| Summary: | The wear-debris particles released by shearing forces during dental implant insertion may contribute to inflammatory reactions or osteolysis associated with peri-implantitis by stimulating inflammasome-activation. The study aim was to examine cytotoxic and pro-inflammatory effects of titanium (TiO<sub>2</sub>) and zirconia (ZrO<sub>2</sub>) particles in macrophages regarding their nature/particle concentration over time under sterile lipopolysaccharide (LPS) inflammation. Macrophages were exposed to TiO<sub>2</sub> and ZrO<sub>2</sub> particles (≤5 µm) in cell culture. Dental glass was used as inert control and LPS (1 μg/mL) was used to promote sterile inflammation. Cytotoxicity was determined using MTT assays and cytokine expression of <i>TNF-</i><i>α</i>, <i>IL-1</i><i>β</i> and <i>IL-6</i> was evaluated by qRT-PCR. Data were analyzed using Student’s <i>t</i>-test and ANOVA (<i>p</i> ≤ 0.05). Cytotoxicity was significantly increased when exposed to higher concentrations of glass, TiO<sub>2</sub> and ZrO<sub>2</sub> (≥10<sup>7</sup> particles/mL) compared to controls (<i>p</i> ≤ 0.05). Macrophages challenged with TiO<sub>2</sub> particles expressed up to ≈3.5-fold higher upregulation than ZrO<sub>2</sub> from 12 to 48 h. However, when exposed to LPS, TiO<sub>2</sub> and ZrO<sub>2</sub> particle-induced pro-inflammatory gene expression was further enhanced (<i>p</i> ≤ 0.05). Our data suggest that ZrO<sub>2</sub> particles produce less toxicity/inflammatory cytokine production than TiO<sub>2</sub>. The present study shows that the biological reactivity of TiO<sub>2</sub> and ZrO<sub>2</sub> depends on the type and concentration of particles in a time-dependent manner.
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