Coordination-driven robust antibacterial coatings using catechol-conjugated carboxymethyl chitosan.

To prevent bacterial contamination on solid surfaces, a simple yet efficient antibacterial coating was developed in a substrate-independent manner by using the catechol-conjugated carboxymethyl chitosan (CMC-DOPA). The CMC-DOPA was firstly synthesized via an aza-Michael reaction with methyl acrylate and the subsequent acyl substitution with dopamine. The coating strategy consists of spin-coating-assisted deposition of CMC-DOPA on polydopamine-coated substrates and coordination-driven crosslinks between catechol groups and Fe3+ ions in sequence, producing the multilayered CMC-DOPA films. The film thickness was controllable depending on the concentration of CMC-DOPA. Compared to bare controls, the CMC-DOPA-coated substrates reduced the bacterial adhesion by up to 99.8 % and 96.2 % for E. coli and S. aureus, respectively. It is demonstrated that the CMC-DOPA coating can be a robust antibacterial coating across various pH environments, inhibiting bacterial adhesion by 78.7 %, 95.1 %, and 93.2 %, respectively, compared to the control, even after 7 days of acidic, physiological, and alkaline pH treatment. The current coating approach could be applied to various substrates including silicon dioxide, titanium dioxide, and polyurethane. Given its simple and versatile coating capability, we think that the coordination-driven CMC-DOPA coating could be useful for various medical devices and implants.

Curcumin-Based Universal Grafting of Poly(OEGMA) Brushes and Their Antibacterial Applications.

Catechol and/or pyrogallol groups are recognized as crucial for the formation of polyphenol coatings on various substrates. Meanwhile, studies on polyphenolic molecules that do not contain such groups are relatively rare. The key molecule in turmeric-based universal (i.e., substrate-independent) coatings is curcumin, which contains no catechol or pyrogallol groups. As chemically reactive hydroxyl groups would remain after curcumin coating, it is hypothesized that curcumin coating can serve as a reactive layer for controlling interfacial properties. In this study, a curcumin-based surface modification method is developed to graft polymer brushes from various substrates, including titanium dioxide, gold, glass, stainless steel, and nylon. α-Bromoisobutyryl bromide, a polymerization initiator, is introduced to the curcumin-coated substrates via esterification; subsequently, poly(oligo(ethylene glycol) methacrylate) (poly(OEGMA)) is grafted from the surfaces. Compared to the control surfaces, poly(OEGMA)-grafted surfaces significantly suppress bacterial adhesion by up to 99.4%, demonstrating their antibacterial properties. Considering its facile and versatile surface modification, curcumin-based polymer grafting can be an efficient method for controlling the chemical/physical properties of surfaces in a substrate-independent manner.

Coordination-Driven Surface Zwitteration for Antibacterial and Antifog Applications.

The enhancement of surface wettability by hydrophilic polymer coatings has been of great interest because it has been used to address several technical challenges such as biofouling and surface fogging. Among the hydrophilic polymers, zwitterionic polymers have been extensively utilized to coat solid surfaces due to their excellent capability to bind water molecules, thereby forming dense hydration layers on the solid surfaces. For these zwitterionic polymers to function appropriately on the solid surfaces, techniques for fixing polymers onto the solid surface with high efficiency are required. Herein, we report a new approach to graft zwitterionic polymers onto solid substrates. The approach is based on the mussel-inspired surface chemistry and metal coordination. It consists of polydopamine coating and the coordination-driven grafting of the zwitterionic polymers. Polydopamine coating enables the versatile surface immobilization of catechols. Zwitterionic polymers are then easily fixed onto the catechol-immobilized surface by metal-mediated crosslinking reactions. Using this approach, nanometer-thick zwitterionic polymer layers that are highly resistant to bacterial adhesion and fog generation could be successfully fabricated on solid substrates in a substrate-independent manner.

Zwitterionic polydopamine coatings suppress silicone implant-induced capsule formation.

