There are many studies concerning titanium dioxide (TiO₂) nanoparticles (NP) toxicity. Nevertheless, there are few publications comparing in vitro and in vivo exposure, and even less comparing air–liquid interface exposure (ALI) with other in vitro and in vivo exposures. The identification and validation of common markers under different exposure conditions are relevant for the development of smart and quick nanotoxicity tests. In this work, cell viability was assessed in vitro by WST-1 and LDH assays after the exposure of NR8383 cells to TiO₂ NP sample. To evaluate in vitro gene expression profile, NR8383 cells were exposed to TiO₂ NP during 4 h at 3 cm² of TiO₂ NP/cm² of cells or 19 μg/mL, in two settings—submerged cultures and ALI. For the in vivo study, Fischer 344 rats were exposed by inhalation to a nanostructured aerosol at a concentration of 10 mg/m³, 6 h/day, 5 days/week for 4 weeks. This was followed immediately by gene expression analysis. The results showed a low cytotoxic potential of TiO₂ NP on NR8383 cells. Despite the absence of toxicity at the doses studied, the different exposures to TiO₂ NP induce 18 common differentially expressed genes (DEG) which are involved in mitosis regulation, cell proliferation and apoptosis and inflammation transport of membrane proteins. Among these genes, we noticed the upregulation of Ccl4, Osm, Ccl7 and Bcl3 genes which could be suggested as early response biomarkers after exposure to TiO₂ NP. On the other hand, the comparison of the three models helped us to validate the alternative ones, namely submerged and ALI approaches.

Titanium dental implants have common clinical applications due to their biocompatibility, biophysical and biochemical characteristics. Although current titanium is thought to be safe and beneficial for patients, there are several indications that it may release toxic metal ions or metal nanoparticles from its alloys into the surrounding environment, which could lead to clinically relevant complications including toxic reactions as well as immune dysfunctions. Hence, an adequate selection and testing of medical biomaterial with outstanding properties are warranted. This study was designed to explore the biocompatibility of smooth titanium-niobium alloy (S_TiNb) versus smooth titanium commercially pure (S_TiCp)—a reference in implantology. All experiments were performed in vitro using human osteoblast-like SaOs-2 and monocyte THP-1 cell lines as models. Cell adhesion and growth morphology were determined by scanning electron microscopy, while cell viability was evaluated using WST-1 assay. Because niobate anions or niobium nanoparticles can be released from implants during biomaterial-cell interaction, potential immunotoxicity of potassium niobate (KNbO₃₎ salt was evaluated by examining both metabolic activity and transcriptomic profiling of treated THP-1 monocytes. The main findings of this study are that S_TiCp and S_TiNb discs do not show an impact on the proliferation and viability of SaOs-2 cells compared to polystyrene surfaces, whereas a significant decrease in THP-1 cells’ viability and metabolic activity was observed in the presence of S_TiNb discs compared to the control group. However, no significant changes were found neither at the metabolic activity nor at the transcriptomic level of THP-1 monocytes exposed to KNbO₃ salt, suggesting that niobium has no effect on the immune system. Overall, these data imply a possible toxicity of S_TiNb discs toward THP-1 cells, which may not be directly related to niobium but perhaps to the manufacturing process of titanium-niobium alloy. Thus, this limitation must be overcome to make titanium alloy an excellent material for medical applications.

Oncotarget | https://doi.org/10.18632/oncotarget.25509 Wanyin Chen, Leonel Nguekeu Zebaze, Jihu Dong, Laëtitia Chézeau, Perrine Inquimbert, Sylvain Hugel, Songlin Niu, Fréderic Bihel, Emmanuel Boutant, Eléonore... WNK1 kinase and its partners Akt, SGK1 and NBC-family Na+/HCO3– cotransporters are potential therapeutic targets for glioblastoma stem-like cells linked to Bisacodyl signaling