Combined angiogenic and osteogenic factor delivery for bone regenerative engineering.

Both osteogenesis and angiogenesis are integrated parts of bone growth and regeneration. Combined delivery of osteogenic and angiogenic factors is a novel approach in bone regenerative engineering. Exogenous addition of mesenchymal stem cells (MSCs), vascular endothelial growth factor (VEGF) and bone morphogenetic proteins (BMPs) together with an osteoconductive scaffold is a very promising method to enhance bone repair. This concept has been incorporated into the development of new strategies for bone tissue engineering and significant advancements have been made in last 10 years. In contrary to previous belief that VEGF modulates bone repair only by enhancing angiogenesis in the proximity of bone injury, recent evidence also suggests that cross-talk between VEGF and BMP signaling pathways in MSCs promotes osteoblastic differentiation of MSCs which aids in fracture repair. Future studies should focus on cross-talk between angiogenesis and osteogenesis, optimization of VEGF/BMP ratios, selection of the most potent BMPs, and optimization of delivery methods for VEGF and BMP. Recent discoveries from basic research including effective delivery of growth factors and cells to the area of interest will help bring VEGF plus BMP for bone healing from the bench to the patient's bedside.