A synthetic zwitterionic dopamine derivative (ZW-DOPA) containing both catechol and amine groups was recently shown to exhibit excellent antifouling activity on marine surfaces. Here, we have extended these analyses to investigate the effects of ZW-DOPA coating on silicone implants. Successful formation of ZW-DOPA coatings on silicone implants was confirmed based on a combination of decreased static water contact angles on silicone implants, evidence of new peaks at 400.2 (N 1s), 232.2 (S 2s), and 168.0 (S 2p) eV, and increased quantitative atomic composition of C 1s with a concurrent decrease of Si 2p. Anti-biofilm formation assays revealed that ZW-DOPA coating prevented biofilm formation on silicone at a non-lethal concentration (0.5 mg mL-1). Capsule formation was also significantly inhibited by ZW-DOPA coating in vivo and the differentiation of fibroblasts into myofibroblasts was significantly suppressed. Together, these data suggest that silicone implants coated with ZW-DOPA may prevent capsular contracture after insertion when used in breast surgery.

Thermosensitive gallic acid-conjugated hexanoyl glycol chitosan as a novel wound healing biomaterial.

In the present study, a novel synthetic tissue adhesive material capable of sealing wounds without the use of any crosslinking agent was developed by conjugating thermosensitive hexanoyl glycol chitosan (HGC) with gallic acid (GA). The degree of N-gallylation was manipulated to prepare GA-HGCs with different GA contents. GA-HGCs demonstrated thermosensitive sol-gel transition behavior and formed irreversible hydrogels upon natural oxidation of the pyrogallol moieties in GA, possibly leading to GA-HGC crosslinks through intra/intermolecular hydrogen bonding and chemical bonds. The GA-HGC hydrogels exhibited self-healing properties, high compressive strength, strong tissue adhesive strength and biodegradability that were adjustable according to the GA content. GA-HGCs also presented excellent biocompatibility and wound healing effects. The results of in vivo wound healing efficacy studies on GA-HGC hydrogels indicated that they significantly promote wound closure and tissue regeneration by upregulating growth factors and recruiting fibroblasts compared to the untreated control group.

Reversed Anionic Hofmeister Effect in Metal-Phenolic-Based Film Formation.

Although metal-phenolic species have emerged as one of the versatile material-independent-coating materials, providing attractive tools for interface engineering, mechanistic understanding of their film formation and growth still remains largely unexplored. Especially, the anions have been overlooked despite their high concentration in the coating solution. Considering that the anions are critical in the reactivity of metal-organic complex and the formation and/or property of functional materials, we investigated the anionic effects on the characteristics of film formation, such as film thickness and properties, in the Fe3+-tannic acid coating. We found that the film characteristics were strongly dictated by the counteranions (e.g., SO42-, Cl-, and Br-) of the Fe3+ ion. Specifically, the film thickness and properties (i.e., mechanical modulus, permeability, and stability) followed the reversed anionic Hofmeister series (Br- > Cl- > SO42-). Mechanistic studies suggested that more chaotropic anions, such as Br-, might induce a more widely extended structure of the Fe3+-TA complexes in the coating solution, leading to thicker, harder, but more porous films. The reversed anionic Hofmeister effect was further confirmed by the additive effects of various sodium salts (NaF, NaCl, NaBr, and NaClO4).

Open-to-Air RAFT Polymerization on a Surface under Ambient Conditions.

Oxygen (O2)-mediated controlled radical polymerization was performed on surfaces under ambient conditions, enabling on-surface polymer brush growth under open-to-air conditions at room temperature in the absence of metal components. Polymerization of zwitterionic monomers using this O2-mediated surface-initiated reversible addition fragmentation chain-transfer (O2-SI-RAFT) method yielded hydrophilic surfaces that exhibited anti-biofouling effects. O2-SI-RAFT polymerization can be performed on large surfaces under open-to-air conditions. Various monomers including (meth)acrylates and acrylamides were employed for O2-SI-RAFT polymerization; the method is thus versatile in terms of the polymers used for coating and functionalization. A wide range of hydrophilic and hydrophobic monomers can be employed. In addition, the end-group functionality of the polymer grown by O2-SI-RAFT polymerization allowed chain extension to form block copolymer brushes on a surface.

