Impact of the chemical composition of poly-substituted hydroxyapatite particles on the in vitro pro-inflammatory response of macrophages

International audienceTo improve the biological properties of calcium phosphate (CaP) bone substitute, new chemical compositions are under development. In vivo such materials are subject to degradation that could lead to particles release and inflammatory reactions detrimental to the bone healing process. This study aimed at investigating the interactions between a murine macrophage cell line (RAW 264.7) and substituted hydroxyapatite particles presenting promising biological properties. Micron size particles of stoichiometric and substituted hydroxyapatites (CO 3 substitution for PO 4 and OH; SiO 4 substitution for PO 4; CO 3 and SiO 4 co-substitution) were obtained by aqueous precipitation followed by spray drying. Cells, incubated with four doses of particles ranging from 15 to 120 µg/mL, revealed no significant LDH release or ROS production, indicating no apparent cytotoxicity and no oxidative stress. TNF-α production was independent of the chemistry of the particles; however the particles elicited a significant dose-dependent pro-inflammatory response. As micron size particles of these hydroxyapatites could be at the origin of inflammation, attention must be paid to the degradation 2 behavior of substituted hydroxyapatite bone substitute in order to limit, in vivo, the generation of particulate debris

Metals distribution in colorectal biopsies: New insight on the elemental fingerprint of tumour tissue

International audienceBackground: Colorectal cancer is considered to be an environmental disease. In this context, the study of environmental risk factors associated with the presence of chemical elements is important, as well as improving our knowledge of the elemental fingerprint of tumor tissuecompared to non-cancer tissue.Aims: The objective was to evaluate the element distribution in colorectal adenocarcinoma biopsies, adjacent non-tumor tissues, and healthy controls (non-cancer colorectal biopsies including occlusion or ischemic colons).Methods: The study is a case-control study which compared the element distribution in colon biopsies from two groups of patients: with colorectal cancer and without colorectal cancer. Patients with colorectal cancer provided 2 different groups of samples: colorectal cancer biopsies and adjacent non-tumor tissues. 15 metal concentrations (Al, B, Cd, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Se, Si, Ti, V, and Zn) in colorectal biopsies were quantified by using acid digestion procedures and then inductively coupled plasma (ICP) atomic emission spectrometry.Results: A total of 104 patients were included. 76 patients in the colorectal cancer group (i.e. tumor and adjacent non-tumor tissues) and 28 patients in the healthy control group (i.e. noncancer colorectal biopsies). Among the 15 elements analyzed by ICP spectrometry, only boron, chromium, zinc, silicon, and magnesium were found in colorectal tissue at clearly detectable concentrations. Our data indicated that colorectal tumor biopsies have significantly elevated concentrations of magnesium as compared to adjacent non-tumor or healthy tissues. Zinc concentration followed the same trend but differences were not statistically significant. In addition, silicon appears to be more accumulated in colorectal cancer tissue than in healthy non-cancer tissue, while chromium was mostly found in adjacent non-tumor tissue. Conclusion: Magnesium, chromium, zinc and silicon were found in noteworthy concentrations in colorectal tumor. Their potential role in colorectal carcinogenesis should be explored

Impact of cerium oxide nanoparticles shape on their in vitro cellular toxicity

International audienceCerium oxides (CeO2) nanoparticles, also referred to as nanoceria, are extensively used with a wide range of applications. However, their impact on human health and on the environment is not fully elucidated. The aim of this study was to investigate the influence of the CeO2 nanoparticles morphology on their in vitro toxicity. CeO2 nanoparticles of similar chemical composition and crystallinity were synthesized, only the shape varied (rods or octahedrons/cubes). Macrophages from the RAW264.7 cell line were exposed to these different samples and the toxicity was evaluated in terms of lactate dehydrogenase (LDH) release, Tumor Necrosis Factor alpha (TNF-α) production and reactive oxygen species (ROS) generation. Results showed no ROS production, whatever the nanoparticle shape. The LDH release and the TNF-α production were significantly and dose-dependently enhanced by rod-like nanoparticles, whereas they did not vary with cubic/octahedral nanoparticles. In conclusion, a strong impact of CeO2 nanoparticle morphology on their in vitro toxicity was clearly demonstrated, underscoring that nanoceria shape should be carefully taken in consideration, especially in a “safer by design” context

