Wild-Type Scandinavian Planarian-Derived Extracellular Vesicles Accelerate Skin Wound Healing in Burn and Mechanical Injuries

Skin wounds remain a clinical challenge, especially for burns and chronic wounds, and existing therapies seldom re-engage the rapid, scar-sparing repair programs observed in nature. Planarians are super-regenerators capable of rebuilding the entire organism from small fragments, and their extracellular vesicles might encode potent prorepair cues. But whether planarian-derived extracellular vesicles (EVs) can enhance mammalian skin healing is unknown. Therefore, we isolated EVs from a wild-type planarian flatworm collected in Sweden and evaluated their therapeutic activity in complementary wound models: a chicken chorioallantoic membrane assay and a human 3D skin model. In our models, planarian EVs significantly accelerated tissue regeneration and wound closure, and improved re-epithelialization and barrier integrity compared to controls. These data indicate that cross-species (xenogeneic) EVs from planarians carry bioactive factors capable of expediting cutaneous repair. Together, the results position planarian-derived EVs as a potential cell-free therapeutic strategy for burns and chronic wounds, motivating additional mechanistic and translational studies for clinical use.