Bone induction and bone repair by composites of bone morphogenetic protein and biodegradable synthetic polymers.

Abstract

We developed adequate delivery systems for bone morphogenetic protein (BMP) to express its bone-inducing activity by combining it with biodegradable synthetic polymers, these causing no unfavorable tissue reaction or anti-BMP effect. Their efficacy was tested for ectopic bone formation in mice and reconstruction of large segmental bone defects of the tibiae in rabbits. Composites of semipurified BMP and polylactic acid--polyethylene glycol block copolymer (PLA-PEG), and composites of BMP, PLA-PEG and lactic acid--glycolic acid copolymer (PLGA) were implanted under the fasciae of the dorsal muscles of mice. Three weeks after implantation, both the BMP/PLA-PEG and BMP/PLA-PEG/PLGA composites were completely absorbed and replaced by newly induced bone with hematopoietic marrow. Because the BMP/PLA-PEG composite is a viscous semiliquid and the BMP/PLA-PEG/PLGA composite is a plastic and moldable, the former can be used as an injectable bone-inducing material and the latter as a plastic mold. The BMP/PLA-PEG/PLGA composites were implanted in large segmental bone defects in the tibiae in rabbits. Twelve weeks after implantation, the bone defect was completely restored by a newly formed bone mass of the original thickness and structure.