Biomaterial strategies for improved bone healing with bone morphogenetic protein-2 delivery

This thesis investigated hybrid biomaterial systems with controlled strategies for bone morphogenetic protein-2 (BMP-2) delivery to promote structural and functional restoration of segmental bone defects. Using a critically sized rat segmental bone defect model, we (i) evaluated the effects of alginate hydrogel oxidation on BMP-2 release and bone regeneration, (ii) elucidated the spatiotemporal effects of high dose BMP-2 on bone healing and gene expression, and (iii) investigated the ability of amniotic membrane to attenuate heterotopic mineralization in critically sized bone defects. Importantly, our rat model recapitulated adverse effects observed clinically with orthotopic high dose BMP-2 delivery, specifically heterotopic mineralization, prolonged local inflammation, and systemic inflammatory effects. By identifying specific alterations in gene expression as a function of time and BMP-2 dose, this thesis contributes to our understanding of the complex process of bone healing during the early stages of large bone defect regeneration. Although the hybrid alginate-PCL delivery system did not reduce heterotopic ossification with high dose BMP-2, extracellular matrix-derived amniotic membrane surrounding collagen sponge scaffolds resulted in less heterotopic mineralization compared to collagen sponge alone, which motivates the accelerated translation of amniotic membrane for bone regeneration applications. The findings here support the overall hypothesis that a biomaterial delivery vehicle that allows for localized growth factor availability and minimal heterotopic bone formation would facilitate structural and functional restoration of segmental bone defects. By considering these fundamental biomaterial parameters, we may more effectively harness endogenous repair mechanisms for successful bone regeneration.Ph.D