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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 2 ) and zirconia (ZrO 2 ) particles in macrophages regarding their nature/particle concentration over time under sterile lipopolysaccharide (LPS) inflammation. Macrophages were exposed to TiO 2 and ZrO 2 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 TNF-  α , IL-1  β and IL-6 was evaluated by qRT-PCR. Data were analyzed using Student's t -test and ANOVA ( p ≤ 0.05). Cytotoxicity was significantly increased when exposed to higher concentrations of glass, TiO 2 and ZrO 2 (≥10 7 particles/mL) compared to controls ( p ≤ 0.05). Macrophages challenged with TiO 2 particles expressed up to ≈3.5-fold higher upregulation than ZrO 2 from 12 to 48 h. However, when exposed to LPS, TiO 2 and ZrO 2 particle-induced pro-inflammatory gene expression was further enhanced ( p ≤ 0.05). Our data suggest that ZrO 2 particles produce less toxicity/inflammatory cytokine production than TiO 2 . The present study shows that the biological reactivity of TiO 2 and ZrO 2 depends on the type and concentration of particles in a time-dependent manner.

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Effect of Titanium and Zirconium Oxide Microparticles on Pro-Inflammatory Response in Human Macrophages under Induced Sterile Inflammation: An In Vitro Study