Harnessing the Power of Surface Engineering for Potential Bone Cancer Therapies

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Background: Survival for patients with primary bone cancers, particularly osteosarcoma which is prevalent in teenagers, is poor despite the advances in surgery, chemotherapy and radiotherapy1. According to the American Cancer Society2, the 5-year survival rate for osteosarcoma is between 24-74% and dependant on if the cancer has metastasised (spread to other areas of the body) or remained localised (within the bone). Where bone loss occurs, medical devices/bone cements are often used to restore biomechanical functionality, albeit not without their limitations including: lack of osseointegration, remnants of tumour after surgery and embolism associated with bone cement 3. In an attempt to enhance both survival rates and regeneration of previously cancerous tissues of patients diagnosed with primary bone sarcomas and bone metastases, more generally, material science strategies have been strongly advocated as an 'additional tool in the armoury' to improve the clinical outcome4-6. Metallic micro and nanoparticles (NPs) are seen as a novel, but yet unfulfilled strategy for selective cytotoxicity of cancer cells. Ag, Cu, Ga and TiO2 NPs7-10 have all shown selective cytotoxicity to osteosarcoma cells. Whilst the exact mechanisms for the selective tumour cytotoxicity is still debated, it is generally thought that it is mediated by increased reactive oxygen species production, which can be promoted by material corrosion11. Although NPs provide a promising and complimentary approach to fighting bone tumours, significant challenges over appropriate particle carriers limit application.Project Aim: To develop and demonstrate novel surface engineering enabled, load bearing multifunctional anti-cancer material systems for the treatment of primary bone cancers. New material interfacial systems will be designed to 1) limit the proliferation of tumours through the safe local delivery of NPs with known cancer toxicity. This will be enabled through tuneable solid state NP-embedded thin-film surface engineering technologies. 2) Promote the remodelling, repair and union of bone fractures via the pro-osteogenic effect and tuneable dissolution of SiN/SiO. If cancer cells can be killed and the reformation of bone promoted, a new biomaterials strategy for the manufacture of orthopaedic implants to replace the tumour site and kill/prevent local recurrence of tumour will be delivered. This strategy is not intended to replace chemotherapy and radiotherapy that are critical in more systemic approaches to cancer management, but to act synergistically to provide new and enhanced treatments.Objectives: Emanating from the research aim, and each corresponding to a work package (WP), the objectives and associated activity with responsible academic and deliverables are:OBJ1 - To Deposition and characterisation of NP embedded Si-based thin film coatings on Mg and Ti based biomedical alloys.OBJ2 - To use engineering assessment of novel material systems to identify material performance. OBJ3 - To assess the biological functionality of the developed materials systems.