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.     

Thermally Stable and Solvent Resistant Mesoporous Honeycomb Films from a Crosslinkable Polymer

The preparation of mesoporous honeycomb films, also known as breath figure arrays (BFAs), from poly(styrene‐co‐maleic anhydride) is reported. Films containing regular arrays of micrometer‐sized air‐holes were prepared by evaporation of a chloroform solution of a mixture of the above polymer including 10 % of an amphiphilic polyion complex under high humidity that leads to the formation of a hexagonally packed monolayer of water droplets in the polymer film. The porous films were characterized by optical and scanning electron microscopy. Crosslinking was achieved by immersion in an ethanol solution of an α, ω alkyldiamine and the chemical reaction was monitored by infrared spectroscopy. The non‐crosslinked films are hydrophobic with a water contact angle of more than 90°, whereas the crosslinked films became hydrophilic, so that a water drop penetrated into the films. After crosslinking, the honeycomb structure was stable to up to 350 °C, an increase of more than 150 K as compared to the non‐crosslinked films.     

Controlled Electrodissolution of Polyelectrolyte Multilayers: A Platform Technology Towards the Surface‐Initiated Delivery of Drugs

A novel method for the electrochemical dissolution of polyelectrolyte multilayers from the surface of an electrode for applications in controlled drug delivery is reported. Biodegradable and biocompatible multilayer films based on poly(L ‐lysine) and heparin have been selected as a model system, and have been built on an indium tin oxide semiconductor substrate. The build‐up and dissolution processes of the multilayers is followed by electrochemical optical waveguide light mode spectroscopy. The formation and stability of the polyelectrolyte multilayers have been found to depend on the applied potential and the ionic strength of the buffer. The application of potentials above a threshold of 1.8 V induces dissolution, which follows single‐exponential kinetics, of the polyelectrolyte multilayer film. The rate of this process can be varied by an on–off profile of the potential, leading to the controlled release of heparin into the bulk. Atomic force microscopy investigations show that the electrodissolution of the polyelectrolyte multilayers is a local phenomenon that leads to the formation of nanoporous films.     

Photopatternable Reflective Films Produced by Nanolayer Extrusion

Novel patternable, light‐reflecting multilayer polymer films are presented. The investigated elements comprise 1024 nanolayers of two different, transparent polymers in strictly alternating fashion. Polymers with different refractive indices were employed and the individual layer thickness was controlled between 50 and 200 nm; as a result the investigated films exhibit pronounced optical interference effects. Different photoreactive additives were integrated into the multilayer films, rendering the optical characteristics of these elements tunable. One approach relied on the use of photoreactive blends of poly(methyl methacrylate) (PMMA) and up to 25 wt.‐% of trans‐cinnamic acid (CA) or trans‐methyl cinnamate (MC). Upon exposure to ultraviolet (UV) radiation, CA and MC undergo dimerization through 2+2 cycloaddition, leading to a significant decrease of the blend's refractive index. As a result, the reflectivity of the multilayer films based on these photoreactive blends changes considerably upon photoreaction. The second approach was based on the use of blends of PMMA and 2‐(2′‐benzoylphenyl)benzoxazole (BzPO), a ‘caged’ photoluminescent dye. This benzoyl ester of 2‐(2′‐hydroxyphenyl)benzoxazole (HPBO) is not photoluminescent, but upon exposure to appropriate UV radiation, the ester bond is cleaved, and the photoluminescent HPBO is quantitatively restored. Thus, using conventional photolithographic techniques, reflective multilayer films were patterned with photoluminescent designs.     

多层介质中多导体拐角结构电容参数的提取

本文给出一种计算多层介质中多导体拐角互连结构的准静态电容参数的快速算法─—维数缩减技术（DRT），并和有限差分法相结合，快速、准确地提取了多层介质中多导体拐角结构的准静态电容矩阵。由于维数缩减技术能充分利用集成电路结构分层的特点，从而大大减少了计算所需的时间和存储空间。文中给出的计算结果与Ansoft软件的计算结果吻合得较好，而计算所需的时间和存储空间大大少于Ansoft软件。     

In vivo Cellular Uptake,Degradation, and Biocompatibility of Polyelectrolyte Microcapsules

Polyelectrolyte microcapsules are made by layer‐by‐layer (LbL) coating of a sacrificial template, followed by decomposition of the template, to produce hollow microcapsules. In this paper, we report on the in vivo cellular uptake, degradation and biocompatibility of polyelectrolyte microcapsules produced from alternating dextran sulphate and poly‐L‐arginine layers on a template of calcium carbonate microparticles. We show that a moderate tissue reaction is observed after subcutaneous injection of polyelectrolyte microcapsules in mice. Within sixteen days after subcutaneous injection, most of the microcapsules are internalized by the cells and start to get degraded. The number of polyelectrolyte layers determines the stability of the microcapsules after cellular uptake.     

