Stimulus-Responsive Polyelectrolyte Surfaces: Switching Surface Properties from Polycationic/Antimicrobial to Polyzwitterionic/Protein-Repellent

Surfaces coated with polyzwitterions are most well-known for their ability to resist protein adsorption. In this article, a surface-attached hydrophobically modified poly(carboxybetaine) is presented. When protonated by changes of the pH of the surrounding medium, this protein-repellent polyzwitterion switches to a polycationic state in which it is antimicrobially active and protein-adhesive. The pH range in which these two states exist are recorded by zeta potential measurements. Adsorption studies at different pH values (monitored by surface plasmon resonance spectroscopy) confirm that the adhesion of protein is pH dependent and reversible, that is, protein can be released upon a pH change from pH 3 to pH 7.4. At physiological pH, the poly(carboxyzwitterion) is antimicrobially active, presumably because it becomes protonated by bacterial metabolites during the antimicrobial activity assay. Stability studies confirm that the here presented material is storage-stable, yet hydrolyses after longer incubation in aqueous media

Poly(oxanorbornene)‐Based Polyzwitterions with Systematically Increasing Hydrophobicity : Synthesis, Physical Characterization, and Biological Properties

Surfaces coated with polyzwitterions are known to resist protein adhesion and to be generally bio-inert. In recent reports, several polyzwitterionic coatings with carboxylate groups and intrinsic antimicrobial activity due to the pH-responsivity of that group are described, but the design rules to obtain such activity remain unclear. Therefore, in this work, a set of surface-attached polyzwitterions with carboxylate groups and varying alkyl residues is studied. The gradually increasing hydrophobicity of these surfaces (verified by contact angle and swellability measurements) has an impact on their biological properties. Hydrophilic surfaces (polyzwitterions bearing short alkyl residues) behave like “classical” polyzwitterions: they repel proteins and human cells and are non-toxic to bacteria. The more hydrophobic polyzwitterionic surfaces are protein-adhesive, cell-toxic, and can kill bacteria. This indicates that the hydrophobicity of polyzwitterionic surfaces needs to be balanced precisely to combine protein-repellency and antimicrobial activity in a single material

Effect of Poly(Oxanorbonene)- and Poly(Methacrylate)-Based Polyzwitterionic Surface Coatings on Cell Adhesion and Gene Expression of Human Keratinocytes

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

A Simultaneously Antimicrobial, Protein-Repellent, and Cell-Compatible Polyzwitterion Network

A simultaneously anti­microbial, protein-repellent, and cell-compatible surface-attached polymer network is reported, which reduces the growth of bacterial biofilms on surfaces through its multi­function­ality. The coating was made from a poly­(oxo­nor­bornene)-based zwitterion (PZI), which was surface-attached and cross-linked in one step by simultaneous UV-activated CH insertion and thiol–ene reaction. The process was applicable to both laboratory surfaces like silicon, glass, and gold and real-life surfaces like poly­urethane foam wound dressings. The chemical structure and physical properties of the PZI surface and the two reference surfaces SMAMP (“synthetic mimic of an antimicrobial peptide”), an antimicrobial but protein-adhesive polymer coating, and PSB (poly­(sulfobetaine)), a protein-repellent but not antimicrobial polyzwitterion coating were characterized by Fourier transform infrared spectroscopy, ellipsometry, contact angle measurements, photoelectron spectroscopy, swellability measurements (using surface plasmon resonance spectroscopy, SPR), zeta potential measurements, and atomic force microscopy. The time-dependent anti­microbial activity assay (time-kill assay) confirmed the high anti­microbial activity of the PZI; SPR was used to demonstrate that it was also highly protein-repellent. Biofilm formation studies showed that the material effectively reduced the growth of <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> biofilms. Additionally, it was shown that the PZI was highly compatible with immortalized human mucosal gingiva keratin­ocytes and human red blood cells using the Alamar Blue assay, the live–dead stain, and the hemolysis assay. PZI thus may be an attractive coating for biomedical applications, particularly for the fight against bacterial biofilms on medical devices and in other applications