Self‐Healing Actuating Adhesive Based on Polyelectrolyte Multilayers

Creating actuators capable of mechanical motion in response to external stimuli is a key for design and preparation of smart materials. The lifetime of such materials is limited by their eventual wear. Here, self‐healable and adhesive actuating materials are demonstrated by taking advantage of the solvent responsive of weak polyelectrolyte multilayers consisting of branched poly(ethylenimine)/poly(acrylic acid) (BPEI/PAA). BPEI/PAA multilayers are dehydrated and contract upon contact with organic solvent and become sticky when wetted with water. By constructing an asymmetric heterostructure consisting of a responsive BPEI/PAA multilayer block and a nonresponsive component through either layer‐by‐layer assembly or the paste‐to‐curl process, smart films that actuate upon exposure to alcohol are realized. The curl degree, defined as degrees from horizontal that the actuated material reaches, can be as high as ≈228.9°. With evaporation of the ethanol, the curled film returns to its initial state, and water triggers fast self‐healing extends the actuator's lifetime. Meanwhile, the adhesive nature of the wet material allows it to be attached to various substrates for possible combination with hydrophobic functional surfaces and/or applications in biological environments. This self‐healable adhesive for controlled fast actuation represents a considerable advance in polyelectrolyte multilayers for design and fabrication of robust smart advanced materials.     

Adenoviral Gene Delivery from Multilayered Polyelectrolyte Architectures

The alternate layer‐by‐layer (LBL) deposition of polycations and polyanions for the build up of multilayered polyelectrolyte films is an original approach that allows the preparation of tunable, biologically active surfaces. The resulting supramolecular nanoarchitectures can be functionalized with drugs, peptides, and proteins, or DNA molecules that are able to transfect cells in vitro. We monitor, for the first time, the embedding of a bioactive adenoviral (Ad) vector in multilayered polyelectrolyte films. Ad efficiently adsorbs on poly(L ‐lysine)–poly(L ‐glutamic acid) (PLL–PGA), PLL–HA (HA: hyaluronan), poly(allylamin hydrochloride)–poly(sodium‐4‐styrenesulfonate) (PAH–PSS), and CHI–HA (CHI: chitosan) films; it preserves its transduction capacity (which can reach 95 %) for a large number of cell types, and also allows vector uptake into receptor‐deficient cells, thus abrogating the restricted tropism of Ad.     

Incorporation of a Hydrophobic Antibacterial Peptide into Amphiphilic Polyelectrolyte Multilayers: A Bioinspired Approach to Prepare Biocidal Thin Coatings

A non‐water‐soluble natural antibacterial peptide, gramicidin A, has been successfully incorporated into polyelectrolyte assemblies to elaborate biocidal thin films. For this, we used a double strategy, the first step of which consists of complexing the peptide by a non‐denaturing anionic amphiphilic polysaccharide, namely a hydrophobically modified carboxymethylpullulan. We demonstrate that the use of this amphiphilic anionic derivative allows to efficiently solubilize the peptide in aqueous solution, without denaturation. The amount of peptide solubilized by the amphiphilic polysaccharide was optimized by systematically varying the hydrophobicity and the molar mass of the CMP derivative. In a second step, the negatively charged complex was layer‐by‐layer assembled with cationic poly(L‐lysine) to form biofunctionalized thin films. The amount of peptide incorporated in the multilayers was controlled by changing the number of deposited complex layers, and was quantified by UV spectroscopy. The antibacterial activity of the resulting biofunctionalized films was evidenced against a gram‐positive bacterium, E. faecalis. We demonstrated that the biocidal activity resulted from a double mechanism: contact between bacteria and the film surface, and release of the peptide into the solution surrounding the film. We also showed that the peptide was not completely removed from the film after rinsing, which insured preservation of the biocidal activity of the film surface.     

