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Silicones
(2014)
Silicones are found in a variety of applications with requirements that range from long life at elevated temperatures to fluidity at low temperatures. This chapter first considers silicone elastomers and their application in room temperature vulcanizing (RTV) and heat curing systems (HTV). Also, new technologies for UV curing are introduced. Coverage of RTVs includes both one-component and two-component systems and the different cure chemistries of each, and is followed by a separate discussion of silicone laminates. Due to the high importance of silicone fluids, they are also discussed. Fluids include polishes, release agents, surfactants, and dielectric fluids.
In the period from the 1950s to 2013, the American Food and Drug Administration (FDA) approved 1346 new molecular entities (NMEs) or new biologics entities (NBEs). On average, the approval rate was 20 NMEs per year. In the past 40 years, the number of new drugs launched into the market increased slightly from 15 NMEs in the 1970s to 25–30 NMEs since the 1990s. The highest number of new drugs approved by FDA was in 1996 and 1997, which might be related to the enactment of the Prescription Drug User Fee Act (PDUFA) in 1993.
Processing
(2014)
In this chapter, some relevant aspects and illustrative examples of online monitoring tools as the basis for process control in the manufacturing and processing of thermosetting resins are briefly discussed. In principle, any chemical or physical information made accessible by sensors can be used for online monitoring of resin formation, resin location in the mold, and resin cure. For instance, changes in the flow properties of the reaction mixture are often routinely recorded in dependence of the reaction time during resin synthesis as a measure for the degree of conversion of raw materials into macromolecules or oligomers by applying rheometry in an in-process environment. Typically, a small sample of the reaction mixture is by-passed, subjected to rheological measurement, and re-introduced into the bulk reactor. In a similar way, pH measurements, turbidimetric measurements, or other analyses are performed. Although rheometry may not always be suitable for following resin cure (especially in cases where there is a very rapid increase in viscosity after initiation of the cure), [1] naturally, the method can in principle also be used in the subsequent processing of the thermosets, for instance in the curing of wood glue applied to wood specimen [2]. Similarly, pH changes during thermoset curing can be followed. Hence, an encyclopedic and comprehensive approach to present process control methods would systematically proceed according to the involved physical measurement principle. However, since only a very Brief sketch of means for monitoring thermoset processing can be given here, only a small, personally biased selection of important methods and application examples is addressed in the following sections. These examples hopefully illustrate some of the general strategies and solutions to problems that are typically encountered when processing thermosets.
Unsaturated polyester resins (UPR) and vinyl ester resins (VER) are among the most commercially important thermosetting matrix materials for composites. Although comparatively low cost, their technological performance is suitable for a wide range of applications, such as fiber-reinforced plastics, artificial marble or onyx, polymer concrete, or gel coats. The main areas of UPR consumption include the wind energy, marine, pipe and tank, transportation, and construction industries. This chapter discusses basic UPR and VER chemistry and technology of manufacturing, and consequent applications. Some important properties and performance characteristics are discussed, such as shrinkage behavior, flame retardance, and property modification by nanoparticles. Also briefly introduced and described are the practical aspects of UPR and VER processing, with special emphasis on the most widely used technological approaches, such as hand and spray layup, resin infusion, resin transfer molding, sheet and bulk molding, pultrusion, winding, and centrifugal casting.
Three different polyols (soluble starch, sucrose, and glycerol) were tested for their potential in the chemical modification of melamine formaldehyde (MF) resins for paper impregnation. MF impregnated papers are widely used as finishing materials for engineered wood. These polyols were selected because the presence of multiple hydroxy groups in the molecules was suspected to facilitate cocondensation with the main MF framework. This should lead to good resin performance. Moreover, they are readily produced from natural feedstock. They are available in large quantities and may serve as economically feasible, environmentally harmless alternative co-monomers suitable to substitute a portion of fossil-based starting material. In the presented work, a number of model resins were synthesized and tested for covalent incorporation of the natural polyol into the MF Framework. Spectroscopic evidence of chemical incorporation of glycerol was found by applying by 1H, 13C, 1H/13C HSQC, 1H/13C HMBC, and 1H DOSY methods. It was furthermore found that covalent incorporation of glycerol in the network took place when glycerol was added at different stages during synthesis. Further, all resins were used to prepare decorative laminates and the performance of the novel resins as surface finishing was evaluated using standard technological tests. The technological performance of the various modified thermosetting resins was assessed by determining flow viscosity, molar mass distribution, the storage stability, and in a second step laminating impregnated paper to particle boards and testing the resulting surfaces according to standardized quality tests. In most cases, the average board surface properties were of acceptable quality. Our findings demonstrate the possibility to replace several percent of the petrol-based product melamine by compounds obtained from renewable resources.
