Injectable Macroporous Hydrogels by Combining the Rapid Evaporation of Perfluorocarbon Emulsions with Dynamic Covalent Cross-Linking Chemistry

While injectable hydrogels are significantly less invasive than other available delivery vehicles for cell therapies, the lack of macroporosity in typical injectable hydrogels (and thus the limited free volume available for cell proliferation and nutrient/waste transport) limits the effectiveness of such therapies. Herein, noncytotoxic and rapidly evaporating perfluorocarbon emulsions are combined with in situ gelling dynamic covalently cross-linked hydrogels to create an injectable hydrogel in which macropore generation can occur simultaneously to gelation as the perfluorocarbon component evaporates upon heating to physiological temperature. Macropores can be generated at different densities dependent on the perfluorocarbon concentration both in vitro and in vivo without inducing any significant cytotoxicity or local or systemic inflammatory responses. Furthermore, live/dead imaging showed a significant improvement in the viability of encapsulated cells in porous hydrogels in comparison to nonporous controls, attributed to the improved mass transport achievable in the presence of macropores. The combination of controllable porosity, noncytotoxicity, and ability to incorporate cells into the porous structure via a single injection offers a unique platform that could be adapted for use in cell therapy and/or tissue engineering applications.