Fuel‐Driven and Enzyme‐Regulated Redox‐Responsive Supramolecular Hydrogels

Chemical reaction networks (CRN) embedded in hydrogels can transform responsive materials into complex self‐regulating materials that generate feedback to counter the effect of external stimuli. This study presents hydrogels containing the β‐cyclodextrin (CD) and ferrocene (Fc) host–guest pair as supramolecular crosslinks where redox‐responsive behavior is driven by the enzyme–fuel couples horse radish peroxidase (HRP)–H(2)O(2) and glucose oxidase (GOx)–d‐glucose. The hydrogel can be tuned from a responsive to a self‐regulating supramolecular system by varying the concentration of added reduction fuel d‐glucose. The onset of self‐regulating behavior is due to formation of oxidation fuel in the hydrogel by a cofactor intermediate GOx[FADH(2)]. UV/Vis spectroscopy, rheology, and kinetic modeling were employed to understand the emergence of out‐of‐equilibrium behavior and reveal the programmable negative feedback response of the hydrogel, including the adaptation of its elastic modulus and its potential as a glucose sensor.