Crosslinked thermoplastics
(2014)
Cross-linked thermoplastics represent an important class of materials for numerous applications such as heat-shrinkable tubing, rotational molded parts, and polyolefin foams. By cross-linking olefins, their mechanical performance can be significantly enhanced. This chapter covers the three main methods for the cross-linking of thermoplastics: radiation cross-linking, chemical cross-linking with organic peroxides, and cross-linking using silane-grafting agents. It also considers the major effects of the cross-linking procedure on the performance of the thermoplastic materials discussed.
Mass-customization is a megatrend that also affects the wood industry. To obtain individually designed laminates in batch size one efficient printing and processing technologies are required. Digital printing was envisaged as it does not depend on highly costly printing cylinders (as used in rotogravure printing) and allows rapid exchange of the printing designs. In the present work, two wellestablished digital printing approaches, the multi-pass and the single-pass technique, were investigated and evaluated for their applicability in decorating engineered wood and low-pressure melamine films. Three different possibilities of implementing digital printing in the decorative laminates manufacturing process were studied: (1) digital printing on coated chipboard and subsequently applying a lacquered top-coat or melamine overlay (designated as “direct printing”, since the LPM was the printing substrate), (2) digital printing on decorative paper which was subsequently impregnated before hot pressing (designated as “indirect printing, variant A”) and (3) digital printing on decorative paper with subsequent interlamination of the paper between impregnated under- and overlay paper layers during the pressing process (designated as “indirect printing, variant B”). Due to various advantages of the resulting cured melamine resin surfaces including a much better technological performance and flexibility in surface texture design, it was decided to industrially further pursue only the indirect digital printing process comprising interlamination and the direct printing process with a melamine overlay-finishing. Basis for the successful trials on production and laboratory scales were the identification of applicable inks (in terms of compatibility with melamine resin) and of appropriate printing paper quality (in terms of impregnation and imprinting ability). After selection and fine tuning of suitable materials, the next challenge to overcome was the initially insufficient bond strength between impregnated overlay and the ink layers which led to unsatisfactory quality of the print appearance and delamination effects. However, the optimization of the pressing program and the development of a modified impregnation procedure for the underlay and overlay papers allowed the successful implementation of digital printing in the production line of our industrial partner FunderMax.
Allyls
(2014)
This chapter addresses the importance and usage of the commercially low volume thermoset plastics group known as allyls. The three significant sub-elements of this group are poly(diallylphthalates), poly(diallylisophthalates), and poly(allyldiglycol carbonate). Chemistry, processing, and properties are also described. Allyl polymers are synthesized by radical polymerizations of allyl monomers that usually do not produce high-molecular-mass macromolecules. Therefore, only a few specific monomers can produce thermosetting materials. Diallyldiglycolcarbonate (CR-39) and diallylphthalates are the most significant examples that have considerably improved our everyday life.
The intelligent recycling of plastics waste is a major concern. Because of the widespread use of polyethylene terephtalate, considerable amounts of PET waste are generated that are ideally re-introduced into the material cycle by generating second generation products without loss of materials performance. Chemical recycling methods are often expensive and entail environmentally hazardous by-products. Established mechanical methods generally provide materials of reduced quality, leading to products of lower quality. These drawbacks can be avoided by the development of new recycling methods that provide materials of high quality in every step of the production cycle. In the present work, oligomeric ethylene terephthalate with defined degrees of polymerization and defined molecular weight is produced by melt-mixing PET with different quantities of adipic acid as an alternative pathway of recycling PET with respect to conventional methods, offering ecofriendly and economical aspects. Additionally, block-copolyesters of defined block length are designed from the oligomeric products.
