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 (M2DExo) 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