Mg2+-containing composite scaffolds mediate macrophage polarization to enhance meniscus regeneration

Meniscal injury, a prevalent and challenging medical condition, is characterized by poor self-healing potential and a complex microenvironment. Tissue engineering scaffolds, particularly those made of silk fibroin (SF)/hyaluronic acid methacryloyl (HAMA) and encapsulating Mg2+, are promising options for meniscal repair. However, the inflammatory response following implantation is a significant concern. In this study, we prepared a composite SF/HAMA-Mg hydrogel scaffold, evaluated its physical and chemical properties, and detected its fibrochondrogenic differentiation effect in vitro and the healing effect in a rabbit meniscus defect model in vivo. Our results showed that the scaffold differentiates pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages after implantation, thereby reducing inflammation and facilitating the growth and repair of meniscus tissue. Further, the composite scaffold provided a conducive milieu for cell proliferation, anticipatory differentiation, and generation of extracellular matrix. In summary, composite SF/HAMA-Mg scaffolds exhibit exceptional biocompatibility and anti-inflammatory properties, demonstrating superior potential for meniscal repair.