Enhanced Electrochromism with Rapid Growth Layer‐by‐Layer Assembly of Polyelectrolyte Complexes

In this work, a facile method to deposit fast growing electrochromic multilayer films with enhanced electrochemical properties using layer‐by‐layer (LbL) self‐assembly of complex polyelectrolyte is demonstrated. Two linear polymers, poly(acrylic acid) (PAA) and polyethylenimine (PEI), are used to formulate stable complexes under specific pH to prepare polyaniline (PANI)/PAA‐PEI multilayer films via LbL deposition. By introducing polymeric complexes as building blocks, [PANI/PAA‐PEI]_n films grow much faster compared with [PANI/PAA]_n films, which are deposited under the same condition. Unlike the compact [PANI/PAA]_n films, [PANI/PAA‐PEI]_n films exhibit porous structure that is beneficial to the electrochemical process and leads to improved electrochromic properties. An enhanced optical modulation of 30% is achieved with [PANI/PAA‐PEI]₃₀ films at 630 nm compared with the lower optical modulation of 11% measured from [PANI/PAA]₃₀ films. The switching time of [PANI/PAA‐PEI]₃₀ films is only half of that of [PANI/PAA]₃₀ films, which indicates a faster redox process. Utilizing polyelectrolyte complexes as building blocks is a promising approach to prepare fast growing LbL films for high performance electrochemical device applications.     

Humidity‐Triggered Self‐Healing of Microporous Polyelectrolyte Multilayer Coatings for Hydrophobic Drug Delivery

Layer‐by‐layer (LbL) self‐assemblies have inherent potential as dynamic coatings because of the sensitivity of their building blocks to external stimuli. Here, humidity serves as a feasible trigger to activate the self‐healing of a microporous polyethylenimine/poly(acrylic acid) multilayer film. Microporous structures within the polyelectrolyte multilayer (PEM) film are created by acid treatment, followed by freeze‐drying to remove water. The self‐healing of these micropores can be triggered at 100% relative humidity, under which condition the mobility of the polyelectrolytes is activated. Based on this, a facile and versatile method is suggested for directly integrating hydrophobic drugs into PEM films for surface‐mediated drug delivery. The high porosity of microporous film enables the highest loading (≈303.5 μg cm^?2 for a 15‐bilayered film) of triclosan to be a one‐shot process via wicking action and subsequent solvent removal, thus dramatically streamlining the processes and reducing complexities compared to the existing LbL strategies. The self‐healing of a drug‐loaded microporous PEM film significantly reduces the diffusion coefficient of triclosan, which is favorable for the long‐term sustained release of the drug. The dynamic properties of this polymeric coating provide great potential for its use as a delivery platform for hydrophobic drugs in a wide variety of biomedical applications.     

Primary Cell Adhesion on RGD‐Functionalized and Covalently Crosslinked Thin Polyelectrolyte Multilayer Films

Polyelectrolyte multilayers (PEMs) are now widely used for biomedical applications. In this work, we investigated the primary osteoblast adhesion properties of PEMs of poly(L ‐lysine) (PLL), poly(L ‐glutamic acid) (PGA), poly(alginic acid) (Palg), and poly(galacturonic acid) (Pgal). In order to compensate for the poor adhesion of the as‐synthesized films, two kinds of film modifications were achieved: a purely physical modification by film crosslinking, and a chemical modification by grafting a arginine–glycine–aspartic acid (RGD) peptide to PGA. Crosslinking was performed using a water‐soluble carbodiimide in combination with N‐hydroxysulfosuccinimide (sulfo‐NHS) to induce amide formation. This reaction was followed by Fourier‐transform IR spectroscopy. For film functionalization, a 15‐amino‐acid peptide was grafted to PGA and deposited as the top layer of the film. PLL/PGA, PLL/Palg, and PLL/Pgal films were crosslinked or functionalized. The films were tested for both short‐term adhesion properties and long‐term proliferation of primary osteoblasts. Whereas the effect of film crosslinking on short‐term adhesion was moderate, it was much more important for the RGD‐functionalized films. On the other hand, the long‐term proliferation was the same or even higher for the crosslinked films as compared with the functionalized films. This effect was particularly enhanced for the PLL/Palg and PLL/Pgal films. Finally, we functionalized PLL/PGA that had been crosslinked prior to PGA‐RGD deposition. These architectures exhibited even higher short‐term adhesion and proliferation. These results clearly show the important role of the physical properties of the films, besides their chemical properties, for the modulation of primary cell‐adhesion behavior.     

