Identification of several high-risk HPV inhibitors and drug targets with a novel high-throughput screening assay.

Human papillomaviruses (HPVs) are oncogenic viruses that cause numerous different cancers as well as benign lesions in the epithelia. To date, there is no effective cure for an ongoing HPV infection. Here, we describe the generation process of a platform for the development of anti-HPV drugs. This system consists of engineered full-length HPV genomes that express reporter genes for evaluation of the viral copy number in all three HPV replication stages. We demonstrate the usefulness of this system by conducting high-throughput screens to identify novel high-risk HPV-specific inhibitors. At least five of the inhibitors block the function of Tdp1 and PARP1, which have been identified as essential cellular proteins for HPV replication and promising candidates for the development of antivirals against HPV and possibly against HPV-related cancers.

An Integrated Data-Driven Strategy for Safe-by-Design Nanoparticles: The FP7 MODERN Project.

The development and implementation of safe-by-design strategies is key for the safe development of future generations of nanotechnology enabled products. The safety testing of the huge variety of nanomaterials that can be synthetized is unfeasible due to time and cost constraints. Computational modeling facilitates the implementation of alternative testing strategies in a time and cost effective way. The development of predictive nanotoxicology models requires the use of high quality experimental data on the structure, physicochemical properties and bioactivity of nanomaterials. The FP7 Project MODERN has developed and evaluated the main components of a computational framework for the evaluation of the environmental and health impacts of nanoparticles. This chapter describes each of the elements of the framework including aspects related to data generation, management and integration; development of nanodescriptors; establishment of nanostructure-activity relationships; identification of nanoparticle categories; hazard ranking and risk assessment.

Enhanced Low-Density Silicone Foams Blown by Water-Hydroxyl Blends.

Water, alcohols, diols, and glycerol are low-cost blowing agents that can be used to create the desired silicone foam structures. Although their combined use can be beneficial, it remains unclear how it affects the physical properties of the resulting materials. We conducted a comparative study of these hydroxyl-bearing blowing agents in fumed silica- and mica-filled polymer composite systems for simultaneous blowing and crosslinking to obtain a low-density, uniform porosity and superior mechanical properties. The foams were optimized for a uniform open-pore structure with densities ranging from 75 to 150 kg‧m-3. Varying the diol chain length (Cn) from one to seven carbons can alter the foam density and structure, thereby enhancing the foam tensile strength while maintaining a low density. Replacing 10 mol% of water with 1,4-butanediol decreased the density by 26%, while increasing the specific strength by 5%. By combining glycerol and water blowing, the resulting foams exhibited a 30% lower apparent density than their water-blown analogs. The results further showed that Cn > 4 alkane chain diols had an odd-even effect on the apparent density and cell wall thickness. All foamable compositions had viscosities of approximately 7000 cSt and curing times below 2 min, allowing for quick dispensing and sufficient time for the foam to cure in semi-industrial volumes.

Microbial growth and adhesion of Escherichia coli in elastomeric silicone foams with commonly used additives.

Silicone is often used in environments where water repellency is an advantage. Contact with water promotes the adhesion of microorganisms and biofilm formation. Depending on the application, this may increase the possibility of food poisoning and infections, the material's degrading appearance, and the likelihood of manufacturing defects. The prevention of microbial adhesion and biofilm formation is also essential for silicone-based elastomeric foams, which are used in direct contact with human bodies but are often difficult to clean. In this study, the microbial attachment in and the retention from the pores of silicone foams of different compositions is described and compared to those of commonly used polyurethane foams. The growth of the gram-negative Escherichia coli in the pores and their leaching during wash cycles is characterised by bacterial growth/inhibition, adhesion assay, and SEM imaging. The structural and surface properties of the materials are compared. Despite using common antibacterial additives, we have found that non-soluble particles stay isolated in the silicone elastomer layer, thus affecting surface microroughness. Water-soluble tannic acid dissolves into the medium and seems to aid in inhibiting planktonic bacterial growth, with a clear indication of the availability of tannic acid on the surfaces of SIFs.

Dip-coating electromechanically active polymer actuators with SIBS from midblock-selective solvents to achieve full encapsulation for biomedical applications.

