| Summary: | <p>The use of bio-materials in medical applications has risen exponentially in recent years, where applications range from the treatment of early stage disease to implants for major trauma. Particularly, research on biodegradable metallic materials have demonstrated potential step-change technologies which may revolutionise the treatment of broken bones. Implants made with biodegradable metals are significantly stronger than their polymer counterparts. They are also fully biodegradable in vivo, removing the need for secondary surgery. After a decade of laboratory and early translational research, these new materials are now showing significant clinical potential with the ability to create a paradigm shift in the way we treat musculoskeletal conditions.</p> <p>To contribute to the clinical translation of the biodegradable metals, this thesis explored the biological response to a novel biodegradable Mg5wt%Ca-1wt%Zn alloy developed for orthopaedic repair, to study the bone remodelling process and assess the potential of the new implant. The main objectives of the research were to explore the impact of active Mg alloy biodegradation on the OB cells cultured in a perfusion bioreactor system and to further understand the bone healing process in and around a degrading Mg alloy by assessing angiogenesis and coupled osteogenesis at the Mg alloy implanted site.</p> <p>Results demonstrate that the simulated key aspects of the in vivo environment recapitulated in these studies such as blood flow-induced magnesium corrosion, hydrogen evolution, and local pH change, contribute to a statistically significant increase in cellular proliferation and differentiation in the presence of degrading Mg alloys. The released ions from both fast and slowly degrading alloy showed a positive effect on the progress of bone formation. However, fast corroding alloy showed a detrimental effect on osteoblast cells, while osteoblast proliferation and differentiation were improved by released metal ions from optimized alloy with a much slower corrosion rate. These findings suggested that the release of metal ions consisting of Mg, Ca and Zn also sufficiently stimulate the bone formation process. In vivo experimental results observed using second harmonic generation and immunohistological staining confirmed that the optimized mechanical properties and corrosion rate of Mg-5wt%wt%Ca alloy leads to release of metallic Mg, Ca and Zn ions at a rate that facilitate both angiogenesis and coupled osteogenesis for better bone healing without causing adverse effect at the implantation site. To conclude, this thesis tests a new in vivo model system to evaluate biodegradable metals and validate the potential of the newly developed Mg-Ca-Zn alloy as orthopaedic implant material. Furthermore, this work supports ongoing development and refinement of biodegradable metal systems to act as crucial portal technology with potential to revolutionize a myriad of clinical applications.</p>
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