Although zwitterionic chemistries are among the most promising materials for producing nonfouling surfaces, their structural diversity has been low until now. Here, we compare the in vitro fouling ...behavior of a set of four systematically varied sulfa-/sulfobetaine-containing zwitterionic hydrogel coatings against a series of proteins and nonmotile as well as motile marine organisms as model foulers. The coatings are prepared by simultaneous photoinduced cross-linking and surface anchoring to elucidate the effect of the molecular structure of the zwitterionic moieties on their antifouling activity. Analogously prepared coatings of poly(butyl methacrylate) and poly(oligoethylene glycol methacrylate) serve as references. Photoreactive polymers are synthesized by the statistical copolymerization of sulfobetaine or sulfabetaine methacrylates and methacrylamides with a benzophenone derivative of 2-hydroxyethyl methacrylate and are applied as a thin film coating. While keeping the density of the zwitterionic and cross-linker groups constant, the molecular structure of the zwitterionic side chains is varied systematically, as is the arrangement of the ion pairs in the side chain by changing the classical linear geometry to a novel Y-shaped geometry. All of the polyzwitterions strongly reduce fouling compared to poly(butyl methacrylate). Overall, the sulfabetaine polyzwitterion coatings studied matches the high antifouling effectiveness of oligo(ethylene glycol)-based ones used as a control. Nevertheless, performances varied individually for a given pair of polymer and fouler. The case of the polysulfobetaines exemplifies that minor chemical changes in the polymer structure affect the antifouling performance markedly. Accordingly, the antifouling performance of such polymers cannot be correlated simply to the type of zwitterion used (which could be generally ranked as better performing or poorer performing) but is a result of the polymer’s precise chemical structure. Our findings underline the need to enlarge the existing structural diversity of polyzwitterions for antifouling purposes to optimize the potential of their chemical structure.
The hydrolytic stability of polymers to be used for coatings in aqueous environments, for example, to confer anti-fouling properties, is crucial. However, long-term exposure studies on such polymers ...are virtually missing. In this context, we synthesized a set of nine polymers that are typically used for low-fouling coatings, comprising the well-established poly(oligoethylene glycol methylether methacrylate), poly(3-(
-2-methacryloylethyl-
-dimethyl) ammoniopropanesulfonate) ("sulfobetaine methacrylate"), and poly(3-(
-3-methacryamidopropyl-
-dimethyl)ammoniopropanesulfonate) ("sulfobetaine methacrylamide") as well as a series of hitherto rarely studied polysulfabetaines, which had been suggested to be particularly hydrolysis-stable. Hydrolysis resistance upon extended storage in aqueous solution is followed by ¹H NMR at ambient temperature in various pH regimes. Whereas the monomers suffered slow (in PBS) to very fast hydrolysis (in 1 M NaOH), the polymers, including the polymethacrylates, proved to be highly stable. No degradation of the carboxyl ester or amide was observed after one year in PBS, 1 M HCl, or in sodium carbonate buffer of pH 10. This demonstrates their basic suitability for anti-fouling applications. Poly(sulfobetaine methacrylamide) proved even to be stable for one year in 1 M NaOH without any signs of degradation. The stability is ascribed to a steric shielding effect. The hemisulfate group in the polysulfabetaines, however, was found to be partially labile.
Combining high hydrophilicity with charge neutrality, polyzwitterions are intensely explored for their high biocompatibility and low-fouling properties. Recent reports indicated that in addition to ...charge neutrality, the zwitterion’s segmental dipole orientation is an important factor for interacting with the environment. Accordingly, a series of polysulfobetaines with a novel architecture was designed, in which the cationic and anionic groups of the zwitterionic moiety are placed at equal distances from the backbone. They were investigated by in vitro biofouling assays, covering proteins of different charges and model marine organisms. All polyzwitterion coatings reduced the fouling effectively compared to model polymer surfaces of poly(butyl methacrylate), with a nearly equally good performance as the reference polybetaine poly(3-(N-(2-(methacryloyloxy)ethyl)-N,N-dimethylammonio)propanesulfonate). The specific fouling resistance depended on the detailed chemical structure of the polyzwitterions. Still, while clearly affecting the performance, the precise dipole orientation of the sulfobetaine group in the polyzwitterions seems overall to be only of secondary importance for their antifouling behavior.
