There is a recognized need to develop and field clinical therapeutics to regenerate bone in the orofacial complex. The investigators have assembled an experienced multidisciplinary team focused on developing and fielding a bone regenerative therapeutic composite of recombinant human bone morphogenetic protein-2 (rhBMP-2), osteoblast precursor cells (OPCs), and """"""""smart"""""""" polymer delivery system (SPS). Developing and optimizing the therapeutic composite will involve a staged set of experimental in vitro and in vivo models culminating in validation of clinical efficacy in the rhesus. Moreover, consistent with the growth in the nation's geriatric population, the investigators will include a geriatric cohort. The proposed study has been formulated to address design and preclinical evaluations of the therapeutic composite and individual component interactions on orofacial bone regeneration. Therefore, overall specific aims will include the fabrication of a """"""""smart"""""""" polymer delivery system (SPS) for rhBMP-2 and OPCs; development and characterization of dog- and rhesus-derived OPCs and genetic modification of these cells as well as human OPCs to express BMP-2; and validation of therapeutic efficacy of the rhBMP-2/OPC/SPS composite to regenerate orofacial bone in adult dog and adult and geriatric nonhuman primates. The general hypothesis is that predictable bone regeneration can be accomplished with the uniquely engineered composition. The composition will be administered to mandibular continuity defects to test the general hypothesis and analyses will involve clinical and morphometric methodologies.
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