Repair of segmental defects in rabbit humeri with titanium fiber mesh cylinders containing recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and a synthetic polymer

Abstract

To develop a new technology that enhances the regeneration potential of bone and the repair of large intercalated defects in long bone, recombinant human bone morphogenetic protein-2 (BMP-2; 20 microg or 40 microg) was mixed in a polymer gel (poly-lactic acid-polyethyleneglycol block copolymer; PLA-PEG; 200 mg) and incorporated into titanium fiber-mesh cylinders. Three 5-mm cylinders were placed end-to-end to fill a 15-mm defect created in the humeri of adult rabbits and were stabilized by an intramedullary rod. In controls, the titanium fiber-mesh cylinders were combined with PLA-PEG in the absence of BMP. Six weeks after implantation, new bone had formed on the surface of the implant and had bridged the defect. All of the defects (5/5) treated by cylinders containing 120 microg (40 microg x 3) of BMP were repaired completely. New bone formation was also found inside the pores of the cylinders. The defect was not repaired in the control animals. These results demonstrate that these new composite implants fabricated by combining rhBMP, synthetic degradable polymers and compatible biomaterials enhance the regeneration potential of bone. Thus, it is possible that large skeletal defects can be repaired using this prosthesis in lieu of autogenous bone graft.

Synthetic biodegradable polymers as drug delivery systems for bone morphogenetic proteins

“…New bone was formed on the anterior aspects of vertebrae after 6 weeks (3D-CT, arrow). [59], with permission from 6 Wiley) requires copyright permission since we previously published in J. Biomed. Mater.…”

“…Res. [59]. A bone defect of 1.5 cm was created in the humerus of rabbits, and three 5-mm implants were placed in it.…”

“…Next, rhBMP-2 (120 µg) was mixed with the polymer (120 mg) and impregnated into titanium fiber-mesh cylinders [59]. Three 5-mm cylinders were placed end-to-end to fill a 15-mm defect created in the humerus of adult rabbits and stabilized with an intramedullary rod.…”

Stimulation of Ectopic Bone Formation in Response to BMP-2 by Rho Kinase Inhibitor: A Pilot Study

“…Implantation of BMP can elicit new bone formation both in orthotopic and heterotopic sites [13,27], and is used as a bone graft substitute in the clinical setting [8,24,30]. Although it is now possible to generate recombinant human BMPs for medical use, more than 1.5 mg/kg of the recombinant protein has been required for bone induction in primates [1,15], probably due to their reduced capability for tissue regeneration.…”

Expression of bone morphogenetic protein 2 and fibroblast growth factor 2 during bone regeneration using different implant materials as an onlay bone graft in rabbit mandibles

“…However, to optimize delivery at the bone repair site, rhBMP-2 requires a suitable carrier. Recently, a synthetic polymer, polylactic acid/polyglycolic acid copolymer and gelatin sponge (PGS), that acts as an effective carrier for rhBMP-2 has been developed 6 .…”