Hydrogels for Tissue Engineering: Addressing Key Design Needs Toward Clinical Translation.

While the soft mechanics and tunable cell interactions facilitated by hydrogels have attracted significant interest in the development of functional hydrogel-based tissue engineering scaffolds, translating the many positive results observed in the lab into the clinic remains a slow process. In this review, we address the key design criteria in terms of the materials, crosslinkers, and fabrication techniques useful for fabricating translationally-relevant tissue engineering hydrogels, with particular attention to three emerging fabrication techniques that enable simultaneous scaffold fabrication and cell loading: 3D printing, in situ tissue engineering, and cell electrospinning. In particular, we emphasize strategies for manufacturing tissue engineering hydrogels in which both macroporous scaffold fabrication and cell loading can be conducted in a single manufacturing step - electrospinning, 3D printing, and in situ tissue engineering. We suggest that combining such integrated fabrication approaches with the lessons learned from previously successful translational experiences with other hydrogels represents a promising strategy to accelerate the implementation of hydrogels for tissue engineering in the clinic.

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.