Freeze–Thawing-Induced Macroporous Catechol Hydrogels with Shape Recovery and Sponge-like Properties

Catechol-containing hydrogels have been exploited in biomedical fields due to their adhesive and cohesive properties, hemostatic abilities, and biocompatibility. Catechol moieties can be oxidized to o-catecholquinone, a chemically active intermediate, in the presence of oxygen to act as an electrophile to form catechol-catechol or catechol-amine/thiol adducts. To date, catechol cross-linking chemistry to fabricate hydrogels has been mostly performed at room temperature. Herein, we report large increases in catechol cross-linking reaction kinetics by the freeze–thawing process. The formation of ice crystals during freezing steps spatially condenses catechol-containing polymers into nearly frozen (yet unfrozen) regions, resulting in decreases in the polymeric chain distances. This environment allows great increases in catechol cross-linking kinetics, a phenomenon that can also occur during thawing steps. The increased cross-linking rate and spatial condensation in the cryogels provide unique wall and pore structures, which result in elastic, spongelike hydrogels. The moduli of the cryogels prepared by glycol-chitosan-catechol (g-chitosan-c) were improved by 3–6-fold compared to room temperature-cured conventional hydrogels, and the degree of improvement increased depending on the freezing time and the number of freeze–thawing cycles. Unlike typical cell encapsulations before cross-linking, which have often been a source of cytotoxicity, the macroporosity of cryogels allows nontoxic cell seeding with ease. This research offers a new way to utilize catechol cross-linking chemistry by freeze–thawing processes to simultaneously regulate mechanical strength and porous structures in catechol-containing hydrogels.