Elastomeric Fibrous Hybrid Scaffold Supports In Vitro and In Vivo Tissue Formation

Biomimetic materials with biomechanical properties resembling those of native tissues while providing an environment for cell growth and tissue formation, are vital for tissue engineering (TE). Mechanical anisotropy is an important property of native cardiovascular tissues and directly influences tissue function. This study reports fabrication of anisotropic cell‐seeded constructs while retaining control over the construct's architecture and distribution of cells. Newly synthesized poly‐4‐hydroxybutyrate (P4HB) is fabricated with a dry spinning technique to create anelastomeric fibrous scaffold that allows control of fiber diameter, porosity, and rate ofdegradation. To allow cell and tissue ingrowth, hybrid scaffolds with mesenchymalstem cells (MSCs) encapsulated in a photocrosslinkable hydrogel were developed. Culturing the cellularized scaffolds in a cyclic stretch/flexure bioreactor resulted in tissue formation and confirmed the scaffold's performance under mechanical stimulation. In vivo experiments showed that the hybrid scaffold is capable of withstanding physiological pressures when implanted as a patch in the pulmonary artery. Aligned tissue formation occurred on the scaffold luminal surface without macroscopic thrombus formation. This combination of a novel, anisotropic fibrous scaffold and a tunable native‐like hydrogel for cellular encapsulation promoted formation of 3D tissue and provides a biologically functional composite scaffold for soft‐tissue engineering applications.     

Mimicking Biological Phenol Reaction Cascades to Confer Mechanical Function

Phenol reaction cascades are commonly used in nature to create crosslinked materials that perform mechanical functions. These processes are mimicked by electrochemically initiating a reaction cascade to examine if the mechanical properties of a biopolymer film can be predictably altered. Specifically, thin films (≈ 30–45 μm) of the polysaccharide chitosan are cast onto gold‐coated silicon wafers, the chitosan‐coated wafers are immersed in catechol‐containing solutions, and the phenol is anodically oxidized. The product of this oxidation is highly reactive and undergoes reaction with chitosan chains adjacent to the anode. After reaction, the flexible chitosan film can be peeled from the wafer. Chemical and physical evidence support the conclusion that electrochemically initiated reactions crosslink chitosan. When gold is patterned onto the wafer, the electrochemical crosslinking reactions are spatially localized and impart anisotropic mechanical properties to the chitosan film. Further, deswelling of chitosan films can reversibly transduce environmental stimuli into contractile forces. Films patterned to have spatial variations in crosslinking respond to such environmental stimuli by undergoing reversible changes in shape. These results suggest the potential to enlist electrochemically initiated reaction cascades to engineer chitosan films for actuator functions.     

Methods and Applications of Multilayer Silk Fibroin Laminates Based on Spatially Controlled Welding in Protein Films

Recent use of biopolymers as interface materials between planar, inorganic electronics and biological tissues has required the adaptation of micro‐ and nanofabrication techniques for use with these nontraditional materials. In this work, a method which builds on this principle for spatial control of adhesion in multilayer silk fibroin laminates is investigated. This is accomplished through the addition of a spatially patterned amorphous silk adhesive layer in between the films to be adhered, before thermally processing them with heat (120 °C) and pressure (80 Psi) according to established procedures. A one‐step method for rapid, high‐throughput fabrication is demonstrated, which establishes a strong (1100 kPa) bond between the layers independent of the initial processing conditions of the films. The adhesive layers can be patterned using existing silk fabrication techniques, allowing for the assembly of complex geometries including bilayers and microbubbles. Additionally, the utility of this method is demonstrated for potential applications in drug delivery and transient electronics. This approach provides a versatile method for construction of complex multilayer structures in silk, which with future work may ultimately improve the utility of this material as a bridge between high technology and the biomedical sciences.     

