Gd@C₈₂(OH)₂₂ harnesses inflammatory regeneration for osteogenesis of mesenchymal stem cells through JNK/STAT3 signaling pathway

Tissue injuries are inevitably accompanied with immune responses. Understanding the effects of biomaterials on immunology regulation is critical for biomaterial development and tissue regeneration. Inflammatory cytokines secreted from macrophages promote the migration of mesenchymal stem cells (MSCs) to the damaged tissue sites and their subsequent participation in tissue repair. However, the effects of inflammatory cytokines caused by tissue injury on MSC behaviors urgently need to be revealed. Understanding and subsequently manipulating the interactions between immune cells and stem cells will provide us with new therapeutic strategies for tissue regeneration. Nanoparticles having immunomodulatory properties can modulate MSCs' functions in the inflammatory microenvironment. In this study, an immunomodulatory nanoparticle Gd@C₈₂(OH)₂₂ was used to manipulate MSC differentiation in inflammatory microenvironment. The results suggested that macrophage-derived inflammation induces osteogenic differentiation of MSCs by activating the JNK/STAT3 pathway. Gd@C₈₂(OH)₂₂ modulates inflammation-induced differentiation of MSCs in a dose-dependent manner through the JNK/STAT3 pathway. Low concentration of Gd@C₈₂(OH)₂₂ facilitates osteogenesis and high concentration suppresses osteogenesis of hMSCs in the inflammatory microenvironment. This study suggests that Gd@C₈₂(OH)₂₂ can act as a promising immunomodulator to differentiate stem cells and improve stem cell-based therapeutic efficiency for biomedical regeneration in inflammatory microenvironments.