pH-Dependent Adsorption of Human Serum Albumin Protein on a Polystyrene-Block-Poly(acrylic acid)-Coated PVDF Membrane.

This study reports the investigation of human serum albumin (HSA) adsorption on a poy-styrene-block-poly(acrylic acid) (PS-b-PAA)-coated PVDF membrane, which is a potential smart material for biomedical applications. First, copolymer coating on the membrane surface was successfully performed, due to the hydrophobic interaction of the PS anchoring group with the PVDF membrane. This was confirmed by Fourier transform infrared spectroscopy (FTIR) characterization of the membrane. Then, HSA adsorption onto the coated membrane was assessed and was proved to be strongly dependent on the pH of the protein solution. Indeed, both FTIR mapping and mass balance calculation using UV-visible spectroscopy displayed a greater HSA adsorption on the membrane at pH 5, even though it still took place at higher pH, but to a lower extent. Afterwards, an ionic strength influence study evinced the role of electrostatic interactions between HSA and the PAA layer on HSA adsorption. Dead-end filtration of HSA through the coated membrane confirmed the pH dependence of HSA adsorption on the coated membrane.

Dopamine-Induced Surface Zwitterionization of Expanded Poly(tetrafluoroethylene) for Constructing Thermostable Bioinert Materials.

Although energy-demanding, the surface modification of polytetrafluoroethylene (PTFE) for biomedical applications is mandatory to mitigate irreversible biofouling that occurs whenever PTFE comes into contact with biological fluids. Here, we propose to take advantage of the adhesive properties of dopamine (DA) and of the antifouling ability of various zwitterionic monomers (sulfobetaine methacrylate (SBMA), sulfobetaine methacrylamide (SBAA), sulfobetaine acrylamide (SBAA'), and 4-vinylpyridine propylsulfobetaine (4VPPS)) and form antifouling coatings by copolymerization on the surface of expanded PTFE membranes. This simple, low-energy, and one-step coating procedure arises in significant biofouling mitigation. All zwitterionic coatings led to important reduction of biofouling by red blood cell conentrate (88-94%), platelet conentrate (70-90%), whole blood (40-66%), or bacteria (83-96%). Also, it is shown that the interactions of polydopamine with ePTFE are stable even at high temperatures. However, the zwitterionic monomers are differently affected. While the performance of SBMA coatings decreased (as SBMA is prone to hydrolysis), those of SBAA, SBAA', and 4VPPS coatings were generally maintained. All in all, this study illustrates that efficient and stable antifouling zwitterionic coatings can be generated onto PTFE membranes for biomedical applications, without the use of conventional high-energy-demanding surface modification processes.

Pearl-necklace assembly of human serum albumin with the poly(acrylic acid) polyelectrolyte investigated using small angle X-ray scattering (SAXS).

In this comprehensive study, the interaction of human serum albumin (HSA) with poly(acrylic acid) (PAA) was explored using small angle X-ray scattering (SAXS) combined with chromatography. The results revealed the formation of a complex between HSA macromolecules and PAA chains but solely under some specific conditions of the ionic strength and pH of the medium. In fact, this binding was found to take place only at pH close to 5 and at low ionic strength (0.15 M). Otherwise, for a higher pH and a salt concentration of 0.75 M 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 radius of gyration of the complex suggests that 4 HSA molecules could bind to each 100 kDa PAA chain. In addition, the Porod volume evaluation for the same range of the HSA/PAA ratio confirms this assumption. Finally, an all-atom SAXS modelling study using the BUNCH program was conducted to find a compatible model that fits the HSA-PAA complex scattering data. This model allows us to portray the HSA/PAA complex as a pearl-necklace assembly with 4 HSA molecules on the 100 kDa PAA chain.

Surface Zwitterionization of Expanded Poly(tetrafluoroethylene) via Dopamine-Assisted Consecutive Immersion Coating.

Expanded polytetrafluoroethylene (ePTFE) is one of the materials widely used in the biomedical field, yet its application is being limited by adverse reactions such as thrombosis when it comes in contact with blood. Thus, a simple and robust way to modify ePTFE to be biologically inert is sought after. Modification of ePTFE without high-energy pretreatment, such as immersion coating, has been of interest to researchers for its straightforward process and ease in scaling up. In this study, we utilized a two-step immersion coating to zwitterionize ePTFE membranes. The first coating consists of the co-deposition of polyethylenimine (PEI) and polydopamine (PDA) to produce amine groups in the surface of the ePTFE for further functionalization. These amine groups from PEI will be coupled with the epoxide group of the zwitterionic copolymer, poly(GMA-co-SBMA) (PGS), via a ring-opening reaction in the second coating. The coated ePTFE membranes were physically and chemically characterized to ensure that each step of the coating is successful. The membranes were also tested for their thrombogenicity via quantification of the blood cells attached to it during contact with biological solutions. The coated membranes exhibited around 90% reduction in attachment with respect to the uncoated ePTFE for both Gram-positive and Gram-negative strains of bacteria (Staphylococcus aureus and Escherichia coli). The coating was also able to resist blood cell attachment from human whole blood by 81.57% and resist red blood cell attachment from red blood cell concentrate by 93.4%. These ePTFE membranes, which are coated by a simple immersion coating, show significant enhancement of the biocompatibility of the membranes, which shows promise for future use in biological devices.

