Exosome‐mimetic vesicle‐encapsulated multi‐responsive antibacterial hydrogel core‐shell microneedle patch promotes scarless healing of infected wounds

Abstract

Clinical stage‐adaptive treatment strategies for infected wounds face temporal challenges due to the varying demands for antibacterial, anti‐inflammatory and anti‐scarring effects during different stages of healing. In this study, a core‐shell microneedle (MN) patch with spatiotemporally programmed release was developed through controlled degradation, reactive oxygen species (ROS) and pH response, termed VP@FNV‐CuO 2 ‐MN. In the mildly acidic microenvironment of early‐stage infected wounds, the moderately crosslinkedboronic ester‐based shell loaded with nano‐copper peroxide (n‐CuO 2 ) was released first, triggering a Fenton‐like reaction that produced antibacterial ROS and pro‐angiogenic Cu 2+ ions. Concurrently, the boronic ester bonds of MN could adaptively neutralize the liberated ROS, thereby preventing excessive oxidative stress. The core of MN was structured with a highly‐crosslinked hydrogel and encapsulated fibroblast‐derived exosome‐mimetic nanovesicles (FNV) loaded with verteporfin (VP@FNV), which ensured targeted suppression of the YAP/En1 signaling pathway in fibroblasts during the late stage of wound healing. Evaluations in Sprague‐Dawley (SD) rat full‐thickness infected wound models and rabbit ear hypertrophic scar models demonstrated accelerated wound healing and scarless regeneration. These findings confirm that VP@FNV‐CuO 2 ‐MN facilitates stage‐adaptive modulation of antibacterial, inflammation resolution, angiogenesis, and extracellular matrix remodeling, offering an innovative solution for scarless healing of infected wounds.