OSSEOUS REGENERATION IN PRECLINICAL MODELS USING BIOABSORBABLE DELIVERY TECHNOLOGY FOR RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN-2 (RHBMP-2)

Novel delivery systems for the bone morphogenetic protein rhBMP-2, consisting of poly(D,L-lactide-co-glycolide) porous microspheres as bioabsorbable filling material with either autologous blood clot or carboxymethylcellulose as binding agent, were tested in several preclinical models including a rat calvarial defect model, a rabbit radius segmental defect model, and a rabbit ulna segmental defect model. In the rat calvarial defect model, these novel delivery systems were shown to be comparable to inactivated collagenous bone matrix as a matrix for rhBMP-2 delivery at the appropriate dose. The incidence of union in the rabbit long bone studies exhibited a rhBMP-2 dose-response, achieving an incidence of union of nearly 100% at the higher doses tested. Histological evaluation showed remodelling of newly generated bone, and biomechanical testing found that the healed limbs were as strong as untreated control limbs. These studies demonstrate that it is possible to obtain osseous regeneration of critical-size defects by combining rhBMP-2 with synthetic delivery systems.