Titanium surfaces characteristics modulate macrophage polarization.

Monocytes/macrophages are one of the first cell types that interact with dental and orthopedic metallic implants, after which these interactions result in a cascade of events that further determine the bone healing performance around implants. This process was recently indicated to be closely dependent on M1/M2 macrophage phenotypes. However, how clinically related physical and chemical implant surface parameters affect macrophage phenotype is incompletely understood. Here, we created and characterized a series of titanium disks with different surface roughness from the submicron to micron level and provided with or without a hydroxyapatite (HA) coating. Human THP-1 derived macrophages were cultured on these different surfaces along with conventional M1 and M2 macrophage controls on glass slides. Macrophage adhesion and polarization were assessed by DNA content, specific cytokine secretion and gene expression profiling, and immunostaining. The data demonstrated that an HA coating rather than roughness remarkably affected macrophage adhesion. Compared to M1 and M2 macrophage controls, different roughness or an HA-coating led to macrophage polarization into a specific surface-associated state. Interestingly, only a narrow range of roughness (Ra = 0.51-1.36 μm; Sa = 0.66-2.91 μm) tended to polarize adherent macrophages toward M2 phenotype by downregulating pro-inflammatory and upregulating anti-inflammatory cytokine secretion, gene expression and surface marker expression. In contrast, the presence of an HA-coating resulted in a hybrid macrophage subtype with both M1 and M2 characteristics. In conclusion, our data demonstrated that physical and chemical surface properties elicit material-activated macrophage polarization and indicate the potential of using physicochemical surface modifications to steer macrophage response and behavior in support of the success of metallic implants.