoinductive material but can be difficult to use clinically, especially in nonspace-maintaining periodontal defects. To solve this problem, we investigated new carriers to assist in placement and retention of the graft and tested the hypothesis that carrier composition and DFDBA concentration affect osteoinductivity. Methods: We first evaluated nine batches of human DFDBA (LifeNet, Virginia Beach, VA) for osteoinductivity in vivo using the athymic nude mouse muscle implantation assay, and selected a batch with high activity and a batch with very low activity as positive and negative controls. A biodegradable hydrogel approved by FDA for use as a sealant in humans (macromer), was used in three forms: macromer alone, unpolmerized macromer + polymerizer, and polymerized macromer. DFDBA (accredited bone bank) was tested alone and with carrier (20, 30 and 40% by weight). Gelatin capsules (15 mg DFDBA) were implanted bilaterally in the quadriceps of nude mice. Tissues were harvested at 56 d, decalcified, and prepared for histology. Sections were evaluated histomorphometrically for residual graft particles, new bone and cartilage. Two independent examiners graded sections for bone induction using a semi-quantitative scoring scheme. Based on these results, three additional batches of DFDBA were formulated at 30% in macromer and tested. Results: All carriers reduced osteoinduction activity but active DFBA remained oteoinductive in macromer. Macromer containing 30% DFDBA was the best formulation when compared to any other combination examined. Conclusions: This indicates carrier composition and DFDBA concentration both play roles and that highly active DFDBA can retain osteoinduction ability when formulated appropriately.