Harnessing the Power of Surface Engineering for Potential Bone Cancer Therapies

利用表面工程的力量进行潜在的骨癌治疗

• 批准号: 2596538
• 金额: --
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2596538
• 关键词: Harnessing; Power; Surface; Engineering; Potential

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.

背景资料：尽管手术、化疗和放疗取得了进展，但原发性骨癌患者的生存率很低，特别是在青少年中普遍存在的骨肉瘤1。根据美国癌症协会2，骨肉瘤的5年生存率在24-74%之间，取决于癌症是否转移（扩散到身体的其他部位）或保持局部（骨内）。在发生骨丢失的情况下，通常使用医疗器械/骨水泥来恢复生物力学功能，尽管并非没有其局限性，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。为了提高诊断为原发性骨肉瘤和骨转移瘤的患者的存活率和先前癌组织的再生，更普遍地，材料科学策略被强烈提倡为改善临床结果的“军械库中的附加工具”4 -6。金属微米和纳米颗粒（NPs）被认为是一种新的，但尚未实现的选择性细胞毒性的癌细胞的策略。Ag、Cu、Ga和TiO 2 NPs 7 -10均显示出对骨肉瘤细胞的选择性细胞毒性。虽然选择性肿瘤细胞毒性的确切机制仍有争议，但通常认为它是通过增加活性氧产生介导的，这可以通过材料腐蚀促进11。虽然纳米粒子提供了一个有前途的和互补的方法来对抗骨肿瘤，在适当的颗粒载体的重大挑战限制了应用。项目目标：开发和展示新的表面工程启用，承载多功能抗癌材料系统，用于治疗原发性骨癌。新材料界面系统将被设计为1）通过安全的局部递送具有已知癌症毒性的NP来限制肿瘤的增殖。这将通过可调固态NP嵌入式薄膜表面工程技术实现。2)通过SiN/SiO的促成骨作用和可调溶解作用，促进骨折的重塑、修复和愈合。如果能够杀死癌细胞并促进骨重建，将提供一种新的生物材料策略，用于制造骨科植入物，以替代肿瘤部位并杀死/预防肿瘤局部复发。这一战略并不是要取代化疗和放疗，这是至关重要的更系统的方法，以癌症管理，但协同作用，以提供新的和增强的治疗。目标：从研究目标，每个对应于一个工作包（WP），目标和相关活动与负责任的学术和可交付成果是：OBJ 1-在Mg和Ti基生物医用合金上沉积和表征NP嵌入的Si基薄膜涂层。OBJ 2-使用新材料系统的工程评估来识别材料性能。目标3-评估开发的材料系统的生物功能性。