The need for functional treatments of fracture non-unions, spinal injuries and bone loss associated with trauma and cancer remains a considerable challenge in orthopaedic surgery. Current treatment involves autologous bone grafting; which occurs in over two million cases annually. Limited tissue availability, donor site pain and morbidity are however significant clinical issues.Direct growth factor delivery has shown therapeutic potential but requires untargeted supra-physiological doses to induce bone regeneration. Issues with retention, deactivation, enzymatic digestion and lack of reproducibility are key clinical limitations. Importantly, an adequate blood supply is essential for bone repair. Currently, there is an influx of research utilising a variety of growth factors either alone or in combination with a variety of cell types which has meant that a defined optimal approach for generation of vascularised bone is currently lacking. This project aims to address this deficit by identifying the optimal cell/growth factor platform for producing stable neo-vascularised regenerated bone. We aim to investigate the release of bone morphogenetic protein-2 (mediator of bone formation) and vascular endothelial growth factor (mediator of angiogenesis) from hyaluronan microspheres, and assess their effect on endothelial progenitor cells (blood vessel precursor cells) and mesenchymal stem cells (precursor bone cells) differentiation. The purpose of this project is to determine the optimal growth factor/cell combination for inducing bone and blood vessel formation. The results from this study will contribute to subsequent assessment of neo-vascularised regenerated bone formation in a preclinical bone defect model.
