Remodeling Characteristics and in vivo Healing of Low Viscosity Polyurethane Biocomposites for Bone Regeneration

Abstract

Approximately 1.5 million bone grafting surgeries are performed annually in the United States for patients suffering traumatic injury, tumor, infection, or degenerative disease. The fiscal burden of these procedures is staggering, with an estimated $215 billion annually associated with direct or indirect costs of musculoskeletal conditions. Current treatment options are limited by accessibility, ease of use, and graft remodeling characteristics. Low viscosity (LV) polyurethane biocomposites effectively heal bone defects in a variety of models and are potential candidates for the delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2), a potent growth factor associated with bone remodeling. LV composites are injectable, settable grafts that are easy to deliver and support cellular infiltration and new bone deposition. The aim of this work was to develop low viscosity (LV) polyurethane biocomposites for bone regeneration and to test growth factor release and remodeling characteristics of the LV grafts in vitro and in vivo. The use of rhBMP-2 enhances cellular infiltration and tissue deposition when delivered to a defect site; however, efficacy can depend significantly on the physical and chemical properties of the chosen delivery system. RhBMP-2 release from the LV grafts in vivo was controlled by both Fickian diffusion and polymer degradation, which led to sustained release of growth factor as compared to the bolus release when delivered via a clinically available collagen sponge carrier. When LV grafts were delivered in vivo to both orthopaedic and craniomaxillofacial models, defect healing was enhanced by the introduction of inorganic ceramic particles that act as an osteoconductive scaffold. These compression resistant grafts were mechanically stable without the need for external fixation. Additionally, the remodeling characteristics of the LV grafts were studied to determine fundamental mechanisms of scaffold and matrix degradation. Degradation is partly dependent on active cellular response to the implanted bone graft, which influences both oxidative degradation and osteoclast resorption associated with polymer and ceramic remodeling respectively. Through these studies, the mechanisms of growth factor release and scaffold remodeling were discovered while also revealing the relevance of this system for clinical applications