Polymer Hydrogel Sheets with Perpendicular Cross-Linking Gradient: Non-Monotonic Actuation and Ion-Specific Effects on the Actuation Kinetics.

Non-monotonous actuation, that is, different kinds of motion in response to a single stimulus, is observed in some natural materials but difficult to implement in synthetic systems. Herein, polymer hydrogel sheets made from polyacrylamide (PAAm) or poly(dimethylacrylamide) (PDMAA) with a cross-linking gradient along the sheet thickness are reported. These are obtained by thermally initiated free radical polymerization using a specially designed Teflon mold with a glass lid. The resulting PAAm hydrogels undergo non-monotonous actuation (rolling into a tube and re-opening) when exposed to aqueous media as a single external stimulus. Their actuation kinetics is tuned with anions that have specific ion effects in their interaction with the surrounding solvent and the polymer itself: structure-breaking chloride enhances the hydration of the polymer backbone, structure-making sulfate decreases it, and is thus slowing down the actuation kinetics of the PAAm hydrogels. The PDMAA gel rolls up instantaneously in aqueous NaCl and only re-opens after 24 h. PDMAA actuation in aqueous Na2 SO4 is only moderate as the gel did not swell in that solvent. Bilayer hydrogels made from PAAm and PDMAA (without gradient) show monotonic actuation, closing in NaCl solution and re-opening in Na2 SO4 .

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.

How Do Polymer Coatings Affect the Growth and Bacterial Population of a Biofilm Formed by Total Human Salivary Bacteria?-A Study by 16S-RNA Sequencing.

Antimicrobial surface modifications are required to prevent biomaterial-associated biofilm infections, which are also a major concern for oral implants. The aim of this study was to evaluate the influence of three different coatings on the biofilm formed by human saliva. Biofilms grown from human saliva on three different bioactive poly(oxanorbornene)-based polymer coatings (the protein-repellent PSB: poly(oxanorbornene)-based poly(sulfobetaine), the protein-repellent and antimicrobial PZI: poly(carboxyzwitterion), and the mildly antimicrobial and protein-adhesive SMAMP: synthetic mimics of antimicrobial peptides) were analyzed and compared with the microbial composition of saliva, biofilms grown on uncoated substrates, and biofilms grown in the presence of chlorhexidine digluconate. It was found that the polymer coatings significantly reduced the amount of adherent bacteria and strongly altered the microbial composition, as analyzed by 16S RNA sequencing. This may hold relevance for maintaining oral health and the outcome of oral implants due to the existing synergism between the host and the oral microbiome. Especially the reduction of some bacterial species that are associated with poor oral health such as Tannerella forsythia and Fusobacterium nucleatum (observed for PSB and SMAMP), and Prevotella denticola (observed for all coatings) may positively modulate the oral biofilm, including in situ.

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.

Progress in the Free and Controlled Radical Homo- and Co-Polymerization of Itaconic Acid Derivatives: Toward Functional Polymers with Controlled Molar Mass Distribution and Architecture.

Polymeric derivatives of itaconic acid are becoming increasingly more interesting for research and industry because itaconic acid is accessible from renewable resources. In spite of the structural similarity of poly(itaconic acid derivatives) to poly(methacrylates), they are much less reactive, homopolymerize only sluggishly by free radical polymerization (FRP), and are often obtained with low molar masses and conversions. This has so far limited their use. The reasons for the low reactivity of itaconic acid derivatives (including itaconimides, diitaconates, and diitaconamides) are combined steric and electronic effects, as demonstrated by the body of literature on the FRP homopolymerization kinetics of these monomers which is summarized herein. These problems can be solved to a large extent by using controlled radical polymerization (CRP) techniques, notably atom transfer radical polymerization (ATRP) and reversible addition and fragmentation chain transfer radical polymerization (RAFT). By optimizing the reaction conditions for the ATRP and RAFT of itaconic acid derivatives, in particular the reaction temperature, linear relations between molar mass and conversion are obtained in many cases, and homopolymers with high molar masses and reasonably narrow polydispersity indices become accessible. This review presents the state-of-the-art FRP and CRP of itaconic acid derivatives, and highlights functional polymers obtained by these methods.