Zwitterionic Polydopamine/Protein G Coating for Antibody Immobilization: Toward Suppression of Nonspecific Binding in Immunoassays.

For the development of immunoassays into sophisticated analyte-sensing methods, it is a priority to suppress nonspecific binding in immunoassays. Herein, we report a one-step surface coating method that can not only optimally immobilize antibodies but also suppress nonspecific binding. Zwitterionic dopamine (ZW-DOPA) exhibits distinct antifouling performance, and protein G enables an antibody to have an optimal orientation. A mixture of ZW-DOPA and protein G can be simply coated onto various kinds of surfaces, and the antibody can be immobilized onto the ZW-DOPA/protein G-coated surfaces. The antifouling property of the zwitterionic group, surface-independent coating property of the catechol and amine groups, and antibody-retaining property of protein G synergistically contribute to surface-independent and oriented immobilization of antibodies without nonspecific binding. The surface characteristics of ZW-DOPA/protein G-coated substrates were analyzed by X-ray photoelectron spectroscopy, contact angle goniometry, atomic force microscopy, and ellipsometry. Importantly, the ZW-DOPA/protein G-coated substrates showed high resistance to nonspecific protein adhesion. We also verified that antibodies could be immobilized onto ZW-DOPA/protein G-coated substrates using fluorescence and biolayer interferometry systems. Finally, ZW-DOPA/protein G-coated substrates were employed as immune substrates for influenza virus detection via the naked eye and surface-enhanced Raman scattering, allowing us to efficiently identify the virus. It is anticipated that the developed ZW-DOPA/protein G coating method will be useful for the advancement of immunoassays.

Antibacterial Film Formation through Iron(III) Complexation and Oxidation-Induced Cross-Linking of OEG-DOPA.

Catechols are prone to oxidative polymerization as well as complex formation with metal ions. These two features of catechols have played an important role in the construction of functional films on various surfaces. For example, marine antifouling films and antibacterial films were successfully prepared by oxidative polymerization and metal complexation of catechol-containing molecules, respectively. However, the effect of simultaneous metal complexation and oxidative polymerization on functional film formation has not yet been fully investigated. Herein, as a derivative of 3-(3,4-dihydroxyphenyl)-l-alanine (DOPA), we synthesized an ethylene glycol-derivatized DOPA (OEG-DOPA) and formed OEG-DOPA thin films based on (1) oxidative polymerization and (2) the complexation between catechol groups of OEG-DOPA and iron(III) (FeIII) ions. Either or both approaches were used for the film formation. OEG-DOPA film formation was characterized by ellipsometry, contact angle goniometry, field emission scanning electron microscopy, and X-ray photoelectron spectroscopy. Among the conditions used, the formation of a uniform film was only achieved with the dual cross-linking system of FeIII complexation and oxidation-induced covalent bond formation. Compared to the uncoated substrate and other OEG-DOPA films prepared under different conditions, the uniform OEG-DOPA film strongly inhibited bacterial adhesion, showing excellent antibacterial capability. We think that our surface-coating strategy can be applied to medical devices, tools, and implants where bacterial adhesion and biofilm formation should be prevented. This work can also serve as a basis for the construction of functional thin films for other catechol-functionalized materials.

Surface-Independent and Oriented Immobilization of Antibody via One-Step Polydopamine/Protein G Coating: Application to Influenza Virus Immunoassay.

For the construction of high-performance biosensor, it is important to interface bioreceptors with the sensor surface densely and in the optimal orientation. Herein, a simple surface modification method that can optimally immobilize antibodies onto various kinds of surfaces is reported. For the surface modification, a mixture of polydopamine (PDA) and protein G was employed. PDA is a representative mussel-inspired polymer, and protein G is an immunoglobulin-binding protein that enables an antibody to have an optimal orientation. The surface characteristics of PDA/Protein G mixture-coated substrates are analyzed and the PDA/protein G ratio is optimized to maximize the antibody binding efficiency. Moreover, the antibody-immobilized substrates are applied to the detection of influenza viruses with the naked eye, providing a detection limit of 2.9 × 103 pfu mL-1 . Importantly, the several substrates (glass, SiO2 , Si, Al2 O3 , polyethylene terephthalate, polyethylene, polypropylene, and paper) can be modified by simple incubation with the mixture of PDA/protein G, and then the anti-influenza A H1N1 antibodies can be immobilized on the substrates successfully. Regardless of the substrate, the influenza viruses are detectable after the sandwich immunoreaction and silver enhancement procedure. It is anticipated that the developed PDA/protein G coating method will extend the range of applicable materials for biosensing.

