A conductive MXene hydrogel reprograms immunity and autophagy to restore neurovascular repair in infected wounds

Abstract Multidrug-resistant bacteria-infected wounds are difficult to heal due to persistent infection, excessive inflammation, impaired angiogenesis, and deficient cutaneous innervation. Here, we develop an antibacterial and conductive bioactive hydrogel based on flower-shaped MXene microspheres for treating methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds. The hydrogel (PDM) is constructed by integrating ε-poly-L-lysine-functionalized MXene microspheres into a dynamically crosslinked oxidized pullulan network via pH-responsive Schiff-base chemistry, conferring injectability, self-healing, tissue adhesion, and environmental responsiveness. PDM effectively eliminates MRSA biofilms, scavenges reactive oxygen species, and attenuates inflammatory responses while promoting adaptive autophagy. These combined properties enable modulation of the wound microenvironment, enhance macrophage polarization toward a regenerative phenotype, and support cell proliferation, endothelial cell migration and angiogenesis. In addition, the conductive hydrogel promotes Schwann cell maturation and neurotrophic factor expression, facilitating reconstruction of the neurogenic microenvironment. In a murine full-thickness MRSA-infected wound model, a single application of PDM significantly accelerates wound closure, enhances cutaneous innervation, and reduces fibrosis. This work presents a multifunctional MXene-based hydrogel platform for antibiotic-free infected wound healing.