Ultrathin Single Bilayer Separation Membranes Based on Hyperbranched Sulfonated Poly(aryleneoxindole)

The layer‐by‐layer method is an attractive technique for the fabrication of ultrathin nanostructured polyelectrolyte multilayer membranes (PEMM). A simple two‐step procedure is described here for the preparation of an ultrathin, nanostructured membrane comprising a 5–7 nm thick selective layer, consisting only of one single bilayer of poly(diallyldimethylammoniumchloride) and hyperbranched sulfonated poly(aryleneoxindole). These single bilayered membranes exhibit an outstanding solvent‐resistant nanofiltration performance, which is superior to that of commercial membranes as well as to previously reported multilayer membranes having 10–20 bilayers. A comparative study between hyperbranched polyelectrolyte (HPE) and linear polyelectrolyte supports the role of the specific 3D structure of the hyperbranched polyelectrolyte in these excellent separation properties. The work thus encompasses the use of HPEs as an ideal choice for PEMMs, which opens up a new route to significantly decrease the overall membrane preparation time while realizing excellent filtration properties.     

Short‐Time Tuning of the Biological Activity of Functionalized Polyelectrolyte Multilayers

This article demonstrates the tuning of the biological activity of a surface functionalized by a polyelectrolyte multilayer. The interaction of protein A with macrophages is used as the model system. The film consists of two polypeptides, poly(lysine) and poly(glutamic acid); each “build‐up” solution is a mixture of the respective D ‐ and L ‐enantiomers (d and l enantiomers). Cells are deposited on top of the film, and they produce tumor necrosis factor alpha (TNF‐α) as they come into contact with the protein. Depending upon the d/l‐enantiomer ratio of the polyelectrolyte solutions used for the film build‐up, and the embedding depth of the protein, the production of TNF‐α commences after a varying induction time and displays a transition from no‐production to full‐production, which takes place over a period of time that depends on the film's composition and embedding depth. Thus, it is shown that by changing these two parameters the timing of the protein's activity can be accurately tuned.     

Polyelectrolyte Blend Multilayers: A Versatile Route to Engineering Interfaces and Films

The ability to reliably engineer surfaces with nanoscale precision is a rapidly developing field of research with applications ranging from biosensing and biomedical materials to antifouling and corrosion protection. The layer‐by‐layer (LbL) approach is a widely utilized method for engineering surfaces, in part because of the large array of polymeric materials that can be integrated and the diverse range of functionality that these materials afford. Herein, we discuss the LbL deposition of multicomponent ‘blend' solutions to form polyelectrolyte blend multilayer films and coatings. This approach is a versatile platform for enhancing film stability, incorporating a wide range of functional materials, controlling film morphology and material properties, and increasing biological response, thereby expanding the range of potential applications.     

Percolation‐Controlled Metal/Polyelectrolyte Complexed Films for All‐Solution‐Processable Electrical Conductors

The use of solution‐processable electrically conducting films is imperative for realizing next‐generation flexible and wearable devices in a large‐scale and economically viable way. However, the conventional approach of simply complexing metallic nanoparticles with a polymeric medium leads to a tradeoff between electrical conductivity and material properties. To address this issue, in this study, a novel strategy is presented for fabricating all‐solution‐processable conducting films by means of metal/polyelectrolyte complexation to achieve controlled electrical percolation; this simultaneously imparts superior electrical conductivity and good mechanical properties. A polymeric matrix comprised of polyelectrolyte multilayers is first formed using layer‐by‐layer assembly, and then Ag nanoparticles are gradually synthesized and gradationally distributed inside the polymeric matrix by means of a subsequent procedure of repeated cationic exchange and reduction. During this process, electrical percolation between Ag nanoparticles and networking of electrical pathways is facilitated in the surface region of the complexed film, providing outstanding electrical conductivity only one order of magnitude less than that of metallic Ag. At the same time, the polymer‐rich underlying region imparts strong, yet compliant, binding characteristics to the upper Ag‐containing conducting region while allowing highly flexible mechanical deformations of bending and folding, which consequently makes the system outperform existing materials.     

