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

Abstract

Silicon (Si)-based biomaterials have been widely applied for bone regeneration. However, the underlying mechanisms remain unknown. T lymphocyte-mediated adaptive immune response plays a vital role in the process of bone regeneration. In the present study, mesoporous silica (MS) was used as a model material of Si-based biomaterials. It showed that the supernatant of CD4 + T cells pretreated with MS extract significantly promoted the vascularized bone regeneration. The potential mechanism is closely related to the fact that MS extract could reduce the expression of regulatory factor X-1 (RFX-1) in CD4 + T cells, which could lead to interleukin-17A (IL-17A) overexpression through increased histone H3 acetylation and decreased DNA methylation and H3K9 trimethylation. Importantly, the in vivo experiments further revealed that MS particles dramatically stimulated 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.