Leveraging polyetheramine-bisepoxide reaction in water and LCST-mediated phase separation toward microstructured poly(amino alcohol ethers) hydrogels

Herein, a two-step “mix-and-click in water” strategy has been developed to enable the preparation of microstructured hydrogels without complex equipments and elaborate synthesis. Capitalizing on the“click” characteristics of nucleophilic opening of epoxide by amines in conjunction with lower critical solution temperature (LCST)-mediated phase separation phenomenon of the in situ formed prepolymers in water, we demonstrate that a new family of microstructured poly(amino alcohol ethers) hydrogels can be prepared readily from off-the-shelf polyetheramines and bisepoxides. The occurrence and extent of phase separation exhibited by the prepolymers derived from various combinations of reactants at the gel preparation temperature have a prominent effect on the structure of the hydrogels, resulting in the versatile outcomes of formation of homogeneous colloidal gels, structurally graded colloidal gels, or colloids-in-gel hybrids. With inherent ability to host hydrophobic molecules and good cytocompatibility toward fibroblast cells in vitro, this new family of microstructured poly(amino alcohol ethers) hydrogels may be exploited further for drug delivery and tissue engineering.