Operant in bone maintenance and repair is a unique class of polypeptides known collectively as bone morphogenetic proteins (BMPs). To date, eight recombinant human (rh) BMPs (designated BMPs 1-8) have been cloned, expressed, and characterized. The development of a three-dimensional construct for rhBMP delivery is pivotal to its successful clinical applications for skeletal repair. Several key characteristics of an rhBMP-delivery system include biocompatibility at implantation and during biodegradation, parous architecture for osteoconduction, biodegradation in harmony with new bone formation, and controlled mass loss of the delivery system releasing an osteoregenerative factor (i.e., rhBMP-2) at the proper dose and time to regenerate deficient skeletal tissue. The purpose of this study will be to investigate the capability of different doses of rhBMP-2 combined with porous, microparticles (PMP) of poly (lactide-co-glycolide) to regenerate osseous contour to critical- size defects (CSDs) in the radii of rabbits. The hypotheses for this study is that at a CSD: 1) the quantity of new bone will develop in a dose- and time-dependent fashion; and 2) at least one dose of rhBMP-2/PMP will be as effective as the autograft. A CSD is an intraosseous wound that will not heal by new bone formation in left untreated. Therefore, to test our hypotheses, CSDs in rabbits will be surgically implanted with one of four different doses of rhBMP-2 delivered by PMP or an autograft (positive control). In addition, one group of CSDs will be left untreated. At 4 and 8 weeks, experimental implant sites will be recovered for either biomechanical testing or quantitative radiography (radiomorphometry) followed by histology preparation. Histology sections will be assessed morphometrically using computer imaging to quantitate new bone formation across the CSDs. Confirmation of the hypotheses will be determined by analyzing biomechanical function and quantitative morphologic data for radiopacity and new bone formation at the CSDs in response to the different treatment at 4 and 8 weeks.
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