Soft and compliant ionic electromechanically active polymer actuators (IEAPs) are a promising class of smart materials for biomedical and soft robotics applications. These materials change their shape in response to external stimuli like the electrical signal. This shape-change results solely from the ion flux inside the composite and hence the material can be miniaturized below the centimeter and millimeter levels-something that still poses a challenge for many other conventional actuation mechanisms in soft robotics (e.g., pneumatic, hydraulic, or tendon-based systems). However, the components used to prepare IEAPs are typically not safe for the biological environment, nor is the environment safe for the actuator. Safety concerns and unreliable operation in foreign liquid environments have been some of the main obstacles for the widespread adoption of IEAPs in many areas, e.g., in biomedical applications. Here we show a novel approach to fully encapsulate IEAP actuators with the biocompatible block copolymer SIBS (poly(styrene-block-isobutylene-block-styrene)) dissolved in block-selective solvents. Reduction in the bending amplitude due to the added passive layers, a common negative side-effect of encapsulating IEAPs, was not observed in this work. In conclusion, the encapsulated actuator is steered through a tortuous vasculature mock-up filled with a viscous buffer solution mimicking biological fluids.

Application of the QSPR approach to the boiling points of azeotropes.

CODESSA Pro derivative descriptors were calculated for a data set of 426 azeotropic mixtures by the centroid approximation and the weighted-contribution-factor approximation. The two approximations produced almost identical four-descriptor QSPR models relating the structural characteristic of the individual components of azeotropes to the azeotropic boiling points. These models were supported by internal and external validations. The descriptors contributing to the QSPR models are directly related to the three components of the enthalpy (heat) of vaporization.

Wider Potential Windows of Cellulose Multiwall Carbon Nanotube Fibers Leading to Qualitative Multifunctional Changes in an Organic Electrolyte.

The trend across the whole of society is to focus on natural and/or biodegradable materials such as cellulose (Cell) over synthetic polymers. Among other usage scenarios, Cell can be combined with electroactive components such as multiwall carbon nanotubes (CNT) to form composites, such as Cell-CNT fibers, for applications in actuators, sensors, and energy storage devices. In this work, we aim to show that by changing the potential window, qualitative multifunctionality of the composites can be invoked, in both electromechanical response as well as energy storage capability. Cell-CNT fibers were investigated in different potential ranges (0.8 V to -0.3 V, 0.55 V to -0.8 V, 1 V to -0.8 V, and 1.5 V to -0.8 V), revealing the transfer from cation-active to anion-active as the potential window shifted towards more positive potentials. Moreover, increasing the driving frequency also shifts the mode from cation- to anion-active. Scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy were conducted to determine the ion species participating in charge compensation under different conditions.

Antagonist Concepts of Polypyrrole Actuators: Bending Hybrid Actuator and Mirrored Trilayer Linear Actuator.

Following the natural muscle antagonist actuation principle, different adaptations for "artificial muscles" are introduced in this work. Polypyrrole (PPy) films of different polymerization techniques (potentiostatic and galvanostatic) were analyzed and their established responses were combined in several ways, resulting in beneficial actuation modes. A consecutive "one-pot" electrosynthesis of two layers with the different deposition regimes resulted in an all-PPy bending hybrid actuator. While in most cases the mixed-ion activity of conductive polymers has been considered a problem or a drawback, here for the first time, the nearly equal expansions upon oxidation and reduction of carefully selected conditions further allowed to fabricate a "mirrored" trilayer laminate, which behaved as a linear actuator.

Ion Mobility in Thick and Thin Poly-3,4 Ethylenedioxythiophene Films-From EQCM to Actuation.

Conductive polymer actuators and sensors rely on controlled ion transport coupled to a potential/charge change. In order to understand and control such devices, it is of paramount importance to understand the factors that determine ion flux at various conditions, including the synthesis potential. In this work, the ion transport in thinner poly-3,4-ethylenedioxythiophene (PEDOT) films during charge/discharge driven by cyclic voltammetry is studied by consideration of the electrochemical quartz crystal microbalance (EQCM) and the results are compared to the actuation responses of thicker films that have been synthesized with the same conditions in the bending and linear expansion modes. The effects of polymerization potentials of 1.0 V, 1.2 V, and 1.5 V are studied to elucidate how polymerization potential contributes to actuation, as well the involvement of the EQCM. In this work, it is revealed that there is a shift from anion-dominated to mixed to cation-dominated activity with increased synthesis potential. Scanning electron microscopy shows a decrease in porosity for the PEDOT structure with increasing synthesis potential. EQCM analysis of processes taking place at various potentials allows the determination of appropriate potential windows for increased control over devices.

