Identification of the safe(r) by design alternatives for nanosilver-enabled wound dressings

The use of silver nanoparticles (NPs) in medical devices is constantly increasing due to their excellent antimicrobial properties. In wound dressings, Ag NPs are commonly added in large excess to exert a long-term and constant antimicrobial effect, provoking an instantaneous release of Ag ions during their use or the persistence of unused NPs in the wound dressing that can cause a release of Ag during the end-of-life of the product. For this reason, a Safe-by-Design procedure has been developed to reduce potential environmental risks while optimizing functionality and costs of wound dressings containing Ag NPs. The SbD procedure is based on ad-hoc criteria (e.g., mechanical strength, antibacterial effect, leaching of Ag from the product immersed in environmental media) and permits to identify the best one among five pre-market alternatives. A ranking of the SbD alternatives was obtained and the safer solution was selected based on the selected SbD criteria. The SbD framework was also applied to commercial wound dressings to compare the SbD alternatives with products already on the market. The iterative procedure permitted to exclude one of the alternatives (based on its low mechanical strength) and proved to be an effective approach that can be replicated to support the ranking, prioritisation, and selection of the most promising options early in the innovation process of nano-enabled medical devices as well as to encourage the production of medical devices safer for the environment

Guiding the development of sustainable nano-enabled products for the conservation of works of art: proposal for a framework implementing the Safe by Design concept

Nanotechnology provides innovative and promising solutions for the conservation of cultural heritage, but the development and application of new nano-enabled products pose concerns regarding their human health and environmental risks. To address these issues, we propose a sustainability framework implementing the Safe by Design concept to support product developers in the early steps of product development, with the aim to provide safer nano-formulations for conservation, while retaining their functionality. In addition, this framework can support the assessment of sustainability of new products and their comparison to their conventional chemical counterparts if any. The goal is to promote the selection and use of safer and more sustainable nano-based products in different conservation contexts. The application of the proposed framework is illustrated through a hypothetical case which provides a realistic example of the methodological steps to be followed, tailored and iterated along the decision-making process

Interaction between copper oxide nanoparticles and amino acids: Influence on the antibacterial activity

The increasing concern about antibiotic-resistance has led to the search for alternative antimicrobial agents. In this effort, different metal oxide nanomaterials are currently under investigation, in order to assess their effectiveness, safety and mode of action. This study focused on CuO nanoparticles (CuO NPs) and was aimed at evaluating how the properties and the antimicrobial activity of these nanomaterials may be affected by the interaction with ligands present in biological and environmental media. Ligands can attach to the surface of particles and/or contribute to their dissolution through ligand-assisted ion release and the formation of complexes with copper ions. Eight natural amino acids (L-Arg, L-Asp, L-Glu, L-Cys, L-Val, L-Leu, L-Phe, L-Tyr) were chosen as model molecules to investigate these interactions and the toxicity of the obtained materials against the Gram-positive bacterium Staphylococcus epidermidis ATCC 35984. A different behavior from pristine CuO NPs was observed, depending on the aminoacidic side chain. These results were supported by physico-chemical and colloidal characterization carried out by means of Fourier-Transform Infrared spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and Thermo-Gravimetric Analysis (TGA), Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and light scattering techniques (Dynamic Light Scattering (DLS), Electrophoretic Light Scattering (ELS) and Centrifugal Separation Analysis (CSA)

Platinum Complexes with a Phosphino-Oxime/Oximate Ligand

The platinum(II) complex [PtCl2(COD)] (2; COD = 1,5- cyclooctadiene) reacted with 1 and 2 equiv. of 2-(diphenylphosphanyl) benzaldehyde oxime (1) to generate [PtCl2{¿2-(P,N)-2- Ph2PC6H4CH=NOH}] (3) and [Pt{¿2-(P,N)-2-Ph2PC6H4CH=NOH}2]- [Cl]2 (4), respectively. Deprotonation of the oxime hydroxyl group of 3 with Na2CO3 led to the selective formation of the dinuclear species (¿-O)-[PtCl{¿2-(P,N)-2-Ph2PC6H4CH=NO}]2 (5), while the related methylated derivative (¿-O)-[PtMe{¿2-(P,N)-2- Ph2PC6H4CH=NO}]2 (7) could be obtained from the direct reaction of [PtMe2(COD)] (6) with the phosphino-oxime ligand 1. In the case of 4, its treatment with Na2CO3 yielded complex [Pt({¿2-(P,N)-2-Ph2PC6H4CH=NO}2H)][Cl] (8), as a result of the deprotonation of only one of the OH groups of 4. On the other hand, contrary to what was observed with 6, no deprotonation of the oxime occurred in the reaction of [PtMe3I]4 (9) with 1, from which the mononuclear PtIV derivative fac-[PtIMe3{¿2-(P,N)- 2-Ph2PC6H4CH=NOH}] (10) was isolated. The solid-state structures of compounds 3, 4, 7 and 10 were determined by X-ray crystallography. In addition, the potential of all the synthesized complexes as catalysts for the dehydrogenative coupling of hydrosilanes with alcohols is also briefly discussed.Peer Reviewe

