Tea Stains-Inspired Antifouling Coatings Based on Tannic Acid-Functionalized Agarose

It is well-known that tannic acid (TA) and its analogs bind strongly to various substrates to produce, for example, the familiar and unpleasant “tea stains”. Functionalization of a polymer or macromolecule with TA would confer the resulting biomacromolecules with similar binding or anchoring ability on many surfaces. To verify the hypothesis, the naturally occurring polysaccharide agarose (Agr) was functionalized with alkyl bromo moieties, followed by etherification with tannic acid under basic conditions via Williamson ether synthesis. The TA-functionalized Agr (AgrTA) so obtained can be deposited onto titanium (Ti), stainless steel (SS), and silicon surfaces via direct adsorption and intermolecular oxidative cross-linking. The AgrTA-deposited SS surfaces show good stability in flowing electrolytes of varying pH. The AgrTA-deposited SS surfaces can also effectively reduce the adsorption of bovine serum albumin and the adhesion of <i>Escherichia coli</i> and 3T3 fibroblasts. In perhaps what is an ironic twist, through proper molecular design, the undesirable “tea stains” have inspired the production of sustainable antifouling coatings

Chitosan-Based Peptidopolysaccharides as Cationic Antimicrobial Agents and Antibacterial Coatings

The rapid spread of multidrug-resistant bacteria has called for effective antimicrobial agents which work on a more direct mechanism of killing. Cationic peptidopolysaccharides are developed in the present work to mimic the peptidoglycan structure of bacteria and to enhance the membrane-compromising bactericidal efficacy. Antimicrobial CysHHC10 peptide was grafted to the C-2 (amino) or C-6 (hydroxyl) position of chitosan backbone via thiol-maleimide “click” conjugation, utilizing the maleimidohexanoic linkers. The peptidopolysaccharide with primary amino backbone intact (CSOHHC) exhibited higher bactericidal activity toward Gram-positive and Gram-negative bacteria, in comparison to that with amino backbone grafted with the peptide (CSNHHC). Both peptidopolysaccharides also exhibited lower hemolytic activity and cytotoxicity than free CysHHC10 peptide due to the moderation effect contributed by the chitosan backbone. For targeting the Gram-positive bacteria in particular, the CSOHHC expressed 4- and 2-fold increases in hemo- and cytoselectivity, respectively, as compared to the CysHHC10 peptide. In an extended application, peptidopolysaccharide antibacterial coatings were formed via layer-by-layer assembly with tannic acid. The peptidopolysaccharide coatings readily killed the adhered bacteria upon contact while being cytocompatible by maintaining more than 60% viability for the adhered fibroblasts. Therefore, the peptidoglycan-mimetic peptidopolysaccharides are potential candidates for anti-infective drugs in biomedical applications

Dextran- and Chitosan-Based Antifouling, Antimicrobial Adhesion, and Self-Polishing Multilayer Coatings from pH-Responsive Linkages-Enabled Layer-by-Layer Assembly

To meet the demand for more environmentally friendly antifouling coatings and to improve fouling-resistant coatings with both “offense” and “defense” functionalities, polysaccharides (PSa)-based self-polishing multilayer coatings were developed for combating biofouling. Dextran aldehyde (Dex-CHO) and carboxymethyl chitosan (CMCS) were synthesized and alternatively incorporated via imine linkage into the multilayer coating in layer-by-layer (LbL) deposition. Surface plasmon resonance (SPR) technique was utilized to monitor the LbL assembly process. With increasing number of assembled bilayers, the antifouling performances against bovine serum albumin (BSA) adsorption, bacterial (<i>S. aureus</i> and <i>E. coli</i>) adhesion, and alga (<i>Amphora coffeaeformis</i>) attachment improved steadily. The self-polishing ability of the multilayer coatings was achieved via cleavage of pH-responsive imine linkage under acidic environments. As such, dense bacterial adhesion induced detachment of the outmost layer of the coatings. The efficacies of antifouling and antimicrobial adhesion were thus enhanced by the self-polishing ability of the multilayer coatings. Therefore, the LbL-deposited self-polishing dextran/chitosan multilayer coatings offer an environmentally friendly and sustainable alternative for combating biofouling in aquatic environments

Thiol Reactive Maleimido-Containing Tannic Acid for the Bioinspired Surface Anchoring and Post-Functionalization of Antifouling Coatings