Biocéramique en hydroxyapatite carbo-silicatée: synthèse, élaboration et étude de biocompatibilité in vitro

National audienc

End-of-life incineration of nanocomposites: new insights on nanofillers partitioning into by-products and biological outcomes of airborne emission and residual ash

International audienceSince the recycling of nanocomposites is limited, nanofillers will inevitably enter the waste stream. To date, the major end-of-life scenario of nanocomposites is their incineration. This process can strongly affect the pristine physico-chemical features of nanofillers inducing a potential alteration of their initial toxicity. Besides, the partitioning of nanofillers into the subsequent formation of by-products (i.e. airborne emission and residual ash from the incineration of nanocomposites) remains uncertain. Through laboratory-scale incineration of nanocomposites (an ethylene vinyl acetate matrix incorporating silica, alumina or boehmite nanofillers), we assessed in vitro the potential hazard of the released particulate matter (PM) in combustion exhaust and of the resulting bottom ash. We also fully characterized the physico-chemical and morphological properties of associated by-products. Our findings demonstrated that the partitioning of nanofillers is mainly into residual ash rather than into combustion aerosol. Our results also showed that the hazard profile of the PM seems mainly governed by the intrinsic hazard profile of the host polymer matrix, while the hazard profile of the residual ash seems mainly governed by the intrinsic hazard profile of the pristine nanofillers. Even if the results can depend on the nanofiller chemistry and loading as well as the polymer composition of the matrix, we support the conclusion that a key safety priority to be addressed on the incineration of nanocomposites is to more deeply investigate the potential physico-chemical transformations of nanoparticles in slags and the hazard assessment of residual ash

Filtration efficiency of medical and community face masks using viral and bacterial bioaerosols

Abstract Face masks are often recommended in community settings to prevent the airborne transmission of respiratory viruses or bacteria. Our first objective was to develop an experimental bench to assess the viral filtration efficiency (VFE) of a mask with a methodology similar to the normative measurement of bacterial filtration efficiency (BFE) used to determine the filtration performance of medical masks. Then, using three categories of masks of increasing filtration quality (two types of community masks and one type of medical mask), filtration performances measured ranged from 61.4 to 98.8% of BFE and from 65.5 to 99.2% of VFE. A strong correlation (r = 0.983) between bacterial and viral filtration efficiency was observed for all types of masks and for the same droplets size in the 2–3 µm range. This result confirms the relevance of the EN14189:2019 standard using bacterial bioaerosols to evaluate mask filtration, to also extrapolate mask performances whatever their filtration quality against viral bioaerosols. Indeed, it appears that the filtration efficiency of masks (for micrometer droplet sizes and low bioaerosol exposure times) depends mainly on the size of the airborne droplet, rather than on the size of the infectious agent contained in that droplet

Caractérisation des transformations physico-chimiques de nanocomposites après incinération et conséquences biologiques des émissions

International audienceAccording to the 2016 OECD report “Nanomaterials in waste streams”, 30 % of waste is incinerated. This process can strongly affect the physical and chemical properties of any nanoparticles in the waste matter, possibly modifying their initial toxicity. Little is known about the spread of nanoparticles in the resulting by-products (smoke and residues from the incineration of the nanomaterials). In the Nano Tox’in project, nanomaterials were incinerated in a laboratory with a two-fold aim: to study their physical and chemical properties and their by-products in detail, and to assess the impact on the in vitro toxicity of the transformation of the nanomaterials’ initial nanoparticles into released particulate matter (PM) in aerosols and in the residues (ash). We showed that the nanoparticles were mainly concentrated in the ash. Our results also confirmed that the toxicological profile of the PM is directly related to the toxicity of the polymer matrix host, while that of the ash seems directly linked to the intrinsic toxicity of the nanoparticles. The size, chemistry, and rate of nanoparticles along with the nature of the matrix therefore affect the in vitro toxicity. The new project, NanoDetox, will enable us to study the impact of mixed waste (representing the waste streams) and assess the physical and chemical transformations and the effects of synergies and antagonisms of nanoparticles on the in vitro toxicity of soot and/or ash.Dans le rapport de l’Organisation de coopération et de développement économiques (OCDE) de 2016 intitulé Nanomaterials in waste streams, 30 % des déchets sont incinérés. Ce processus peut affecter fortement les caractéristiques physico-chimiques de nanoparticules, éventuellement présentes dans ces déchets, induisant une modification potentielle de leur toxicité initiale. La répartition des nanoparticules dans les sous-produits formés (fumées et résidus provenant de l’incinération des nanocomposites) reste incertaine. Dans le projet Nano Tox’in, des nanocomposites ont été incinérés à l’échelle de laboratoire. Les objectifs étaient de faire une étude complète des propriétés physico-chimiques et des sous-produits associés et d’évaluer l’impact sur la toxicité in vitro de la transformation des nanoparticules initiales des nanocomposites en particules libérées (particles matter [PM]) dans les aérosols et dans les résidus (mâchefers). Nous avons pu montrer que les nanoparticules étaient principalement concentrées dans les mâchefers. Nos résultats ont également confirmé que le profil toxicologique des PM est directement régi par la toxicité de la matrice polymère hôte, tandis que celui des mâchefers semble directement lié à la toxicité intrinsèque des nanoparticules. La taille, la chimie et le taux des nanoparticules ainsi que la nature de la matrice ont donc un impact sur la toxicité in vitro. Le nouveau projet, NanoDetox, va nous permettre d’étudier l’impact des mélanges de déchets (représentatif de flux de déchets) et d’évaluer les transformations physico-chimiques ainsi que les effets de synergies/antagonismes liés aux nanoparticules sur la toxicité in vitro des suies et/ou les mâchefers

