Triamcinolone acetonide-loaded nanoparticles encapsulated by CD90+ MCSs-derived microvesicles drive anti-inflammatory properties and promote cartilage regeneration after osteoarthritis

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-inflammatory effects, but long-term IA injections cause loss of cartilage. Synovial mesenchymal stem cells (MSCs) reportedly promote cartilage proliferation and increase cartilage content. Methods: CD90(+) MCS-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 the CD90(+) MCSs, stimulating CD90@MV secretion. Poly (lactic-co-glycolic acid) (PLGA) nanoparticle was coated with CD90@MV, and a model glucocorticoid, triamcinolone acetonide (TA), was encapsulated in the CD90@NP (T-CD90@NP). The chondroprotective effect ofT-CD90@NP was validated in rabbit and rat OA models. Results: The CD90@MV membrane proteins were similar to that of CD90(+) MCSs, indicating that CD90@MV bioactivity was similar to the cartilage proliferation-inducing CD90(+) MCSs. CD90@NP binding to injured primary cartilage cells was significantly stronger than to erythrocyte membrane-coated nanoparticles (RNP). In the rabbit OA model, the long-term IA treatment with T-CD90@NP showed significantly enhanced repair of damaged cartilage compared to TA and CD90(+) MCS treatments. In the rat OA model, the short-term IA treatment with T-CD90@NP showed effective anti-inflammatory ability similar to that of TA treatment. Moreover, the long-term IA treatment with T-CD90@NP induced cartilage to restart the cell cycle and reduced cartilage apoptosis.T-CD90@NP promoted the regeneration of chondrocytes, reduced apoptosis via the FOXO pathway, and influenced type 2 macrophage polarization to regulate inflammation through IL-10. Conclusion: This study confirmed that T-CD90@NP promoted chondrocyte proliferation and anti-inflammation, improving the effects of a clinical glucocorticoid treatment plan.

Automated summary

This study developed CD90(+) MSC-derived micro-vesicle (CD90@MV)-coated nanoparticle (CD90@NP) and validated its chondroprotective effect in rabbit and rat osteoarthritis (OA) models. The results showed that CD90@MV bioactivity was similar to that of CD90(+) MSCs, and T-CD90@NP significantly enhanced cartilage repair compared to TA and CD90(+) MSC treatments in the rabbit OA model. In the rat OA model, T-CD90@NP demonstrated effective anti-inflammatory ability similar to that of TA treatment, and also promoted chondrocyte proliferation, reduced apoptosis, and regulated inflammation through IL-10.