Photo-Enzyme-Polymerized Hydrogel Platform Exhibits Photo-Switchable Redox Reversibility for Diabetic Wound Healing

Redox homeostasis catalyzed by series oxidoreductases is important to maintain normal physiological functions, including mutually contradictory reactive oxygen species generation or reduction by separated enzyme regulation during cellular metabolism. The unidirectional enzyme regulation of redox homeostasis by biocatalytic reaction is an emerging catalytic medicine approach to disease biomimetic treatments. Bioinspired by photosynthesis, an efficient photo-enzyme-coupled hydrogel platform (Gel) with a spatio-temporally controlled hydrogel network was constructed through photoenzymatic-initiated radical polymerization in the absence of the corresponding enzyme substrate. Then, the coupling mechanism of light-induced electron transfer-enzyme activity center allosteric was explored through free radical analysis and theoretical calculations. The photo-switchable redox performance has been demonstrated based on the special anaerobic dehydrogenases, the flavin adenine dinucleotide (FAD)-centered dihydrolipoamide dehydrogenase (DLD) platform. At last, both in vitro and in vivo biological effects have been verified to evaluate the bidirectional oxidation/antioxidant modulation for the complicated wound healing in diabetic mice and wound-infected animals. The photoenzymatic coupling dehydrogenase-laden hydrogel platform proposed in this work provides ideas for the engineering design of enzymes, and the physical-biochemical regulatory mechanisms also offers a theoretical basis for controllable activation of enzyme activity, allowing for potential biomedical applications in metabolic processes. [Display omitted] •The coupling mechanism of light-photon coupled electron transfer-enzyme activity center allosteric was realized through proton-coupled electron transfer, which provides the possibility of light-activated redox reversibility and offers a new conceptual advance and greener strategies for the synthesis of hydrogels in a spatiotemporally controllable photo-enzyme coupling system.•The novel photo-enzyme coupling hydrogel platform with the spatiotemporally controlled three-dimensional network has been developed for enzyme immobilization by the proposed photo-enzymatic coupled radical polymerization strategy in the absence of the corresponding enzyme substrate. The physical-biochemical regulatory mechanisms offer a theoretical basis for controllable activation of enzyme activity, allowing for potential advanced in metabolic regulation within the biomedical field.•B