Abstract
Chronic wounds often experience delayed healing due to a disrupted microenvironment marked by persistent inflammation and excessive fibrosiswhich leads to tissue dysfunction. Excessive mitochondrial reactive oxygen species (ROS) at the injury siteworsen this by hindering healing and promoting scarring. This study presents a multifunctional microneedle array (MNA) that combines ROS scavenging with accelerated tissue formation. The array contains Flightless I (Flii) siRNA-loaded arginine-functionalized poly (β-amino ester)-alginate (APA) particles within a hyaluronic acid methacrylate (HaMA) matrix. These siRNA-APA particles enhance ROS scavenging through nitric oxide (NO) delivery and silence Flii expression in HaCaT cells. The synergistic release of NO, arginine, and siRNA reduces pro-inflammatory gene expression (TNF-α and IL6), transforming M1 macrophages into the M2 phenotype and aiding the transition from inflammation to proliferation. Studies in a rat chronic wound model demonstrate that applying the siRNA-APA-laden MNA transdermally mitigates scar formation and promotes wound healing by reducing inflammatory responses. This siRNA-APA-laden HaMA MNA, with ROS scavenging and immunomodulatory activity, offers promising insights into effective chronic wound managementand wound dressing applications.