In vitro and in vivo responses of macrophages to magnesium-doped titanium

Modulating immune response to biomaterials through changing macrophage polarization has been proven to be a promising strategy to elicit beneficial outcomes in tissue repair. The objective of this study was to evaluate the response of macrophage polarization to titanium doped with magnesium (0.1~0.35%), which was prepared through the magnesium plasma immersion ion implantation (Mg PIII) technique. The M1/M2 polarization profile of macrophages was investigated using a murine cell line RAW 264.7 in vitro and a murine air pouch model in vivo. Our results demonstrated that the Mg PIII-treated titanium induced a higher percentage of M2 macrophages and higher concentrations of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10. Genes encoding two growth factors, bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) were up-regulated, thus indicating the ability of the M2 phenotype to promote wound healing. The nuclear factor κB (NF-κB) signalling pathway was down-regulated. In vivo the Mg PIII -treated titanium elicited a similar effect on macrophage polarization and induced thinner fibrous capsule formation and a decrease in infiltrated cells. These results indicate that Mg PIII treatment has the immunomodulatory potential to elicit the pro-healing M2-polarized macrophage phenotype, thus providing new insight into the development of immunomodulatory biomaterials.