Inspired by tea stains, a new surface anchor, maleimido-containing tannic acid (TAMA), was developed to introduce the maleimido functionality onto stainless steel (SS) surfaces. The feasibility of maleimido groups to serve as anchoring sites for surface functionalization via Michael addition was explored in a model experiment using thiol-containing 1<i>H</i>,1<i>H</i>,2<i>H</i>,2<i>H</i>-perfluorodecanethiol. The surface conjugation efficiency of TAMA with the thiol-containing compounds via Michael addition was also compared to that of the surface with tannic acid (TA) only. Water-soluble thiolated carboxymethyl chitosan (CMCSSH) was then grafted on the SS surface preanchored with TAMA via solution immersion and spin coating. The deposition of CMCSSH was characterized by contact angle measurement, surface zeta potential, and X-ray photoelectron spectroscopy (XPS). The antifouling efficacy of the CMCSSH coatings was evaluated by protein adsorption and bacterial adhesion. The cytotoxic effect of the CMCSSH coatings on mammalian cells was evaluated using the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with 3T3 fibroblasts

Antifouling Coatings via Tethering of Hyperbranched Polyglycerols on Biomimetic Anchors

Hyperbranched polyglycerols (HPG) bearing terminal thiol moieties (HPG-SH) were synthesized via anionic-ring-opening multibranching polymerization of glycidol from pentaerythritol and subsequent 1,1′-carbonyldiimidazole (CDI) coupling with cysteamine. Bioinspired (1) <i>N</i>-dopamine maleimide (DM), (2) tannic acid (TA), and (3) polydopamine (PDA) were employed to produce monolayer, multilayer, and polymeric anchors, respectively, on stainless-steel (SS) substrates. Postfunctionalization of the biomimetic anchor-modified SS surfaces was enacted by tethering of HPG-SH via Michael addition or thiol–ene “click” reaction to confer surface hydrophilicity. The thickness and grafting density of HPG coatings could be controlled by tuning the degree of thiolation. In comparison to the pristine SS surface, the HPG-modified surfaces exhibited substantially reduced initial adhesion and inhibition of the biofilm formation of Gram-negative Pseudomonas sp. and Gram-positive Staphylococcus epidermidis. Qualitative and quantitative assays of settlement of the microalgae Amphora coffeaeformis further demonstrate the low fouling characteristics of the HPG-modified surfaces. Therefore, tethering of HPG coatings on biomimetic anchors provides an environmentally benign alternative to antifouling surfaces

Arginine-Based Polymer Brush Coatings with Hydrolysis-Triggered Switchable Functionalities from Antimicrobial (Cationic) to Antifouling (Zwitterionic)

Arginine polymer based coatings with switchable properties were developed on glass slides (GS) to demonstrate the smart transition from antimicrobial (cationic) to fouling-resistant (zwitterionic) surfaces. l-Arginine methyl ester-methacryloylamide (Arg-Est) and l-arginine-methacryloylamide (Arg-Me) polymer brushes were grafted from the GS surface via surface-initiated reversible addition–fragmentation chain-transfer (SI-RAFT) polymerization. In comparison to the pristine GS and Arg-Me graft polymerized GS (GS-Arg-Me) surfaces, the Arg-Est polymer brushes-functionalized GS surfaces exhibit a superior antimicrobial activity. Upon hydrolysis treatment, the strong bactericidal efficacy switches to good resistance to adsorption of bovine serum albumin (BSA), the adhesion of Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli, as well as the attachment of Amphora coffeaeformis. In addition, the switchable coatings are proven to be biocompatible. The stability and durability of the switchable coatings are also ascertained after exposure to filtered seawater for 30 days. Therefore, deposition of the proposed “smart coatings” offers another environmentally friendly alternative for combating biofouling

Conjugation of Polyphosphoester and Antimicrobial Peptide for Enhanced Bactericidal Activity and Biocompatibility

Enhancing the bactericidal activity and moderating the toxicity are two important challenges in the design of upcoming antimicrobial compounds. Herein, antimicrobial macromolecules were developed by conjugating CysHHC10 peptide and polyphosphoester for the modulation of microbiocidal activity and biocompatibility. The conjugation was carried out via thiol-yne “click” chemistry between the cysteine terminal of the peptide and the pendant propargyl moieties of the polyphosphoester. The bactericidal efficacy of the polyphosphoester–peptide conjugates were investigated by microbial growth inhibition toward the Gram-positive and Gram-negative bacteria. On the basis of peptide mass fraction, the polyphosphoester–peptide conjugates exhibited lower values of minimum inhibitory concentration than that of the free peptide. The polyphosphoester–peptide conjugates also exhibited ultralow hemolytic characteristic at a concentration of 4000 μg/mL, indicating significant improvement of erythrocytes compatibility as compared to the free peptide that readily caused lysis of 50% of red blood cells at 1000 μg/mL. Cytotoxicity of the polyphosphoester–peptide conjugates toward 3T3 fibroblast cells was also reduced in comparison to that of the free peptide. Conjugation of the polyphosphoester thus improves the bactericidal efficacy and biocompatibility of the antimicrobial peptide

