Spatially controlled hydrogel mechanics to modulate stem cell interactions

Local control of the stem cell microenvironment with biomaterial design is of critical importance for tissue engineering. Matrix mechanics is one aspect of biomaterial design that has received considerable attention recently due to the effect of mechanics on stem cell proliferation, morphology, and differentiation. In order to investigate the effect of locally controlled mechanics on human mesenchymal stem cells (hMSCs), a sequentially crosslinked hyaluronic acid hydrogel system was developed that permits spatial patterning of mechanics ( distinct patterns and gradients). Methacrylated hyaluronic acid was synthesized to allow for crosslinking via both Michael-type addition using a dithiol and radical polymerization using light. By varying the initial methacrylate consumption through addition crosslinking, restricting UV light to specified regions, and varying UV exposure time, a wide range of mechanics (from similar to 3 kPa to similar to 100 kPa) was possible in both uniform and patterned hydrogels. hMSCs exhibited increased spreading and proliferation on stiffer gels compared to cells cultured on softer gels. Furthermore, cells grown on gels with patterned mechanics exhibited spreading and proliferation behavior that correlated with the local mechanics. This method to spatially control matrix mechanics represents a novel hydrogel system to tune the stem cell microenvironment.