Oxidation-Mediated, Zwitterionic Polydopamine Coatings for Marine Antifouling Applications.

We synthesized a zwitterionic dopamine derivative ( ZW-DOPA) containing both catechol and amine groups, and we demonstrated an excellent marine antifouling surface by controlling the oxidation of ZW-DOPA. The oxidation was mediated by the deprotonation of catechol or the addition of an oxidant (ammonium persulfate (AP) or sodium periodate (NaIO4)). The oxidation and subsequent molecular transformation of ZW-DOPA was investigated over time by UV-vis spectroscopy. Among the different oxidation conditions tested, NaIO4-induced ZW-DOPA coating was the most efficient and successfully formed on various substrates, such as titanium dioxide, stainless steel, and nylon. Compared with uncoated substrates, ZW-DOPA-coated substrates showed high resistance to marine diatom adhesion. Considering the ease of use and substrate independence of the ZW-DOPA coating, this method shows promise as a basis for inhibiting marine fouling on a variety of substrates used in the marine industry and aquatic environments.

Salt-Induced, Continuous Deposition of Supramolecular Iron(III)-Tannic Acid Complex.

One-step assembly of iron(III)-tannic acid (Fe3+-TA) complex forms nanothin (∼10 nm) films on various substrates within minutes. In this deposition scheme, however, the film does not grow continuously over time even though Fe3+-TA complex is still abundant in the coating solution. In this paper, we report that the salt addition dramatically changes the one-off coating characteristic to continuous one, and each salt has its optimum concentration ( CMFT) that produces maximum film thickness. For detailed investigation of the salt effects, we employed various salts, including LiCl, NaCl, KCl, CaCl2, SrCl2, BaCl2, NaBr, and NaNO3, and found that only cations played an important role in the continuous deposition of the Fe3+-TA complex, with smaller CMFT values for the cations of higher valency and larger size. On the basis of the results, we suggested that the positively charged cations screened the negative surface charges of Fe3+-TA complex particles, leading to coagulation and continuous deposition, further supported by the ζ-potential measurement and time-resolved dynamic light-scattering analysis.

Multipurpose Antifouling Coating of Solid Surfaces with the Marine-Derived Polymer Fucoidan.

The control of biofouling, which is the unwanted adsorption of biomolecules and organisms on solid surfaces, is a prerequisite for wider applicability of the functional materials that are currently being used in biomedical industries. One of the frequently used methods for controlling biofouling is the use of surface coatings with antifouling materials. Herein, fucoidan, which is a marine-derived polysaccharide, is reported as a new type of antifouling material that is safe and broadly applicable. Fucoidan is conjugated with catechols, which are known to act as adhesives for grafting functional molecules onto solid substrates. Fucoidan catechol (FD-C) is subsequently utilized for robust fucoidan coatings of solid substrates, and the FD-C-coated surfaces show excellent antifouling capability for fouling organisms, including platelets and bacteria. The FD-C coating is also confirmed to be nonirritating upon skin contact, demonstrating its potential use in public places for inhibiting contagions.

Nanotopography-Promoted Formation of Axon Collateral Branches of Hippocampal Neurons.

