Bioelectrochemically Powered Out-of-Equilibrium Hydrogels Enable Feedback-Regulated Functions

Biological systems sustain functions by continuously converting energy into regulated processes through coupled reaction networks and feedback mechanisms. Achieving such functionality in synthetic materials remains challenging, as most energy-driven molecular assembly only forms transient structures and cannot sustain operations under continuous energy input. Here, we report a bioelectrochemically powered hydrogel that operates far-from-equilibrium via a fully electrochemical antagonistic redox cycle coupled to enzymatic feedback. We establish a fully electrochemical cycle in which reduced vitamin B₁₂ and oxidized ferrocene mediate disulfide cleavage and reformation within a disulfide-cross-linked polyrotaxane-based hydrogel, enabling dissipative growth and temporal modulation of mechanical properties. Embedding glucose oxidase within the hydrogel introduces a glucose-dependent enzymatic pathway that competes for ferrocene against disulfide reformation, inducing partial network decrosslinking and increased permeability under high-glucose level. This enzymatic feedback mechanism enables a glucose-responsive insulin delivery platform with enhanced release at high glucose and suppressed release at low glucose. These findings establish a general strategy to couple electrochemical energy input with biochemical feedback, enabling adaptive regulation of structure, mechanics and transport in soft materials under nonequilibrium conditions.