Morinda Officinalis-Derived Extracellular Vesicle-like Particles Promote Wound Healing via Angiogenesis.

Wound healing is a multistage process, related to complex cellular and molecular interactions that manipulate the cell behaviors to promote regeneration and repair of skin. Interestingly, plant-derived extracellular vesicles-like particles (EVs) show great potential as preparations for skin diseases. In this study, extracellular vesicle-like particles derived from Morinda Officinalis (MOEVLPs) were isolated and effectively promoted the proliferation, migration, and tube formation of endothelial cells in vitro. Mechanistically, MOEVLPs significantly activated the MAPK/YAP1 signaling pathway, confirmed by proteomics analysis and immunofluorescence staining, with an increase in YAP1 expression level in a full-thickness skin wound model. Subsequently, MOEVLPs were further integrated into a hydrogel carrier, enabling them to affect wound microenvironments and accelerate wound healing at the molecular level. The functional hydrogel exhibited a prolonged release of MOEVLPs, promoting angiogenesis and wound healing in vivo, which provided a promising strategy for clinical applications in advanced skin healthcare.