M2 macrophages-derived exosomes combined with acellular cartilage matrix scaffolds promote osteochondral regeneration via modulatory microenvironment

Articular cartilage (AC) regeneration has always been a difficult problem for clinicians. Anti-inflammatory (M2) macrophages have anti-inflammatory and tissue repair effects. Exosomes are reported to have multiple complicated biological functions. It has been shown that M2 macrophages-derived exosomes (M2D-Exo) can influence the course of certain diseases, but their effect on the repair of cartilage defects has not been reported. The aim of this study was to verify whether M2D-Exo could enhance the repair of acellular cartilage extracellular matrix (ACECM) scaffolds. Here, we characterized the ACECM scaffolds and identified the M2D-Exo by transmission electron microscopy (TEM), Western blotting (WB), and nanoparticle tracking analysis (NTA). In vitro, the results showed that M2D-Exo could promote the migration, proliferation and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). It was also found that M2D-Exo could reduce the expression of proinflammatory factors and promote M2 polarization, which ultimately protected chondrocytes and inhibited chondrocyte apoptosis. In vivo results confirmed that M2D-Exo could promote the repair effect of ACECM scaffolds, promote osteochondral regeneration and regulate the joint cavity inflammatory microenvironment. In conclusion, this study confirms that M2D-Exo can be used as a new therapeutic strategy for osteochondral regenerative repair.