HEALINSYNERGY · Material-driven Fibronectin Fibrillogenesis to Engineer Synergistic Growth Factor Microenvironments

Cells within tissues are surrounded by fibrillar extracellular matrices (ECM) that support cell adhesion, migration, proliferation and differentiation. Fibronectin (FN) is an ECM protein organized into fibrillar networks by cells through an integrin-mediated process. This assembly allows the unfolding of the molecule, exposing cryptic domains not available in the native globular FN structure and activating intracellular signalling complexes.This project aims to engineer functional interfaces between living cells and synthetic biomaterials, making use of the fundamental role of fibronectin (FN) to direct cell-material interactions. First, we will engineer material surfaces able to direct the physiological organization of FN into fibrillar networks in absence of cells, so-called material driven fibronectin fibrillogenesis. These surfaces will trigger the organization of FN upon simple adsorption of FN from solutions and will provide a biomimetic interface better recognized by cells, since it resembles the nature ECM environment in tissues. The mechanisms that promote the organization of FN at the material interface will be elucidated making use of different FN fragments and key modifications of the protein. The enhanced cellular activities of the material-driven FN matrices will be used to direct the behavior of human mesenchymal stem cells (hMSCs), seeking to direct either cell lineage or multipotency in combination with the properties of the underlying surface.Secondly, we will engineer functional – living biointerphases, on which the intermediate layer of proteins between the material surfaces and the cell population is expressed on the surface of non-pathogenic bacteria. This radical idea will provide the field with a living interphase that consists of genetically modified bacteria with FN fragments in the membrane.These bacteria will be modified to secrete the desired proteins or factors in response to external stimuli, to direct the cell behavior of hMSCs.""