Antifouling and Antimicrobial Coatings from Zwitterionic and Cationic Binary Polymer Brushes Assembled via “Click” Reactions

Controlled architecture of bifunctional polymers on surfaces is highly challenged because of the stringent reaction conditions or tedious operations required for surface modification. Herein, a simple and effective method was developed to assemble zwitterionic and cationic binary polymer brushes onto polydopamine-anchored stainless steel (SS) surfaces. Zwitterionic poly­(2-methacryloyloxyethyl phosphorylcholine) (PMPC) was first graft polymerized from the functionalized SS surface via thiol–ene “click” reaction. Alkynyl-modified cationic poly­(2-(methacryloyloxy) ethyl trimethylammonium chloride) (alkynyl-PMETA) was subsequently introduced via azide–alkyne “click” reaction. After the grafting of PMPC/PMETA binary polymer brushes, the resulting functionalized SS surfaces can cooperatively reduce the adhesion of Gram-positive bacteria Staphylococcus aureus (S. aureus) and Gram-negative bacteria Pseudomonas sp., as well as the attachment of microalgae Amphora coffeaeformis. In addition, the binary polymer brushes coatings were ascertained to be stable and durable after 30-day exposure to filtered seawater. Thus, surface functionalization with zwitterionic and cationic binary polymer brushes offers an environmentally friendly alternative for biofouling inhibition in the marine and aquatic environments. In addition, surface modification via dual “click” reactions provides another alternation for developing surface coatings with multifunctionalities

pH-Sensitive Zwitterionic Polymer as an Antimicrobial Agent with Effective Bacterial Targeting

It is highly desirable to develop new and more potent biocompatible antimicrobial agents to reduce the increasing risk of bacterial infection worldwide. To address this problem, we prepared a smart pH-sensitive polymer, poly­(<i>N</i>′-citraconyl-2-(3-aminopropyl-<i>N</i>,<i>N</i>-dimethylammonium)­ethyl methacrylate), or P­(CitAPDMAEMA), which can undergo change in functionality from a biocompatible zwitterionic polymer to an antimicrobial cationic polymer at acidic bacterial infection sites. The precursor polymer, poly­(2-(3-aminopropyl-<i>N</i>,<i>N</i>-dimethylammonium)­ethyl methacrylate) (P­(APDMAEMA)), was first prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization, and then modified with citraconic anhydride to obtain the zwitterionic P­(CitAPDMAEMA). P­(CitAPDMAEMA) is zwitterionic at physiological pH and exhibits low hemotoxicity and good biocompatibility. However, P­(CitAPDMAEMA) can change from neutral to cationic with decreasing pH because of the hydrolysis of citraconic amide under low pH conditions. This switch leads to pronounced bacteria binding of cationic P­(CitAPDMAEMA) under acidic conditions of the infection sites and significantly inhibits the growth of <i>Escherichia coli</i> (<i>E. coli</i>) and <i>Staphylococcus aureus</i> (<i>S. aureus</i>). These results indicate that P­(CitAPDMAEMA) is potentially a new on-demand antimicrobial agent

Layer-by-Layer Click Deposition of Functional Polymer Coatings for Combating Marine Biofouling

“Click” chemistry-enabled layer-by-layer (LBL) deposition of multilayer functional polymer coatings provides an alternative approach to combating biofouling. Fouling-resistant <i>azido</i>-functionalized poly­(ethylene glycol) methyl ether methacrylate-based polymer chains (<i>azido</i>-poly­(PEGMA)) and antimicrobial <i>alkynyl</i>-functionalized 2-(methacryloyloxy)­ethyl trimethyl ammonium chloride-based polymer chains (<i>alkynyl</i>-poly­(META)) were click-assembled layer-by-layer via alkyne–azide 1,3-dipolar cycloaddition. The polymer multilayer coatings are resistant to bacterial adhesion and are bactericidal to marine Gram-negative Pseudomonas sp. NCIMB 2021 bacteria. Settlement of barnacle (Amphibalanus (=Balanus) amphitrite<i></i>) cyprids is greatly reduced on the multilayer polymer-functionalized substrates. As the number of the polymer layers increases, efficacy against bacterial fouling and settlement of barnacle cyprids increases. The LBL-functionalized surfaces exhibit low toxicity toward the barnacle cyprids and are stable upon prolonged exposure to seawater. LBL click deposition is thus an effective and potentially environmentally benign way to prepare antifouling coatings