Temperature-Responsive Supramolecular Hydrogels by Ternary Complex Formation with Subsequent Photo-Cross-linking to Alter Network Dynamics

Supramolecular hydrogels prepared from host-guest physical cross-linking of polymers have versatile utility in a number of applications. Routes to integrate stimuli-responsive features in these materials are intended to add another dimension to enhance their functionality. Herein, a guest which forms a homoternary complex with the cucurbit[8]uril macrocycle was appended to the ends of Pluronic F-127 polymers. This polymer undergoes temperature-responsive micelle formation, upon which CB[8] promotes their physical cross-linking via its host-guest interactions with the appended guests yielding a percolated hydrogel network. The particular guests used to form the homoternary complex can further be photo-dimerized to replace the physical host-guest interaction with a covalently bonded interaction. This change results in a reduction in hydrogel dynamics of roughly 2 orders of magnitude, yet temperature-responsive gelation and overall network architecture remain apparently unchanged. Hydrogels composed of micelles cross-linked by both supramolecular and photo-dimerized interactions support the injection and encapsulation of cells and enable inclusion and release of macromolecular payloads in vitro and in vivo. Thus, this approach points to a strategy to integrate external stimuli into supramolecular hydrogels through a combination of responsive polymers and light-directed supramolecular motifs.