Regenerative Approaches for the Treatment of Large Bone Defects

A variety of engineered materials have gained acceptance in orthopedic practice as substitutes for autologous bone grafts, although the regenerative efficacy of these engineered grafts is still limited compared with that of transplanted native tissues. For bone defects greater than 4-5 cm, however, common bone grafting procedures are insufficient and more complicated surgical interventions are required to repair and regenerate the damaged or missing bone. In this review, we describe current grafting materials and surgical techniques for the reconstruction of large bone defects, followed by tissue engineering (TE) efforts to develop improved therapies. Particular emphasis is placed on graft vascularization, because for both autologous bone and engineered alternatives, achieving adequate vascular development within the regenerating bone tissues remains a significant challenge in the context of large bone defects. To this end, TE and surgical strategies to induce development of a vasculature within bone grafts are discussed. Impact statement This review aims to present an accessible and thorough overview of current orthopedic surgical techniques as well as bone tissue engineering and vascularization strategies that might one day offer improvements to clinical therapies for the repair of large bone defects. We consider the lessons that clinical orthopedic reconstructive practices can contribute to the push toward engineered bone.