Fabricating hemocompatible bi-continuous PEGylated PVDF membranes via vapor-induced phase inversion

Lack of knowledge on their hemocompatibility limit the use of PVDF membranes in biomedical applications. Herein, we investigated the in situ modification of PVDF membranes by a PEGylated copolymer (PS60-b-PEGMA108) using vapor-induced phase separation (VIPS) process. Efforts were first oriented toward the characterization of the effect of copolymer on membrane formation, membranes physical properties and membranes surface chemistry. Then, biofouling was investigated before moving onto the hemocompatibility of membranes. Membranes structure tended to evolve from nodular to bi-continuous with PS60-b-PEGMA108 content, evidencing a change of dominating phenomena during phase inversion (crystallization-gelling vs. non-crystallization gelling), associated to a change of prevailing crystalline polymorph (β-polymorph vs. α-polymorph). Furthermore, the hydration of membranes was importantly enhanced, affecting nano-biofouling: bovine serum albumin, lysozyme and fibrinogen adsorption were drastically reduced, despite rough surfaces, highlighting the efficiency of the copolymer. Bacterial attachment tests revealed that macro-biofouling was inhibited as well. Results of erythrocytes, leukocytes, and thrombocytes adhesion indicated that membranes prepared from a casting solution containing 5 wt% copolymer are highly hemocompatible, result supported by low hemolysis ratio (1%) and delay of plasma clotting time. Overall, this study unveils that in situ modification coupled to the VIPS method can readily lead to hemocompatible PVDF membranes

Self-Cleaning Interfaces of Polydimethylsiloxane Grafted with pH-Responsive Zwitterionic Copolymers

International audienceSelf-cleaning surfaces allow the reversible attachment and detachment of microorganisms which show great promise in regards to their reusability as smart biomaterials. However, a widely used biomaterial such as polydimethylsiloxane (PDMS) suffers from high biofouling activity and hydrophobic recovery that results in decreased efficiency and stability. A current challenge is to modify and fabricate self-cleaning PDMS surfaces by incorporating antifouling and pH-sensitive properties. To address this, we synthesized a zwitterionic and pH-sensitive random poly(glycidyl methacrylate-co-sulfobetaine methacrylate-co-2-(dimethylamino)ethyl methacrylate) polymer, poly(GMA-co-SBMA-co-DMAEMA). In this work, chemical modification of PDMS was done by grafting onto poly(GMA-co-SBMA-co-DMAEMA) after surface activation via UV and ozone for 90 min to ensure the formation of covalent bonds necessary for stable grafting. The PDMS grafted with G20-S40-D40 exhibit antifouling and pH-sensitive properties by mitigating fibrinogen adsorption, blood cell adhesion, and releasing 98% adhered E. coli bacteria after immersion at basic pH. The grafting of poly(GMA-co-SBMA-co-DMAEMA) presented in this work shows attractive potential for biomedical and industrial applications as a simple, smart, and effective method for the modification of PDMS interface

Design of PVDF/PEGMA- b -PS- b -PEGMA membranes by VIPS for improved biofouling mitigation

Literature on the design of efficient nonfouling membranes by in-situ modification is poor, which can be explained by the difficulty to control membrane formation mechanisms when a third material is added to the casting solution, or by the lack of stability of matrix polymers with surface-modifiers. We present polyvinylidene fluoride membranes formed by vapor-induced phase separation and modified with a tri-block copolymer of poly(styrene) and poly(ethylene glycol) methacrylate moieties (PEGMA124-b-PS54-b-PEGMA124). After characterizing the copolymer, we move onto membrane formation mechanisms. Membrane formation is well controlled and leads to structure close to bi-continuous. Considering the formulation chosen, PVDF/PEGMA124-b-PS54-b-PEGMA124 solutions are less viscous and more hydrophilic than virgin PVDF solutions. Both effects promote non-solvent transfer, thus decreasing the chances for crystallization. Hydrophilic capability of membranes is increased from about 59 mg/cm3 to 650 mg/cm3, leading to a severe drop of non-specific protein adsorption, up to 85–90%, also depending on its nature. Biofouling at the micro-scale by modified Escherichia coli and Streptococcus mutans is almost totally inhibited. Finally, biofouling is importantly reduced in dynamic conditions, as measured from the water flux recovery ratio of 69.4%, after 3 water-BSA filtration cycles, much higher than with a commercial hydrophilic PVDF membrane (47.3%). These membranes hold promise as novel materials for water-treatment or blood filtration

FTIR mapping as a simple and powerful approach to study membrane coating and fouling