Phosphorescent Polymeric Thermometers for In Vitro and In Vivo Temperature Sensing with Minimized Background Interference

Temperature plays a crucial role in many biological processes. Accurate temperature determination is important for diagnosis and treatment of diseases. Autofluorescence is an unavoidable interference in luminescent bioimaging. Hence, a large amount of research works has been devoted to reducing background autofluorescence and improving signal‐to‐noise ratio (SNR) in biodetection. Herein, a dual‐emissive phosphorescent polymeric thermometer has been developed by incorporating two long‐lived phosphorescent iridium(III) complexes into an acrylamide‐based thermosensitive polymer. Upon increasing temperature, this polymer undergoes coil‐globule transition, which leads to a decrease in polarity of the microenvironment surrounding the iridium(III) complexes and hence brings about emission enhancement of both complexes. Owing to their different sensitivity to surrounding environment, the emission intensity ratio of the two complexes is correlated to the temperature. Thus, the polymer has been used for temperature determination in vitro and in vivo via ratiometric luminescence imaging. More importantly, by using the long‐lived phosphorescence of the polymer, temperature mapping in zebrafish has been demonstrated successfully with minimized autofluorescence interference and improved SNR via time‐resolved luminescence imaging. To the best of our knowledge, this is the first example to use photoluminescent thermometer for in vivo temperature sensing.     

Dextran Microgels for Time‐Controlled Delivery of siRNA

To apply siRNA as a therapeutic agent, appropriate attention should be paid to the optimization of the siRNA gene silencing effect, both in terms of magnitude and duration. Intracellular time‐controlled siRNA delivery could aid in tailoring the kinetics of siRNA gene knockdown. However, materials with easily tunable siRNA release properties have not been subjected to thorough investigation thus far. This report describes cationic biodegradable dextran microgels which can be loaded with siRNA posterior to gel formation. Even though the siRNAs are incorporated in the hydrogel network based on electrostatic interaction, still a time‐controlled release can be achieved by varying the initial network density of the microgels. To demonstrate the biological functionality of the siRNA loaded gels, we studied their cellular internalization and enhanced green fluorescent protein (EGFP) gene silencing potential in HUH7 human hepatoma cells.     

Highly Biocompatible Carbon Nanodots for Simultaneous Bioimaging and Targeted Photodynamic Therapy In Vitro and In Vivo

Photosensitizers (PSs) are light‐sensitive molecules that are highly hydrophobic, which poses a challenge to their use for targeted photodynamic therapy. Hence, considerable efforts have been made to develop carriers for the delivery of PSs. Herein, a novel design is described of highly biocompatible, fluorescent, folic acid (FA)‐functionalized carbon nanodots (CDs) as carriers for the PS zinc phthalocyanine (ZnPc) to achieve simultaneous biological imaging and targeted photodynamic therapy. FA is modified on PEG‐­passivated CDs (CD‐PEG) for targeted delivery to FA‐positive cancer cells, and ZnPc is loaded onto CD‐PEG‐FA via π–π stacking interactions. CD‐PEG‐FA/ZnPc exhibits excellent targeted delivery of the PS, leading to simultaneous imaging and significant targeted photodynamic therapy after irradiation in vitro and in vivo. The present CD‐based targeted delivery of PSs is anticipated to offer a convenient and effective platform for enhanced photodynamic therapy to treat cancers in the near future.     

Copper Clusters: An Effective Antibacterial for Eradicating Multidrug-Resistant Bacterial Infection In Vitro and In Vivo

Infections caused by multidrug-resistant (MDR) bacteria pose a threat to human health worldwide, making new effective antibacterial agents urgently desired. To date, it is still a great challenge to develop new antibiotics for MDR bacteria with clear antibacterial mechanisms. Herein, a novel alternative antibacterial copper clusters (CuCs) molecule is precisely synthesized utilizing an artificially designed theanine peptide. The prepared CuCs exhibit excellent broad-spectrum antibacterial activity in vitro, including gram-positive bacteria (methicillin-resistant Staphylococcus aureus [MRSA], Staphylococcus aureus, and Staphylococcus epidermidis) and gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). The robust antibacterial effect is due to its ability to not only destroy the bacterial wall structure, but also regulate the ratio of GSH/GSSG by inhibiting the activity of glutathione reductase, thus causing the outbreak of reactive oxygen species and ultimately leading to bacterial death. In addition, in vivo studies demonstrate that CuCs can significantly rescue skin wound infections and sepsis in mice caused by MRSA, and has the same therapeutic efficacy as mupirocin ointment and first-line clinically anchored anti-MRSA drug vancomycin. Moreover, CuCs exhibit extremely low cytotoxicity to normal mammalian cells compared to silver and platinum clusters. With further development and optimization, CuCs has great potential as a new class of antibacterial agents to fight antibiotic-resistant pathogens.     

