Formulation, characterization, and in vivo remodeling mechanisms of polyurethane biocomposites for bone tissue engineering

Abstract

There is a compelling clinical need for grafts with initial bone-like mechanical properties that remodel and promote healing of bone defects. This dissertation describes the development and characterization of biodegradable lysine-derived polyurethane (PUR) foams and moldable PUR composite formulations that actively participate in the bone healing process. The PUR foams incorporate a mixture of D-amino acids and represent the first biofilm-dispersive graft capable of reducing bacterial burden within infected wounds. Additionally, surface modified beta-tricalcium phosphate (TCP) particles improved the mechanical performance of PUR/TCP biocomposites without affecting in vitro differentiation of bone cells. PUR biocomposites incorporating different loadings of allograft bone particles (ABP), with various porosities, and matrix particle size induced progressive healing in vivo in femoral plug defects (New Zealand White rabbits) from 6 to 12 weeks. High and low porosity PUR/ABP composites with large matrix particles (105-500 microns) healed to a similar extent although through different mechanisms. Augmentation of PUR/ABP grafts with recombinant human bone morphogenetic protein-2 (rhBMP-2) not only increased the rate of new bone formation, but also matched the polymer degradation rate to that of new bone deposition which resulted in more extensive healing at later time points. These results underscore the importance of balancing the rates of new bone formation and scaffold degradation to preserve an interconnected structure, thus promoting the healing of bone grafts that maintain bone-like strength while actively remodeling.

Finally, this work introduces an in vitro cell culture protocol to study the differentiation and resorptive activity of murine bone marrow cells in the presence of different matrices. This method enables quantitation and direct comparison between volumetric resorptive rates of synthetic matrices and acts as a screening tool in the design of effective biocomposite bone scaffolds.