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

While injectable hydrogels are significantly less invasivethanother available delivery vehicles for cell therapies, the lack ofmacroporosity in typical injectable hydrogels (and thus the limitedfree volume available for cell proliferation and nutrient/waste transport)limits the effectiveness of such therapies. Herein, noncytotoxic andrapidly evaporating perfluorocarbon emulsions are combined with in situ gelling dynamic covalently cross-linked hydrogelsto create an injectable hydrogel in which macropore generation canoccur simultaneously to gelation as the perfluorocarbon componentevaporates upon heating to physiological temperature. Macropores canbe generated at different densities dependent on the perfluorocarbonconcentration both in vitro and in vivo without inducing any significant cytotoxicity or local or systemicinflammatory responses. Furthermore, live/dead imaging showed a significantimprovement in the viability of encapsulated cells in porous hydrogelsin comparison to nonporous controls, attributed to the improved masstransport achievable in the presence of macropores. The combinationof controllable porosity, noncytotoxicity, and ability to incorporatecells into the porous structure via a single injection offers a uniqueplatform that could be adapted for use in cell therapy and/or tissueengineering applications.