| Summary: | Introduction: The health care socio-economic environment is changing due to the population ageing, rising resultant functional impairment and patient quality of life expectations. These factors introduce increasing complexity of ensuing clinical scenarios, compelling a critical search for novel musculoskeletal regenerative and replacement strategies. Although joint arthroplasty is a highly effective treatment for arthritis, further innovation and refinement of uncemented implants are essential in order to improve implant integration and reduce the revision rate. This is critical within the current NHS environment of financial restraints and the drive to improve cost-effectiveness in arthroplasty. Methods: Biological skeletal stem cell (SSC)-mediated responses to surface nanotopographies were investigated. Passage one STRO 1 SSCs were cultured on nanotopographies in vitro, while in vivo examination of nanotopographies was conducted in subcutaneous mouse and calvarial rat models. Results: The following results were observed in relation to a range of surface modifying techniques: 1. Lithography -nanotopographies containing 20 nm tall pillars with near-square surface pattern arrangement generated significant enhancement of osteogenic gene induction (ALP, Collagen type I, OPN and OCN), osteogenic morphology and extracellular OPN synthesis in vitro and in vivo. In addition, histological evidence of collagen fibre organisation and early de novo mineralisation was observed in vivo. 2. Large Area Electron Beam melting -in vitro SSC osteogenic morphological alterations, bone matrix gene activation and OPN synthesis were directly correlated to the surface roughness within Ra range of 20-60 nm, with increasing Ra resulting in enhancement of osteogenic differentiation. 3. Thermal oxidation -nanowires 300 generated significant enhancement of osteogenic gene expression, osteogenic morphology, and OPN and Collagen type I protein synthesis in vitro. Significant enhancement of bone volume deposition at implant/bone interface was observed in vivo. 4. Electrochemical Jet Machining -nanotopographical elements of hierarchical scale texture triggered enhanced osteogenic gene expression. Conclusions: This work has demonstrated the ability of various nanotopographical surface-finishes to trigger an enhanced SSC-mediated osteogenic response, providing a clear rational for their potential application in orthopaedic implant.
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