Biofouling resistance of ultrafiltration membranes controlled by surface self-assembled coating with PEGylated copolymers.

Block and random PEGylated copolymers of poly(ethylene glycol) methacrylate (PEGMA) and polystyrene (PS) were synthesized with a controlled polydispersity using an atom transfer radical polymerization method and varying molar mass ratios of PS/PEGMA. Two types of PEGylated copolymers were self-assembly coated onto the surface of poly(vinylidene fluoride) (PVDF) ultrafiltration membranes for enhancing biofouling resistance. It was found that the adsorption capacities of random copolymers on PVDF membranes were all higher than those of block copolymers. However, the specific and overall protein resistance of bovine serum albumin (BSA) on PVDF membranes coated with block copolymers was much higher than that with random copolymers. The increase in styrene content in copolymer increased the amount of polymer coating on the membrane, and the increase in PEGMA content enhanced the protein resistance of membranes. The optimum PS/PEGMA ratio was found to be close to 2 for the best resistance of protein adsorption and bacterial adhesion on the PEGylated diblock copolymer-coated membranes. The PVDF membrane coated with such a copolymer owned excellent biofouling resistance to BSA, humic acid, negatively surface charged bacteria E. coli, and positively surface charged bacteria S. maltophilia.

Hemocompatible mixed-charge copolymer brushes of pseudozwitterionic surfaces resistant to nonspecific plasma protein fouling.

In this work, the hemocompatibility of a sulfobetaine-like copolymer brush resulting from a mixed-charge copolymerization of the positively charged 11-mercapto-N,N,N-trimethylammonium chloride (TMA) and negatively charged 11-mercaptoundecylsulfonic acid (SA) was studied. Mixed charge distribution in the prepared poly(TMA-co-SA) copolymer brushes was controlled by the regulation of the reaction rate of the surface-initiated atom transfer radical polymerization (ATRP). The adsorption behavior of plasma proteins on a surface grafted with poly(TMA-co-SA) was measured by a surface plasmon resonance (SPR) sensor. The effects of varying temperature, solution pH, and ionic strength on the antifouling characteristics of the mixed-charge copolymer brushes were systematically evaluated, and the protein-fouling resistance was discussed in detail, especially with respect to the effect of ionic strength on the intra- and intermolecular interactions of the poly(TMA-co-SA) with proteins. The adhesion and activation of blood cells on the poly(TMA-co-SA)-grafted surface in contact with human whole blood was also demonstrated. The results suggest that mixed-charge copolymer brushes of poly(TMA-co-SA), which, like zwitterionic homopolymer brushes, have overall charge neutrality, can be used in similar applications for protein-fouling resistance and have excellent hemocompatibility with human whole blood at physiologic temperatures.

Dual-thermoresponsive phase behavior of blood compatible zwitterionic copolymers containing nonionic poly(N-isopropyl acrylamide).

Thermoresponsive statistical copolymers of zwitterionic sulfobetaine methacrylate (SBMA) and nonionic N-isopropylacrylamide (NIPAAm) were prepared with an average molecular weight of about 6.0 kDa via homogeneous free radical copolymerization. The aqueous solution properties of poly(SBMA-co-NIPAAm) were measured using a UV--visible spectrophotometer. The copolymers exhibited controllable lower and upper critical solution temperatures in aqueous solution and showed stimuli-responsive phase transition in the presence of salts. Regulated zwitterionic and nonionic molar mass ratios led to poly(SBMA-co-NIPAAm) copolymers having double-critical solution temperatures, where the water-insoluble polymer microdomains are generated by the zwitterionic copolymer region of polySBMA or nonionic copolymer region of polyNIPAAm depending on temperature. A high content of the nonionic polyNIPAAm in poly(SBMA-co-NIPAAm) exhibits nonionic aggregation at high temperatures due to the desolvation of polyNIPAAm, whereas relatively low content of polyNIPAAm in poly(SBMA-co-NIPAAm) exhibits zwitterionic aggregation at low temperatures due to the desolvation of polySBMA. Plasma protein adsorption on the surface coated with poly(SBMA-co-NIPAAm) was measured with a surface plasmon resonance (SPR) sensor. The copolymers containing polySBMA above 29 mol % showed extremely low protein adsorption and high anticoagulant activity in human blood plasma. The tunable and switchable thermoresponsive phase behavior of poly(SBMA-co-NIPAAm), as well as its high plasma protein adsorption resistance and anticoagulant activity, suggests a potential for blood-contacting applications.

Preservation of hematopoietic stem and progenitor cells from umbilical cord blood stored in a surface derivatized with polymer nanosegments.