Dry granular flows – rheological measurements of the μ

Granular materials do not always flow homogeneously like fluids when submitted to external stress, but often form rigid regions that are separated by narrow shear bands where the material yields and flows. This shear localization impacts their apparent rheology, which makes it difficult to infer a constitutive behavior from conventional rheometric measurements. Moreover, they present a dilatant behavior, which makes their study in classical fixed-volume geometries difficult. These features led numerous groups to perform extensive studies with inclined plane flows, which were of crucial importance for the development and the validation of the μ(I)-rheology. Our aim is to develop a method to characterize granular materials with rheometrical tools. Using rheometry measurements in an annular shear cell, dense granular flows of 0.5mm spherical and monodisperse beads are studied. A focus is placed on the comparison between the present results and the μ(I)-rheology

Toxicity of copper oxide and basic copper carbonate nanoparticles after short-term oral exposure in rats

Copper oxide (CuO) nanoparticles (NPs) and copper carbonate nanoparticles (Cu2CO3(OH)(2) NPs have applications as antimicrobial agents and wood preservatives: an application that may lead to oral ingestion via hand to mouth transfer. Rats were exposed by oral gavage to CuO NPs and Cu2CO3(OH)(2) NPs for five consecutive days with doses from 1 to 512 mg/kg and 4 to 128 mg/kg per day, respectively, and toxicity was evaluated at days 6 and 26. Both CuO NPs and Cu2CO3(OH)(2) NPs induced changes in hematology parameters, as well as clinical chemistry markers (e.g. increased alanine aminotransferase, ALT) indicative of liver damage For CuO NPs histopathological alterations were observed in bone marrow, stomach and liver mainly consisting of an inflammatory response, ulceration, and degeneration. Cu2CO3(OH)(2) NPs induced morphological alterations in the stomach, liver, intestines, spleen, thymus, kidneys, and bone marrow. In spleen and thymus lymphoid, depletion was noted that warrants further immunotoxicological evaluation. The NPs showed partial dissolution in artificial simulated stomach fluids, while in intestinal conditions, the primary particles simultaneously shrank and agglomerated into large structures. This means that both copper ions and the particulate nanoforms should be considered as potential causal agents for the observed toxicity. For risk assessment, the lowest bench mark dose (BMD) was similar for both NPs for the serum liver enzyme AST (an indication of liver toxicity), being 26.2 mg/kg for CuO NPs and 30.8 mg/kg for Cu2CO3(OH)(2) NPs. This was surprising since the histopathology evidence demonstrates more severe organ damage for Cu2CO3(OH)(2) NPs than for CuO NPs

