Reduced inflammatory response by incorporating magnesium into porous TiO₂ coating on titanium substrate

The implant materials with proper anti-inflammatory and osteogenic properties may be promising for orthopedic applications. The inflammatory response induced by biomaterials has been regarded as one of the critical factors in determining in vivo fate of implants. Therefore, a novel bone biomaterial should have inflammation regulatory effects instead of being completely bio-inert. In the present work, the inflammation regulatory effects of exogenous magnesium (Mg) ions were investigated. Under the stimulation of lipopolysaccharide (LPS), macrophages exposed to Mg²⁺ exhibited down-regulated gene expressions of M1 markers (CD86, CD11c and inducible nitric oxide synthase (iNOS)) and pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β), up-regulated gene expression of M2 marker CD163 and decreased TNF-α release, indicating that Mg²⁺ could switch macrophages from M1 to M2 phenotype. Thereafter, micro-arc oxidation (MAO) technique was employed to fabricate Mg-containing ceramic coatings on titanium substrates. Macrophages grown on Mg-containing surface were switched from M1 to M2 phenotype with the stimulation of LPS, evidenced by suppressed gene expressions of M1 markers (CD86, CD11c and iNOS) and pro-inflammatory cytokines (TNF-α and IL-1β), promoted gene expression of M2 marker CD163 and decreased TNF-α release. Moreover, gene expressions of bone morphogenetic protein-2 (BMP-2), BMP-6 and vascular endothelial growth factor (VEGF) were up-regulated on Mg incorporated MAO surface without LPS stimulation. Together, Mg could be used as an anti-inflammatory agent for suppressing inflammation and mediating osteogenesis. The integration of Mg in biomaterials could endow bone biomaterials with anti-inflammatory property.