Cytophilic Agarose-Epoxide-Amine Cryogels Engineered with Granulated Microstructures.

Abstract

Inherent cytophobicity of agarose limits its direct use for the growth of anchorage-dependent cells. Here, we report a simple strategy allowing the development of agarose-based hydrogels entailed with both cytophilicity and microstructured morphology. Through the reaction of water-soluble 1,4-butanediol diglycidyl ether (BDDE) with trifunctional polyetheramine Jeffamine T403 in agarose solution followed by cryogelation of the mixtures, a series of macroporous agarose-epoxide-amine cryogels were prepared readily. Results from fluorescent labeling and energy-dispersive X-ray elemental mapping showed the formation of granulated microstructures in the cryogels. Such features closely correlated to the phase separation of BDDE-T403 polymers within the agarose matrix. Cytophilicity of the microstructured cryogels due to the integrated amine moieties was demonstrated through the adhesion of fibroblasts. Functional enrichment of the cryogels was further highlighted by leveraging the granulates as micro-reservoirs for polyphenol proanthocyanidin to enable antioxidation and protection of fibroblasts from H2O2-induced cytotoxic effect in vitro.