From mechanical control to shape-shifting in supramolecular biomaterials to guide stem cell fate

ongoing

The biochemical and biophysical cues of the stem cell environment that act in a concerted and spatiotemporal manner lead to the formation of the 200 cell types and organs of the human body, but how this precisely occurs remains unclear and it is necessary to guide their production for use in the biomedical area. Standard differentiation protocols in vitro mimic known stages in development by the timed addition of biochemical cues on 2D substrates, however these protocols lack the complexity of the 3D natural extracellular matrix (ECM), with its mechanical character that evolves in time. Supramolecular materials can recapitulate the structural and dynamic character of the ECM being based on non-covalent interactions. Moreover, as I have shown, their mechanical soft character can mimic embryonic microenvironment for induced pluripotent stem cell (iPSC) culture but renders them unable to mimic stiff and tough tissues. Double networks using covalent polymers have demonstrated to achieve such mechanical properties, however these materials lack the cytocompatibility for use in 3D cell culture. In this proposal, I will synthesize hybrid covalent-supramolecular polymer networks that use biocompatible chemical and light-activated ligation approaches to apply them to guide the fate of iPSCs to cardiomyocytes by controlling their mechanical properties in time. I will exploit the unique properties of these double networked materials to interface them with biomechanical devices, and as an actuatable culture platform by 3-D printing a miniature beating heart ventricle. These advanced culture platforms based on hybrid-covalent supramolecular materials that go from soft to stiff and tough in time and space with shifting-shapes, with the potential to decouple the presentation of bioactive cues in an integrated manner, will provide uncharted opportunities to understand the spatiotemporal evolution of active and passive mechanical cues in development from cell to organ.