Poly(oxanorbornene)-Coated CdTe Quantum Dots as Antibacterial Agents.

In this study, synthetic mimics of antimicrobial peptides based on poly(oxanorbornene) molecules (or PONs) were used to coat CdTe quantum dots (QDs). These PONs-CdTe QDs were investigated for their activity against Escherichia coli, a bacterium with antibiotic resistant strains. At the same time, the antibacterial activity of the PONs-CdTe QDs was compared to the antibacterial activity of free PONs and free CdTe QDs. The observed antibacterial activity of the PONs-CdTe QDs was additive and concentration dependent. The conjugates had a significantly lower minimum inhibitory concentration (MIC) than the free PONs and QDs, particularly for PONs-CdTe QDs which contained PONs of high amine density. The maximum activity of PONs-CdTe QDs was not realized by conjugating PONs with the highest intrinsic antibacterial activity (i.e., the lowest MIC in solution as free PONs), indicating that the mechanism of action for free PONs and PONs-CdTe QDs is different. Equally important, conjugating PONs to CdTe QDs decreased their hemolytic activity against red blood cells compared to free PONs, lending to higher therapeutic indices against E. coli. This could potentially enable the use of higher, and therefore more effective, PONs-QDs concentrations when addressing bacterial contamination, without concerns of adverse impacts on mammalian cells and organisms.

Bioinspired All-Polyester Diblock Copolymers Made from Poly(pentadecalactone) and Poly(3-hydroxycinnamate): Synthesis and Polymer Film Properties.

A bioinspired diblock copolymer was synthesized from pentadecalactone and 3-hydroxy cinnamic acid. Poly(pentadecalactone) (PPDL) with a molar mass of up to 43,000 g mol-1 was obtained by ring-opening polymerization initiated propargyl alcohol. Poly(3-hydroxy cinnamate) (P3HCA) was obtained by polycondensation and end-functionalized with 3-azido propanol. The two functionalized homopolymers were connected via 1,3-dipolar Huisgen addition to yield the block copolymer PPDL-triazole-P3HCA. The structure the block copolymer was confirmed by proton NMR, FTIR spectroscopy and GPC. By analyzing the morphology of polymer films made from the homopolymers, from a 1:1 homopolymer blend, and from the PPDL-triazole-P3HCA block copolymer, clearly distinct micro- and nanostructures were revealed. Quantitative nanomechanical measurements revealed that the block copolymer PPDL-triazole-P3HCA had a DMT modulus of 22.3 ± 2.7 MPa, which was lower than that of the PPDL homopolymer (801 ± 42 MPa), yet significantly higher than that of the P3HCA homopolymer (1.77 ± 0.63 MPa). Thermal analytics showed that the melting point of PPDL-triazole-P3HCA was similar to PPDL (89-90 °C), while it had a glass transition was similar to P3HCA (123-124 °C). Thus, the semicrystalline, potentially degradable all-polyester block copolymer PPDL-triazole-P3HCA combines the thermal properties of either homopolymer, and has an intermediate elastic modulus.

Bioinspired All-Polyester Diblock Copolymers Made from Poly(pentadecalactone) and Poly(2-(2-hydroxyethoxy)benzoate): Synthesis and Polymer Film Properties.

The bioinspired diblock copolymers poly(pentadecalactone)-block-poly(2-(2-hydroxyethoxy)-benzoate) (PPDL-block-P2HEB) were synthesized from pentadecalactone and dihydro-5H-1,4-benzodioxepin-5-one (2,3-DHB). No transesterification between the blocks was observed. In a sequential approach, PPDL obtained by ring-opening polymerization (ROP) was used to initiate 2,3-DHB. Here, the molar mass Mn of the P2HEB block was limited. In a modular approach, end-functionalized PPDL and P2HEB were obtained separately by ROP with functional initiators, and connected by 1,3-dipolar Huisgen reaction ("click-chemistry"). Block copolymer compositions from 85:15 mass percent to 28:72 mass percent (PPDL:P2HEB) were synthesized, with Mn of from about 30,000-50,000 g mol-1. The structure of the block copolymer was confirmed by proton NMR, FTIR spectroscopy, and gel permeation chromatography. Morphological studies by atomic force microscopy (AFM) further confirmed the block copolymer structure, while quantitative nanomechanical AFM measurements revealed that the DMT moduli of the block copolymers ranged between 17.2 ± 1.8 MPa and 62.3 ± 5.7 MPa, i.e. between the values of the parent P2HEB and PPDL homopolymers (7.6 ± 1.4 MPa and 801 ± 42 MPa, respectively). Differential scanning calorimetry showed that the thermal properties of the homopolymers were retained by each of the copolymer blocks (melting temperature 90 °C, glass transition temperature 36 °C).

