|The world population is ageing. Ageing is associated with many musculoskeletal problems, including primary or secondary osteoporosis (OP), osteoarthritis (OA), and chronic tendon-bone insertion disorder or injury, which often lead to bone fractures, joint deformity and disability. Our current research focuses on these skeletal disorders and injuries with limited repair and healing potential, including osteoporotic fracture, avascular osteonecrosis (AVN) around joints with extremely high incidence of OA, and tendon-bone insertion reconstruction. A significant reduction in quantity and quality of stem cells, especially bone marrow stem cells (BMSCs), are the most common features in these disorders. Substantial costs are involved in surgeries and subsequent rehabilitations for these severe musculoskeletal conditions and injuries that imposes huge socioeconomic and healthcare burden to the patient, family, healthcare system, and society in Hong Kong and worldwide. Therefore, our collaborative and multidisciplinary research focuses on enhancing treatment outcome of these skeletal disorders or injuries by augmenting the regenerative potential of autologous BMSCs and mobilizing circulating stem cells to bone defects for bone regeneration. To enhance osteogenesis, we will investigate the recruitment of circulating stem cells, mobilization of local BMSCs onto surface of the implanted biomaterials, and cell-matrix signalling with modulation of biophysical stimulation. To achieve our study objectives for targeting above mentioned musculoskeletal problems, this project is divided into three stages: 1) Osteogenic modulation of BMSCs for skeletal tissue engineering; 2) Investigation on the treatment efficacy of implanted innovative biomaterials and postoperative non-invasive biophysical modulation for maximizing the osteogenic efficacy using our well-established preclinical animal models; 3) Completion of the required biosafety testing for Class III medical implants for product registration and prepare for subsequent clinical trials. Our efforts will focus not only on high quality scientific research but also or more importantly, the research and development (R&D) of effective treatment protocols or strategies for achieving functional bone regeneration of challenging bone disorders. Ultimately, our innovative functional biomaterials and treatment protocols will benefit our patients with a significant reduction on healthcare burden both locally and internationally.