Porcine umbilical cord exosomes promote regenerative skin repair through miR-192-5p/DSC1-mediated angiogenesis and collagen matrix optimization.

The clinical application of human umbilical cord blood-derived exosomes (UCB-Exo) for wound healing is limited by ethical concerns and donor scarcity. To address these challenges, we propose porcine UCB-derived exosomes (PUCB-Exo) as an ethically acceptable alternative, which, when combined with a propolis complex (PC), demonstrates enhanced therapeutic efficacy. In a murine skin injury model, PUCB-Exo monotherapy significantly accelerated wound closure through the promotion of angiogenesis and modulation of extracellular matrix composition-specifically reducing excessive collagen deposition and optimizing the collagen I/III ratio compared to PBS controls. The combination therapy with PC further synergized this effect, resulting in superior tissue regeneration and wound repair outcomes compared to monotherapies. Transcriptomic profiling identified 26 differentially expressed genes (DEGs) in PUCB-Exo-treated wounds, predominantly associated with immune regulation and skin function pathways. Integrated miRNA-mRNA analysis highlighted miR-192-5p as a key regulatory molecule targeting DSC1, an essential component of desmosomal junctions involved in epidermal repair. Our findings establish PUCB-Exo as a promising substitute for UCB-Exo that overcomes translational barriers while offering improved scar management, supported by mechanistic insights into its synergistic interaction with natural product adjuvants.