Surface-based modified 3D-printed BG/GO scaffolds promote bone defect repair through bone immunomodulation

Abstract

Successful bone defect repair requires a favorable immunomodulation. Macrophages are among the frontline cells activated after biomaterial implantation, and biomaterials play a role in the final determination of their fate. The surface properties of biomaterials such as roughness and hydrophilicity can activate macrophages to have an anti-inflammatory phenotype for improving tissue regeneration. Because of its known characteristics, graphene oxide (GO) is widely used in the biomaterials field. GO directly promotes stem cell proliferation and osteogenic differentiation, properties that have been extensively investigated. The aim of this study is to research the effects of the surface-based modified three-dimensional (3D) porous bioactive glass (BG)/GO scaffolds on macrophage activation and bone regeneration. In vivo, compared with the control group receiving BG with a relatively smooth surface, the group receiving the porous implant showed a decreased proinflammatory response in the skin around the implant with increasing GO density, and the 3D porous implant was covered with new bone tissue. In vitro, both Raw264.7 cells and rat bone marrow mesenchymal stem cells (rBMSCs) can adhere and stretch well on rough, hydrophilic BG/GO scaffolds. When Raw264.7 cells were cultured on scaffolds, GO significantly promoted the polarization of M0 macrophages to the M2 type to a certain extent and further promoted the secretion of osteogenic and angiogenic factors, enhancing the osteogenic differentiation of rBMSCs and the angiogenesis of endothelial cells. Further experiments showed that the rough hydrophilic surface of BG/GO might lead to the upregulation of the surface-dependent WNT-3A protein induced by the enhancement of integrin signalling and the accumulation and activation of β-catenin protein in cells. However, excessive content of GO has the opposite regulatory result. These results demonstrate that BG/GO biomaterials with surface-based modification play an important role in bone repair by adjusting the response of macrophages to biomaterials through their surface properties.