A New Direction in Microfluidics: Printed Porous Materials.

In this work, the feasibility of a novel direction for microfluidics is studied by demonstrating a set of new methods to fabricate microfluidic systems. Similarly to microfluidic paper-based analytical devices, porous materials are being used. However, alternative porous materials and different printing methods are used here to give the material the necessary pattern to act as a microfluidic system. In this work, microfluidic systems were produced by the following three separate methods: (1) by curing a porous monolithic polymer sheet into a necessary pattern with photolithography, (2) by screen printing silica gel particles with gypsum, and (3) by dispensing silica gel particles with polyvinyl acetate binder using a modified 3D printer. Different parameters of the printed chips were determined (strength of the printed material, printing accuracy, printed material height, wetting characteristics, repeatability) to evaluate whether the printed chips were suitable for use in microfluidics. All three approaches were found to be suitable, and therefore the novel approach to microfluidics was successfully demonstrated.

The Use of Laminates of Commercially Available Fabrics for Anti-Stab Body-Armor.

Modern personal protective armor has been generally based on the Kevlar fabrics, with the main goal to offer defense against bullets. In addition to the high cost and poor processability, Kevlar has the disadvantage of limited stab-proofing capability. On the other hand, a large number of crimes involving deadly injures represent knife attacks. Our goal in this work was to investigate composites based on traditional commercially available fabrics of linen and silk, using different adhesives-polymers for forming laminates. The silk composites also contained different amounts of in-woven polyester. Three different water-based adhesives of polyurethane, urea formaldehyde and polyvinyl alcohol were considered. It was found, that besides the strength of the fabrics themselves, the adhesives polymers played a crucial role in the obtained performance of the laminates. The laminates were characterized in their mechanical properties, as well as with scanning electron microscopy and FTIR spectroscopy.

Metabolism Control in 3D-Printed Living Materials Improves Fermentation.

The three-dimensional (3D) printing of cell-containing polymeric hydrogels creates living materials (LMs), offering a platform for developing innovative technologies in areas like biosensors and biomanufacturing. The polymer material properties of cross-linkable F127-bis-urethane methacrylate (F127-BUM) allow reproducible 3D printing and stability in physiological conditions, making it suitable for fabricating LMs. Though F127-BUM-based LMs permit diffusion of solute molecules like glucose and ethanol, it remains unknown whether these are permissible for oxygen, essential for respiration. To determine oxygen permissibility, we quantified dissolved oxygen consumption by the budding yeast-laden F127-BUM-based LMs. Moreover, we obtained data on cell-retaining LMs, which allowed a direct comparison between LMs and suspension cultures. We further developed a highly reliable method to isolate cells from LMs for flow cytometry analysis, cell viability evaluation, and the purification of macromolecules. We found oxygen consumption heavily impaired inside LMs, indicating that yeast metabolism relies primarily on fermentation instead of respiration. Applying this finding to brewing, we observed a higher (3.7%) ethanol production using LMs than the traditional brewing process, indicating improved fermentation. Our study concludes that the present F127-BUM-based LMs are useful for microaerobic processes but developing aerobic bioprocesses will require further research.

Cellulose-Multiwall Carbon Nanotube Fiber Actuator Behavior in Aqueous and Organic Electrolyte.

As both consumers and producers are shifting from fossil-derived materials to other, more sustainable approaches, there is a growing interest in bio-origin and biodegradable polymers. In search of bio-degradable electro-mechanically active materials, cellulose-multi wall carbon nanotube (Cell-CNT) composites are a focus for the development of actuators and sensors. In the current study, our aim was to fabricate Cell-CNT composite fibers and study their electro-mechanical response as linear actuators in aqueous and propylene carbonate-based electrolyte solutions. While the response was (expectedly) strongly solvent dependent, the different solvents also revealed unexpected phenomena. Cell-CNT fibers in propylene carbonate revealed a strong back-relaxation process at low frequencies, and also a frequency dependent response direction change (change of actuation direction). Cell-CNT fibers operated in aqueous electrolyte showed response typical to electrochemical capacitors including expansion at discharging with controllable actuation dependence on charge density. While the response was similarly stable in both electrolyte solution systems, the aqueous electrolytes were clearly favorable for Cell-CNT with 3.4 times higher conductivities, 4.3 times higher charge densities and 11 times higher strain.

