Fast Thermoresponsive Poly(oligoethylene glycol methacrylate) (POEGMA)-Based Nanostructured Hydrogels for Reversible Tuning of Cell Interactions

Reactive electrospinning is demonstrated as a viable method to create fast-responsive and degradable macroporous thermoresponsive hydrogels based on poly(oligoethylene glycol methacrylate) (POEGMA). Hydrazide- and aldehyde-functionalized POEGMA precursor polymers were coelectrospun to create hydrazone cross-linked nanostructured hydrogels in a single processing step that avoids the need for porogens, phase separation-driving additives, or scaffold postprocessing. The resulting nanostructured hydrogels can respond reversibly and repeatedly to changes in external temperature within seconds, in contrast to the minutes-to-hours response time observed with bulk hydrogels. Furthermore, nearly quantitative cell delamination can be achieved within 2 min of incubation at 4 °C, resulting in the recovery of as many or more (as well as more proliferatively active) cells from the substrate relative to the conventional trypsinization protocol. The combined macroporosity, nanoscale feature size, and interfacial switching potential of these nanostructured hydrogels thus offer promise for manipulating cell–hydrogel interactions as well as other applications in which rapid responses to external stimuli are desirable.