Interleukin‐10 Derived Apoptotic Vesicles Enhance Scarless Skin Healing by Modulating Fibroblast Metabolism and Fibrosis Pathways

Open skin wounds caused by burns, trauma, or underlying diseases impose substantial clinical challenges and significantly compromise patients' quality of life due to their complex management and high risk of scarring. In this study, we explore the therapeutic potential of apoptotic vesicles derived from interleukin-10-treated fibroblasts (IL10_ApoEVs) in promoting cutaneous wound healing and mitigating fibrotic scar formation. Our results demonstrate that IL10_ApoEVs enhance mitochondrial function and oxidative phosphorylation (OXPHOS), while concurrently suppressing glycolytic activity in fibroblasts. Importantly, IL10_ApoEVs markedly inhibit the Hedgehog signalling pathway, a key driver of fibrogenesis in various tissues, as evidenced by the downregulation of Shh and Gli1 expression. This modulation leads to attenuated aberrant extracellular matrix (ECM) deposition and promotes a favourable shift in collagen composition. This is characterized by increased type III collagen and reduced type I collagen, which is indicative of more elastic and functionally integrated tissue remodelling. These findings suggest that IL10_ApoEVs contribute to a regenerative microenvironment that supports scarless or minimally fibrotic healing. Collectively, our work highlights the promising application of IL10_ApoEVs in regenerative medicine and provides mechanistic insights into their dual role in metabolic reprogramming and antifibrotic signalling modulation during tissue repair.