Clostridioides difficile Flagella.

Clostridioides difficile is an important pathogen for humans with a lead in nosocomial infection, but it is also more and more common in communities. Our knowledge of the pathology has historically been focused on the toxins produced by the bacteria that remain its major virulence factors. But the dysbiosis of the intestinal microbiota creating the conditions for the colonization appears to be fundamental for our understanding of the disease. Colonization implies several steps for the bacteria that do or do not use their capacity of motility with the synthesis of flagella. In this review, we focus on the current understanding of different topics on the C. difficile flagellum, ranging from its genetic organization to the vaccinal interest in it.

Impact of lock solutions on the mechanical performance of polyurethane central venous catheters: A comparative study.

The impact of ethanol locks on the mechanical performances of central venous catheters was compared to that of aqueous-based locks. Several mechanical tests were performed to evaluate catheter behavior: kinking radius measurements, burst pressure, and tensile tests. Different polyurethanes were studied to assess the impact of radio-opaque charge and polymer chemical composition on catheter behavior. The results were correlated to swelling measurements and calorimetric measurements. In particular, ethanol locks have a higher impact on long contact time than aqueous-based locks: stresses and strains at break were lower, and kinking radii were higher. However, for all catheters, the mechanical performances remain much higher than the normative requirements.

Surface and mechanical properties of polyurethane central venous catheters after repeated contact with chemotherapy excipient solutions.

This article investigates the impact of the interactions between polyurethane central venous catheters and solutions containing excipients used in cisplatin and paclitaxel formulations. Changes to the properties of catheters and the leaching of catheter additives into the infused solutions were studied while these solutions were infused cyclically for several months. Chemotherapy treatment was mimicked in vitro in compliance with hospital practices. The treatment cycle was repeated 10 times, using solutions containing only the excipients. After 10 treatment cycles, no physical or chemical degradation of the catheter was observed. Mechanical performances were stable, but surface modifications occurred, causing the surface to become more hydrophobic. A loss in polyurethane antioxidant amount was observed in part due to a leaching phenomenon.

Impact of simulated biological aging on physicochemical and biocompatibility properties of cyclic olefin copolymers.

We study the effect of simulated biological aging on the properties of cyclic olefin copolymers and particularly their biocompatibility. Already reported as biocompatible polymers according to ISO/EN 10993 guidelines, COC are good candidates for medical devices. The influence of two major additives (antioxidants and lubricants) was investigated and comparison with non-aging COC was done. Four in vitro simulated biological conditions were tested: 2 extreme pH (1 and 9) to simulate digestive tract environment; THP-1-derived macrophages contact and pro-oxidant medium with hypochlorite solution simulating the oxidative attack during the foreign body reaction. After one month of incubation with the different media at 37 °C, surface topography was studied by atomic force microscopy (AFM) and IR spectroscopy. Extracts of incubated media were also analysed in chromatography to investigate potential degradation products. Cytotoxicity (MTT and LDH) of the materials was evaluated using cell culture methods with L929 fibroblasts. Oxidative stress (ROS and SOD analysis) and two inflammatory biomarkers (Il-6 and TNF-α secretion) were explored on THP-1-derived macrophages in direct contact with aged COC. Surface topography of COC was modified by aging conditions with an influence of antioxidant presence and under some conditions. HPLC analysis realized on freeze-dried solutions issued from the different incubations showed the presence of traces of low molecular weight compounds issued from polyphenolic antioxidant and from COC degradation. GC-MS analysis carried out directly on the different incubated COC, showed no detectable leachable molecules. No cytotoxicity has been observed with the different aged COC. However, results show that the pH environment had an influence on the cytotoxicity tests with a protecting effect of antioxidant presence; and pro-oxidant incubating conditions decreased cellular viability on COC. pH 1 and pH 9 conditions also induced an increase of ROS production which was partially reduced for COC containing an antioxidant or a lubricant. Il-6 production was globally more important for aged COC compared with basal condition and particularly for oxidative simulated environment. Those results indicate that physiological factors like pH or oxidant conditions have an impact on surface topography and on COC interaction with the biological environment but without compromising their biocompatibility. Antioxidant or lubricant presence could modulate these variations pointing out the necessity of a thoroughly investigation for biocompatibility assessment of COC as a component of implantable devices. COCs show a good biocompatibility even after accelerated aging under extreme biological conditions.

