Multifunctional Microneedle Patch Based on Metal-Phenolic Network with Photothermal Antimicrobial, ROS Scavenging, Immunomodulatory, and Angiogenesis for Programmed Treatment of Diabetic Wound Healing.

Abstract

In diabetic patients with skin injuries, bacterial proliferation, accumulation of reactive oxygen species (ROS) in the tissues, and impaired angiogenesis make wound healing difficult. Therefore, eliminating bacteria, removing ROS, and promoting angiogenesis are necessary for treating acute diabetic wounds. In this study, benefiting from the ability of polyphenols to form a metal-phenolic network (MPN) with metal ions, TA-Eu MPN nanoparticles (TM NPs) were synthesized. The prepared photothermal agent CuS NPs and TM NPs were then loaded onto the supporting base and needle tips of PVA/HA (PH) microneedles, respectively, to obtain PH/CuS/TM microneedles. Antibacterial experiments showed that microneedles loaded with CuS NPs could remove bacteria by the photothermal effect. In vitro experiments showed that the microneedles could effectively scavenge ROS, inhibit macrophage polarization to the M1 type, and induce polarization to the M2 type as well as have the ability to promote vascular endothelial cell migration and angiogenesis. Furthermore, in vivo experiments showed that PH/CuS/TM microneedles accelerated wound healing by inhibiting pro-inflammatory cytokines and promoting angiogenesis in a diabetic rat wound model. Therefore, PH/CuS/TM microneedles have efficient antibacterial, ROS scavenging, anti-inflammatory, immunomodulatory, and angiogenic abilities and hold promise as wound dressings for treating acute diabetic wounds.