Axon collateral branches, as a key structural motif of neurons, allow neurons to integrate information from highly interconnected, divergent networks by establishing terminal boutons. Although physical cues are generally known to have a comprehensive range of effects on neuronal development, their involvement in axonal branching remains elusive. Herein, it is demonstrated that the nanopillar arrays significantly increase the number of axon collateral branches and also promote their growth. Immunostaining and biochemical analyses indicate that the physical interactions between the nanopillars and the neurons give rise to lateral filopodia at the axon shaft via cytoskeletal changes, leading to the formation of axonal branches. This report, demonstrates that nanotopography regulates axonal branching, and provides a guideline for the design of sophisticated neuron-based devices and scaffolds for neuro-engineering.

Formation of Turmeric-Based Thin Films: Universal, Transparent Coatings.

Curry stains on clothes and dishes in daily life inspired us to investigate the potential use of turmeric powder, the major ingredient in curry, as a universal coating material. After condition optimization, the coating solution was made by boiling and filtering a turmeric slurry, and the coating was formed at pH 3, leading to the formation of ultrathin, transparent films. Various inorganic and polymeric substrates were successfully coated with turmeric-based materials, including gold, TiO2, SiO2, glass, stainless steel, indium tin oxide, nylon, polyethylene, polycarbonate, polypropylene, acryl, and poly(ethylene terephthalate). The turmeric-based coating was also applied to poly(tetrafluoroethylene) (PTFE, Teflon) and cyclic olefin copolymer (COC), and after double dip-coating, the water contact angle was changed from 118.2° to 49.1° for PTFE and from 91.2° to 44.7° for COC. The water contact angles for the other substrates converged to 35° after coating, confirming the substrate-independent universal coating capability of turmeric. The X-ray photoelectron spectroscopic analysis indicated the presence of nitrogen in the film, and the possible involvement of amines in film formation was investigated with several amine compounds.

Comparative Study on Surface-Initiated ATRP and SI-ARGET ATRP of Oligo(Ethylene Glycol) Methacrylate on Gold.

Oligo(ethylene glycol) methacrylate (OEGMA) was polymerized from a polymerization initiator-presenting gold substrate by Activator ReGenerated by Electron Transfer Atom Transfer Radical Polymerization (ARGET ATRP) in water. Compared with the normal surface-initiated ATRP (SI-ATRP), SI-ARGET ATRP of OEGMA proceeded smoothly in the presence of air with L-ascorbic acid as a reducing agent and a CuBr2/2,2'-bipyridyl complex at the ppm level. In addition, SI-ARGET ATRP did not require the additional steps for removing a polymerization inhibitor from the OEGMA monomer and for deoxygenating the solvent. The ellipsometric measurements showed that the polymerized OEGMA (pOEGMA) films prepared by SI-ARGET ATRP were on average 10 times thicker than those prepared by normal SI-ATRP with the same monomer concentration and polymerization time.

Micro/Nanostructured Films and Adhesives for Biomedical Applications.

The advanced technologies available for micro/nanofabrication have opened new avenues for interdisciplinary approaches to solve the unmet medical needs of regenerative medicine and biomedical devices. This review highlights the recent developments in micro/nanostructured adhesives and films for biomedical applications, including waterproof seals for wounds or surgery sites, drug delivery, sensing human body signals, and optical imaging of human tissues. We describe in detail the fabrication processes required to prepare the adhesives and films, such as tape-based adhesives, nanofilms, and flexible and stretchable film-based electronic devices. We also discuss their biomedical functions, performance in vitro and in vivo, and the future research needed to improve the current systems.

One-step functionalization of zwitterionic poly[(3-(methacryloylamino)propyl)dimethyl(3-sulfopropyl)ammonium hydroxide] surfaces by metal-polyphenol coating.

The non-biofouling properties of a zwitterionic sulfobetaine polymer surface were easily made attractive to bioentities (e.g., proteins and cells) by metal-polyphenol coating, and spatio-selective functionalization of the zwitterionic polymer surface was achieved by using a soft lithographic technique.

Mussel-inspired, perfluorinated polydopamine for self-cleaning coating on various substrates.

We designed a perfluorinated dopamine derivative, which, upon oxidative polymerization, formed a structurally rough film of extremely low surface energy on various substrates. The static water contact angles larger than 150° and the low water sliding angles less than 7° confirmed the formation of superhydrophobic, self-cleaning surfaces.