Silicon-Based Biomaterials Modulate the Adaptive Immune Response of T Lymphocytes to Promote Osteogenesis/Angiogenesis via Epigenetic Regulation

Silicon (Si)-based biomaterials are widely applied for bone regeneration. However, the underlying mechanisms of the materials function remain largely unknown. T lymphocyte-mediated adaptive immune response plays a vital role in the process of bone regeneration. In the current study, mesoporous silica (MS) is used as a model material of Si-based biomaterials. It shows that the supernatant of CD4+ T lymphocytes pretreated with MS extract significantly promotes the vascularized bone regeneration. The potential mechanism is closely related to the fact that MS extract can reduce the expression of regulatory factor X-1 (RFX-1) in CD4+ T lymphocytes. This may result in the overexpression of interleukin-17A (IL-17A) by boosting histone H3 acetylation and lowering DNA methylation and H3K9 trimethylation. Importantly, the in vivo experiments further reveal that MS particles significantly enhance bone regeneration with improved angiogenesis in the critical-sized calvarial defect mouse model accompanied by upregulation of IL-17A in peripheral blood and the proportion of Th17 cells. This study suggests that modulation of the adaptive immune response of T lymphocytes by silicate-based biomaterials plays an important role for bone regeneration. The extract of mesoporous silica (MS) reduces the expression of regulatory factor X-1 (RFX-1) in CD4+ T lymphocytes, which results in the overexpression of interleukin-17A (IL-17A) and enhances in vivo bone regeneration. These findings suggest that modulation of the adaptive immune response of T lymphocytes by silicate-based biomaterials plays an important role for bone regeneration.image