Material-based strategies to engineer fibronectin matrices for regenerative medicine

Engineering biomaterials for regenerative medicine involves a myriad of aspects to be considered for the successful design, interaction with cells and integration with living tissues (i.e. pore size, mechanical properties, degradation rate, biological activity). Among different technologies used to functionalise synthetic biomaterials and promote cell adhesion, cell growth and cell differentiation, this review focuses on strategies to organise extracellular matrix (ECM) proteins in a biomimetic way, as cells do in natural tissues in vivo (the ECM is a mesh of proteins that surrounds cells, and therefore, constitutes the scaffolding of a tissue), but using functional materials instead of living cells. The authors critically review material-based strategies to organise fibronectin (FN), a core component in the ECM of many tissues, and engineer microenvironments that recapitulate the structure and properties of the ECM. Material-driven organisation of FN in analogy with their natural cell-mediated assembly is a powerful route to engineer the network structure and biological activity of FN fibrillar matrices, seeking to develop biomimetic scaffolds for regenerative medicine. Here, the authors discuss different routes to promote the cell-free formation of FN fibrils as well as the biological impact of these engineered cellular microenvironments.