Free‐Standing Cell Sheet Assembled with Ultrathin Extracellular Matrix as an Innovative Approach for Biomimetic Tissues

Current artificial tissue‐substitutes have limited clinical applications due to unmatched complex combination of cells and extracellular matrix (ECM) as seen in native tissues. From a developmental perspective, the construction of effective biomimetic tissues is from the bottom (one‐dimensional nanoparticles or two‐dimensional membranes) up (three‐dimensional scaffolds or more complex composite). In a hierarchical architecture, each sub‐structure can be assembled in a flexible way with specific regulators and cells, which overcomes the deficiency of one‐for‐all scaffold. Here, a cell‐compatible cell‐lined layered nano‐membrane is developed. Bioactive molecules are mounted on a nano‐membrane and later released to its lined cell sheet. The cell‐lined membrane is in a free‐standing form to regulate cellular functions. The major advantage of this methodology is to provide a versatile approach to construct biomimetic tissues for clinical applications.     

Multilayered Lipid Membrane Stacks for Biocatalysis Using Membrane Enzymes

Multilayered or stacked lipid membranes are a common principle in biology and have various functional advantages compared to single‐lipid membranes, such as their ability to spatially organize processes, compartmentalize molecules, and greatly increase surface area and hence membrane protein concentration. Here, a supramolecular assembly of a multilayered lipid membrane system is reported in which poly‐l ‐lysine electrostatically links negatively charged lipid membranes. When suitable membrane enzymes are incorporated, either an ubiquinol oxidase (cytochrome bo ₃ from Escherichia coli) or an oxygen tolerant hydrogenase (the membrane‐bound hydrogenase from Ralstonia eutropha), cyclic voltammetry (CV) reveals a linear increase in biocatalytic activity with each additional membrane layer. Electron transfer between the enzymes and the electrode is mediated by the quinone pool that is present in the lipid phase. Using atomic force microscopy, CV, and fluorescence microscopy it is deduced that quinones are able to diffuse between the stacked lipid membrane layers via defect sites where the lipid membranes are interconnected. This assembly is akin to that of interconnected thylakoid membranes or the folded lamella of mitochondria and has significant potential for mimicry in biotechnology applications such as energy production or biosensing.     

Fabrication of Organized Porphyrin‐Nanotube‐Attached Heat‐Sensitive Polyelectrolyte Capsules

A facile method of connecting fluorescent meso‐tetrakis(4‐sulfonatophenyl)porphine tetranion nanotubes to polyelectrolyte capsules is developed. Heat‐sensitive robust polyelectrolyte capsules consisting of poly(diallyldimethylammonium chloride) and poly(styrene sulfonate) multilayers have been fabricated using the conventional layer‐by‐layer technique. Supramolecular aggregation of porphyrin monomers to nanotubes is induced in the microenvironment of the capsules by sequential addition of salt and acid. Scanning electron microscopy, transmission electron microscopy, and atomic force microscopy images reveal satellite‐like structures consisting of a central capsule core with porphyrin nanotubes emerging radially from the capsule walls. The growth and the distribution of the porphyrin units have been monitored by UV‐vis spectroscopy, fluorescence spectroscopy, and confocal laser scanning microscopy. Changing the temperature alters the dimensions and the arrangement of the nanotubes on the capsule walls. Such an attachment of porphyrin tubes onto robust functional capsules should help in developing an artificial light‐harvesting system.     

Copper‐Assisted Weak Polyelectrolyte Multilayer Formation on Microspheres and Subsequent Film Crosslinking

The formation of weak polyelectrolyte films on planar and spherical supports has recently evoked major interest, as such coatings allow novel material properties to be tunable by pH and salt adjustment of the polyelectrolyte deposition conditions. We report on the build up of multilayers of the weak polyelectrolytes poly(acrylic acid) (PAA) and poly(allylamine hydrochloride) (PAH) on submicrometer‐sized polystyrene (PS) and silica colloid spheres (～ 500 nm) with the aid of copper ion templating. The copper ions complex to the carboxylate groups of PAA, facilitating the formation of PAA/PAH multilayers on the particles. Regular growth of the layers on the colloid spheres with each polyelectrolyte deposition step was confirmed by microelectrophoresis, single‐particle light scattering (SPLS), and transmission electron microscopy (TEM), with an average bilayer thickness of ～ 3 nm. The polyelectrolyte multilayer‐coated particles formed stable colloidal dispersions, with ζ‐potentials ranging from 30 mV (PAH outer layer) and –50 mV (PAA outer layer). Complementary quartz‐crystal microbalance and UV‐vis spectrophotometry studies on PAA/PAH multilayers formed on planar supports were performed to examine the film formation and the role of copper ion binding to the layers. PAA/PAH multilayers formed on colloid particles were also chemically crosslinked by using the activator 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide (EDC). The degree of film crosslinking could be readily controlled by varying the concentration of EDC employed. Following solvent decomposition of the template particles coated with crosslinked PAA/PAH multilayers, intact hollow polymer capsules were obtained. These capsules were found to be impenetrable to polystyrene.     

