Repair of segmental rabbit radial defects with Cu/Zn co-doped calcium phosphate scaffolds incorporating GDF-5 carrier

Repair of segmental bone defects is a challenge in orthopaedics. A bone substitute is a potential solution for this challenge, and angiogenesis and osteogenesis are critical to the performance of scaffold materials. For enhancing angiogenesis and osteogenesis activities of implanted scaffolds, Cu/Zn co-doped calcium phosphate scaffolds carrying GDF-5-release microspheres were prepared and implanted into surgically created critical-sized rabbit radial defects. Radiological examination, histological analysis and biomechanical tests were used to evaluate the bone healing-union. Results showed that, with increasing Cu/Zn concentrations, new bone area, new blood vessel density, and bending failure load all increased significantly. Furthermore, Cu/Zn co-doped scaffolds incorporating GDF-5-release microspheres exhibited further increased angiogenesis and osteogenesis (vs. Cu/Zn co-doped alone), as well as a superior bending failure load. These show that, simultaneous incorporation of trace essential ions and GDF-5 combines pro-angiogenic and pro-osteogenic actions of these bioactive substances, potentially offering an effective approach to assist the healing of critical-sized bone defects.