Abstract

Skin, as the most crucial natural shields that envelopes human body, the integrity and function of which is destroyed by various harmful stimuli. Skin damage often involves excessive oxidative stress, which impairs the healing process. Thus, it is urgent to explore novel and effective strategy to tackle this problem. While superoxide dismutase (SOD) has strong antioxidant capacity, its clinical use is limited by poor stability and low penetration. Bacterial extracellular vesicles (BEVs), functioning as the messenger of intercellular communication and the carrier of parental cargos, offer an ideal nano-delivery platform due to their excellent biocompatibility, efficient cellular uptake, and high stability. This study developed a novel antioxidant delivery system by displaying SOD on Bacillus subtilis -derived extracellular vesicles (SEVs) using surface display technology. The resulting SEVs exhibited enhanced stability, high SOD activity, and strong free radical scavenging capacity in vitro. The administration of SEVs significantly improved healing outcomes in a full-thickness skin wound model. SEVs treatment led to faster wound closure, enhanced re-epithelialization, greater collagen deposition, and alterations in the expression of inflammatory and angiogenic genes. Additionally, SEVs protected human keratinocytes (HaCaT) from H 2 O 2 -induced oxidative damage by reducing ROS levels, restoring mitochondrial function, and enhancing antioxidant enzyme activity. These findings highlighted the potential of SEVs as an effective nanotherapeutic strategy for treating oxidative stress-related skin injuries.