Chargeable Hydrogels with Dual Modulatory Effects of Bacterial Killing and Immune Remodeling toward Wound Healing

Wound infections challenge clinical medicine, and developing novel therapies is critically important in overcoming antimicrobial resistance and an off-balanced immune microenvironment. Electrical stimulation as a biocompatible, easy-to-operate, and controllable technique has great potential in eradicating pathogens and modulating the immune system. However, safe and soft platforms that integrate both bactericidal and immunological modulatory effects of electrical stimulation are rarely reported. In this study, we propose a new strategy targeting infectious wound healing that utilizes chargeable hydrogels as the carrier of electrical stimulation to deploy timely bacterial disinfection and subsequently reprogram the macrophage phenotype. The chargeable platform (AT-PP@MnO₂) is constructed by doping manganese dioxide (MnO₂) microparticles into acid-treated PEDOT:PSS hydrogels (AT-PP), in which MnO₂ acts as the collector for charge storage and release. Upon a safe charging process at 0.8 V, AT-PP@MnO₂ achieves 99% bacterial inactivation within 15 min. The bactericidal mechanism is attributed to charging-evoked electron deprivation from bacteria, inducing an intracellular reactive oxygen species (ROS) burst to damage bacterial structure. Furthermore, the <i>in vivo</i> mouse model of wound infection demonstrates that AT-PP@MnO₂ can timely eradicate invasive bacteria to prevent infection from aggravation and then reprogram macrophages from proinflammatory to anti-inflammatory for immune remodeling, thus achieving nearly 100% wound healing within 14 days. This study introduces an emerging physical paradigm to the design of multifunctional wound dressing, offering broad potential in combating bacterial infections and immune modulation.