The Cu-containing TiO2 coatings with modulatory effects on macrophage polarization and bactericidal capacity prepared by micro-arc oxidation on titanium substrates.

The implant materials with both osteogenic and anti-bacterial properties are promising for orthopedic and dental applications. Moreover, the inflammatory response induced by biomaterials has been recently recognized as one of the critical factors in determining implantation fate. A new generation of implant materials should have modulatory effects on the local inflammatory environment such that it favors osteogenesis and osteointegration instead of being bio-inert. In this study, the micro-arc oxidation (MAO) technique was employed to fabricate Cu-containing ceramic coatings on titanium substrates. The macrophages cultured on Cu-containing MAO-fabricated surfaces were polarized to M1 phenotype, evidenced by the high expression levels of inducible nitric oxide synthase (iNOS), low expression levels of arginase1 (Arg1), enhanced pro-inflammatory cytokine interleukin-6 (IL-6) release and inhibited IL-4 and IL-10 (anti-inflammatory cytokines) release. The MAO-treated surface incorporated with larger amounts of Cu (referred as Cu(h)-MAO) could modulate a favorable inflammatory microenvironment for osteoblast-like cell differentiation. Moreover, the macrophages cultured on Cu(h)-MAO surface exhibited enhanced bacteria uptake and killing rate, indicating that the Cu(h)-MAO surface promoted the bactericidal capacity of macrophages. Together, Cu could be used as a promising modulatory agent for macrophage functions. The integration of Cu in biomaterials could lead to enhanced macrophage-mediated osteogenesis and bactericidal capacity.