Injectable Photo-cross-linkable Porous Composite Hydrogels with Exosomes for M2 Macrophage Polarization and Cartilage Defect regeneration

In the initial stages of osteoarthritis(OA), the deterioration of cartilage in the superficial region results in the formation of superficial cartilage defects. It is anticipated that a therapy based on human umbilical cord mesenchymal stem cell exosomes(hUCMSCs-Exos) will make a notable contribution to the promotion of M2 macrophage polarization and the facilitation of cartilage repair. This study demonstrates that injectable photo-cross-linkable porous gelatin methacryloyl(GelMA)/silk fibroin glycidyl methacrylate(SilMA) hydrogels encapsulating human umbilical cord mesenchymal stem cell exosomes(hUCMSCs-Exos)represent a straightforward and effective approach for cartilage regeneration. The encapsulation of exosomes in hydrogels has been demonstrated to have no significant impact on the physical properties, as evidenced by physical studies. Furthermore, studies based on in vitro cell models and in vivo models in rats have demonstrated that exosomes released from hydrogels can promote M2 polarization, inhibit M1 polarization, and facilitate cartilage regeneration by regulating the PI3K/AKT signaling pathway. This process facilitates the repair of cartilage defects. The findings of our research have led to the development of an injectable photo-cross-linkable hydrogel for superficial cartilage regeneration, which represents a promising minimally invasive treatment for cartilage defects with the aid of arthroscopy.