Tissue culture flasks were prepared with immobilized amphiphilic nanosegments of Pluronic F68 and F127, polyethylene oxide (PEO)-polypropylene oxide (PPO)-PEO triblock copolymers, on their surfaces. These so-called "Pluronic-immobilized flasks" were used for the preservation of hematopoietic stem and progenitor cells from umbilical cord blood. The expression ratio of surface markers (CD34) on hematopoietic stem and progenitor cells stored in Pluronic-immobilized flasks was significantly higher than that in polystyrene tissue culture flasks or commercially available bioinert flasks (i.e., low cell-binding cultureware). This was due to the presence of flexible brushlike segments of Pluronic on the Pluronic-immobilized flask. A good correlation was found between the number of CD34+ cells and the ratio of viable CD34+ cells from cord blood in several flasks after five days of storage. Therefore, the high number of CD34+ cells was thought to have originated from the high viability of these cells stored in Pluronic-immobilized flasks. It was found that there was an optimal surface concentration of Pluronic on the Pluronic-immobilized flask surfaces for the preservation (high number and survival) of these stem and progenitor cells. The foregoing results were attributable to the high density of Pluronic nanosegments on the flask surface, limiting the movement of these flexible segments.

Zwitterionic fibrous polypropylene assembled with amphiphatic carboxybetaine copolymers for hemocompatible blood filtration.

UNLABELLED: The present study serves three main functions. First, it presents a novel random copolymer, made of octadecyl acrylate hydrophobic blocks and 2-(dimethylamino)ethyl methacrylate hydrophilic groups, and it zwitterionic form. Second, random copolymer and zwitterionic random copolymer, OmDn and Z-OmDn, are used to modify polypropylene membranes by evaporation coating. Our investigations unveil that this method leads to sufficiently stable self-assembling provided a minimum number of hydrophobic repeat units of 77, which also corresponds to a hydrophobic degree of 74%. Third, antifouling and hemocompatible properties of membranes are thoroughly investigated using all types of blood cells separately, as well as challenging membranes against whole blood in static and dynamic conditions. Membranes modified with zwitterionic copolymer containing 26% of zwitterionic groups are shown to be highly antifouling and hemocompatible, for a coating density as low as 0.2mg/cm(2). Their application in a specially designed blood filtration module enabled to almost totally inhibit blood cells interactions with membrane material, as well as to importantly reduce platelet activation in the permeate (2.5-fold reduction). STATEMENT OF SIGNIFICANCE: The design of new zwitterionic copolymer material is proposed and demonstrated in this study. It was showed that hydrophobicoctadecyl acrylate segments can be introduced in the zwitterioniccarboxybetaine polymer chain with a well-controlled random sequence. Stable, efficient, and effective surface zwitterionization of hydrophobic polypropylene are obtained via grafting onto approach by evaporation-induced self-assembling coating. In the perspective of potential application, hemocompatible blood filtration was demonstrated with the excellent results of non-activated platelets obtained. DESIGN: New zwitterionicmaterial, amphiphatic carboxybetaine copolymers. DEVELOPMENT: Evaporation-induced self-assembling grafting. APPLICATION: Hemocompatible blood filtration.

Bacterial resistance control on mineral surfaces of hydroxyapatite and human teeth via surface charge-driven antifouling coatings.

This works reports a set of new functionalized polyethyleneimine (PEI) polymers, including a neutral PEGylated polymer PEI-g-PEGMA, a negatively charged polymer PEI-g-SA, and a zwitterionic polymer PEI-g-SBMA, and their use as antibiofouling coating agent for human teeth protection. Polymers were synthesized by Michael addition, XPS analysis revealed that each polymer could be efficiently coated onto hydroxyapatite, ceramic material used as a model tooth. Polymers carrying a negative net charge were more efficiently adsorbed, because of the establishment of electrostatic interactions with calcium ions. Protein adsorption tests revealed that two factors were important in the reduction of protein adsorption. Both the surface charge and the surface ability to bind and entrap water molecules had to be considered. PEI-g-SBMA, which zeta potential in PBS solution was negative, was efficient to inhibit the adsorption of BSA, a negative protein. On the other hand, it also resisted the adsorption of lysozyme, a positive protein, because zwitterionic molecules can easily entrap water and provide a very hydrophilic environment. Streptococcus mutans attachment tests performed unveiled that all modified polymers were efficient to resist this type of bacteria responsible for dental carries. Best results were also obtained with PEI-g-SBMA coating. This polymer was also shown to efficiently resist the adsorption of positively charged bacteria (Stenotrophomonas maltophilia). Tests performed on real human tooth showed that PEI-g-SBMA could inhibit up to 70% of bacteria adhesion, which constitutes a major result considering that surface of teeth is very rough, therefore physically promoting the attachment of proteins and bacteria.

