Developing novel bioactive materials for bone cancer applications

开发用于骨癌应用的新型生物活性材料

• 批准号: 2601655
• 金额: --
• 依托单位: Aston University
• 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-2601655
• 关键词: Developing; novel; bioactive; materials; bone

Bone cancer typically occurs in children and young adults. Current treatments involve removal of the tumorous area followed by chemotherapy. Following surgery a large bone defect is present due to the removal of the tumour and care must be taken to ensure that the cancer does not return. If the cancer reoccurs at the primary site then survival rates drop significantly. Currently these two key factors, repairing the bone defect and preventing tumour reoccurrence, are treated as two different problems. A common treatment and the ability to treat the cancer promptly can lead to a better clinical outcome and thus, there is an urgent need to develop new therapeutic strategies based on the use of third-generation biomaterials that can simultaneously target cancer cells, prevent further reoccurrence, and stimulate the regeneration of damaged tissue. Bioactive glasses containing gallium hold great potential for this purpose as has been shown in previous studies undertaken in our laboratory. These materials display remarkable osteoconductive and osteoinductive properties and can be tailored to carry therapeutic ions such as gallium, zinc, and cobalt, to name a few. Furthermore, bone is after blood the most transplanted tissue worldwide and bioactive glasses are seen as some of the most promising materials to replace conventional surgical reconstruction procedures such as prostheses, orthopaedic implants, allografts, and autografts.Gallium is a metal ion widely used for cancer treatment due to its ability to inhibit tumour growth. It shares certain chemical properties with iron that enable it to bind to transferrin, a cellular ion receptor. Since iron plays a critical role in cell function, the intake of gallium disrupts the ion homeostasis within the cell leading to cell apoptosis. Cancer cells exhibit an increased dependence on iron compared with healthy cells which can be harnessed to develop novel strategies for cancer treatment using gallium. The inhibitory effects of gallium on malignant cells not only depend on the dose delivered, but also on the duration of exposure. Therefore, the release of ions needs to be strictly controlled in order to enhance their therapeutic effect and avoid adverse cell behaviour. Bioactive glasses are excellent carriers for bioactive molecules and therapeutic drugs as their degradation rate can be tailored by modifying their molecular structure. In addition, when bioactive glasses dissolve their basic components form a mineral layer that greatly enhances bone regeneration as it mimics the innate structure of bone, providing a framework for new tissue and blood vessels to grow into. However, ossification is a process that involves several stages from the osteogenic differentiation of stem cells to the formation of bone-like structures known as bone nodules. A large part of the current literature with regards to bone tissue engineering claims to generate bone using bioactive glasses though the characterisation methods used to prove these claims fall short. Gallium bioactive glasses have generally been studied for their antibacterial properties, but little research has been made on their potential clinical applications for bone cancer.This project will build on previous studies that successfully inhibit cell proliferation of osteosarcoma cells in vitro using silica-based bioactive glasses containing gallium. The overall project aim will be to synthesise bioactive glasses containing different concentrations of gallium, investigate their effects on different cell lines and optimise them to target bone cancer cell lines while promoting healthy cell proliferation. The ability of these bioactive glasses to form bone structures will also be thoroughly examined.

骨癌通常发生在儿童和年轻人中。目前的治疗方法包括切除肿瘤区域，然后进行化疗。手术后，由于肿瘤切除，会出现较大的骨缺损，必须注意确保癌症不会复发。如果癌症在原发部位再次发生，那么存活率就会显着下降。目前，修复骨缺损和防止肿瘤复发这两个关键因素被视为两个不同的问题。常见的治疗方法和迅速治疗癌症的能力可以带来更好的临床结果，因此，迫切需要开发基于第三代生物材料的新治疗策略，这种材料可以同时靶向癌细胞，防止进一步复发，并刺激受损组织的再生。含有镓的生物活性玻璃具有很大的潜力，正如我们实验室以前进行的研究所表明的那样。这些材料表现出显著的骨传导和骨诱导性能，并可以定制为携带治疗性离子，如镓、锌和钴，仅举几例。此外，骨是仅次于血液的世界上移植最多的组织，生物活性玻璃被认为是最有希望取代传统外科重建程序的材料，如假体、矫形植入物、同种异体移植和自体移植。镓是一种金属离子，由于其抑制肿瘤生长的能力，被广泛用于癌症治疗。它与铁具有某些化学性质，使其能够与细胞离子受体转铁蛋白结合。由于铁在细胞功能中起着关键作用，镓的摄入破坏了细胞内离子的动态平衡，导致细胞凋亡。与健康细胞相比，癌细胞对铁的依赖程度更高，这可以被利用来开发使用镓治疗癌症的新策略。镓对肿瘤细胞的抑制作用不仅与给药剂量有关，还与暴露时间有关。因此，需要严格控制离子的释放，以提高其治疗效果，避免不利的细胞行为。生物活性玻璃是生物活性分子和治疗药物的良好载体，因为其降解速度可以通过改变其分子结构来调节。此外，当生物活性玻璃溶解其基本成分时，会形成一层矿物层，极大地增强骨骼再生，因为它模仿了骨骼的固有结构，为新组织和血管的生长提供了框架。然而，骨化是一个从干细胞的成骨分化到形成骨样结构的几个阶段的过程，称为骨结节。目前关于骨组织工程的大部分文献声称使用生物活性玻璃来生成骨，尽管用于证明这些说法的表征方法是不足的。镓生物活性玻璃的抗菌性能已被普遍研究，但其潜在的临床应用研究很少。本项目将建立在先前的研究基础上，利用含镓的硅基生物活性玻璃在体外成功地抑制骨肉瘤细胞的增殖。整个项目的目标是合成含有不同浓度镓的生物活性玻璃，研究它们对不同细胞系的影响，并优化它们以靶向骨癌细胞系，同时促进健康的细胞增殖。这些生物活性玻璃形成骨骼结构的能力也将得到彻底检查。