Multifunctional hyaluronic acid microneedle patch enhances diabetic wound healing in diabetic infections.

Diabetic wounds often exhibit a chronic non-healing state due to the combined effects of multiple factors, including hyperglycemia, impaired angiogenesis, immune dysfunction, bacterial infection, and excessive oxidative stress. Despite the availability of various therapeutic strategies, effectively managing the complex and prolonged healing process of diabetic infected wounds remains challenging. In this study, we combined the natural antidiabetic drug lipoic acid (LA) with the RADA16-YIGSR (RY) peptide obtained through solid-phase synthesis, utilizing reversible hydrogen bonds and coordination bonds for binding. Driven by strong electrostatic interactions and the spontaneous hydrophobic aggregation of LA molecules, the peptide underwent a self-assembly process without requiring additional external stimuli. Subsequently, this self-assembled peptide was loaded into a microneedle (MN) system composed of hyaluronic acid (HA).HA(RY/LA) MNs utilize LA's sustained release to effectively eliminate S. aureus and E. coli, reduce ROS, promote M2 macrophage polarization via NF-κB, and induce neovascularization through synergistic LA and RY release via MAPK. This significantly improves tissue regeneration in diabetic skin infections, highlighting the promising potential of this multifunctional system.