Janus Biofuel Cells for Electrosynergistic Enhancement of Microenvironment-Adaptive Cascade Catalysis in Infected Diabetic Wound Healing

Abstract The treatment of infectious diabetic wound is greatly hampered by hyperglycemia, inflammation, and microcirculatory dysfunction. Bioelectric stimulation and nanozyme catalysis provide a potential strategy for chronic wound repair but suffer from limitations including external electric power, low activity, and competitive multienzyme reactions. Given this, we developed microenvironment-responsive Janus GOx-Au@PCH–Pt nanoparticles (NPs) as biofuel cells, integrating cascade enzymatic catalysis and self-powered electrical stimulation. The biofuel cell features hydroxylated polyaniline (PCH) NPs as conductive bridges, Pt nanoclusters as the cathode, and glucose oxidase (GOx)-grafted Au (GOx-Au) as the anode. Under infection (acidic pH), conductive PCH shuttles electrons to generate microcurrent that accelerates enzyme catalysis on both the Au anode (GOx) and Pt cathode (peroxidase, POD). The enhanced GOx-POD cascade strengthens ·OH generation, and the self-powered electric field enhances ·OH diffusion across phospholipid bilayers, achieving significant bacterial killing and biofilm dispersion. During tissue repair, neutral/alkaline conditions switch Pt nanozyme from POD to catalase (CAT) and transform PCH into a benzoquinone structure as the electron acceptor. Reversed electron flow boosts the GOx-CAT cascade catalysis on the electrodes, accelerating glucose consumption, suppressing advanced glycation end product formation, and alleviating oxidative stress, while electrical stimulation reduces hypoxia-inducible factor-1α expressions. This synergistic effect promotes collagen deposition and orderly arrangement and normalizes microenvironment with oxygen-generating, hypoglycemic, anti-inflammatory, and macrophage phenotype-shifted features, thereby accelerating wound healing. This designed nanoscale biofuel cells realize adaptive microcurrent modulation and spatiotemporal cascade catalysis, offering a minimally invasive paradigm for infected diabetic wound therapy.