Synergistic Magneto-Electro-Thermal Biochemical Cascade Modulation Enables Rapid Healing and Functional Restoration of Infected Wounds.

Abstract

The treatment of infected wounds is severely hampered by uncontrolled antimicrobial release and wired stimulation. To address these challenges, a magnetoresponsive smart dressing for on-demand antibacterial and wireless electrical stimulation is fabricated via a dopamine-mediated cascade assembly strategy. Based on electromagnetic induction, the dressing functions as a magneto-electro-thermal biochemical cascade stimulator, wirelessly delivering stable and controllable microcurrents (7.08-19.66 μA) and using thermal effects to trigger on-demand Ag⁺ release. In vitro experiments demonstrated that under a rotating magnetic field (90 mT, 600 rpm, 1 h), the bacterial relative viability of the smart dressing dramatically decreased from 49.84% to 0.68%. Cellular experiments further confirmed that it effectively regulated cell proliferation and spreading, promoted the polarization of macrophages towards an anti-inflammatory phenotype, and enhanced the secretion of neurotrophic factors. Consequently, the system markedly accelerates the healing of Staphylococcus aureus-infected full-thickness wounds by 1.25-fold while driving functional recovery, evidenced by 3.58-fold and 16.35-fold increases in hair follicle and nerve regeneration, respectively. Mechanistic studies reveal the the wireless microcurrent generated by the dressing under RMF activated voltage-gated calcium channels, promoting calcium ion (Ca²⁺) influx and subsequent activation of the calmodulin-dependent protein kinase II and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathways. Overall, this work develops a therapeutic strategy for the treatment of infected wounds and establishes a paradigm for the design of smart responsive materials in bioelectronic medicine. STATEMENT OF SIGNIFICANCE: Antimicrobial therapy and electrical stimulation are key modalities for infected wounds. However, their efficacy is severely limited by uncontrolled drug release and wired stimulation. To address these challenges, we have developed a magnetically-responsive smart dressing that enables on-demand antibacterial and wireless electrical stimulation, fabricated via a dopamine-mediated cascade assembly strategy. Based on electromagnetic induction, the dressing generates a stable and controllable microcurrent and utilizes its thermal effect to trigger the on-demand release of Ag⁺, precisely matching the dynamic needs of the wound healing process. This wireless and controllable magneto-electrical-biochemical cascade stimulation system not only offers a transformative strategy for the treatment of infected wounds but also provides a robust platform for developing next-generation smart responsive materials for advanced bioelectronic medicine.