Healing kinetics of diabetic wounds controlled with charge-biased hydrogel dressings.

The present study investigates the properties and use as wound-dressing materials of hydrogels made of negatively charged 3-sulfopropyl methacrylate (SA) and positively charged [2-(methacryloyloxy)ethyl]trimethylammonium (TMA) to form poly(SA-co-TMA) gels with/without a charge bias. Their actual chemical compositions were ascertained by XPS which revealed a fair control of the final gel composition obtained from the initial molar ratio in the reaction solution. Zeta potential measurements confirmed the controlled charge bias on which swelling ratio was found to strongly depend, i.e., positively charged or negatively charged gels have a higher tendency to swell than poly(SA-co-TMA) made of 50 mol% of each unit. The anti-biofouling properties were also correlated to the charge bias, i.e., negatively charged and neutral gels resisted well to biofouling by fibrinogen and whole blood, and were much less cytotoxic than their positive counterparts. Applied as wound-dressing materials onto diabetic wounds, it was found that wound closure was almost reached after 21 days, regardless of the gel composition. However, histological analysis revealed that positively charged gels accelerated hemostasis, while neutral gels, much less cytotoxic, were more efficient in the following stages during which the granulation layer and dermis were fully remodelled leading to a dense fibroblast population and thick collagen with no sign of inflammation. All in all, this study sheds light on the effects of charge bias on different wound healing stages and proves the efficiency of pseudo-zwitterionic poly(SA-co-TMA) to heal diabetic wounds for the first time.

A Nondestructive Surface Zwitterionization of Polydimethylsiloxane for the Improved Human Blood-inert Properties.

Polydimethylsiloxane (PDMS) is extensively used in the field of biomaterials. However, its hydrophobicity still limits its range of applications and makes it prone to biofouling. Various techniques are currently utilized to overcome this limitation, but most of them reduce some of the PDMS prime characteristics, such as its mechanical strength and optical transparency. In this work, we employed an original two-step coating process to bypass harsh treatments on PDMS like UV-ozone or plasma treatment. A pre-coating step of tannic acid-Fe(III) complex was performed prior to the zwitterionization of the PDMS with poly(glycidyl methacrylate-co-sulfobetaine methacrylate) or poly(GMA-co-SBMA) by a "grafting-to" approach. Successful coating was evidenced by a decrease of the water-contact angle from 118° to 79°. The process was optimized, and the optimized coating condition led to a significant improvement of the PDMS biocompatibility while maintaining its mechanical property and optical transparency. In addition, a 90% reduction of Escherichia coli attachment and fibrinogen plasma protein, an 80% reduction of red blood cells and cells from whole-blood attachment, and a 60% reduction of platelets adhesion were measured. We further tested the potential of the zwitterionic PDMS material as a storage vessel for platelet-rich plasma under physiological conditions. Platelet activation was decreased from 10.95% using virgin PDMS to 3.35% with the coated sample in a period of 2 days.

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

Self-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 interfaces.

Bioinspired Pseudozwitterionic Hydrogels with Bioactive Enzyme Immobilization via pH-Responsive Regulation.

Hydrogels are hydrated networks of flexible polymers with versatile biomedical applications, and their resistance to nonspecific protein adsorption is critical. On the other hand, functionalization with other biomacromolecules would greatly enhance their biotechnological potential. The aim of this research is to prepare low fouling hydrogel polymers for selective protein immobilization. Initially, hydrogels were prepared by controlling the composition ratios of 2-carboxyethyl acrylate (CA) and 2-dimethylaminoethyl methacrylate (DMAEMA) monomers in an N, N-methylene-bis-acrylamide (NMBA) cross-linked free radical polymerization reaction. This series of hydrogels (C1D9 to C9D1) were then analyzed by X-ray photoelectron spectroscopy (XPS) and dynamic laser scattering to confirm the actual polymer ratios and surface charge. When the composition ratio was set at CA:6 vs DMEAMA:4 (C6D4), the hydrogel showed nearly neutral surface charge and an equivalent reaction ratio of CA vs DMAEMA in the hydrogel. Subsequent analysis showed excellent antifouling properties, low blood cell adhesion, hemocompatibility, and platelet deactivation. Moreover, this hydrogel exhibited pH responsiveness to protein adsorption and was then used to facilitate the immobilization of lipase as an indication of active protein functionalization while still maintaining a low fouling status. In summary, a mixed-charge nonfouling pseudozwitterionic hydrogel could be prepared, and its pH-responsive adsorption holds potential for designing a biocompatible tissue engineering matrix or membrane enzyme reactors.

Surface self-assembled PEGylation of fluoro-based PVDF membranes via hydrophobic-driven copolymer anchoring for ultra-stable biofouling resistance.

