Biodegradable Hybrid Tissue Engineering Scaffolds For Reconstruction Of Large Bone Defects

Complex skeletal injuries and large bone fractures are still a significant clinical problem in US. Approximately 1.5 million Americans (veterans, their families, and civilians) every year suffer from bone loss due to traumatic skeletal injuries, infection, and resection of primary tumors that require extensive grafting to bridge the gap. The US bone graft market is over $2.2 billion a year. Due to insufficient mechanical stability, lack of vascularity, and inadequate resorption of the graft, patients with traumatic large skeletal injuries undergo multiple costly operations followed by extensive recovery steps to maintain proper bone alignment and length. Current strategies for repairing damaged or diseased bones include autologous or allograft bone transplantations. However, limited availability of autografts and risk of disease transmission associated with allografts have necessitated the search for the development of new bone graft options and strategies. The overall goal of this project is to develop a much-needed bone-mimetic engineered graft as a substitute for current strategies providing required bone grafts for reconstruction of large bone defects. This project will use the structure of natural cortical bone as a guide to produce an engineered bone graft with balanced strength, osteogenesis, vascularization, and resorption. The outcome of this project will be a biodegradable hybrid scaffold system (similar to natural cortical bone) including a mechanically strong scaffold allowing for mechanical stability of the load-bearing defect site and a soft and highly porous structure such as a hydrogel phase which will allow for efficient cell and growth factor delivery into the defect implantation site, cell niche establishment and promotion of mineralization. Successful completion of this project will transform bone graft technology for regeneration of complex bone defects from a frozen or freeze-dried allograft to a safe, infection-free, mechanically-stable, osteoinductive, and vasculogenic graft that is ultimately displaced by the patient’s own tissue