Macrophage Polarization by Titanium Dioxide (TiO) Particles: Size Matters.

Wear particles of total joint replacements may lead to an inflammatory response driven by cells of the monocyte/macrophage lineage. Today, there is a general agreement that the continuous release of wear particles by the implant has a critical impact on periprosthetic osteolysis, which can eventually lead to aseptic loosening of the implant. The focus of this study lay on the determination of the polarization of macrophages (M0) toward the pro-inflammatory M1 phenotype or the anti-inflammatory M2-like phenotype upon exposure to differently sized TiO particles. The analysis was done with an in vitro model using THP-1 monocytes. It offers a direct characterization of the polarization profile of the macrophages exposed to nano- (<100 nm, measured hydrodynamic diameter: 518.5 nm) and micro- (<5 μm, measured hydrodynamic diameter: 2213 nm) sized TiO particles in different concentrations (4 × 10 -4 × 10 particles/mL). The polarization profile was analyzed by the quantitative assessment of relative gene expression levels as well as by the determination of specific proteins by enzyme linked immunosorbent assay (ELISA). Analysis by qRT-PCR revealed significantly elevated levels of pro-inflammatory markers such as TNF-α and CD197 at the highest concentration of stimulation by the microsized particles. This was confirmed on the protein level in the cytokine expression profile of TNF-α. Furthermore, no significant differences were found for the markers CCL22 and CD206, which are specific for the M2-like phenotype. In contrast, stimulation by nanoparticles did not induce macrophage polarization toward M1 or M2-like phenotype in any applied concentration. We conclude that the size of the particle is a determinant factor in driving the biological response of macrophages and an increased understanding of this relationship may potentially guide the design of new biomaterials.