Dual-Strategy Pullulan-Soluble Microneedles Based on LL37@ZIF-8 and Artificial Nanozyme Antioxidation for Infected Wound Healing

Infected skin wound healing involves a series of dynamic and complex physiological processes. In this study, we reported a dissolvable microneedle (MN) with pullulan as the matrix material. The antimicrobial peptide LL37 was immobilized <i>in situ</i> within ZIF-8 to form hybrid nanoparticle LL37@ZIF-8 (LZ). This nanoparticle was then loaded onto the tip of the microneedle along with Prussian Blue (PB) nanozymes to obtain PB+LZ@MN, which exhibits both antimicrobial and antioxidative activities, for the healing of infected skin wounds. The MN, with good mechanical properties, could rapidly dissolve its tip upon insertion into the skin, releasing LZ and PB into the wound within 3 min. The MN had good physicochemical properties and biocompatibility and was shown to reduce inflammation and stimulate angiogenesis by enhancing collagen deposition and re-epithelialization in the Sprague-Dawley (SD) rat skin defect infection model. On the 10th day of wound healing, the healing rate of the PB+LZ@MN group was as high as 99%, which was significantly higher than that of the control at 84%, significantly accelerating the healing of the infected wound. This multifunctional MN is expected to provide a competitive biomaterial for accelerated infected wound healing.