Bioengineering a 3D microencapsulated model of breast cancer to reflect tumour microenvironment complexity and disease progression

Drug testing in cancer clinical trials has a drastically low success rate therefore more accurate pre-clinical disease models are urgently needed to translate knowledge gained from basic cancer research to patient benefit. Cancer cell lines cultured on a 2D surface fail to recapitulate the complex 3D tumour microenvironment that contributes to tumourigenesis whilst animal models cannot fully replicate human tumour physiology. Therefore, new 3D pre-clinical cancer models need to be engineered in order to bridge the gap between in vitro and in vivo cancer research.

Microencapsulation of cells, where individual cell types or multiple cell types are entrapped within a semi-permeable or solid material to form microcapsules or microspheres, can be used as a 3D cancer model and is amenable for applications in pre-clinical drug testing. This project aims to bioengineer a model of the breast tumour microenvironment using microencapsulation to study the relationship between breast cancer cells and mesenchymal stem cells (MSCs), the role of which has not been fully elucidated in the literature. Membrane emulsification will be employed to produce monodisperse and reproducible microcapsules of biocompatible hydrogels that will be used to encapsulate the two cell types. Membrane emulsification offers advantages over other possible techniques as it is scalable and particle uniformity can be tightly controlled which will allow the study of the impact of microcapsule size on formation of the in vivo model. The importance of microcapsule stiffness and viscoelasticity has also not yet been determined in microencapsulation-based cancer models, therefore hydrogel stiffness will be modulated to represent different stages of disease progression and the effect on cell behaviour and migration will be determined. Importantly, the learning on how to formulate the 'ideal' microcapsule with these specific parameters (e.g. size, material stiffness) will be applicable to the development of other in vivo models and other uses of hydrogel-based microparticles.

In summary, membrane emulsification will be used to bioengineer an in vivo-like breast tumour microenvironment that allows the study of the relationship between cancer cells and MSCs and the influence of other environmental factors such as oxygen tension, in a microcapsule format that can be easily adapted for high-throughput drug screening.