Restructuration kinetics of amphiphilic intraocular lenses during aging.

Photooxidation and hydrolysis are the two primary aging factors of intraocular lenses. Opacifications, dislocations, glistening and yellowing of the implanted acrylic lenses, which are due to chain scissions and depolymerization, are the consequences of aging from the clinical perspective. The purpose of this study was to examine the consequence of the aging of intraocular lenses on chemical and surface properties. Acrylic lenses made of poly acrylic-co-polystyrene polymer were artificially aged by photooxidation and hydrolysis from 2 to 20 years. Degradation products were observed by Reverse-phase High-Performance Liquid Chromatography RP-HPLC and thermogravimetric analysis (TGA). The surface, which was analyzed by atomic force microscopy (AFM) and fibronectin adhesion kinetics, was chosen as an indicator of intraocular biocompatibility. Low-molecular-weight degradation products (LMWP) result from chain scission under both hydrolysis and photooxidation. The osmotic effects of water enable degradation products to migrate through the polymer. A portion of the degradation products exudate in the surrounding center, whereas a portion link with lateral chains of the polymer. At the same time, the surface roughness evolves to externalize the most hydrophilic chains. As a result, the fibronectin adhesion level decrease with time, which indicates the existence of a biocompatible kinetic for implanted intraocular lenses.

Biocompatibility assessment of cyclic olefin copolymers: Impact of two additives on cytotoxicity, oxidative stress, inflammatory reactions, and hemocompatibility.

This work reports the biocompatibility evaluation of cyclic olefin copolymers (COC) as candidates for implantable medical devices. The focus was to establish the influence of two major additives (antioxidant and lubricant) on the overall biocompatibility. The cytotoxicity was evaluated according to ISO 10993-5 guidelines using L929 fibroblasts, HUVEC, and THP-1-derived macrophages. Oxidative stress (ROS, GSH/GSSG, and SOD analysis) and pro-inflammatory cytokines (Il-6 and TNF-α secretion) were quantified using THP-1 cells in direct contact with films. Hemocompatibility was assessed through haemolysis testing, dynamic blood coagulation, platelet adhesion, and activation (membranous P-selectin expression). Results show that the different types of COC have successfully passed the in vitro biocompatibility tests. The presence of antioxidant induces however a slight decrease in ROS production in correlation with a high SOD activity and a modification in blood coagulation profile probably linked to antioxidant recrystallization phenomenon on the surface of COC. The lubricant presence reduced haemolysis, fibrinogen adhesion, and platelet activation. Surface nanotopography of COC highlights different types of needles and globules according to the present additive. Those primary results indicate that COC are promising biomaterial. However, additives influenced some biological parameters pointing out the necessity of a global approach of risk analysis for biocompatibility evaluation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3333-3349, 2017.

Exudation of additives to the surface of medical devices: impact on biocompatibility in the case of polyurethane used in implantable catheters.

Surface state is one of the most important parameters determining the biocompatibility of an implantable medical device, any change on the surface once in contact with body tissues can impact the biological response (cytotoxicity, inflammation, irritation, thrombosis, etc.). In the present study, we use (Pellethane® ) catheter-based polyurethane (PU), because of its many applications in the field of medical devices, to evaluate the impact of additives blooming on the biocompatibility. Four different antioxidants and two anti-ultraviolet stabilizers were included in this study. A comprehensive study was conducted to evaluate the consequences of cellular exposure to theses additives in the following three forms: in dissolved form and after surface blooming, in amorphous and in crystalized ones, and finally in the overall biocompatibility of the native PU. Surface roughness was analyzed with atomic force microscopy. Endothelial cells' viability was studied in contact with all the three physical forms. A preliminary hemocompatibility evaluation was performed through the measurement of whole blood hemolysis, as well as platelet adhesion in contact with the different PU samples. The study of the proinflammatory IL-α and TNF-α production by macrophages in contact with these films is also reported. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2954-2967, 2016.

Modification of the bacterial adhesion of Staphylococcus aureus by antioxidant blooming on polyurethane films.

