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

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-1β 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.