Ethylene terephthalate and ethylene naphthalate oligomers of defined degree of polymerization were synthesized via chemical recycling of the parent polymers. The oligomers were used as defined building blocks for the preparation of novel block-co-polyesters having tailored sequence compositions. The sequence lengths were systematically varied using Design of Experiments. The dispersive surface energy and the specific desorption energy of the co-polymers were determined by inverse gas chromatography. The study shows that polyethylene terephthalate-polyethylene naphthalate (PET-PEN) block-co-polyesters of defined sequence lengths can be prepared. Furthermore, the specific and dispersive surface energies of the obtained block-co-polyesters showed a linear dependence on the oligomer molecular weight and it was possible to regulate and control their interfacial properties. In contrast, with the corresponding random-block-co-polyesters no such dependence was found. The synthesized block-co-polyesters could be used as polymeric modifying agents for stabilizing PET-PEN polymer blends.
Melamine formaldehyde (MF) resins are widely used for the gluing and surface coating of wood-based consumer products in the interior design of living environments. MF resins are especially relevant in decorative laminate applications because of their good performance-to-price ratio. In their industrial processing, an important intermediate state is the liquid MF prepolymer that is used for decorative paper impregnation. Here, the drying of impregnated papers is investigated with respect to premature curing. A new method to quantify water release upon drying that allows estimation of the degree of undesired precuring is described. Since curing proceeds via polycondensation, crosslinking brings about the release of water molecules. By thermogravimetric analysis (TGA), drying was studied in terms of water release due to physical drying (elimination of “dilution water”) and chemical crosslinking of the prepolymer to a three-dimensional MF network (elimination of chemically liberated water). The results obtained by TGA/IR spectroscopic analysis of the liberated volatiles show that the emission of water from b-stage MF can be clearly analytically separated into a physical (evaporation of dilution water) and a chemical (liberation via condensation) sequence. TGA experiments were correlated with curing experiments performed with differential scanning calorimetry (DSC) to estimate the residual crosslinking capacities of the impregnated papers. The drying conditions used during the preparation of impregnated decorative papers seemed to significantly affect their remaining reactivity only when harsh drying conditions were used. Upon heat exposure for prolonged time, precuring of the oligomer units results in a shift of the temperature maxima in TGA.
The fiber deformations of once-dried, bleached and never-dried unbleached kraft pulps were studied with respect to their behavior in high- and low-consistency refining. The pulps were stained with congo red to experimentally highlight areas where the arrangement of the fibrils was altered by refining such as dislocated zones or slip planes. The stained fibers were analyzed with conventional Metso Fiberlab but also with a novel prototype measurement device utilizing a color imaging setup. The local intensity of the stain in the fiber was expressed as degree of overall damage (Overall fiber damage index, OFDI). The rewetted zero span tensile index (RWZSTI) was used to verify the OFDI with respect to the pulp strength. High consistency refining resulted in a clear increase in the number of kinks which negatively influenced the pulp strength. The OFDI which was used to detect the intensity of local fiber defects also responded accordingly. A higher OFDI resulted in a lower pulp strength. Low consistency refining removed a significant amount of kinks and resulted in an increase in fiber swelling. A slight increase in fibrillation and a significant increase in flake-like fines were also observed. The OFDI, however, was not reduced in low consistency refining as it would be expected by the removal of less severe dislocations. One reason proposed here is that low consistency refining created new fiber pores that allowed the dye to penetrate into the fiber wall similarly as it does in the zones of the dislocations.
Hardboards (HBs) (wet-process high-density fibreboards) were made in an industrial trial using a binder system consisting of cationic mimosa tannin and laccase or just cationic tannin without any thermosetting adhesive. The boards displayed superior mechanical strength compared to reference boards made with phenol–formaldehyde, easily exceeding the European standards for general-purpose HBs. The thickness swell of most of the boards was slightly greater than the standards would allow, so some optimisation is required in this area. The improved board properties appear to be mainly associated with ionic interactions involving quaternary amino groups in cationic tannin and negatively charged wood fibres rather than to cross-linking of fibres via laccase-assisted formation and coupling of radicals in tannin and fibre lignin.