Rhéologie des matériaux granulaires non saturés

With this doctoral research, we report on the solid and liquid-like mechanical behaviors of wet granular materials, which exhibit viscous and capillary effects. Such systems, standing between dry and immersed granular materials, are studied both in experiments and discrete numerical simulations, from the microstructural aspects to the mechanical behavior. We therefore adopt a multiscale approach whose purposes are to understand the origins and roles of capillary and viscous effects in constitutive laws and to include a microstructural description within these laws. We are interested in the simple bridge model for the illustration of viscous and capillary effects in the case of quasistatic and inertial flows, where the confining forces, the Coulomb friction and the liquid quantity can vary. To answer such questions, this thesis is articulated around the 3 following topics :- A study based on macroscopic rheological experiments with a simple model material (monodisperse polystyrene beads, wetted with a Newtonian silicon oil) which enables us to distinguish the flow regimes and to characterize the influence of cohesive effects. The experimental framework allows for long time shearing experiments, where the materials can reach their steady state behavior. Alike dry systems, wet granular materials still exhibit a quasistatic and an inertial regime with increasing flow velocity. We show the noticeable influence of capillary effects which strongly increases the shear resistance and reduces the materials density.- X-ray microtomographic experiments enabling the microstructural study of static samples. We witness a good homogeneity of our samples whether slightly or strongly saturated. A non-negligible number of very complex capillary bonds were detected, which stresses, when compared with macroscopic rheological results, their lack of influence on the flow properties. This result is very noticeable as it demonstrates the ability of the simple bridge model to illustrate the behavior of materials which would not be included a priori within its reach.- Discrete numerical simulations allowing us to strongly improve the range of the parameters of the study, especially in the case of material characteristics such as Coulomb friction. The micromechanical study emerging from simulations, allows us to analyze anisotropy, coordination and capillary stresses questions. We underline the great importance of long-range capillary interactions when using an effective stress model. The limits of such model, usually adopted to describe the behavior in the quasistatic regime, are also tested and debated in the inertial regime. The good agreement between numerical and experimental results enabled us to validate and calibrate a numerical model which, in return, offered a reliable analysis of microstructural effects for the understanding of the mechanical behavior and for the transition from the microscopic to the macroscopic scaleNous reportons dans ce travail le comportement mécanique, dans le régime solide et en écoulement, de matériaux granulaires liés par un liquide non saturant, qui intervient par sa viscosité et par des effets capillaires. De tels matériaux, intermédiaires entre les assemblages granulaires secs et les suspensions très concentrées, sont étudiés expérimentalement et par simulations discrètes depuis la microstructure jusqu'au comportement macroscopique. Ainsi, on adopte une démarche multi-échelle, dont l’objectif est d’établir les fondements de la compréhension des phénomènes capillaires et/ou visqueux, qui interviennent dans la formulation de lois de comportement, et d'y intégrer une caractérisation de la microstructure de ces matériaux. Nous nous intéressons notamment au modèle d'interactions capillaire et visqueuse par ponts simples, dans un cadre où l'on fait varier l'inertie, le degré de confinement, le degré de friction du matériau ainsi que la quantité de liquide introduite. Pour répondre à cet objectif, ce travail de thèse s’articule autour des trois volets suivants :- Un travail de rhéologie expérimentale macroscopique sur matériau modèle (billes de polystyrènes monodisperses, mouillées avec une huile de silicone newtonienne) qui nous permet de délimiter des régimes d'écoulement et de caractériser l'influence de l'effet cohésif. Le format expérimental adopté nous permet de cisailler les échantillons sur des temps très longs et d'atteindre des régimes d'écoulement stationnaires. Ainsi, à l'instar des matériaux secs, on retrouve des régimes quasistatiques puis inertiels à mesure que la vitesse d'écoulement augmente. On met aussi en avant une très forte influence de l'effet cohésif qui tend à augmenter drastiquement la résistance au cisaillement et à diminuer la compacité de nos échantillons.- Des expériences de microtomographie à rayons X qui permettent d'étudier la microstructure à l'état statique. On remarque notamment une bonne homogénéité des échantillons, qu'ils soient faiblement ou fortement saturés. On détecte aussi un nombre non-négligeable de morphologies capillaires complexes, ce qui, par comparaison aux résultats de rhéologie macroscopique, ne semble pas influencer les propriétés d'écoulement. Ce résultat est particulièrement intéressant puisqu’il montre la capacité du modèle d’interactions par pont simple à décrire le comportement de systèmes à priori hors de sa portée descriptive.- Des simulations numériques discrètes qui nous permettent d'élargir fortement la gamme de paramètres étudiés, notamment avec des caractéristiques du matériau comme la friction de Coulomb. L'étude micromécanique, permise par les simulations, autorise aussi l'analyse des questions d'anisotropie, de coordination et de contraintes capillaires. On met en avant l'importance des interactions capillaires à distance lors de l'utilisation d'un modèle de contraintes effectives. Les limites de ce modèle, usuellement adapté à la description du comportement en régime quasi-statique, sont aussi testées et discutées dans le régime inertiel. La bonne concordance entre résultats expérimentaux et numériques nous aura permis de valider et calibrer un modèle numérique qui, en retour, aura donc fourni une analyse viable des effets microstructurels pour la compréhension du comportement et la transition de l'échelle microscopique à l'échelle macroscopiqu