Harnessing the Power of Surface Engineering for Potential Bone Cancer Therapies

背景：尽管手术、化疗和放射治疗取得了进步，但原发性骨癌患者的存活率很低，尤其是在青少年中流行的骨肉瘤。根据美国癌症协会的数据，骨肉瘤的5年存活率在24-74%之间，这取决于癌症是否已经转移(扩散到身体的其他部位)或仍然局限于局部(在骨骼内)。在发生骨丢失的情况下，医疗器械/骨水泥经常被用来恢复生物力学功能，尽管不是没有它们的局限性，包括：缺乏骨整合，手术后肿瘤残留和与骨水泥相关的栓塞3。为了提高被诊断为原发骨肉瘤和骨转移的患者的存活率和先前癌症组织的再生，更广泛地说，材料科学策略被大力倡导为改善临床结果的“武器库中的额外工具”。金属微米和纳米颗粒(NPs)被认为是一种新的、但尚未实现的肿瘤细胞选择性细胞毒策略。银、铜、镓和二氧化钛NPs7-10对骨肉瘤细胞均表现出选择性细胞毒作用。虽然选择性肿瘤细胞毒性的确切机制仍然存在争议，但人们普遍认为它是通过增加活性氧物种的产生来调节的，这可以通过材料腐蚀来促进11。尽管纳米粒子为抗骨肿瘤提供了一种很有前途的免费方法，但在合适的颗粒载体方面的巨大挑战限制了其应用。项目目标：开发和展示新型表面工程支持的、承载多功能的抗癌材料系统用于治疗原发性骨癌。新的材料界面系统将被设计成1)通过安全地局部输送具有已知癌症毒性的纳米颗粒来限制肿瘤的扩散。这将通过可调固态NP嵌入薄膜表面工程技术来实现。2)通过SiN/SiO的促成骨作用和可调溶解作用，促进骨折的改建、修复和愈合。如果能够杀死癌细胞，促进骨的重建，将为骨科植入物的制造提供一种新的生物材料战略，以取代肿瘤部位，杀死/防止肿瘤的局部复发。这一战略并不是为了取代化疗和放射治疗，而是协同行动，提供新的和增强的治疗方法。目标：源于研究目标，每个都对应于一个工作包(WP)，目标和相关活动与负责任的学术和交付成果是：OBJ1-在镁和钛基生物医学合金上沉积和表征NP嵌入的硅基薄膜涂层。OBJ2-使用新材料系统的工程评估来确定材料性能。OBJ3-评估开发的材料系统的生物功能。

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.