Kartogenin-loaded cell membrane nanovesicle-modified electrospun silk fibroin nanofibers for enhanced cartilage regeneration.

Articular cartilage, characterized by its avascular, aneural, and hypometabolic nature, exhibits limited intrinsic healing capacity following injury, significantly compromising patients' quality of life. Current clinical interventions, including microfracture and autologous chondrocyte implantation, are associated with drawbacks such as inferior mechanical properties of repaired tissue, donor site morbidity, and phenotypic dedifferentiation. To address these limitations, this study explored a functional cartilage repair strategy combining electrospinning technology with a cell membrane biomimetic modification approach. Specifically, we fabricated a Kartogenin-loaded mesenchymal stem cell membrane nanovesicle-functionalized silk fibroin nanofibrous scaffold (KGN@NVs-NF). The composite scaffold displayed favorable fibrous morphology, excellent hydrophilicity, antioxidant activity, and cytocompatibility. In vitro experiments revealed efficient cellular uptake of KGN@NVs without compromising cell proliferation. In a rat osteochondral defect model, implantation of KGN@NVs-NF scaffold contributed to improved cartilage-like tissue regeneration, increased proteoglycan deposition, and improved subchondral bone integration to some extent. Furthermore, the scaffold attenuated local pro-inflammatory cytokine expression and exerted mild regulatory effects on the inflammatory microenvironment. Collectively, this functionalized composite scaffold shows potential dual effects in anti-inflammation and chondrogenesis, providing a novel strategy for cartilage tissue engineering and repair.