The purpose of this work is to apply FTIR mapping to the analysis of the coating and fouling behaviour of PVDF membranes coated with two different types of PS-PEGMA copolymers – diblock and random. The coating conditions involve the variation of coating solution concentration and of coating time. We have carried out adsorption experiments with BSA as the foulant, and also filtration experiments. The analysis of the results is mainly performed by image analysis of the mapped surfaces with two approaches: taking the average grey value/peak height of the whole surface for the coating and foulant signals, and by defining coating/fouling levels as an initial approach to analyse heterogeneity. Our results show that there is an heterogeneous distribution of the coating and fouling layers on the membrane surface at a millimetre scale. Moreover, the diblock copolymer has a slightly better anti-adsorption performance than the random one. Coating conditions should be carefully chosen and conclusions regarding the anti-fouling properties of the membranes should be drawn by taking into account both adsorption and filtration tests. All in all, FTIR mapping is a technique that should be taken into account for the study of fouling phenomena

Pearl-necklace assembly of Human serum albumin with poly (acrylic acid) polyelectrolyte explored by small angle X-ray scattering (SAXS)

In this comprehensive study, interaction of human serum albumin (HSA) with poly(acrylic acid) (PAA) was explored using Small Angle X-ray Scattering (SAXS) combined to chromatography. Results revealed the formation of a complex between HSA macromolecules and PAA chains but solely at some specific conditions of ionic strength and pH of the medium. In fact, this binding has found to take place only at pH close to 5 and low ionic strength (0.15M). Otherwise, for higher pH and salts concentration 0.75M the HSA-PAA complex tends to dissociate completely showing the reversibility of the complexation. The assessment of the influence of the HSA/PAA molar ratio on the complex radius of gyration suggests that 4 HSA molecules could bind to each PAA 100kDa chain. Besides the Porod volume evaluation for the same range of HSA/PAA ratio confirms this assumption. Finally, an all atom SAXS modelling study using BUNCH program has been conducted to find a compatible model that fit HSA-PAA complex scattering data. This model allows to portray the HSA/PAA complex as a pear-necklace assembly with 4 HSA on the 100 kDa PAA chain

Low-biofouling membranes prepared by liquid-induced phase separation of the PVDF/polystyrene-b-poly (ethylene glycol) methacrylate blend

In the present work, the focus is laid on the formation, and low-biofouling properties of polyvinylidene fluoride (PVDF) membranes modified using an amphiphilic copolymer additive: polystyrene-b-poly (ethylene glycol) methacrylate (PS-b-PEGMA). PVDF was blended with PS-b-PEGMA and membranes were prepared by liquid-induced phase separation. The additive played a significant role on membrane formation, slightly decreasing surface porosity, reducing the shrinkage during phase separation, and increasing both the size and porosity of macrovoids. Owing to its numerous hydrophilic moieties, the copolymer was believed to promote solvent and nonsolvent exchanges during phase inversion. In addition, it significantly enhanced surface hydrophilicity and matrix hydration capability. Indeed, water was easily trapped by the PEGylated chains spread onto the surface and within the matrix, and then stored in the larger macrovoids. It led to an important reduction of protein adsorption, including bovine serum albumin (65%) and lysozyme (89%). Bacterial attachment tests revealed that adhesion of Escherichia coli and Staphylococcus epidermidis was almost totally prevented (over 99% reduction of attachment), which demonstrates the excellent efficiency of PS-b-PEGMA copolymer to provide PVDF membranes with low-biofouling properties

A zwitterionic interpenetrating network for improving the blood compatibility of polypropylene membranes applied to leukodepletion

Although widely used in blood-contacting devices, polypropylene (PP) membranes are prone to biofouling by plasma proteins and blood cells. The present study explores the effect of a surface zwitterionization process on the improvement of the biofouling resistance of PP membranes for leukocyte reduction filters. The modification strategy consists in forming an interpenetrating network of poly(glycidyl methacrylate-co-sulfobetaine methacrylate) (poly(GMA-co-SBMA) around the fibers of coated PP membranes, using a cross-linking agent: ethylenediamine (EDA). It is shown that with EDA, a range of poly(GMA-co-SBMA) concentration (1–5 mg/mL) leads to a 0°-water contact angle and high hydration of the networks without affecting the intrinsic porous structure of the material. Besides, the related membranes show excellent resistance to biofouling by Escherichia coli, fibrinogen, leukocytes, erythrocytes, thrombocytes and cells from whole blood with reductions in adsorption of 97%, 86%, 90%, 95%, 97% and 91%, respectively, compared to unmodified PP. Used in whole blood filtration, it is demonstrated that in the best conditions (5 mg/mL copolymer, with EDA), leukocytes can be efficiently removed (>99.99%) without altering the erythrocytes concentration in the permeate, and that leukodepletion is more efficient than that measured with a commercial hydrophilic PP blood filter (about 50% retention). Physical retention of leukocytes is only efficient if the membrane material is anti-biofouling, and so, does not interact with other blood components able to trigger leukocyte attachment/deformation