Powder coating of engineered wood panels such as medium density fibreboards (MDF) is gaining industrial interest due to ecological and economic advantages of powder coating technology. For transferring powder coating technology to temperature-sensitive substrates like MDF, a thorough understanding of the melting, flowing and curing behaviour of the used low-bake resins is required. In the present study, thermo-analysis in combination with iso-conversional kinetic data analysis as well as rheometry is applied to characterise the properties of an epoxy-based powder coating. Neat resin and cured powder coating films are examined in order to define an ideal production window within which the resin is preferably applied and processed to yield satisfactory surface performance on the one hand and without exposing the carrier MDF too high a temperature load on the other hand to prevent the panel from deteriorating in mechanical strength. In order to produce powder coated films of high surface gloss – a feature that has not yet successfully been realized on MDF with powder coatings – a new curing technology, in-mould surface finishing, has been applied.
In vivo, cells encounter different physical and chemical signals in the extracellular matrix (ECM) which regulate their behavior. Examples of these signals are micro- and nanometer-sized features, the rigidity, and the chemical composition of the ECM. The study of cell responses to such cues is important to understand complex cell functions, some diseases, and is basis for the development of new biomaterials for applications in medical implants or regenerative medicine. Therefore, the development of new methods for surface modifications with controlled physical and chemical features is crucial. In this work, we report a new combination of micelle nanolithography (BCML) and soft micro-lithography, for the production of polyethylene glycol (PEG) hydrogels, with a micro-grooved surface and decoration with hexagonally precisely arranged gold nanoparticles (AU NPs). The Au-NPs are used for binding adhesive ligands in a well-defined density. First tests were performed by culturing human fibroblasts on the gels. Adhesion and alignment of the cells along the parallel grooves of the surface were investigated. The substrates could provide a new platform for studying cell contact guidance by micro structures, and may enable a more precise control of cell behavior by nanometrically controlled surface functionalization.
Poly(dimethylsiloxane) can be covalently coated with ultrathin NCO-sP(EO-stat-PO) hydrogel layers which permit covalent binding of cell adhesive moieties, while minimizing unspecific cell adhesion on non-functionalized areas. We applied long term uniaxial cyclic tensile strain (CTS) and revealed (a) the preservation of protein and cell-repellent properties of the NCO-sP(EO-stat-PO) coating and (b) the stability and bioactivity of a covalently bound fibronectin (FN) line pattern. We studied the adhesion of human dermal fibroblast (HDFs) on non-modified NCO-sP(EO-stat-PO) coatings and on the FN. HDFs adhered to FN and oriented their cell bodies and actin fibers along the FN lines independently of the direction of CTS. This mechanical long term stability of the bioactive, patterned surface allows unraveling biomechanical stimuli for cellular signaling and behavior to understand physiological and pathological cell phenomenon. Additionally, it allows for the application in wound healing assays, tissue engineering, and implant development demanding spatial control over specific cell adhesion.
It is well established that the mechanical environment influences cell functions in health and disease. Here, we address how the mechanical environment influences tumor growth, in particular, the shape of solid tumors. In an in vitro tumor model, which isolates mechanical interactions between cancer tumor cells and a hydrogel, we find that tumors grow as ellipsoids, resembling the same, oft-reported observation of in vivo tumors. Specifically, an oblate ellipsoidal tumor shape robustly occurs when the tumors grow in hydrogels that are stiffer than the tumors, but when they grow in more compliant hydrogels they remain closer to spherical in shape. Using large scale, nonlinear elasticity computations we Show that the oblate ellipsoidal shape minimizes the elastic free energy of the tumor-hydrogel system. Having eliminated a number of other candidate explanations, we hypothesize that minimization of the elastic free energy is the reason for predominance of the experimentally observed ellipsoidal shape. This result may hold significance for explaining the shape progressio.
The powder coating of veneered particle boards by the sequence electrostatic powder application -powder curing via hot pressing is studied in order to create high gloss surfaces. To obtain an appealingaspect, veneer Sheets were glued by heat and pressure on top of particle boards and the resulting surfaceswere used as carrier substrates for powder coat finishing. Prior to the powder coating, the veneeredparticle board surfaces were pre-treated by sanding to obtain good uniformity and the boards werestored in a climate chamber at controlled temperature and humidity conditions to adjust an appropriate electrical surface resistance. Characterization of surface texture was done by 3D microscopy. The surfaceelectrical resistance was measured for the six veneers before and after their application on the particleboard surface. A transparent powder top-coat was applied electrostatically onto the veneered particleboard surface. Curing of the powder was done using a heated press at 130◦C for 8 min and a smooth, glossy coating was obtained on the veneered surfaces. By applying different amounts of powder thecoating thickness could be varied and the optimum amount of powder was determined for each veneer type.