Medical device-related infections are a major problem in hospital. The risk of developing an infection is linked to the bacterial adhesion ability of pathogen strains on the device and their ability to form a biofilm. Here we focused on polymer surfaces exhibiting a blooming of antioxidant (Irganox 3114® and Irganox 1076®) on their surface. We tried to put into evidence the effect of such a phenomenon on the bacterial adhesion in terms of number of viable cultivable bacteria and bacteria localization on the surface. We showed that the blooming has a tendency to increase the Staphylococcus aureus adhesion phenomenon in part for topographic reasons.

Interaction of intraocular lenses with fibronectin and human lens epithelial cells: Effect of chemical composition and aging.

The aim of this study is to investigate in vitro interactions between hydrophobic acrylate intraocular lenses (IOLs) and their biological environment. The influence of lens chemical composition and aging on fibronectin (FN) adsorption and on IOLs cytotoxicity on human lens epithelial cells was examined. Cytotoxicity of acrylate monomers used in IOLs manufacture was also investigated. Four different IOLs were included in the study: Acrysof(®), Tecnis(®), EnVista(®), and iSert(®). Implants were artificially aged in a xenon arc chamber to simulate 2 years of light exposure. Fibronectin adsorption on IOL surface was quantified using ELISA and correlated to surface roughness determined with AFM. Direct contact cytotoxicity was determined with the MTT assay and cell morphology was observed with light microscopy. Results showed that fibronectin adsorption did not differ significantly among IOLs, whatever their chemical composition. Moreover, aging conditions did not impact fibronectin adsorption. All IOLs were biocompatible even after applying 2-year aging conditions, with cell viability higher than 70%. Five acrylate monomers appeared to be toxic in the range of concentrations tested, but no monomer release from the IOLs could be detected during accelerated 2-year incubation with saline solution. This study did not reveal an influence of chemical composition and aging on protein adsorption and on biocompatibility.

Modification of a cyclo-olefin surface by radio-sterilization: is there any effect on the interaction with drug solutions?

A cyclo-olefin copolymer was subjected to an e-beam ionizing treatment. Two doses were studied: one corresponding to the recommended dose for the sterilization of pharmaceutical packaging (25 kGy), and a greater one to enhance the modifications caused by the treatment (150 kGy). The surface modifications were studied by X-ray photoelectron spectroscopy (XPS), contact angle measurements and atomic force microscopy (AFM). The roughness and the wettability of the surface were enhanced by the treatment. The consequences of the surface modifications on the drug interaction with the polymer were studied.

A multiscale approach to assess the complex surface of polyurethane catheters and the effects of a new plasma decontamination treatment on the surface properties.

Polyurethane catheters made of Pellethane 2363-80AE® were treated with a low temperature plasma developed for the decontamination of reusable polymer devices in hospitals. We investigated the modifications of the polymer surface by studying the topographic modifications, the chemical modifications, and their consequences on the wettability and bacterial adhesion. This study showed that plasma treatment modified the topography and grafted oxygen and nitrogen species onto the surface, resulting in an increase in the surface polarity. This effect could be correlated to the number of nitrogen atoms interacting with the surface. Moreover, this study demonstrated the significance of multiscale heterogeneities, and the complexity of industrial medical devices made from polymers. Their surface can be heterogeneous, and they contain additives that can migrate and change the surface composition.

Polymorphism of Irganox 1076: Discovery of new forms and direct characterization of the polymorphs on a medical device by Raman microspectroscopy.

Irganox 1076(R) (octadecyl-3,5-di-tert-butyl-4-hydroxyhydrocinnamate) is a common phenolic antioxidant used in many polymer-based medical devices. As with many organic compounds, several polymorphs exist. However, in literature, only two forms of Irganox 1076(R) have been mentioned. In this study, we were able to produce, by crystallization in different solvents, three distinct polymorphs, which were characterized by DSC, FTIR and PXRD. Moreover, the three polymorphs have long-time stability at ambient pressure and temperature, meaning that they can potentially be present in or on polymeric devices. During DSC measurements, a fourth polymorph, which was only stable at low temperature, was evidenced. Thanks to Raman microspectroscopy, Irganox 1076(R) was identified directly on commercial polyurethane catheters which exhibited a blooming phenomenon. This study proves that the polymorph identified on the surface is different from the commercially available Irganox 1076(R). These results emphasize the importance of the screening of polymorphs before any study of the biocompatibility of antioxidants used in medical devices.