Johanna Saunier

Resonance enhanced AFM-IR: A new powerful way to characterize blooming on polymers used in medical devices

In this paper we demonstrated the application of resonance enhanced AFM-IR to the study of the medical device surfaces. Surface state is one of the most important parameter on the biocompatibility of an implantable medical device. By using this new technique, it was possible to obtain with high resolution topographic and chemical maps and to identify the chemical nature of very thin deposit observed on the surface. This was illustrated with the case of lubricant exudation on polyurethane used in the making of implantable catheters.

Studying DEHP migration in plasticized PVC used for blood bags by coupling Raman confocal microscopy to UV spectroscopy

Plasticized PVC is widely used to make medical devices such as tubing, perfusion bags and blood bags. By using confocal Raman microscopy on a PVC sheet plasticized with around 40% of di-(2-ethylhexyl)phthalate (DEHP), we propose a simple and sensitive approach to studying and understanding the diffusion of plasticizers from polymers into the surrounding media. Moreover, we sought to correlate our findings to standard measurements conducted by UV spectroscopy. This study showed differences in the concentration gradient observed due to the diffusion of the plasticizer inside a PVC sheet. We can thus follow the critical DEHP ratios that can impact the diffusion process. Water and ethanol were chosen as storage media: in ethanol, the lowest concentration of DEHP was observed at the surface resulting in the formation of a less plasticized layer near the interface; unlike ethanol, PVC sheets stored in water showed a greater concentration of DEHP on the film surface as an exudation of DEHP onto the surface.

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.

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.

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.

Impact of the nature and concentration of plasticizers on the ability of PVC to sorb drug.

The sorption of a drug by an infusion set may dramatically reduce the drug delivery efficiency. In this paper, we investigated how the drug sorption, in static conditions, is affected by the plasticizers nature and ratio in the case of plasticized PVC, one of the most common material for infusion set tubing. Within the study, the drug concentration in diazepam solutions was studied after contact with PVC films containing different amounts of DEHP, DEHT, TOTM and DINCH® plasticizers. Moreover the partition coefficients between material and water were calculated. The drug sorption levels were equivalent for the different plasticizers and there was a plasticizer ratio for which the drug uptake was enhanced. As a consequence, the amount of sorbed drug might not be only linked to the amount of plasticizer in the film and to the solubility of the drug in the plasticizer alone: it must probably depend on specific interactions between plasticizer and PVC.

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.

Blooming of Irganox 3114® antioxidant onto a medical grade elastomer. Impact of the recrystallization conditions on the antioxidant polymorphism, on the film wettability and on the antioxidant leachability.

Studying the blooming and recrystallization of additives onto the surface of polymer medical devices is of a great interest because it can affect the biocompatibility of the material. The polymorphism of a phenolic antioxidant (Irganox 3114(®)) used as an additive in medical devices and pharmaceutical packaging was studied: two different polymorphs were characterized by differential scanning measurements, FTIR and X-ray diffraction analyses. Then, the behavior of the additive in medical grade polyurethane films was described: a recrystallization into the stable polymorphic form was observed onto the polymer surface after annealing at different temperatures. The morphology observed depends not only on the additive/polymer ratio but also on the whole amount of additive in the polymer film. Depending on the recrystallization morphology, the wettability with water could be lowered and the leachability of the additives into aqueous media could be favored.

Characterization of the surface physico-chemistry of plasticized PVC used in blood bag and infusion tubing

Commercial infusion tubing and blood storage devices (tubing, blood and platelets bags) made of plasticized PVC were analyzed by spectroscopic, chromatographic and microscopic techniques in order to identify and quantify the additives added to the polymer (lubricants, thermal stabilizers, plasticizers) and to put into evidence their blooming onto the surface of the devices. For all the samples, deposits were observed on the surface but with different kinds of morphologies. Ethylene bis amide lubricant and metallic stearate stabilizers were implicated in the formation of these layers. In contact with aqueous media, these insoluble deposits were damaged, suggesting a possible particulate contamination of the infused solutions.

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.