Developing novel bioactive materials for bone cancer applications

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.