Decorative laminates based on melamine formaldehyde (MF) resin impregnated papers are used at great extent for surface finishing of engineered wood that is used for furniture, kitchen, and working surfaces, flooring and exterior cladding. In all these applications, optically flawless appearance is a major issue. The work described here is focused on enhancing the cleanability and antifingerprint properties of smooth, matt surface-finished melamine-coated particleboards for furniture fronts, without at the same time changing or deteriorating other important surface parameters such as hardness, roughness or gloss. In order to adjust the surface polarity of a low pressure melamine film, novel interface-active macromolecular compounds were prepared and tested for their suitability as an antifingerprint additive. Two hydroxy-functional surfactants (polydimethysiloxane, PDMS-OH and perfluoroether, PF-OH) were oxidized under mild conditions to the corresponding aldehydes (PDMS-CHO and PF-CHO) using a pyridinium chlorochromate catalyst. With the most promising oxidized polymeric additive, PDMS-CHO, the contact angles against water, n-hexadecane, and squalene increased from 79.8°, 26.3° and 31.4° for the pure MF surface to 108.5°, 54.8°, and 59.3°, respectively, for the modified MF surfaces. While for the laminated MF surface based on the oxidized fluoroether the gloss values were much higher than required, for the surfaces based on oxidized polydimethylsiloxane the technological values as well as the lower gloss values were in agreement with the requirements and showed much improved surface cleanability, as was also confirmed by colorimetric measurements.
Clay minerals play an increasingly important role as functional fillers and reinforcing materials for clay polymer nanocomposites (CPN) in advanced applications. Among the prerequisites necessary for polymer improvement by clay minerals are homogeneous and stable Distribution of the clay mineral throughout the CPN, good compatibility of the reinforcement with the Matrix component and suitable processability. Typically, clay minerals are surface-modified with organic interface active compounds like detergents or silanes to obtain favorable properties as filler. They are incorporated into the polymer matrix using manufacturing Equipment like extruders, batch reactors or other mixing machines. In order for the surface modification to survive the stresses and strains during incorporation, the modified clay minerals must display sufficient thermal and mechanical stability to retain the compatibilizing effect. In the present study, thermogravimetry was used in combination with isoconversional kinetic analysis to determine the thermal stability of a silane-modified clay mineral based on bentonite. These findings were compared with the stability of the same clay mineral that was only surfactant-modified. It was found that silane modification leads to significantly improved thermal stability, which depends strongly on the type of silane employed.
A vapor permeation processes for the separation of aromatic compounds from aliphatic compounds
(2014)
A number of rubbery and glassy membranes have been prepared and evaluated in vapor permeation experiments for separation of aromatic/aliphatic mixtures, using 5/95 (wt:wt) toluene/methylcyclohexane (MCH) as a model solution. Candidate membranes that met the required toluene/MCH selectivity of ≥ 10 were identified. The stability of the candidate membranes was tested by cycling the experiment between higher toluene concentrations and the original 5 wt% level. The best membrane produced has a toluene permeance of 280 gpu and a toluene/MCH selectivity of 13 when tested with a vapor feed of the model mixture at its boiling point and at atmospheric pressure. When a series of related membrane materials are compared, there is a sharp trade-off between membrane permeance and membrane selectivity. A process design study based on the experimental results was conducted. The best preliminary membrane design uses 45% of the energy of a conventional distillation process.
Plasma polymerization is used for the modification and control of surface properties of a highly transparent, thermoplastic elastomeric silicone copolymer, GENIOMER® 80 (G80). PEG-like diglyme plasma polymer films were deposited with ether retentions varying between 20% and 70% as measured by X-ray photoelectron spectroscopy analysis which did not affect the transparency of the substrate. Films with ether retentions of greater than 70% inhibit protein binding (bovine serum albumin and fibrinogen) and cell proliferation. A short oxygen plasma pretreatment enhances the adhesion and stability of the film as shown by protein binding and cell adhesion experiments. The transparency of the material and the stability of the coating makes this material a versatile bulk material for technical (e.g., lab-on-a-chip) and biomedical (e.g., intraocular lens) applications. The G80/plasma polymer composite is stable against vigorous washing and storage over 5 months and, therefore, offers an attractive alternative to poly(dimethylsiloxane).