Nano to micron-sized particle detection in patients' lungs and its pathological significance

International audienceMineralogical analyses of clinical samples have been proven useful to identify a causal relationship between exposure to airborne particles and pulmonary diseases. However, this type of analysis only considers the micron-sized fraction of the particles, neglecting the specific impact of submicron/nano-sized particles which have been otherwise shown to be reactive and able to induce biological effects. To fill this gap, we previously developed an innovative protocol to isolate micron-sized particles from submicron/nano-sized particles contained in 100 bronchoalveolar lavage (BAL) and bronchial washing (BW) samples from patients who suffered from interstitial lung diseases (ILDs) (NanoPI, ClinicalTrials.gov Identifier: NCT02549248). We then determined qualitatively and quantitatively the metal load in each of these fractions. The aim of the present paper is to investigate correlations between these mineralogical analyses and clinical data. The mean concentration of submicron silica particles was found to be significantly higher in the BAL and BW samples from patients suffering from sarcoidosis than those from patients suffering from other ILDs (501 vs. 246 ng mL−1 for BAL and 564 vs. 292 ng mL−1 for BW, respectively). This finding suggests a potential role of submicron silica particles in the etiology of sarcoidosis and highlights the usefulness of comprehensive mineralogical analyses to obtain new insights into the role of inhaled biopersistent particles in lung diseases

Metal load assessment in patient pulmonary lavages: towards a comprehensive mineralogical analysis including the nano-sized fraction

International audienc

Impact of power level and refill liquid composition on the aerosol output and particle size distribution generated by a new-generation e-cigarette device

The new high-power Electronic Nicotine Delivery System (ENDS) can generate aerosols with higher nicotine concentrations than older ENDS . Aerosol particle sizes affect deposition patterns and then plasma nicotine levels in vapers. Consequently, understanding the factors influencing particle size distribution of high-power ENDS is relevant to assess their performance in terms of nicotine delivery. The particle size distribution and the aerosol output (aerosol mass) were measured using cascade impactors. The effects of the refill liquid composition (80% PG/20% VG vs. 80% VG/20% PG; PG refers to propylene glycol and VG to vegetable glycerin) and the power level of the battery (from 7 W to 22 W) were investigated. The aerosol output increases significantly with the power level following a logarithmic law. The PG/VG ratio also has an impact on the aerosol output. The higher the VG content in the refill liquid, the higher is the aerosol output. Besides, particle size distribution is positively related to the power level, following linear correlations between the mass median aerodynamic diameter (MMAD) and the power level in the range of 7-22 W. A moderate impact of the PG/VG ratio on size distribution is equally observed. Changes in the power level allow the transition between a dominant mode with MMAD from 613 nm to 949 nm. We demonstrated that the power level can strongly change the aerodynamic properties of high-power ENDS, especially at high voltage. Associated with the aerosol nicotine level assessment, MMAD could be determined as a means for comparing ENDS devices and nicotine delivery