Antifouling pseudo-zwitterionic poly(vinylidene fluoride) membranes with efficient mixed-charge surface grafting via glow dielectric barrier discharge plasma-induced copolymerization

This work reports on the glow dielectric barrier discharge (GDBD) plasma-induced surface grafting of poly(vinylidene fluoride) (PVDF) membranes with mixed-charge copolymers of [2-(methacryloyloxy)ethyl] trimethylammonium (TMA) and sulfopropyl methacrylate (SA). The aim is to investigate the antifouling properties and the hemocompatibility of this system. We first characterize the physico-chemical properties of the membranes. With SA alone in the coating solution, efficient grafting cannot be achieved as monomer is blown away during grafting. Membranes grafted with a mixture of SA and TMA, or TMA alone do not meet this problem and grafting density ranged between 0.29 and 0.41 mg/cm2. Bovine-serum-albumin and lysozyme adsorption tests (70% reduction) and Escherichia coli attachment test (annihilation of adhesion) unveil that pseudo-zwitterionic PVDF membranes are very efficient to reduce biofouling in static condition. Different fouling resistance behaviors are observed in dynamic conditions. Permeability of virgin membranes progressively decreases over the cycles, arising from a gradual pore blockage and irreversible fouling. All potential adsorption sites of pseudo-zwitterionic membrane and membrane with positive charge-bias are fouled after the first cycle, and flux recovery is maximal in the following cycles. This behavior is ascribed to the lack of homogeneity of the surface grafting. Finally, pseudo-zwitterionic membranes are hemocompatible (resistance to blood cells, low hemolysis activity). Provided a better tuning of surface uniformity, the method and system presented in this work are a promising approach to the new generation of antifouling mixed-charge membranes for water treatment or blood contacting devices

Nouvelles données sur l’agglomération antique d’<i>Epomanduodurum</i> (Mandeure et Mathay, Doubs)

International audienceDem antiken Mandeure-Mathay (Epomanduodurum), dem aufgrund seiner Größe und seiner bedeutenden Monumentalbauten im Sequanerland der zweite Platz nach dem Civitas-Hauptort Besançon zukommt, ist seit 2001 ein pluridisziplinäres Forschungsprojekt gewidmet. Im Anschluß an einen im Jahrgang 2007 dieser Zeitschrift vorgelegten Beitrag berichtet das vorliegende Dossier über die Forschungen der Jahre 2005 bis 2011. Parallel zur Weiterführung und Vertiefung der im Bereich der Kult- und Monumentalbauten begonnenen Arbeiten, trieb das Forschungsteam während dieses zweiten Projektabschnittes verschiedene Studien zur gesamten antiken Stadtanlage und der sie umgebenden Mikroregion voran. Diese Untersuchungen liefern neue Einsichten zur Entstehung, Entwicklung und zum Niedergang von Epomanduodurum und tragen zu einem vertieften Verständnis der Gestalt dieser Stadt und ihrer religiösen, ökonomischen und sozialen Organisation im Zeitraum vom Ende der Eisenzeit bis zum Frühmittelalter bei.A collective research program is studying since 2001 the ancient agglomeration of Mandeure-Mathay (Epomanduodurum), considered as second one after the chief town Besançon, in the Sequani territory, by its size and its impressive monumental buildings. This article, following a previous paper published in Gallia in 2007, draws up a report of the researches completed between 2005 and 2011. In this second stage, alongside the ongoing in-depth investigations on cult and monumental area, the PCR (Collective Program Research) team intensified its different studies and researches on the ancient agglomeration and its microregional environment. These studies lead to a better understanding of the appearance, development and decline of Epomanduodurum ; a better knowledge of its morphology, and its religious, economic and social organization between the end of the Iron Age and the Early Middle Ages.L’agglomération antique de Mandeure-Mathay (Epomanduodurum), considérée comme la seconde du pays séquane par ses dimensions et l’ampleur de sa parure monumentale, derrière la capitale de cité, Besançon, fait l’objet d’un programme collectif de recherche (PCR), pluridisciplinaire, depuis 2001. Le présent dossier, qui fait suite à un précédent article paru dans Gallia en 2007, dresse un bilan des recherches réalisées entre 2005 et 2011. Dans cette seconde étape, parallèlement à la poursuite et à l’approfondissement des actions engagées sur le secteur cultuel et monumental, l’équipe du PCR a accentué les études et investigations de diverses natures portant sur l’ensemble de l’agglomération antique et sur l’espace microrégional dans lequel celle-ci s’insère. Ces recherches aboutissent à une meilleure compréhension des modalités d’émergence, de développement et de déclin de la ville d’Epomanduodurum, et à une connaissance plus approfondie de sa morphologie et de son organisation religieuse, économique et sociale, entre la fin de l’âge du Fer et le haut Moyen Âge