Electrical stimulation to promote osteogenesis using conductive polypyrrole films.

In this study, we developed an electrical cell culture and monitoring device. Polypyrrole (PPy) films with different resistances were fabricated as conductive surfaces to investigate the effect of substrate-mediated electrical stimulation. The physical and chemical properties of the devices, as well as their biocompatibilities, were thoroughly evaluated. These PPy films had a dark but transparent appearance, on which the surface cells could be easily observed. After treating with the osteogenic medium, rat bone marrow stromal cells cultured on the PPy films differentiated into osteoblasts. The cells grown on the PPy films had up-regulated osteogenic markers, and an alkaline phosphatase activity assay showed that the PPy films accelerated cell differentiation. Alizarin red staining and calcium analysis suggested that the PPy films promoted osteogenesis. Finally, PPy films were subjected to a constant electric field to elucidate the effect of electrical stimulation on osteogenesis. Compared with the untreated group, electrical stimulation improved calcium deposition in the extracellular matrix. Furthermore, PPy films with lower resistances allowed larger currents to stimulate the surface cells, which resulted in higher levels of mineralization. Overall, these results indicated that this system exhibited superior electroactivity with controllable electrical resistance and that it can be coated directly to produce medical devices with a transparent appearance, which should be beneficial for research on electrical stimulation for tissue regeneration.

Interfacially polymerized layers for oxygen enrichment: a method to overcome Robeson's upper-bound limit.

Interfacial polymerization of four aqueous phase monomers, diethylenetriamine (DETA), m-phenylenediamine (mPD), melamine (Mela), and piperazine (PIP), and two organic phase monomers, trimethyl chloride (TMC) and cyanuric chloride (CC), produce a thin-film composite membrane of polymerized polyamide layer capable of O2/N2 separation. To achieve maximum efficiency in gas permeance and O2/N2 permselectivity, the concentrations of monomers, time of interfacial polymerization, number of reactive groups in monomers, and the structure of monomers need to be optimized. By controlling the aqueous/organic monomer ratio between 1.9 and 2.7, we were able to obtain a uniformly interfacial polymerized layer. To achieve a highly cross-linked layer, three reactive groups in both the aqueous and organic phase monomers are required; however, if the monomers were arranged in a planar structure, the likelihood of structural defects also increased. On the contrary, linear polymers are less likely to result in structural defects, and can also produce polymer layers with moderate O2/N2 selectivity. To minimize structural defects while maximizing O2/N2 selectivity, the planar monomer, TMC, containing 3 reactive groups, was reacted with the semirigid monomer, PIP, containing 2 reactive groups to produce a membrane with an adequate gas permeance of 7.72 × 10(-6) cm(3) (STP) s(-1) cm(-2) cm Hg(-1) and a high O2/N2 selectivity of 10.43, allowing us to exceed the upper-bound limit of conventional thin-film composite membranes.

A systematic SPR study of human plasma protein adsorption behavior on the controlled surface packing of self-assembled poly(ethylene oxide) triblock copolymer surfaces.

A well-controlled biocompatible nonfouling surface is significant for biomedical requirements, especially for the improvement of biocompatibility. We demonstrate the low or nonbiofouling surfaces by coating hydrophobic-hydrophilic triblock copolymers of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) on the CH(3)-terminated self-assembled monolayer (SAM). Two types of copolymers are used to modify the surface, one with different PEO/PPO ratios ( approximately 20/80, 40/60, and 80/20, w/w) but the same PPO molecular weight ( approximately 2 k), the other with different copolymer MWs ( approximately 9, 11, and 15 k) but the same PEO/PPO ratio (80/20, w/w). In situ surface plasmon resonance (SPR) sensor is used to evaluate polymer adsorption on the SAMs and subsequent protein adsorption on the copolymer-treated surface. The effects of PEO-PPO-PEO molecular weight, PPO-to-PEO ratio, and ionic strength on protein adsorption from single protein solutions of fibrinogen, BSA, and complex mixed proteins are systematically investigated. A Pluronic F108 treated surface is highly resistant to nonspecific protein adsorption under the optimized conditions (MW of 15 k and PEO/PPO ratio of 80/20). This work demonstrates that the PEO-PPO-PEO polymer is able to achieve ultra low fouling surface via surface modification by controlling surface packing density of polymers (molecular weight, hydrophobic/hydrophilic ratio, and hydrophilic group coverage).