An injectable antibacterial wet-adhesive for meniscal cartilage regeneration via immune homeostasis mediated by SMSC-derived extracellular vesicles

Surgical repair is recommended for meniscus tear to avoid knee degeneration. However, postoperative meniscal healing remains challenging due to limited blood supply, particularly the avascular zone. Tissue-engineering techniques had limited outcomes in meniscus repair due to the highly irregular interface of meniscus and the wet joint environment. Additionally, it was proved that the inflammation status and the recruitment of endogenous cells are crucial for meniscal healing. This study represents a versatile extracellular vesicles (EVs)-based wet-adhesive employed in meniscus repair. A novel injectable hydrogel adhesive, designated as oxidized dextran/carboxymethyl chitosan/poly-l-lysine/synovial mesenchymal stem cell-derived EVs (OD/CS-PL@EVs), was fabricated and demonstrated effective antibacterial activity against S. aureus and E. coli. This adhesive also exhibited effective adhesion to the waterish meniscus with a lap shear strength of 134 KPa. Additionally, it promoted the proliferation, migration, chondrogenic differentiation, and extracellular matrix formation of SMSCs and meniscus cells and induced the polarization of macrophages towards the M2 phenotype in vitro. The RNA sequencing results further proved that four inflammation-related signaling pathways were inhibited by the prepared products. After being administered into the rabbit meniscal defect model, OD/CS-PL@EVs hydrogel adhesive effectively regulated the inflammatory balance and facilitated the meniscal cartilage regeneration in the avascular area, further remarkably delaying the progression of osteoarthritis. In summary, OD/CS-PL@EVs hydrogel adhesive provided a promising strategy to promote meniscal repair in avascular zone repair of meniscus for future clinical applications, holding great potential in preventing osteoarthritis.