Vascularizing Bone Scaffolds for Craniofacial Reconstruction

摘要

This project addresses a deployment-related research gap, Biocompatible craniofacial implant for use in craniofacial reconstruction due to combat trauma within an FY08 DRMRP topic area. Extensive injuries to the head and face require immediate and follow-up reconstructive surgeries to restore skeletal structures. Current surgical procedures commonly involve the use of autografts, allografts or polymeric and metallic implants, which fall short of the ideal with numerous limitations. An ideal bone substitute would be a biocompatible and biodegradable material that can serve as a transient scaffold while guiding and stimulating host bone tissue regeneration. While impressive progress has been made particularly in material sciences and fabrication technologies, clinical application of bone tissue engineering remains elusive, particularly to repair large defects. This limitation can be traced largely to a difficulty of introducing a stable and functional vascular network into engineered constructs. Thus, the goal of this project was to develop a cell and growth factor-based regenerative tissue engineering approach to the repair of a large bony defect. In this study, we demonstrate that inclusion of both angiogenic and osteogenic cells was critically important to ensure rapid vascularization of the bone construct. We also prepared and characterized biodegradable PLGA microspheres that release angiogenic and osteogenic factors in a temporally controlled manner. These microspheres were highly effective for supporting survival and differentiation of co-implanted cells in bone scaffolds implanted in animals.