DEVISE: Engineered viscoelasticity in regenerative microenvironments

Tissues are viscoelastic materials whose mechanical properties evolve with time and yet this important property has not been incorporated in the design of regenerative biomaterials. Mechanical properties of biomaterials are known to influence fundamental cellular process, including cell migration, cell growth and cell differentiation. However, most of the work to understand the mechanical properties of substrates on mesenchymal stem cell (MSC) differentiation has made use of pure elastic materials. Cells probe their environment by pulling forces and receiving mechanical feedback through membrane receptors. Since viscoelastic materials respond with a time dependent process to force, we hypothesise that viscoelasticity will play a fundamental role in the differentiation of mesenchymal stem cells and hence in the design of regenerative biomaterials. This project will develop (a) a new family of viscoelastic hydrogels with controlled properties that include biochemical functionalities (recapitulating the properties of the extracellular matrix in vivo), extreme mechanical properties (i.e. very low/high elastic and viscous properties) and mechanical gradients; and (b) Brillouin microscopy to follow the evolution of the local viscoelastic properties of these cell-laden materials as a function of time. we will use viscoelastic materials to promote bone regeneration in vivo using our critical-sized defect in the mouse radius model and, in a major attempt to move the field forward, we will further develop Brillouin microscopy to monitor the viscoelastic properties of regenerative microenvironments in vivo.