Degradable Polymer Films Made from Poly(salicylic-acid-co-sebacic acid) and Poly(sebacic anhydride)/Poly(adipic anhydride) Blends: Degradation Kinetics and Use as Sacrificial Layers for Polymer Multilayer Systems.

Two approaches to obtain fast-degrading polymer films based on poly(sebacic anhydride) (PSA) are presented, both of which target polymer films with a lower degree of crystallinity than pure PSA homopolymer: first, thin films were prepared from poly(adipic anhydride)/poly(sebacic anhydride) blends at different ratios, and second, films were made from the copolymer poly(salicylic acid-co-sebacic acid). These films are intended as sacrificial layers for self-regenerating functional coatings, for example to regenerate antimicrobial surface activity. The degradation kinetics of these films were analyzed by surface plasmon resonance spectroscopy (SPR). The results of the blends approach indicate that the blend degradation rate was accelerated only in the initial degradation phase (compared to PSA). The degradation kinetics study of the poly(salicylic-acid-co-sebacic acid) film shows that this copolymer degraded faster than poly(sebacic anhydride) initially, releasing antimicrobial salicylic acid in the process. However, its degradation rate slowed down at a mass loss > 60% and approached the PSA degradation curve at longer degradation times. When tested as sacrificial layer in self-regenerating antimicrobial polymer stacks, it was found that the degradation rate was too low for successful layer shedding.

Stimulus-Responsive Polyzwitterionic Surfaces Made from Itaconic Acid: Self-Triggered Antimicrobial Activity, Protein Repellency, and Cell Compatibility.

A functional monomer carrying a carboxylate and a protected primary ammonium group is synthesized from itaconic acid. When copolymerized with dimethyl acrylamide and 4-methacryloyloxybenzophenone, cross-linkable polyzwitterions are obtained. These are converted to surface-attached polyzwitterion networks by simultaneous UV-triggered C,H insertion reactions. The resulting polyzwitterion-coated substrates were studied by surface plasmon resonance spectroscopy measurements, ζ potential and various biological assays. They were (expectedly) protein repellent, yet at the same time (and unexpectedly) cell-adhesive and antimicrobially active. This was attributed to stimulus-responsiveness of the polyzwitterion (confirmed by the ζ potential measurements), which enables charge adjustment at different pH values. When protonated, the polyzwitterions become amphiphilic polycations and, in this state, kill bacteria upon contact like their parent structures (polymer-based synthetic mimics of antimicrobial peptides, SMAMPs).

Quantified Membrane Permeabilization Indicates the Lipid Selectivity of Membrane-Active Antimicrobials.

Most antimicrobial peptides (AMPs) and their synthetic mimics (SMAMPs) are thought to act by permeabilizing cell membranes. For antimicrobial therapy, selectivity for pathogens over mammalian cells is a key requirement. Understanding membrane selectivity is thus essential for designing AMPs and SMAMPs to complement classical antibiotics in the future. This study focuses on membrane permeabilization induced by SMAMPs and their selectivity for membranes with different lipid compositions. We measure release and fluorescence lifetime of a self-quenching dye in lipid vesicles. Apart from the dose-response, we quantify the strength of individual leakage events, and, employing cumulative kinetics, categorize permeabilization behavior. We propose that differing selectivities in a series of SMAMPs arise from a combination of the effect of the antimicrobial agent and the susceptibility of the membrane (with a given lipid composition) for certain types of leakage behavior. The unselective and hemolytic SMAMP is found to act mainly by the asymmetry stress mechanism, mediated by hydrophobic insertion of SMAMPs into lipid layers. The more selective SMAMPs induced leakage events occurring stochastically over several hours. Lipid intrinsic properties might additionally amplify the efficiency of leakage events. Leakage behavior changes with both the design of the SMAMP and the lipid composition of the membrane. Understanding how leakage behavior contributes to the selectivity and activity of antimicrobial agents will aid the design and screening of antimicrobials. An understanding of the underlying processes facilitates the comparison of membrane permeabilization across in vitro and in vivo assays.