A Kirigami Approach of Patterning Membrane Actuators.

Ionic electroactive polymer actuators are typically implemented as bending trilayer laminates. While showing high displacements, such designs are not straightforward to implement for useful applications. To enable practical uses in actuators with ionic electroactive polymers, membrane-type film designs can be considered. The significantly lower displacement of the membrane actuators due to the lack of freedom of motion has been the main limiting factor for their application, resulting in just a few works considering such devices. However, bioinspired patterning designs have been shown to significantly increase the freedom of motion of such membranes. In this work, we apply computer simulations to design cutting patterns for increasing the performance of membrane actuators based on polypyrrole doped with dodecylbenzenesulfonate (PPy/DBS) in trilayer arrangements with a polyvinylidene fluoride membrane as the separator. A dedicated custom-designed device was built to consistently measure the response of the membrane actuators, demonstrating significant and pattern-specific enhancements of the response in terms of displacement, exchanged charge and force.

A Biomimetic Approach to Increasing Soft Actuator Performance by Friction Reduction.

While increasing power output is the most straight-forward solution for faster and stronger motion in technology, sports, or elsewhere, efficiency is what separates the best from the rest. In nature, where the possibilities of power increase are limited, efficiency of motion is particularly important; the same principle can be applied to the emerging biomimetic and bio-interacting technologies. In this work, by applying hints from nature, we consider possible approaches of increasing the efficiency of motion through liquid medium of bilayer ionic electroactive polymer actuations, focusing on the reduction of friction by means of surface tension and hydrophobicity. Conducting polyethylene terephthalate (PET) bilayers were chosen as the model actuator system. The actuation medium consisted of aqueous solutions containing tetramethylammonium chloride and sodium dodecylbenzenesulfonate in different ratios. The roles of ion concentrations and the surface tension are discussed. Hydrophobicity of the PET support layer was further tuned by adding a spin-coated silicone layer to it. As expected, both approaches increased the displacement-the best results having been obtained by combining both, nearly doubling the bending displacement. The simple approaches for greatly increasing actuation motion efficiency can be used in any actuator system operating in a liquid medium.

Concept of an artificial muscle design on polypyrrole nanofiber scaffolds.

Here we present the synthesis and characterization of two new conducting materials having a high electro-chemo-mechanical activity for possible applications as artificial muscles or soft smart actuators in biomimetic structures. Glucose-gelatin nanofiber scaffolds (CFS) were coated with polypyrrole (PPy) first by chemical polymerization followed by electrochemical polymerization doped with dodecylbenzensulfonate (DBS-) forming CFS-PPy/DBS films, or with trifluoromethanesulfonate (CF3SO3-, TF) giving CFS-PPy/TF films. The composition, electronic and ionic conductivity of the materials were determined using different techniques. The electro-chemo-mechanical characterization of the films was carried out by cyclic voltammetry and square wave potential steps in bis(trifluoromethane)sulfonimide lithium solutions of propylene carbonate (LiTFSI-PC). Linear actuation of the CFS-PPy/DBS material exhibited 20% of strain variation with a stress of 0.14 MPa, rather similar to skeletal muscles. After 1000 cycles, the creeping effect was as low as 0,2% having a good long-term stability showing a strain variation per cycle of -1.8% (after 1000 cycles). Those material properties are excellent for future technological applications as artificial muscles, batteries, smart membranes, and so on.

Multifunctionality of Polypyrrole Polyethyleneoxide Composites: Concurrent Sensing, Actuation and Energy Storage.

In films of conducting polymers, the electrochemical reaction(s) drive the simultaneous variation of different material properties (reaction multifunctionality). Here, we present a parallel study of actuation-sensing-energy storage triple functionality of polypyrrole (PPy) blends with dodecylbenzenesulfonate (DBS-), PPy/DBS, without and with inclusion of polyethyleneoxide, PPy-PEO/DBS. The characterization of the response of both materials in aqueous solutions of four different salts indicated that all of the actuating, sensing and charge storage responses were, independent of the electrolyte, present for both materials, but stronger for the PPy-PEO/DBS films: 1.4× higher strains, 1.3× higher specific charge densities, 2.5× higher specific capacitances and increased ion-sensitivity towards the studied counterions. For both materials, the reaction energy, the material potential and the strain variations adapt to and sense the electrical and chemical (exchanged cation) conditions. The driving and the response of actuation, sensing and charge can be controlled/read, simultaneously, via just two connecting wires. Only the cooperative actuation of chemical macromolecular motors from functional cells has such chemical multifunctionality.