Encapsulation of Water‐Immiscible Solvents in Polyglutamate/ Polyelectrolyte Nanocontainers

A novel approach for encapsulation of hydrophobic materials into a hydrophilic multifunctional shell is presented, based on combining an ultrasonic technique and a layer‐by‐layer protocol. Polyglutamate/polyethyleneimine (PEI)/polyacrylic acid (PAA) and polyglutamate/PEI/PAA/silver nanocontainers loaded with a hydrophobic dye, 5,10,15,20‐tetraphenylporphin, dissolved in toluene, are fabricated. Uniform, stable, and monodisperse polyglutamate/PEI/PAA nanocontainers of about 600 nm are obtained. The hydrophobic core of the nanocontainers might contain a huge variety of water‐insoluble drugs and the outer polyelectrolyte shell may provide controlled permeability and desired multifunctionality. Confocal fluorescence microscopy and scanning electron microscopy are employed for the characterization of the resulting nanocontainers. Using sodium dodecyl sulfate as surfactant, the amount of nanocontainers, their monodispersity, and stability can be increased dramatically.     

Nanoengineering Hybrid Supramolecular Multilayered Biomaterials Using Polysaccharides and Self‐Assembling Peptide Amphiphiles

Developing complex supramolecular biomaterials through highly dynamic and reversible noncovalent interactions has attracted great attention from the scientific community aiming key biomedical and biotechnological applications, including tissue engineering, regenerative medicine, or drug delivery. In this study, the authors report the fabrication of hybrid supramolecular multilayered biomaterials, comprising high‐molecular‐weight biopolymers and oppositely charged low‐molecular‐weight peptide amphiphiles (PAs), through combination of self‐assembly and electrostatically driven layer‐by‐layer (LbL) assembly approach. Alginate, an anionic polysaccharide, is used to trigger the self‐assembling capability of positively charged PA and formation of 1D nanofiber networks. The LbL technology is further used to fabricate supramolecular multilayered biomaterials by repeating the alternate deposition of both molecules. The fabrication process is monitored by quartz crystal microbalance, revealing that both materials can be successfully combined to conceive stable supramolecular systems. The morphological properties of the systems are studied by advanced microscopy techniques, revealing the nanostructured dimensions and 1D nanofibrous network of the assembly formed by the two molecules. Enhanced C2C12 cell adhesion, proliferation, and differentiation are observed on nanostructures having PA as outermost layer. Such supramolecular biomaterials demonstrate to be innovative matrices for cell culture and hold great potential to be used in the near future as promising biomimetic supramolecular nanoplatforms for practical applications.     

Pyridylamino‐β‐cyclodextrin as a Molecular Chaperone for Lipopolysaccharide Embedded in a Multilayered Polyelectrolyte Architecture

Layer‐by‐layer self‐assembled polyelectrolyte films containing a charged cyclodextrin and lipopolysaccharide (LPS) are developed for the first time as a potential model for local endotoxin antagonist delivery. We have examined the biological activity of a lipopolysaccharide from E. coli incorporated into multilayered architectures made of poly‐(L ‐lysine) and poly‐(L ‐glutamic acid). Used in such build‐ups, a polycationic cyclodextrin, heptakis(6‐deoxy‐6‐pyridylamino)‐β‐cyclodextrin showed molecular chaperone properties by enabling restoration of the LPS biological activity whenever lost upon interaction with poly‐(L ‐lysine).