The development of 3D cancer cell models using shear-spun fibrous scaffolds

Cancer is one of the leading causes of mortality worldwide. Despite the recent advance, the need for more effective anticancer therapies seems more compelling than ever, but the development of novel drugs is a time and money consuming process, involving extensive pre-clinical and clinical studies. A range of established cancer cell lines have been used extensively to study the biology of cancer and to set up high-throughput screens (HTS). The 3D culture of cancer cells has long been advocated as a better model of the malignant phenotype than 2D culture that is most closely related to tumourigenicity in vivo. However, the use of 3D models is limited to academic research while most of cancer research and HTS assays are still depending on 2D models. This is because the current 3D culture platforms have challenges in standardisation, upscaling and integration. Here, shear-spinning technology developed by Xanofi was utilised to produce novel 3D scaffolds made of fully integrated interwoven sub-microfibres and microfibres. This study aims to optimise shear-spun scaffolds for 3D cell culturing and drug testing and to employ them for developing 3D cancer cell models. Initially, the best candidate shear-spun scaffolds were identified after testing various fibrous scaffolds and their suitability for 3D cell culturing was demonstrated by culturing a wide range of established cell types. It was important to compare the cell behaviour between 2D and 3D cell cultures. By doing so, differential growth curves and significant differences in response to therapeutic drugs were found between 2D and 3D cultures. Various seeding and co-culturing methods were explored, which allowed us to develop a basic prototype of an in vitro 3D breast cancer model. The data from this thesis has demonstrated the potential of utilising shear-spun fibrous scaffolds for efficient 3D culturing of mammalian cells and for developing in vitro 3D cancer models