Development of 3D vascularised cancer models

Cancer is a becoming a huge social and economic burden on society, being the most significant barrier to life expectancy in the 21st century. One of the most significant difficulties to finding efficient therapies for specific cancers, such as breast cancer, is the efficiency and ease of drug development and testing. Micro-physiological systems (MPS) are under development to mimic the structural and biological complexity of human tissue, thus, becoming increasingly popular as an alternative to animal testing for pharmaceuticals. High molecular weight polycaprolactone methacrylate (PCL-M) was used to fabricate polymerised high internal phase emulsions (polyHIPEs) scaffolds to support 3D breast cancer (MDA-MB-231) cell culture within MPS. The effect of varying production parameters on the polyHIPE properties was assessed. MDA-MB-231 cells were used to assess cell growth on PCL-M polyHIPE scaffolds. An ex-ovo chick chorioallantoic membrane (CAM) assay was used to assess the biocompatibility and potential for vascular invasion. We demonstrated the tenability of the properties of the polyHIPEs via varying production processes. Ex-ovo CAM assays identified the scaffolds as bioinert. Further studies identified breast cancer cell seeded gelatin-containing PCL-M polyHIPE scaffolds as promising substrates to support angiogenesis. Furthermore, in vitro assessment of cell growth showed promising potential for the use of PCL-M polyHIPEs to support breast cancer cell growth. This indicates that PCL-M polyHIPE scaffolds show promise as a substrate for MPS to study 3D breast cancer cell culture with potential for vascularisation. The project also included an industrial element, with research undertaken at GlaxoSmithKline. This research focussed on developing an in vitro vascularised tumour model for oncology applications, initially using histology and fluorescence microscopy to characterise tumour spheroids before integration within a commercial MPS to assess tumour-vascular connection and the capability of the system to assess the efficacy of two common oncology therapies.