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

Liza L Ramenzoni,Patrick R Schmidlin,Laura B Flückiger,Thomas Attin

doi:10.3390/ma14154166

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.

Highlights

Dental implants have been a breakthrough healthcare solution since their invention by Brånemark in the 1960s, and are currently a worldwide standard treatment for partial or total tooth loss [1,2,3]
To investigate the influence of different concentrations of TiO2, ZrO2 and inert glass microparticles on cell viability, we determined the cytotoxicity of these particles in various particle concentrations of, and particles/mL using the MTT assay on the cultures of phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells
After 12, 24 and 48 h of exposure, macrophage viability was significantly reduced when exposed to higher concentrations of TiO2 and ZrO2 particles (≥107 ) compared to the untreated negative controls and glass (p < 0.05)

Summary

Introduction

Dental implants have been a breakthrough healthcare solution since their invention by Brånemark in the 1960s, and are currently a worldwide standard treatment for partial or total tooth loss [1,2,3]. Dental implant use on edentulism treatment routinely presents a success rate of more than 90% [4,5,6]. Peri-implantitis prevalence has been rising on account of mucosa biofilm-related inflammation and alveolar bone dismantling [7,8]. Peri-implantitis prevalence rates typically range from 11% to 53%. Immunopathological events that regulate peri-implantitis development were shown to closely mirror those of periodontitis, and even oral bacterial species were found to have strong similarities to periodontitis [16,17]. Peri-implantitis or mucositis may occur on account of previously well-established risk factors, such as smoking, non-controlled type 2 diabetes mellitus, lack of oral hygiene or maintenance, history of periodontitis and obesity [18,19]

Methods

Results

Conclusion