Films of zwitterionic polymers are increasingly explored for conferring fouling resistance to materials. Yet, the structural diversity of polyzwitterions is rather limited so far, and clear ...structure-property relationships are missing. Therefore, we synthesized a series of new polyzwitterions combining ammonium and sulfate groups in their betaine moieties, so-called poly(sulfabetaine)s. Their chemical structures were varied systematically, the monomers carrying methacrylate, methacrylamide, or styrene moieties as polymerizable groups. High molar mass homopolymers were obtained by free radical polymerization. Although their solubilities in most solvents were very low, brine and lower fluorinated alcohols were effective solvents in most cases. A set of sulfabetaine copolymers containing about 1 mol % (based on the repeat units) of reactive benzophenone methacrylate was prepared, spin-coated onto solid substrates, and photo-cured. The resistance of these films against the nonspecific adsorption by two model proteins (bovine serum albumin-BSA, fibrinogen) was explored, and directly compared with a set of references. The various polyzwitterions reduced protein adsorption strongly compared to films of poly(
butyl methacrylate) that were used as a negative control. The poly(sulfabetaine)s showed generally even somewhat higher anti-fouling activity than their poly(sulfobetaine) analogues, though detailed efficacies depended on the individual polymer-protein pairs. Best samples approach the excellent performance of a poly(oligo(ethylene oxide) methacrylate) reference.
The resistance of zwitterionic polymer coatings against the adsorption of proteins and the attachment of pathogenic bacteria is influenced by the precise molecular architecture of the polymers. Two ...until now rarely studied molecular variables in this context are side chain spacer groups separating the zwitterionic moieties from the polymer backbone and spacer groups separating the cationic and anionic groups within the zwitterionic moiety. Therefore, a set of six poly(sulfobetaine)s and poly(sulfabetaine)s is prepared, in which these spacer groups are systematically varied, incorporating ethylene, propylene, and undecylene side chain spacers, as well as ethylene, propylene, and butylene inter‐charge spacers, and their effects on the antifouling behavior are explored. Hence, the corresponding zwitterionic methacrylates are copolymerized with a photo‐reactive methacrylate bearing a benzophenone moiety. All zwitterionic coatings reveal hydrophilic properties when immersed in water and those with relatively short spacers show effective suppression of non‐specific protein adsorption. Polysulfobetaines outperform the polysulfabetaine ones in terms of resistance against adhesion of bacteria. The overall best fouling protection is observed for the polysulfobetaine bearing a propylene side chain spacer, which coincides with their relatively highest water solubility. The results corroborate previous findings that even apparently minor molecular changes of polyzwitterions can strongly affect their antifouling performance.
Hydrophilic sulfobetaine‐based polymers with relatively short inter‐charges and side‐chain spacers outperform analogous sulfabetaines in terms of bacterial fouling resistance. An extended undecyl side‐chain spacer results in increased hydrophobicity in the air but retains rapid reorientation and hydrophilicity underwater, whereby the resistance to proteins and bacterial accumulation is partially compromised.
Nonionic-zwitterionic diblock copolymers are designed to feature a coil-to-globule collapse transition with an upper critical solution temperature (UCST) in aqueous media, including physiological ...saline solution. The block copolymers that combine presumably highly biocompatible blocks are synthesized by chain extension of a poly(ethylene glycol) (PEG) macroinitiator via atom transfer radical polymerization (ATRP) of sulfobetaine and sulfabetaine methacrylates. Their thermoresponsive behavior is studied by variable temperature turbidimetry and ¹H NMR spectroscopy. While the polymers with polysulfobetaine blocks exhibit phase transitions in the physiologically interesting window of 30⁻50 °C only in pure aqueous solution, the polymers bearing polysulfabetaine blocks enabled phase transitions only in physiological saline solution. By copolymerizing a pair of structurally closely related sulfo- and sulfabetaine monomers, thermoresponsive behavior can be implemented in aqueous solutions of both low and high salinity. Surprisingly, the presence of the PEG blocks can affect the UCST-transitions of the polyzwitterions notably. In specific cases, this results in "schizophrenic" thermoresponsive behavior displaying simultaneously an UCST and an LCST (lower critical solution temperature) transition. Exploratory experiments on the UCST-transition triggered the encapsulation and release of various solvatochromic fluorescent dyes as model "cargos" failed, apparently due to the poor affinity even of charged organic compounds to the collapsed state of the polyzwitterions.
