Repair of long intercalated rib defects in dogs using recombinant human bone morphogenetic protein-2 delivered by a synthetic polymer and beta-tricalcium phosphate.

Abstract

Long intercalated defects in canine ribs can be repaired successfully using porous beta-tricalcium phosphate (beta-TCP) cylinders, infused with a biodegradable polymer (poly D,L-lactic acid-polyethylene block copolymer) containing recombinant human bone morphogenetic protein-2 (rhBMP-2). We previously reported the successful regeneration of bony rib and periosteum defects using beta-TCP cylinders containing 400 microg of rhBMP-2. To reduce the amount of rhBMP-2 and decrease the time required for defect repair, we utilized a biodegradable polymer carrier, in combination with rhBMP-2 and the porous beta-TCP cylinders. An 8 cm long section of rib bone was removed and replaced with an implant comprised of the porous beta-TCP cylinders and the polymer containing 80 microg of rhBMP-2. Six weeks after surgical placement of the beta-TCP cylinder/polymer/BMP-2 implants, new rib bone with an anatomical configuration and mechanical strength similar to the original bone was regenerated at the defect site. The stiffness of the regenerated ribs at 3, 6, and 12 weeks after implantation of the composite implant was significantly higher than that of ribs regenerated by implantation of rhBMP-2/beta-TCP implants. Thus, addition of the synthetic polymer to the drug delivery system for BMP potentiated the bone-regenerating ability of the implant and enabled the formation of mechanically competent rib bone. This new method appears to be applicable to the repair of intercalated long bone defects often encountered in clinical practice.