Engineering an Anaerobic Microenvironment to Empower Hydrogenase‐Catalyzed Hydrogen Therapy for Diabetic Wound Healing

ABSTRACT The inherent oxygen sensitivity of hydrogenases has limited their biomedical use. We report a hybrid peptide–nanocluster hydrogel that establishes a self‐sustained anaerobic microenvironment, enabling hydrogenase‐catalyzed hydrogen therapy under aerobic conditions. The Fmoc‐KYF peptide network traps O 2 in hydrophobic pockets, while photoexcited silver nanoclusters rapidly scavenge residual oxygen, ensuring stable hydrogen evolution. In vitro, the generated hydrogen mitigates oxidative stress and inflammation. In diabetic mice, the light‐activated system accelerates wound closure, promotes angiogenesis, and drives macrophage polarization toward a reparative phenotype. This study introduces a bioengineering strategy that integrates material design, enzyme catalysis, and photodynamics to overcome oxygen limitation and advance hydrogenase‐based therapeutic applications.