Bifunctional Bioactive Polymer Surfaces with Micrometer and Submicrometer-sized Structure: The Effects of Structure Spacing and Elastic Modulus on Bioactivity.

This study presents a comparison of two types of bifunctional structured surface that were made from the same polymer -- an antimicrobial polycation (a synthetic mimic of an antimicrobial peptide, SMAMP) and a protein-repellent polyzwitterion (poly(sulfobetaines), PSB). The first type of bifunctional surface was fabricated by a colloidal lithography (CL) based process where the two polymers were immobilized sequentially onto pre-structured surfaces with a chemical contrast (gold on silicon). This enabled site-selective covalent attachment. The CL materials had a spacing ranging from 200 nm to 2 µm. The second type of structured surface (spacing: 1 - 8.5 µm) was fabricated using a microcontact printing (µCP) process where SMAMP patches were printed onto a PSB network, so that 3D surface features were obtained. The thus obtained materials were studied by quantitative nanomechanical measurements using atomic force microscopy (QNM-AFM). The different architectures led to different local elastic moduli at the polymer-air interface, where the CL surfaces were much stiffer (Derjaguin-Muller-Toporov (DMT) modulus = 20 ± 0.8 GPa) compared to the structured 3D networks obtained by µCP (DMT modulus = 42 ± 1.1 MPa). The effects of the surface topology and stiffness on the antimicrobial activity against Escherichia coli, the protein repellency (using fibrinogen), and the compatibility with human gingival mucosal keratinocytes were investigated. The softer 3D µCP surfaces had simultaneous antimicrobial activity, protein repellency, and cell compatibility at all spacings. For the stiffer CL surfaces, quantitative simultaneous antimicrobial activity and protein repellency was not obtained. However, the cell compatibility could be maintained at all spacings. The optimum spacing for the CL materials was in the range of 500 nm-1 µm, with significantly reduced antimicrobial activity at 2 µm spacing. Thus, the soft polymer network obtained by µCP could be more easily optimized than the stiff CL surface, and had a broader topology range of optimal or near-optimal bioactivity.

Electrochemically Controlled Drug Release from a Conducting Polymer Hydrogel (PDMAAp/PEDOT) for Local Therapy and Bioelectronics.

In this study, the release of fluorescein from a photo-crosslinked conducting polymer hydrogel made from a hydrogel precursor poly(dimethylacrylamide-co-4-methacryloyloxy benzophenone (5%)-co-4-styrenesulfonate (2.5%)) (PDMAAp) and the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) is investigated. Fluorescein, here used as a model for a drug, is actively released through application of an electrical trigger signal. The detected quantity is more than six times higher in comparison to that released from a conventional PEDOT/polysterene sulfonate (PSS) system. Release profiles, drug dose, and timing can be tailored by the application of different trigger signals and pretreatments. To demonstrate that the novel drug release system can be used for a drug relevant for local delivery to a neural interface, experiments are furthermore performed with the anti-inflammatory drug dexamethasone (Dex). The conducting polymer hydrogel facilitates the active release of Dex, in comparison to the previously used PEDOT/Dex. It is suggested that PEDOT/PDMAAp is an interesting alternative for conducting polymer based drug release systems, with the potential to offer more volume for storage, yet retaining the excellent electrochemical properties known for PEDOT electrodes.

Surface Structuring Combined with Chemical Surface Functionalization: An Effective Tool to Manipulate Cell Adhesion.

