Calcium silicate enhances immunosuppressive function of MSCs to indirectly modulate the polarization of macrophages

Bioactive silicate ceramics (BSCs) have been widely reported to be able to induce bone tissue regeneration, but the underlying mechanisms have not been fully elucidated. Previous studies have reported that ionic products of BSCs can promote bone regeneration by directly simulating osteogenic differentiation of mesenchymal stem cells (MSCs) and modulating the polarization of macrophages to create a favorable inflammation microenvironment for initiating bone regeneration cascades. However, the immunomodulatory ability of MSCs also plays a critical role in bone regeneration but the effects of BSCs on the immunomodulatory ability of MSCs have been rarely investigated. This study aims to investigate the effects of ionic products of BSCs on the immunoregulatory ability of MSCs to further understand the mechanism of BSCs enhancing bone regeneration. Results showed that ionic products of calcium silicate (CS), one of the representative BSCs, could enhance the immunosuppressive function of human bone marrow mesenchymal stem cells (HBMSCs) by up-regulating the expression of immunosuppressive factors in HBMSCs via NF-κB pathway. In addition, CS-activated HBMSCs showed stronger stimulatory effects on M2 polarization of macrophages than CS ionic products. Furthermore, the macrophages educated by CS-activated HBMSCs showed stronger stimulatory effects on the early osteogenic differentiation of HBMSCs than the ones regulated by CS ionic products. These results not only provide further understanding on the mechanism of BSCs enhancing bone regeneration but also suggest that it is critical to consider the effects of biomaterials on the immunomodulatory function of the tissue forming cells when the immunomodulatory function of biomaterials is investigated.