In the powder coating of veneered particle boards the highly reactive hybrid epoxy/polyester powder transparent Drylac 530 Series from TIGER Coatings GmbH & Co. KG, Wels, Austria was used. Curing is accelerated by a mixture of catalysts reaching curing times of 3 min at 150 °C or 5 min at 135 °C which allows for energy and time savings making Drylac Series 530 powder suitable for the coating of temperaturesensitive substrates such as MDF and wood.
Powder coatings provide several advantages over traditional coatings: environmental friendliness, freedom of design, robustness and resistance of surfaces, possibility to seamlessly all-around coating, fast production process, cost-effectiveness. In the last years these benefits of the powder coating technology have been adopted from metal to heat-sensitive natural fibre/ wood based substrates (especially medium density fibre boards- MDF) used for interior furniture applications. Powder coated MDF furniture parts are gaining market share already in the classic furniture applications kitchen, bathroom, living and offices. The acceptance of this product is increasing as reflected by excellent growth rates and an increasing customer base. Current efforts of the powder coating industry to develop new powders with higher reactivity (i.e. lower curing temperatures and shorter curing times; e.g. 120°C/5min) will enable the powder coating of other heat-sensitive substrates like natural fibre composites, wood plastic composites, light weight panels and different plastics in the future. The coating could be applied and cured by the conventional powder coating process (electrostatic application, and melting and curing in an IR-oven) or by a new powder coating procedure based on the in-mould-coating (IMC) technique which is already established in the plastic industry. Extra value could be added in the future by the functional powder toner printing of powder coated substrates using the electrophotographic printing technology, meeting the future demand of both individualization of the furniture part surface by applying functional 3D textures and patterns and individually created coloured images and enabling shorter delivery times for these individualized parts. The paper describes the distinctiveness of powder coating on natural fibre/ wood based substrates, the requirements of the substrate and the coating powder.
Cyanate esters
(2014)
Cyanate ester resins are an important class of thermosetting compounds that have experienced an ever-increasing interest as matrix systems for advanced polymer composite materials, which among other applications, are especially suitable for highly demanding functions in the aerospace or microelectronics industries. Other names for cyanate ester resins are cyanate resins, cyanic esters, or triazine resins. The various types of cyanate ester monomers share the aOCN functional group that trimerizes in the course of resin formation to yield a highly branched heterocyclic polymeric network based on the substituted triazine core structure. The basic reaction sequence leading to the typical cyanate ester polymer molecule is depicted in Figure 11.1. The curing reaction may take place with or without catalyst.
Increasing number of studies are focused on how adherent cells respond, in vitro, to different properties of a material. Typical properties are the surface chemistry, topographical cues (at the nano- and micro-scale) of the surface, and the substrate stiffness. Cell Response studies are of importance for designing new biomaterials with applications in cell culture technologies, regenerative medicine, or for medical implants. However, only very few studies take the cell age factor, respectively the donor age, into account. In this work, we tested two types of human vascular cells (smooth muscle and endothelial cells) from old and young donors on (a) micro-structured surfaces made of pol (dimethylsiloxane) or on (b) flat polyacrylamide hydrogels with varying stiffnesses. These experiments reveal age-dependent and cell typedependent differences in the cell response to the topography and stiffness, and may establish the Basis for further studies focusing on cell age-dependent responses.
