Mechanotransduction and growth factor signaling in hydrogel-based microenvironments

The extracellular matrix (ECM) is a highly-hydrated mesh of fibrillar proteins a glycosaminoglycans that surrounds cells and provides biophysical and biochemical stimuli. The ECM allows cell adhesion and mechanotransductive cues but it is also a reservoir of growth factors, which are of critical importance in shaping cell phenotypes. Hydrogels have been engineered as materials that can recapitulate the properties of the ECM, by controlling their physical properties and incorporating growth factors. This article provides an overview of the latest findings about the control of cell mechanotransduction and growth factor signaling using hydrogels. Hydrogels can be fabricated with controlled stiffness (i.e., to mimic properties of soft and hard tissues), viscoelasticity (tissues have dynamic properties, e.g., cartilage) or degradability (e.g., triggered by cell secreted proteases). Furthermore, hydrogels can be tuned to present specific ligands and ligand spacing, to control cell adhesion and mechanotransductive signaling cascades. Further, hydrogels can be engineered to present or immobilize growth factors, providing a sustainable release of them. To conclude, some examples are presented here to show the use of hydrogels as tools to exploit the synergistic effect of growth factors and cell mechanosensing to drive (stem) cell differentiation.