Enhanced osteogenic differentiation of BMSCs and M2-phenotype polarization of macrophages on a titanium surface modified with graphene oxide for potential implant applications

Abstract

Osseointegration at the bone–implant interface is a complex biological process that is triggered by the immune-inflammatory response and mediated by various cell types such as, bone-forming cells and immune cells, especially macrophages. The polarization of macrophages to inflammatory/regenerative (M1/M2) phenotypes, as well as the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) at the bone–implant interface, significantly affects implant osseointegration and even causes implant failure. Graphene oxide (GO) is a promising candidate for performing implant surface functionalization to modulate the interactions between implants and cells. Herein, we explored the effects of a GO coating on the osteogenic differentiation of BMSCs and the polarization of macrophages to enhance the application of GO surface modification in improving bone–implant integration. In the present study, a large particle sandblasting and acid etching (SLA) surface that is commonly used in clinical practice was selected as the control group, and GO was deposited on the SLA surface by the ultrasonic atomization spraying technique. The surface characteristics of these two groups, including the surface morphology, roughness, wettability, protein adsorption capacity and cell compatibility, were assessed. Then, the effects of GO surface modification on the osteogenic differentiation of BMSCs and the polarization of macrophages were evaluated. The results showed that the GO coating was successfully fabricated on the titanium substrates, which endowed the SLA surface with improved hydrophilicity and protein adsorption capacity and reduced roughness. Compared with the SLA surface, the GO-modified surface significantly enhanced the osteogenic differentiation of BMSCs and the M2-phenotype polarization of macrophages in vitro. This dual-regulatory role is of great significance in achieving rapid osseointegration as well as resolving the poor osseointegration associated with macrophage-related inflammation.