Extracellular Vesicle-embedded alginate hydrogel patch for accelerated wound healing

The process of skin wound healing is markedly impaired by elevated levels of reactive oxygen species (ROS) and the persistent presence of pro-inflammatory macrophages in the injured tissue. To address these pathological challenges, we herein developed an alginate-based hydrogel patch (EGEV-Gel) engineered for the sustained release of human adipose stem cell-derived extracellular vesicles (hASC-EVs) and epigallocatechin gallate (EGCG). hASC-EVs were incorporated to promote tissue regeneration, while EGCG served as a potent ROS scavenger. In an in vitro wound healing model using the transwell insert system, EGEV-Gel demonstrated remarkable efficacy in suppressing M1 macrophage polarization, scavenging excessive ROS, and restoring the functional capacity of dermal fibroblasts and endothelial cells compromised by oxidative stress. When applied to the acute wound-induced mouse, EGEV-Gel significantly reduced the M1 macrophage population and the ROS level at 3 days post-treatment. Histological analysis of the skin layers further confirmed restoration of skin architecture, as demonstrated by the normalized thickness of key structural components, including the epidermis, collagen layer, and granulation tissue. These findings highlight the therapeutic potential of the hASC-EVs/EGCG-loaded hydrogel patch as a promising platform for promoting wound repair and modulating the inflammatory microenvironment in cutaneous injuries.