Developing novel bioactive materials for bone cancer applications

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，由于肿瘤的切除而存在大的骨缺损，必须小心确保癌症不会复发。如果癌症在原发部位复发，那么存活率就会显著下降。目前，这两个关键因素，修复骨缺损和防止肿瘤复发，被视为两个不同的问题。一种常见的治疗方法和迅速治疗癌症的能力可以导致更好的临床结果，因此，迫切需要开发基于使用第三代生物材料的新的治疗策略，这些生物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。含镓的生物活性玻璃在这方面具有很大的潜力，这在我们实验室以前的研究中已经证明。这些材料显示出显著的骨传导性和骨诱导性，并且可以被定制为携带治疗离子，例如镓、锌和钴等。此外，骨是世界范围内仅次于血液的最易移植的组织，生物活性玻璃被认为是最有前途的材料，可以替代传统的外科重建手术，如假体、骨科植入物、同种异体移植物和自体移植物。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，使其能够与转铁蛋白（一种细胞离子受体）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的离子稳态，导致细胞凋亡。与健康细胞相比，癌细胞表现出对铁的依赖性增加，这可以用来开发使用镓治疗癌症的新策略。镓对恶性细胞的抑制作用不仅取决于所递送的剂量，还取决于暴露的持续时间。因此，需要严格控制离子的释放，以增强其治疗效果并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，因为它们的降解速率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时，其基本成分形成矿物质层，极大地增强了骨再生，因为它模仿了骨的先天结构，为新组织和血管生长提供了框架。然而，骨化是一个涉及从干细胞的成骨分化到称为骨结节的骨样结构形成的几个阶段的过程。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生成骨，尽管用于证明这些声明的表征方法不足。镓生物活性玻璃的抗菌性能已被广泛研究，但其在骨癌治疗方面的潜在临床应用研究较少。本项目将在以往研究的基础上，利用含镓硅基生物活性玻璃成功抑制骨肉瘤细胞的体外增殖。该项目的总体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，同时促进健康细胞增殖。这些生物活性玻璃形成骨结构的能力也将被彻底检查。

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.