In Vitro Fabrication of Microscale Secretory Granules

Advanced medical treatments involving drug delivery require fully biocompatible materials with the ability to release functional drugs in a time-prolonged way. Ideally, the delivered molecules should be self-contained as chemically homogenous entities to prevent the use of potentially toxic scaffolds or hold matrices. In nature, peptidic hormones are self-stored in protein-only secretory granules formed by the reversible coordination of Zn²⁺ and histidine residues. Inspired by this concept, an in vitro transversal procedure is developed, analyzed, and comparatively applied for the fabrication of protein-only secretory granules at the microscale. These materials can be produced from any polyhistidine-tagged protein using physiological concentrations of Zn²⁺ as a potent and versatile glue-like agent. The screening of granules formed by 12 engineered and nonengineered proteins at different Zn²⁺ concentrations revealed optimal fabrication conditions and the consequent release profiles. Moreover, the functional and structural properties of the delivered protein are fully validated using a drug-targeting protein platform in a mouse model of human colorectal cancer. In summary, short histidine tags allow the packaging of structurally and functionally dissimilar polypeptides, which supports the proposed fabrication method as a powerful protocol extensible to diverse clinical scenarios in which slow protein drug delivery is required.     

Macrophage Hitchhiking Nanoparticles for the Treatment of Myocardial Infarction: An In Vitro and In Vivo Study

Myocardial infarction (MI) is the leading cause of death worldwide. However, current therapies are unable to restore the function of the injured myocardium. Advanced approaches, such as stimulation of cardiomyocyte (CM) proliferation are promising, but suffer from poor pharmacokinetics and possible systemic adverse effects. Nanomedicines can be a solution to the above-mentioned drawbacks. However, targeting the cardiac tissue still represents a challenge. Herein, a MI-selective precision nanosystem is developed, that relies on the heart targeting properties of atrial natriuretic peptide (ANP) and lin-TT1 peptide-mediated hitchhiking on M2-like macrophages. The system based on pH-responsive putrescine-modified acetalated dextran (Putre-AcDEX) nanoparticles, shows biocompatibility with cultured cardiac cells, and ANP receptor-dependent interaction with CMs. Moreover, treatment with nanoparticles (NPs) loaded with two pleiotropic cellular self-renewal promoting compounds, CHIR99021 and SB203580, induces a 4-fold increase in bromodeoxyuridine (BrdU) incorporation in primary cardiomyocytes compared to control. In vivo studies confirm that M2-like macrophages targeting by lin-TT1 peptide enhances the heart targeting of ANP. In addition, NP administration does not alter the immunological profile of blood and spleen, showing the short-term safety of the developed system in vivo. Overall, the study results in the development of a peptide-guided precision nanosystem for delivery of therapeutic compounds to the infarcted heart.     

Extracellular Matrix Control of Collagen Mineralization In Vitro

Collagen biomineralization is a complex process and the controlling factors at the molecular level are still not well understood. A particularly high level of spatial control over collagen mineralization is evident in the anchorage of teeth to the jawbone by the periodontal ligament. Here, unmineralized ligament collagen fibrils become mineralized at an extremely sharp mineralization front in the root of the tooth. A model of collagen biomineralization based on demineralized cryosections of mouse molars in the bone socket is presented. When exposed to metastable calcium and phosphate‐containing solutions, mineral re‐deposits selectively into the natively mineralized tissues with high fidelity, demonstrating that the extracellular matrix retains sufficient information to control the rate of mineralization at the tissue level. While solutions of simulated bodily fluid produce amorphous calcium phosphate within the tissue section, a more highly supersaturated solution stabilized with polyaspartic acid produces oriented, crystalline calcium phosphate with diffraction patterns consistent with hydroxyapatite. The model thus replicates both spatial control of mineral deposition, as well as the matrix‐mineral relationships of natively mineralized collagen fibrils, and can be used to elucidate roles of specific biomolecules in the highly controlled process of collagen biomineralization. This knowledge will be critical in the design of collagen‐based scaffolds for tissue engineering of hard‐soft tissue interfaces.     

