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

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 V2C/VSe2 heterojunctions (V2R-HJs) to drive bioenergetic pathogen disruption and peripheral nerve regeneration. Vanadium-vacancy-boosted atomic-level charge polarization enables V2R-HJs to form potent Lewis acid-base pairs to capture electrons and protons, exerting enhanced catalytic, multienzyme-mimetic, and H2Se release activities. In infection, V2R-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, V2R-HJs exhibit multienzyme-like activities and release trace H2Se, 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, V2R-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.