Silver‐Based Nanozyme Hydrogel with Enhanced Multienzyme Activity for Infected Wound Treatment

Highly effective antibacterial wound dressings are essential for improving the treatment of infected wounds. This study constructs a nitrogen-doped carbon-based silver single-atom/nanoparticle composite carrier (2% Ag_SA/NP-NC) and anchors it in a cationic guar matrix (CG) to develop a smart dressing with synergistic antibacterial-healing-promoting function. Benefiting from the doped Ag_SA/NP, the triple enzyme catalytic efficiencies of oxidase, peroxidase, and glutathione peroxidase are enhanced. Through the synergistic ROS burst mechanism, the biofilm matrix is effectively disintegrated and the bacterial membrane permeability is enhanced. Mechanistic studies show that the synergistic effect of Ag⁺/ROS triggers an "oxidative stress-metabolic inhibition" cascade reaction at the molecular level. The change in membrane permeability promotes the inward flux of Ag⁺, exacerbates the oxidative stress damage of bacteria, and downregulates the expression of genes related to sugar degradation, the TCA cycle, and the electron transport chain, leading to energy depletion and genetic material damage. Furthermore, the dressing activates the Wnt, MAPK, and PI3K-Akt signalling pathways to promote cell proliferation, angiogenesis, and epidermal growth to remodel the infection microenvironment. This antibacterial-tissue regeneration treatment provides a systematic solution for infected wound treatment.s.