The impact of the orientation of zwitterionic groups, with respect to the polymer backbone, on the antifouling performance of thin hydrogel films made of polyzwitterions is explored. In an extension ...of the recent discussion about differences in the behavior of polymeric phosphatidylcholines and choline phosphates, a quasi‐isomeric set of three poly(sulfobetaine methacrylate)s is designed for this purpose. The design is based on the established monomer 3‐N‐2‐(methacryloyloxy)ethyl‐N,N‐dimethylammonio‐propane‐1‐sulfonate and two novel sulfobetaine methacrylates, in which the positions of the cationic and the ionic groups relative to the polymerizable group, and thus also to the polymer backbone, are altered. The effect of the varied segmental dipole orientation on their water solubility, wetting behavior by water, and fouling resistance is compared. As model systems, the adsorption of the model proteins bovine serum albumin (BSA), fibrinogen, and lysozyme onto films of the various polyzwitterion surfaces is studied, as well as the settlement of a diatom (Navicula perminuta) and barnacle cyprids (Balanus improvisus) as representatives of typical marine fouling communities. The results demonstrate the important role of the zwitterionic group's orientation on the polymer behavior and fouling resistance.
The orientation of the zwitterionic groups with respect to the polymer backbone is shown to be an important structural parameter affecting the antifouling properties of polyzwitterion hydrogel films. This is exemplified by a set of quasi‐isomeric poly(sulfobetaine methacrylate)s exhibiting specific profiles of fouling resistance against a series of model systems that include proteins, passively and actively settling marine fouling organisms.
Hydrophilic coatings exhibit ultra-low fouling properties in numerous laboratory experiments. In stark contrast, the antifouling effect of such coatings in vitro failed when performing field tests in ...the marine environment. The fouling release performance of nonionic and zwitterionic hydrophilic polymers was substantially reduced compared to the controlled laboratory environment. Microscopy and spectroscopy revealed that a large proportion of the accumulated material in field tests contains inorganic compounds and diatomaceous soil. Diatoms adhered to the accumulated material on the coating, but not to the pristine polymer. Simulating field tests in the laboratory using sediment samples collected from the test sites showed that incorporated sand and diatomaceous earth impairs the fouling release characteristics of the coatings. When exposed to marine sediment from multiple locations, particulate matter accumulated on these coatings and served as attachment points for diatom adhesion and enhanced fouling. Future developments of hydrophilic coatings should consider accumulated sediment and its potential impact on the antifouling performance.
Hydrogel coatings effectively reduce the attachment of proteins and organisms in laboratory assays, in particular when made from zwitterionic monomers. In field experiments with multiple species and ...non-living material, such coatings suffer from adsorption of particulate matter. In this study, the zwitterionic monomer 3-N-(2-methacryloyloxyethyl)-N,N-dimethylammonio propanesulfonate (SPE) was copolymerized with increasing amounts of the photo-crosslinker benzophenon-4-yloxyethyl methacrylate (BPEMA) to systematically alter the density of crosslinks between the polymer chains. The effect of increasing crosslink density on the antifouling (AF) performance of the coatings was investigated in laboratory assays and fields tests. In both cases, the AF performance was improved by increasing the crosslinker content. The coatings reduced protein, diatom, and barnacle accumulation, and showed better resistance to biomass accumulation. The findings underline that the marine AF performance of hydrogel coatings does not only depend on the specific chemical structure of the polymers, but also on their physico-chemical properties such as rigidity and swelling.
Polyzwitterions are generally known for their anti‐adhesive properties, including resistance to protein and cell adhesion, and overall high bio‐inertness. Yet there are a few polyzwitterions to which ...mammalian cells do adhere. To understand the structural features of this behavior, a panel of polyzwitterions with different functional groups and overall degrees of hydrophobicity is analyzed here, and their physical and biological properties are correlated to these structural differences. Cell adhesion is focused on, which is the basic requirement for cell viability, proliferation, and growth. With the here presented polyzwitterion panel, three different types of cell‐surface interactions are observed: adhesion, slight attachment, and cell repellency. Using immunofluorescence methods, it is found that human keratinocytes (HaCaT) form focal adhesions on the cell‐adhesive polyzwitterions, but not on the sample that has only slight cell attachment. Gene expression analysis indicates that HaCaT cells cultivated in the presence of a non‐adhesive polyzwitterion have up‐regulated inflammatory and apoptosis‐related cell signaling pathways, while the gene expression of HaCaT cells grown on a cell‐adhesive polyzwitterion does not differ from the gene expression of the growth control, and thus can be defined as fully cell‐compatible.
Human kerationcytes (HaCaT) cannot form focal adhesions on many highly hydrated polyzwitterionic surface coatings. Gene expression analysis indicates that HaCaT cells cultivated in the presence of poly(zwitterions) on which they cannot adhere have up‐regulated inflammatory and apoptosis‐related cell signaling pathways.
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