Heparinized Magnetic Nanoparticles: In‐Vitro Assessment for Biomedical Applications

Superparamagnetic magnetite nanoparticles are of great interest owing to their numerous existing and potential biomedical applications. In this study, superparamagnetic magnetite nanoparticles with average diameters of 6–8 nm have been prepared and surface‐functionalized with poly(N‐isopropylacrylamide) (poly(NIPAAM)) via a surface‐initiated atom‐transfer radical polymerization, followed by immobilization of heparin. The success of the various surface‐functionalization steps has been ascertained using Fourier transform infrared spectroscopy and X‐ray photoelectron spectroscopy. The rate of internalization of the as‐synthesized and surface‐functionalized magnetite nanoparticles by mouse macrophage cells has been investigated. The nanoparticle internalization into the macrophages has been visualized using optical microscopy and quantified by inductively coupled plasma spectroscopy. The effectiveness of the heparinized nanoparticles in preventing thrombosis has been determined using the plasma recalcification time. The results indicate that the above‐mentioned surface modifications of the magnetite nanoparticles are effective in delaying phagocytosis and preventing blood clotting in vitro. Such properties can be expected to enable their use in biomedical applications.     

多层结构氧化锌薄膜制备

介绍了高频声体波微波延迟线用多层结构氧化锌薄膜的制作方法，并对这种交替排列不同结晶取向的多层氧化锌薄膜的微观结构、成膜机理进行了分析和阐述。用具有不同机电耦合系数、厚度为半波长的交替排列多层氧化锌薄膜制成了中心频率为８ＧＨｚ的声体波微波延迟线。同时亦给出了这种新结构的氧化锌压电材料的生长条件及相应的实验结果     

Multilayer Hybrid Films Consisting of Alternating Graphene and Titania Nanosheets with Ultrafast Electron Transfer and Photoconversion Properties

Alternating graphene (G) and titania (Ti_0.91O₂) multilayered nanosheets are fabricated using layer‐by‐layer electrostatic deposition followed by UV irradiation. Successful assemblies of graphene oxide (GO) and titania nanosheets in sequence with polyethylenimine as a linker is confirmed by UV–vis absorption and X‐ray diffraction. Photocatalytic reduction of GO into G can be achieved upon UV irradiation. Ultrafast photocatalytic electron transfer between the titania and graphene is demonstrated using femtosecond transient absorption spectroscopy. Efficient exciton dissociation at the interfaces coupled with cross‐surface charge percolation allows efficient photocurrent conversion in the multilayered Ti_0.91O₂/G films.     

激光制备多层薄膜及铁电性能的研究

利用脉冲准分子激光淀积（ＰＬＤ）方法，在Ｓｉ基片上制备了ＢＩＴ／Ｓｉ〔１００〕、ＰＺＴ／ＢＩＴ／Ｓｉ〔１００〕和ＢＩＴ／ＰＺＴ／ＢＩＴ／Ｓｉ〔１００〕铁电薄膜。用ＸＲＤ分析了多层铁电薄膜的晶相结构；用Ｓａｗｙｅｒ－Ｔｏｗｅｒ电路研究了这些单层和多层铁电薄膜的铁电性能。结果表明，单层ＢＩＴ的矫顽场Ｅｃ为４ｋＶ／ｃｍ，剩余极化强度为３．４μＣ／ｃｍ２；ＰＺＴ／ＢＩＴ的矫顽场Ｅｃ为８２ｋＶ／ｃｍ，剩余极化强度Ｐｒ为３６μＣ／ｃｍ２；ＢＩＴ／ＰＺＴ／ＢＩＴ夹层铁电薄膜的矫顽场Ｅｃ为５７ｋＶ／ｃｍ，剩余极化强度Ｐｒ为２９μＣ／ｃｍ２。最后讨论了薄膜的铁电性能与多层结构的关系