Abstract
Background: Osteoarthritis (OA) is a highly prevalent human degenerative joint disorder that has long plagued patients. Glucocorticoid injection into the intra-articular (IA) cavity provides potential short-term analgesia and anti-inflammation, but long-term IA causes loss of cartilage content. Synovial mesenchymal stem cells (MSCs) reportedly promote cartilage proliferation and increase cartilage content. Methods: The CD90+ MCSs-derived micro-vesicle (CD90@MV)-coated nanoparticle (CD90@NP) was developed. CD90+ MCSs were extracted from human synovial tissue. Cytochalasin B (CB) relaxed the interaction between the cytoskeleton and the cell membranes of CD90+ MCSs, stimulating CD90@MV secretion. The poly (lactic-co-glycolic acid) (PLGA) nanoparticle was coated with CD90@MV, and a model glucocorticoid, triamcinolone acetonide (TA), was encapsulated in CD90@NP (T-CD90@NP). Results: CD90@MV membrane proteins were similar to CD90+ MCSs, indicating that the CD90@MV bio-activity is similar to the cartilage proliferation-inducing CD90+ MCSs. The CD90@NP binding to injury cartilage primary cells was significantly stronger than the erythrocyte membrane-coated nanoparticles (RNP). In the rabbit OA model, long-term IA of T-CD90@NP showed significantly enhanced repair of damaged cartilage than TA and CD90+ MCSs treatments. In the rat OA model, short-term IA of T-CD90@NP showed effective anti-inflammatory ability similar to TA treatment. Moreover, long-term IA of T-CD90@NP induced cartilage to restart the cell cycle and reduced cartilage apoptosis. T-CD90@NP promotes regeneration of chondrocytes, reduces apoptosis via the FOXO pathway, and influences type 2 macrophage polarization to regulate inflammation through IL-10. Conclusion: This study confirms that T-CD90@NP promotes chondrocyte proliferation and anti-inflammation, improving the clinical glucocorticoid treatment plan.