Positively charged metallic oxides prevent blood coagulation whereas negatively charged metallic oxides are thrombogenic. This study was performed to examine whether this effect extends to metallic oxide nanoparticles. Oscillation shear rheometry was used to study the effect of zinc oxide and silicon dioxide nanoparticles on thrombus formation in human whole blood. Our data show that oscillation shear rheometry is a sensitive and robust technique to analyze thrombogenicity induced by nanoparticles. Blood without previous contact with nanoparticles had a clotting time (CT) of 16.7 ± 1.0 min reaching a maximal clot strength (CS) of 16 ± 14 Pa (G') after 30 min. ZnO nanoparticles (diameter 70 nm, +37 mV zeta-potential) at a concentration of 1 mg/mL prolonged CT to 20.8 ± 3.6 min and provoked a weak clot (CS 1.5 ± 1.0 Pa). However, at a lower concentration of 100 µg/mL the ZnO particles dramatically reduced CT to 6.0 ± 0.5 min and increased CS to 171 ± 63 Pa. This procoagulant effect decreased at lower concentrations reaching the detection limit at 10 ng/mL. SiO2 nanoparticles (diameter 232 nm, −28 mV zeta-potential) at high concentrations (1 mg/mL) reduced CT (2.1 ± 0.2 min) and stimulated CS (249 ± 59 Pa). Similar to ZnO particles, this procoagulant effect reached a detection limit at 10 ng/mL. Nanoparticles in high concentrations reproduce the surface charge effects on blood coagulation previously observed with large particles or solid metal oxides. However, nanoparticles with different surface charges equally well stimulate coagulation at lower concentrations. This stimulation may be an effect which is not directly related to the surface charge.
The interaction between lipid bilayers in water has been intensively studied over the last decades. Osmotic stress was applied to evaluate the forces between two approaching lipid bilayers in aqueous solution. The force–distance relation between lipid mono- or bilayers deposited on mica sheets using a surface force apparatus (SFA) was also measured. Lipid stabilised foam films offer another possibility to study the interactions between lipid monolayers. These films can be prepared comparatively easy with very good reproducibility. Foam films consist usually of two adsorbed surfactant monolayers separated by a layer of the aqueous solution from which the film is created. Their thickness can be conveniently measured using microinterferometric techniques. Studies with foam films deliver valuable information on the interactions between lipid membranes and especially their stability and permeability. Presenting inverse black lipid membrane (BLM) foam films supply information about the properties of the lipid self-organisation in bilayers. The present paper summarises results on microscopic lipid stabilised foam films by measuring their thickness and contact angle. Most of the presented results concern foam films prepared from dispersions of the zwitterionic lipid 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) and some of its mixtures with the anionic lipid — 1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DMPG).
The strength of the long range and short range forces between the lipid layers is discussed. The van der Waals attractive force is calculated. The electrostatic repulsive force is estimated from experiments at different electrolyte concentrations (NaCl, CaCl2) or by modification of the electrostatic double layer surface potential by incorporating charged lipids in the lipid monolayers. The short range interactions are studied and modified by using small carbohydrates (fructose and sucrose), ethanol (EtOH) or dimethylsulfoxide (DMSO). Some results are compared with the structure of lipid monolayers deposited at the liquid/air interface (monolayers spread in Langmuir trough), which are one of most studied biomembrane model system. The comparison between the film thickness and the free energy of film formation is used to estimate the contribution of the different components of the disjoining pressure to the total interaction in the film and their dependence on the composition of the film forming solution.
Several diseases occur due to asbestos exposure. Until today, asbestos predicted mortality and morbidity will increase because of the long latency period. Actually, the methods to investigate asbestos related disease are mostly invasive. Therefore, the aim of the present paper was to investigate, whether signals in human breath could be correlated to Asbestos related lung diseases using a multi-capillary column (MCC) connected to an ion mobility spectrometer (IMS) as non-invasive method. Here, the breath samples of 10 mL of 25 patients suffering from asbestos related diseases. This group includes patients with asbestos related pleural thickening with and without pulmonary fibrosis. Twelve healthy persons constitute the control group and the breath samples are compared with those of the BK4103 patients. In total 83 peaks are found in the IMS-Chromatogram. A discrimination was possible with p-values <0.001 for two peaks (99.9 %), <0.01 (99 %) for 5 peaks and <0.05 (95 %) for 17 peaks. The most discrimination peaks alpha pinene and 4-ethyltoluol were identified among some others with lower p-values. The corresponding Box-and-Whisker-Plots comparing both groups are presented. In addition, a decision tree including all peaks was created that shows a differentiation with alpha pinene between BK4103 (pleural plaques group) and the control group. In addition, the sensitivity was calculated to 96 %, specificity was 50 %, positive and negative predictive values were 80 % and 86 %. Ion mobility spectrometry was introduced as non-invasive method to separate both groups Asbestos related and healthy. Naturally, the findings need further confirmation on larger population groups, but encourage further investigations, too.
