Engineering Musculoskeletal Tissue: In vitro and in vivo evaluation of novel scaffolds and growth factors for bone regeneration

Abstract

Introduction: The management of bony non-unions and large bone defects due to congenital deformities, trauma, degenerative disease, and oncological resection remains a complex challenge for orthopaedic surgeons. Currently, autologous bone grafting is the ‘gold standard’ treatment for non-unions and large bone defects because it is the only material that is osteoconductive, osteoinductive and osteogenic. Whilst effective, autologous bone grafting is limited by the finite amount of bone that can be safely harvested and by the unacceptably high complication rates. Aim: The aim of my research was to evaluate a number of growth factors and scaffolds that have the potential to be used as clinically applicable bone graft substitutes. Methods: A systematic method was adopted in the evaluation of bone graft substitutes. Novel materials were first tested using in vitro methods to assess cytocompatibility, proliferative effects and osteoinductive potential on osteoblasts. Bone graft substitutes demonstrating potential were then tested in vivo using our rat critical-sized calvarial defect model. Findings: In total, we evaluated five bone graft substitutes, including bone dust (autologous material), lactoferrin (growth factor), MHC-Cal™ (xenograft), PHB-HV and Gellan gum/hydroxyapatite (scaffolds). Bone dust showed promise as a proliferative agent and osteoinductive material. Lactoferrin demonstrated potent bone regenerative effects in our rat critical-sized calvarial defect model. Whilst the scaffolds (MHC-Cal™, PHB-HV and Gellan gum/HA) demonstrated anabolic effects in vitro, their therapeutic potential failed to translate into our rat critical-sized calvarial defect model. Conclusion: Our research lends further insight on the therapeutic potential for a range of bone graft substitutes for bone regeneration. The two materials with the most potential from our research are bone dust and lactoferrin. Further studies are required to translate any significant findings into the clinical setting. It is hoped that with advances in tissue engineering and regenerative medicine techniques, once formidable clinical entities – large bony defects and bony non-unions can be overcome.