Biophysical parameters in the microenvironment, such as stiffness and topography, play a prominent role in determining cell proliferation and differentiation in vivo during health and disease. An example of this is epithelial to mesenchymal transition (EMT), an essential process during embryonic development and recapitulated during wound healing and tissue regeneration, but also significant in pathological settings such as cancer metastasis. A better understanding of EMT mechanisms and the influence of the microenvironment in this process hold significant value. Harnessing these mechanisms, through engineering the microenvironment in vitro, would provide a powerful tool for creating optimised cell substrates that could be utilised for enhancing cell bioprocessing, bioengineering tissue constructs and promoting tissue regeneration in vivo. However, identifying which physicochemical properties that achieve the target response is currently challenging. This project will use a fractional factorial design based approach to create combinatorial arrays of biomaterial-based cell substrates that will be used to screen reprogramming of epithelial cells into mesenchymal cells.
(1) Parmar, N., Day, R.M. (2015) TIPS to manipulate myogenesis: retention of myoblast differentiation capacity using microsphere culture. Eur Cell Mater. 30:41-50. doi:10.1155/2014/713631
(2) Lowe V, Wisniewski L, Sayers J, Evans I, Frankel P, Mercader N, Zachary C, Pellet-Many C (2019) Neuropilin 1 mediates epicardial activation and revascularization in the regenerating zebrafish heart. Development (in press)
(3) Discuss the Epithelial to Mesenchymal Transition by the View of Mechanics. https://link.springer.com/chapter/10.1007/978-3-319-12262-5_20
(4) Svystonyuk et al. Using Acellular Bioactive Extracellular Matrix Scaffolds to Enhance Endogenous Cardiac Repair. Front. Cardiovasc. Med., 11 April 2018 doi.org/10.3389/fcvm.2018.00035