Vanadium‐Vacancy‐Induced Atomically Polarized Heterojunctions for Synergistic Bioenergetic Pathogen Disruption and Peripheral Nerve Regeneration

ABSTRACT Drug‐resistant bacterial infections and persistent oxidative stress severely impair nerve endings in burn wounds, presenting a formidable clinical challenge. Current treatment modalities generally fail to achieve simultaneous pathogenic eradication and neuro‐regeneration. Here, we design vanadium‐vacancy‐induced atomically polarized V 2 C/VSe 2 heterojunctions (V 2 R‐HJs) to drive bioenergetic pathogen disruption and peripheral nerve regeneration. Vanadium‐vacancy‐boosted atomic‐level charge polarization enables V 2 R‐HJs to form potent Lewis acid‐base pairs to capture electrons and protons, exerting enhanced catalytic, multienzyme‐mimetic, and H 2 Se release activities. In infection, V 2 R‐HJs synergistically disrupt electron transport and collapse the proton motive force within the bacterial respiratory chain with sonocatalytic therapy, achieving 99.5% and 96.2% antibacterial efficiencies against Cl‐MRSA and Cl‐DREC , respectively. During healing, V 2 R‐HJs exhibit multienzyme‐like activities and release trace H 2 Se, alleviating oxidative injury and restoring the nerve regeneration microenvironment. Mechanistic investigations reveal that selenoprotein biosynthesis and PI3K/Akt/Nrf2 pathway activation accelerate neural cell growth. In Cl‐MRSA ‐infected burn wounds, V 2 R‐HJs demonstrate superior therapeutic efficacy by reprogramming macrophages, boosting neovascularization, peripheral neural regeneration, and extracellular matrix remodeling, achieving 98.5% wound closure by Day 15. This atomic‐level charge‐polarized vacancy‐rich hetero‐architecture offers a paradigm for integrating pathogen bioenergetic disruption and targeted tissue restoration, opening a promising avenue for treating recalcitrant infection‐driven pathologies.