Stable biofouling resistance is significant for general filtration requirements, especially for the improvement of membrane lifetime. A systematic group of hyper-brush PEGylated diblock copolymers containing poly(ethylene glycol) methacrylate (PEGMA) and polystyrene (PS) was synthesized using an atom transfer radical polymerization (ATRP) method and varying PEGMA lengths. This study demonstrates the antibiofouling membrane surfaces by self-assembled anchoring PEGylated diblock copolymers of PS-b-PEGMA on the microporous poly(vinylidene fluoride) (PVDF) membrane. Two types of copolymers are used to modify the PVDF surface, one with different PS/PEGMA molar ratios in a range from 0.3 to 2.7 but the same PS molecular weights (MWs, ∼5.7 kDa), the other with different copolymer MWs (∼11.4, 19.9, and 34.1 kDa) but the similar PS/PEGMA ratio (∼1.7 ± 0.2). It was found that the adsorption capacities of diblock copolymers on PVDF membranes decreased as molar mass ratios of PS/PEGMA ratio reduced or molecular weights of PS-b-PEGMA increased because of steric hindrance. The increase in styrene content in copolymer enhanced the stability of polymer anchoring on the membrane, and the increase in PEGMA content enhanced the protein resistance of membranes. The optimum PS/PEGMA ratio was found to be in the range between 1.5 and 2.0 with copolymer MWs above 20.0 kDa for the ultrastable resistance of protein adsorption on the PEGylated PVDF membranes. The PVDF membrane coated with such a diblock copolymer owned excellent biofouling resistance to proteins of BSA and lysozyme as well as bacterium of Escherichia coli and Staphylococcus epidermidis and high stable microfiltration operated with domestic wastewater solution in a membrane bioreactor.

Effects of ionic strength on bacteriophage MS2 behavior and their implications for the assessment of virus retention by ultrafiltration membranes.

Bacteriophage MS2 is widely used as a surrogate to estimate pathogenic virus elimination by membrane filtration processes used in water treatment. Given that this water technology may be conducted with different types of waters, we focused on investigating the effects of ionic strength on MS2 behavior. For this, MS2 was analyzed while suspended in solutions of various ionic strengths, first in a batch experiment and second during membrane ultrafiltration, and quantified using (i) quantitative reverse transcriptase PCR (qRT-PCR), which detects the total number of viral genomes, (ii) qRT-PCR without the RNA extraction step, which reflects only particles with a broken capsid (free RNA), and (iii) the PFU method, which detects only infectious viruses. At the beginning of the batch experiments using solutions containing small amounts of salts, losses of MS2 infectivity (90%) and broken particles (20%) were observed; these proportions did not change during filtration. In contrast, in high-ionic-strength solutions, bacteriophage kept its biological activity under static conditions, but it quickly lost its infectivity during the filtration process. Increasing the ionic strength decreased both the inactivation and the capsid breakup in the feed suspension and increased the loss of infectivity in the filtration retentate, while the numbers of MS2 genomes were identical in both experiments. In conclusion, the effects of ionic strength on MS2 behavior may significantly distort the results of membrane filtration processes, and therefore, the combination of classical and molecular methods used here is useful for an effective validation of the retention efficiency of ultrafiltration membranes.

[Removal of bisphenol A and tetrabromobisphenol A membrane by nanofiltration from water source].

The removal efficiency of BPA and TBBPA by nanofiltration membrane Desal 5 DK has been investigated with a lab-scale dead-end filtration module and the role of adsorption of two molecules on membrane was also explored to understand the filtration mechanism. The results showed that the R(obs) of BPA decreased from 89% to 47% as the accumulated adsorption quantity of BPA onto the membrane increased to 30 microg x m(-2). The high BPA concentration in adsorption layer caused the water flux decline especially at high pressure. The high TBBPA rejection of over 95% by Desal 5 DK was obtained due to the molecular weight and molecular structure although the accumulated adsorption quantity of TBBPA reached 50 microg x m(-2). The desorption test showed that the TBBPA could not pass through the membrane for its structure at the 5 x 10(5) Pa, while BPA could diffuse through the membrane and the peak concentration was obtained after 30 mL filtration. The quantity of BPA released from the membrane contributed 30% of the total amount adsorbed by the membrane Desal 5 DK.

Filtration method characterizing the reversibility of colloidal fouling layers at a membrane surface: analysis through critical flux and osmotic pressure.

A filtration procedure was developed to measure the reversibility of fouling during cross-flow filtration based on the square wave of applied pressure. The principle of this method, the apparatus required, and the associated mathematical relationships are detailed. This method allows for differentiating the reversible accumulation of matter on, and the irreversible fouling of, a membrane surface. Distinguishing these two forms of attachment to a membrane surface provides a means by which the critical flux may be determined. To validate this method, experiments were performed with a latex suspension at different degrees of destabilization (obtained by the addition of salt to the suspension) and at different cross-flow velocities. The dependence of the critical flux on these conditions is discussed and analysed through the osmotic pressure of the colloidal dispersion.