Programmed modulation of inflammation in diabetic wounds via a dual-stage CuTA/RvD1 microneedle system

The pathological environment of diabetic infected wounds is complex, involving multiple aspects such as bacterial infection, oxidative stress, and persistent inflammation, which has seriously affected the health of diabetic patients. We propose a novel hierarchical microneedle (MN) that promotes the healing of diabetic infected wounds through multi-target intervention. This microneedle is composed of hyaluronic acid (HA) tips loaded with copper tannate (CuTA) and methacrylate hyaluronic acid (HAMA) base loaded with Resolvin D1 (RvD1). The tip of the microneedle rapidly dissolves and releases CuTA, preventing bacterial colonisation in the early stage of inflammation and scavenging local reactive oxygen species (ROS). The basal layer slowly degrades to release RvD1, which promotes the phenotypic transformation of macrophages during inflammation and accelerates wound healing. The microneedle system showed antibacterial and antioxidant properties and promoted the transformation of macrophages into M2 type in vitro. In rat models of diabetic infected wounds, the microneedle system can accelerate wound contraction, promote collagen deposition and tissue regeneration, and regulate the secretion of inflammatory factors. As a novel design of microneedle drug delivery platform, it demonstrates the potential application of precise intervention and synergistic treatment in diabetic wound repair.