Mesenchymal stem cells derived extracellular vesicles modified PLGA electrospinning nanofibrous scaffolds for corneal and retinal repair

• Reported PLGA electrospinning nanofibrous scaffolds (PLGA ENS ) for promoting the repair of corneal damage and retinal holes. • Extracellular vesicles modified PLGA ENS could further accelerate the healing process of cornea and retina. • MiR-21-5p downregulates the expression of genes related to fibrosis and collagen deposition via targeting PDCD4. • Provided new insights into the treatment strategy of wound healing and may lay a profound foundation for clinical utility. Tissue self-renewal is crucial for ocular diseases such as corneal damage and retinal holes. In this study, a novel Poly (lactic-co-glycolic acid) (PLGA) electrospinning nanofibrous scaffold (PLGA ENS ), loaded with mesenchymal stem cells-derived extracellular vesicles (MSC-EVs), was developed to accelerate the healing of the cornea and retina. In-vitro experiments confirmed the supportive properties of PLGA ENS , demonstrating its ability to promote cellular proliferation, migration, and extension. In the rat corneal alkali burn model and rabbit retinal hole model, MSC-EVs modified PLGA ENS (PLGA MSC-EVs ) accelerated the restoration of the corneal epithelium and stroma, as well as the closure of retinal holes. Additionally, miR-21-5p was identified as being enriched in MSC-EVs. Mechanistically, miR-21-5p suppressed scar formation by targeting the programmed cell death protein 4 (PDCD4) gene, reducing fibrosis and the expression of collagen-related genes, which helped maintain corneal transparency and retinal integrity. Overall, these findings underscored the potential of PLGA MSC-EVs in promoting ocular wound healing and suggested a promising new therapeutic strategy for the clinical treatment of corneal damage and retinal holes.