Antibacterial Conductive Polysaccharide-Based Hydrogel Microneedle Patches Accelerate Infected Diabetic Wound Healing through Anti-Inflammatory and Pro-Angiogenesis.

Diabetic ulcers (DUs) are a main category of nonhealing chronic wounds that tend to be vulnerable and prone to recurrence, posing a significant clinical challenge for DUs healing. DUs are frequently plagued by bacterial infections, oxidative stress, persistent inflammation, suppressed angiogenesis, and reduced growth factor expression, ultimately leading to persistent barriers to tissue regeneration and even amputation. Herein, we developed a multifunctional polysaccharide-based conductive hydrogel microneedle patch (MN-EP) integrating hyaluronic acid (HA) needle shafts, carboxymethyl chitosan-oxidized HA (CMCS-OHA) hydrogel backing, and oregano essential oil (OEO)-loaded polypyrrole (PPy) nanoparticles (EP NPs). MN-EP exhibited sufficient mechanical strength to penetrate stratum corneum, favorable conductivity matching skin tissue due to EP NPs, broad-spectrum antibacterial activity (nearly 100% against Staphylococcus aureus and Escherichia coli), and potent antioxidant capacity. It was demonstrated that MN-EP can scavenge intracellular reactive oxygen species (ROS), induce macrophage polarization toward the anti-inflammatory M2 phenotype, and promote fibroblast migration. In diabetic rats with infected full-thickness wounds, the electroactive MN-EP effectively eliminated harmful microorganisms at the wound site and modulated the immune microenvironment, thereby accelerating the resolution of inflammation, enhancing collagen deposition, and upregulating angiogenesis markers (CD31, VEGF), which promoted vascular and tissue regeneration and accelerated wound closure (98.28% by day 14). Overall, the multifunctional conductive hydrogel microneedle platform with antibacterial, anti-inflammatory, and pro-angiogenic properties represents a promising strategy for infected chronic diabetic wound healing.