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Effect of Titanium and Zirconium Oxide Microparticles on Pro-Inflammatory Response in Human Macrophages under Induced
Liza L Ramenzoni1,2, Laura B Flückiger1, Thomas Attin1
1Clinic of Conservative and Preventive Dentistry, Center of Dental Medicine, University of Zurich, 8032 Zurich, Switzerland.
Abstract:
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 (TiO2) and zirconia (ZrO2) particles in macrophages regarding their nature/particle concentration over time under sterile lipopolysaccharide (LPS) inflammation. Macrophages were exposed to TiO2 and ZrO2 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, TiO2 and ZrO2 (≥107 particles/mL) compared to controls (p ≤ 0.05). Macrophages challenged with TiO2 particles expressed up to ≈3.5-fold higher upregulation than ZrO2 from 12 to 48 h. However, when exposed to LPS, TiO2 and ZrO2 particle-induced pro-inflammatory gene expression was further enhanced (p ≤ 0.05). Our data suggest that ZrO2 particles produce less toxicity/inflammatory cytokine production than TiO2. The present study shows that the biological reactivity of TiO2 and ZrO2 depends on the type and concentration of particles in a time-dependent manner.
Insights
Titanium dioxide (TiO2) and zirconia (ZrO2) particles from dental implants can cause inflammation. Zirconia particles showed less toxicity and inflammatory response compared to TiO2 particles in macrophage studies.
Area of Science:
- Biomaterials Science
- Immunology
- Dental Materials
Background:
- Dental implant wear debris can trigger inflammatory responses and osteolysis, potentially leading to peri-implantitis.
- Inflammasome activation by wear particles is a proposed mechanism for these adverse reactions.
- Understanding the differential biological effects of titanium (TiO2) and zirconia (ZrO2) particles is crucial for implant material selection.
Purpose of the Study:
- To investigate the cytotoxic and pro-inflammatory effects of TiO2 and ZrO2 particles on macrophages.
- To evaluate the influence of particle type, concentration, and time on cellular responses.
- To assess particle behavior under sterile inflammation induced by lipopolysaccharide (LPS).
Main Methods:
- Macrophages were cultured and exposed to TiO2 and ZrO2 particles (≤5 µm) at varying concentrations.
- Dental glass served as an inert control, and LPS (1 μg/mL) was used to induce sterile inflammation.
- Cytotoxicity was measured using MTT assays, and pro-inflammatory cytokine gene expression (TNF-α, IL-1β, IL-6) was quantified via qRT-PCR.
Main Results:
- Higher concentrations of TiO2 and ZrO2 particles (≥10^7 particles/mL) significantly increased cytotoxicity compared to controls.
- TiO2 particles induced approximately 3.5-fold higher pro-inflammatory gene upregulation than ZrO2 particles between 12 and 48 hours.
- Exposure to LPS further enhanced the pro-inflammatory gene expression induced by both TiO2 and ZrO2 particles.
Conclusions:
- Zirconia (ZrO2) particles exhibit lower cytotoxicity and induce less pro-inflammatory cytokine production than titanium dioxide (TiO2) particles.
- The biological reactivity of TiO2 and ZrO2 particles is dependent on particle type, concentration, and exposure time.
- These findings have implications for understanding material-related inflammatory responses around dental implants.
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