In this study, we investigate how a surface structure underneath a surface-attached polymer coating affects the bioactivity of the resulting material. To that end, structured surfaces were fabricated using colloidal lithography (lateral dimensions: 200 nm to 1 µm, height ~15 to 50 nm). The surface structures were further functionalized either with antimicrobial, cell-adhesive polycations or with protein-repellent polyzwitterions. The materials thus obtained were compared to non-functionalized structured surfaces and unstructured polymer monolayers. Their physical properties were studied by contact-angle measurements and atomic force microscopy (AFM). Protein adhesion was studied by surface plasmon resonance spectroscopy, and the antimicrobial activity against Escherichia coli bacteria was tested. The growth of human mucosal gingiva keratinocytes on the materials was analyzed using the Alamar blue assay, optical microscopy, and live-dead staining. The data shows that the underlying surface structure itself reduced protein adhesion and also bacterial adhesion, as evidenced by increased antimicrobial activity. It also enhanced cell adhesion to the surfaces. Particularly in combination with the adhesive polycations, the surfaces increased the cell growth compared to the unstructured reference materials. Thus, functionalizing structured surfaces with adhesive polymer could be a valuable tool for improved tissue integration.

Antibacterial Activity of Polymers: Discussions on the Nature of Amphiphilic Balance.

The purpose of this Viewpoint is to discuss the molecular design principles that guide development of synthetic antimicrobial polymers, especially those intended to mimic the structure of host defense peptides (HDPs). In particular, we focus on the principle of "amphiphilic balance" as it relates to some recently developed polyphosphoniums with somewhat atypical structure. We find that the fundamental concept of amphiphilic balance is still applicable to these new polymers, but that the method to achieve such balance is somewhat unique. We then briefly outline the future challenges and opportunities in this field.

Degradation of Polymer Films on Surfaces: A Model Study with Poly(sebacic anhydride).

There is compelling evidence that the degradation kinetics of thin polymer films differ significantly from those of bulk materials, as interfacial effects become dominant. Therefore, it is crucial to investigate these kinetics separately. Qualitative analytics of thin film degradation exist, e.g. by scanning electron microscopy or atomic force microscopy (AFM), but a quantitative study is so far missing. In this work, poly(sebacic anhydride) (PSA), an aliphatic polyanhydride, is used as a model system for a quantitative degradation study. PSA was spin-coated onto silicon or gold substrates. The degradation of these PSA films was monitored by ellipsometry, surface-plasmon resonance spectroscopy (SPR), and Fourier transform infrared spectroscopy (FTIR). Two kinetic regimes were observed when plotting the relative layer thickness determined by FTIR and SPR against the degradation time. The data obtained by FTIR showed a single process for the rate of ester bond cleavage. Overall, the degradation rate constants of PSA determined by the different methods were consistent. The degradation rate constants of PSA film up to 378 nm thickness were constant. Several thicker free-standing samples studied gravimetrically had a degradation rate constant that was one order of magnitude slower, thus confirming thickness-dependent degradation rate constants.

Self-Regenerating Antimicrobial Polymer Surfaces via Multilayer-Design - Sequential and Triggered Layer Shedding under Physiological Conditions.

Regeneration of materials properties through surface regeneration could extend the lifetime of devices and is still an emerging field of research. (Self-)regenerating antimicrobial polymer surfaces could help to fight biofilm formation and related bacterial infections. In this paper, four different polymer multilayer designs for the regeneration of antimicrobial surfaces by layer shedding are presented. The multilayer architectures consist of 100-200 nm thick, discrete polymer layers. They are made from poly(guanidinium oxanorbornene) networks as the antimicrobial component, and different interlayers made from degradable poly(adipic anhydrides), depolymerizable poly(ethyl glyoxylate), or water-soluble poly(acrylamide). Layer shedding is designed to occur after hydrolysis, dissolution or depolymerization under simulated physiological conditions. The multilayer fabrication and disassembly is monitored by fluorescence microscopy, ellipsometry FT-IR spectroscopy and atomic force microscopy. By testing the antimicrobial activity of the restored surfaces, their functional integrity after layer shedding is confirmed.

Wafer-Scale Fabrication of Conducting Polymer Hydrogels for Microelectrodes and Flexible Bioelectronics.