Physical Confinement Impacts Cellular Phenotypes within Living Materials.

Additive manufacturing allows three-dimensional printing of polymeric materials together with cells, creating living materials for applications in biomedical research and biotechnology. However, an understanding of the cellular phenotype within living materials is lacking, which is a key limitation for their wider application. Herein, we present an approach to characterize the cellular phenotype within living materials. We immobilized the budding yeast Saccharomyces cerevisiae in three different photo-cross-linkable triblock polymeric hydrogels containing F127-bis-urethane methacrylate, F127-dimethacrylate, or poly(alkyl glycidyl ether)-dimethacrylate. Using optical and scanning electron microscopy, we showed that hydrogels based on these polymers were stable under physiological conditions, but yeast colonies showed differences in the interaction within the living materials. We found that the physical confinement, imparted by compositional and structural properties of the hydrogels, impacted the cellular phenotype by reducing the size of cells in living materials compared with suspension cells. These properties also contributed to the differences in immobilization patterns, growth of colonies, and colony coatings. We observed that a composition-dependent degradation of polymers was likely possible by cells residing in the living materials. In conclusion, our investigation highlights the need for a holistic understanding of the cellular response within hydrogels to facilitate the synthesis of application-specific polymers and the design of advanced living materials in the future.

Printed PEDOT:PSS Trilayer: Mechanism Evaluation and Application in Energy Storage.

Combining ink-jet printing and one of the most stable electroactive materials, PEDOT:PSS (poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)), is envisaged to pave the way for the mass production of soft electroactive materials. Despite its being a well-known electroactive material, widespread application of PEDOT:PSS also requires good understanding of its response. However, agreement on the interpretation of the material's activities, notably regarding actuation, is not unanimous. Our goal in this work is to study the behavior of trilayers with PEDOT:PSS electrodes printed on either side of a semi-interpenetrated polymer network membrane in propylene carbonate solutions of three different electrolytes, and to compare their electroactive, actuation, and energy storage behavior. The balance of apparent faradaic and non-faradaic processes in each case is discussed. The results show that the primarily cation-dominated response of the trilayers in the three electrolytes is actually remarkably different, with some rather uncommon outcomes. The different balance of the apparent charging mechanisms makes it possible to clearly select one electrolyte for potential actuation and another for energy storage application scenarios.

Improving the Electrochemical Performance and Stability of Polypyrrole by Polymerizing Ionic Liquids.

Polypyrrole (PPy) based electroactive materials are important building blocks for the development of flexible electronics, bio-sensors and actuator devices. As the properties and behavior of PPy depends strongly on the operating environment-electrolyte, solvent, etc., it is desirable to plant immobile ionic species into PPy films to ensure stable response. A premade ionic polymer is not optimal in many cases, as it enforces its own structure on the conducting polymer, therefore, polymerization during fabrication is preferred. Pyrrole (Py) was electropolymerized at low temperature together with a polymerizable ionic liquid (PIL) monomer in a one-step polymerization, to form a stable film on the working electrode. The structure and morphology of the PPyPIL films were investigated by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), Fourier-transform infrared (FTIR) spectroscopy and solid-state NMR (ssNMR) spectroscopy. The spectroscopy results confirmed the successful polymerization of Py to PPy and PIL monomer to PIL. The presence of (TFSI-) anions that balance the charge in PPyPIL was confirmed by EDX analysis. The electrical properties of PPyPIL in lithium bis(trifluoromethanesulfonyl)-imide (LiTFSI) aqueous and propylene carbonate solutions were examined with cyclic voltammetry (CV), chronoamperometry, and chronopotentiometry. The blend of PPyPIL had mixed electronic/ionic conductive properties that were strongly influenced by the solvent. In aqueous electrolyte, the electrical conductivity was 30 times lower and the diffusion coefficient 1.5 times higher than in the organic electrolyte. Importantly, the capacity, current density, and charge density were found to stay consistent, independent of the choice of solvent.