Porous, lithium-doped calcium polyphosphate composite scaffolds containing vascular endothelial growth factor (VEGF)-loaded gelatin microspheres for treating glucocorticoid-induced osteonecrosis of the femoral head

Glucocorticoids-induced osteonecrosis of femoral head (GIONFH) is difficult to treat due to the pathophysiology remains uncertain. Core decompression and bone grafting are regarded as effective measures for treating early GIONFH. Furthermore, commonly used bone graft materials at nowadays are still unsatisfactory. We generated a novel calcium polyphosphate (CPP) composite scaffold, which contains Li and VEGF-loaded gelatin microspheres (LiCPP/GMs/VEGF). The LiCPP/GMs/VEGF scaffold also demonstrated a porosity of 70.5% ± 2.3% with interconnected porous structures, and pore sizes of 100-200 μm and compressive strength of 3.7 MPa. Additionally, bone marrow mesenchymal stem cells (BMSCs) were seeded on scaffolds in vitro. Further characterization showed that the LiCPP/GMs/VEGF scaffolds were biocompatible and enhanced osteogenesis and angiogenesis in vitro. Using a rabbit model of GIONFH, LiCPP/GMs/VEGF scaffolds were implanted into the bone tunnels of core decompression in the femoral head for 12 weeks. Radiographic, histological analysis and western blot analysis demonstrated that the LiCPP/GMs/VEGF scaffolds exhibited good biocompatibility, and osteogenic and angiogenic activity in vivo. Besides, the osteogenic and angiogenic factors were increased along with VEGF release and the activation of factors in Wnt signal pathway. In conclusion, the LiCPP/GMs/VEGF scaffold has an effect on improving the osteogenesis and angiogenesis, which benefited to repair the GIONFH.