Future-oriented directions in neural interface technologies point towards the development of multimodal devices that combine different functionalities such as neural stimulation, neurotransmitter sensing, and drug release within one platform. Conducting polymer hydrogels (CPHs) are suggested as materials for the coating of standard metal electrodes to add functionalities such as local delivery of therapeutic drugs. However, to make such coatings truly useful for multimodal devices, it is necessary to develop process technologies that allow the micropatterning of CPHs onto selected electrode sites. In this study, a wafer-scale fabrication procedure is presented, which is used to coat the CPH, based on the hydrogel P(DMAA-co-5%MABP-co-2,5%SSNa) and the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT), onto flexible neural probes. The resulting material has favorable properties for the generation of recording electrodes and in addition offers a convenient platform for biofunctionalization. By controlling the PEDOT content within the hydrogel matrix, charge injection limits of up to 3.7 mC cm-2 are obtained. Long-term stability is tested by immersing coated samples in phosphate-buffered saline solution at 37 °C for 1 year. Non-cytotoxicity of the coatings is confirmed with a direct cell culture test using a fluorescent neuroblastoma cell line.

Three-Dimensional, Bifunctional Microstructured Polymer Hydrogels Made from Polyzwitterions and Antimicrobial Polymers.

Biofilm-associated infections of medical devices are a global problem. For the prevention of such infections, biomaterial surfaces are chemically or topographically modified to slow down the initial stages of biofilm formation. In the bifunctional material here presented, chemical and topographical cues are combined, so that protein and bacterial adhesion as well as bacterial proliferation are effectively inhibited. Upon changes in the surface topography parameters and investigation of the effect of these changes on bioactivity, structure-property relationships are obtained. The target material is obtained by microcontact printing (µCP), a soft lithography method. The antimicrobial component, poly(oxanorbornene)-based synthetic mimics of an antimicrobial peptide (SMAMP), was printed onto a protein-repellent polysulfobetaine hydrogel, so that bifunctional 3D structured polymer surfaces with 1, 2, and 8.5 µm spacing are obtained. These surfaces are characterized with fluorescence microscopy, surface plasmon resonance spectroscopy, atomic force microscopy, and contact angle measurements. Biological studies show that the bifunctional surfaces with 1 and 2 µm spacing are 100% antimicrobially active against Escherichia coli and Staphylococcus aureus, 100% fibrinogen-repellent, and nontoxic to human gingival mucosal keratinocytes. At 8.5 µm spacing, the broad-band antimicrobial activity and the protein repellency are compromised, which indicates that this spacing is above the upper limit for effective simultaneous antimicrobial activity and protein repellency of polyzwitterionic-polycationic materials.

Surface-Attached Poly(oxanorbornene) Hydrogels with Antimicrobial and Protein-Repellent Moieties: The Quest for Simultaneous Dual Activity.

By copolymerizing an amphiphilic oxanorbornene monomer bearing N- tert-butyloxycarbonyl (Boc) protected cationic groups with an oxanorbornene-functionalized poly(ethylene glycol) (PEG) macromonomer, bifunctional comb copolymers were obtained. Varying the comonomer ratios led to copolymers with PEG contents between 5⁻25 mol %. These polymers were simultaneously surface-immobilized on benzophenone-bearing substrates and cross-linked with pentaerythritoltetrakis(3-mercaptopropionate). They were then immersed into HCl to remove the Boc groups. The thus obtained surface-attached polymer hydrogels (called SMAMP*-co-PEG) were simultaneously antimicrobial and protein-repellent. Physical characterization data showed that the substrates used were homogeneously covered with the SMAMP*-co-PEG polymer, and that the PEG moieties tended to segregate to the polymer⁻air interface. Thus, with increasing PEG content, the interface became increasingly hydrophilic and protein-repellent, as demonstrated by a protein adhesion assay. With 25 mol % PEG, near-quantitative protein-adhesion was observed. The antimicrobial activity of the SMAMP*-co-PEG polymers originates from the electrostatic interaction of the cationic groups with the negatively charged cell envelope of the bacteria. However, the SMAMP*-co-PEG surfaces were only fully active against E. coli, while their activity against S. aureus was already compromised by as little as 5 mol % (18.8 mass %) PEG. The long PEG chains seem to prevent the close interaction of bacteria with the surface, and also might reduce the surface charge density.