A synthetic cell strategy to remodel the fibrotic disease microenvironment

Fibrosis is the pathological end-product of a tissue’s response to chronic damage/inflammation including cancer, thus can affect most organ systems and represents a major medical problem. It is defined by dramatic changes in tissue composition and organisation, often including local and global alignment of the extracellular matrix (ECM) that affects the tissue’s material properties and cell behaviour. Using skin scars as an example, we discovered fibrotic ECM patterning is initiated by fibroblast cell-cell adhesions, which inhibit cellular overlap leading to nematic organization of cells and focal adhesions and ultimately parallel bundling of the collagen matrix. Synthetic cells (SynCells) offer a powerful opportunity to disrupt such cell-driven tissue architecture. This project will design biomimetic, membrane-encapsulated particles, SynCells, with features including key cell-cell and cell-matrix adhesion molecules, and machinery to synthesise and secrete anti-fibrotic signalling molecules. These novel approaches have significant potential to therapeutically remodel fibrotic microenvironments associated with multiple diseases.