The Immunomodulatory Effects Of Magnesium-doped Titanium

Titanium and its alloys are commonly used in implantable medical devices because of their good biocompatibility and desirable physical properties,such as their low modulus,good corrosion resistance,and high fatigue strength.However,the undesirable inflammation caused by the implant itself and injuries following the surgical procedure of implantationlimited its further application.The inflammation will lead togranulation tissue development,foreign body reaction,and fibrouscapsule formation,which impairs the tissue regeneration and integration between the adjacent tissue and implantsor even cause the implant failure.Macrophages play a critical role in host reactions following the insertion of biomaterials.Modulating the host immune response to biomaterials through changing macrophage polarization has been proven to be a promising strategy to elicit beneficial outcomes in tissue repair.Magnesium(Mg)as the second-most abundant divalent cation in cellular systemsplays important roles in the immune system,in both innate andacquired immune response,also known as nonspecific and specific immune response.Mg also exerts an anti-inflammatory effect which is used clinically for multiple purposes.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 in vitro.Genes encoding two growth factors,bone morphogenetic protein 2(BMP2)and vascular endothelial growth factor(VEGF)were found up-regulated,thus indicating the ability of the M2 phenotype to promote wound healing.The nuclear factor κB(NF-κB)signalling pathway was found to be involved in the immunomodulatory effects of Mg PIII treatment.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 elicitthe pro-healing M2-polarized macrophage phenotype,thus providing new insight into the development of immunomodulatory biomaterials.