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 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) was used as a model material of Si‐based biomaterials. It showed that the supernatant of CD4+ T lymphocytes 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 lymphocytes. This might 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 revealed that MS particles significantly enhanced 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. Our study suggests that modulation of the adaptive immune response of T lymphocytes by Silicate‐based biomaterials plays an important role for bone regeneration.This article is protected by copyright. All rights reserved

The foreign body response: emerging cell types and considerations for targeted therapeutics

“…Xia et al found a higher proportion of Th17 cells in mice receiving an implant of mesoporous silica particles, relative to the control group at 2 weeks, but found no differences at 4 weeks. 59 Hotchkiss et al profiled the T-helper cells around titanium implants in the femur of mice and found, in contrast to the previously cited studies, a reduced presence of Th17 cells around the implant relative to sham at 3 days. However, there were fewer differences by day 7.…”

“…Most studies, however, only study the FBR in the context of one sex. Some studies are performed only in female mice, 19,98 while others use male mice 59,60 without explaining why a specific sex was chosen. Given that sex differences can affect immune responses, an essential outcome in future studies will be to compare the FBR in both sexes.…”