Children undergoing systemic chemotherapy often suffer from severe immunosuppression usually associated to severe neutropenia (neutrophils < 0.5 x 109/l). Clinical courses during those periods range from asymptomatic to septic general conditions. Development of septic symptoms can be very fast and life-threatening. Swift detection of risk factors in those patients is therefore needed. So far no early, rapid and reliable marker or tool exists. Ion-Mobility-Spectrometry coupled with a Multi-Capillary-Column (IMS-MCC) can analyze more than 600 volatile components from exhaled air within a few minutes and hence is a potential, rapid detection-tool. As a proof of concept we measured the exhaled breath of 11 patients with neutropenia and 10 healthy controls ranging from 3 to 18 years of age at the time of measurement. Ten milliliters breath samples were taken at the outpatient clinic and analyzed with an onsite IMS-MCC (BreathDiscovery, B&S Analytik, Dortmund, Germany). Dead-space-volume was adapted to two groups (small 250 ml, large 500 ml). Interestingly 59 differing peaks were measured. Eleven were significantly different (p ≤ 0.05), three of which highly significant (p ≤ 0.01) in Mann-Whitney-Rank-Sum-testing. The corresponding analytes used in the decision tree are 2-Propanol, D-Limonene and Acetone. The analytes with the lowest rank sum identified are 2-Hexanone, Iso-Propylamine and 1-Butanol. Eventually we were able to show a three-step-decision-tree, which discerns the 21 samples except one from each group. Sensitivity was 90 % and specificity was 91 %. Naturally these findings need further confirmation within a bigger population. Our pilot-study proves that Ion-Mobility-Spectrometry coupled with a Multi-Capillary-Column is a feasible rapid diagnostic tool in the setting of a pediatric oncology out-patient clinic for patients 3 years and older. Our first results furthermore encourage additional analysis as to whether patients at risk for septic events during immunosuppression can be diagnosed in advance by rapidly assessing risk factors such as Neutropenia in exhaled breath.
Background: Conventional methods for lung cancer detection including computed tomography (CT) and bronchoscopy are expensive and invasive. Thus, there is still a need for an optimal lung cancer detection technique. Methods: The exhaled breath of 50 patients with lung cancer histologically proven by bronchoscopic biopsy samples (32 adenocarcinomas, 10 squamous cell carcinomas, 8 small cell carcinomas), were analyzed using ion mobility spectrometry (IMS) and compared with 39 healthy volunteers. As a secondary assessment, we compared adenocarcinoma patients with and without epidermal growth factor receptor (EGFR) mutation. Results: A decision tree algorithm could separate patients with lung cancer including adenocarcinoma, squamous cell carcinoma and small cell carcinoma. One hundred-fifteen separated volatile organic compound (VOC) peaks were analyzed. Peak-2 noted as n-Dodecane using the IMS database was able to separate values with a sensitivity of 70.0% and a specificity of 89.7%. Incorporating a decision tree algorithm starting with n-Dodecane, a sensitivity of 76% and specificity of 100% was achieved. Comparing VOC peaks between adenocarcinoma and healthy subjects, n-Dodecane was able to separate values with a sensitivity of 81.3% and a specificity of 89.7%. Fourteen patients positive for EGFR mutation displayed a significantly higher n-Dodecane than for the 14 patients negative for EGFR (p<0.01), with a sensitivity of 85.7% and a specificity of 78.6%. Conclusion: In this prospective study, VOC peak patterns using a decision tree algorithm were useful in the detection of lung cancer. Moreover, n-Dodecane analysis from adenocarcinoma patients might be useful to discriminate the EGFR mutation.
Ion mobility spectrometry coupled to multi capillary columns (MCC/IMS) combines highly sensitive spectrometry with a rapid separation technique. MCC\IMS is widely used for biomedical breath analysis. The identification of molecules in such a complex sample necessitates a reference database. The existing IMS reference databases are still in their infancy and do not allow to actually identify all analytes. With a gas chromatograph coupled to a mass selective detector (GC/MSD) setup in parallel to a MCC/IMS instrumentation we may increase the accuracy of automatic analyte identification. To overcome the time-consuming manual evaluation and comparison of the results of both devices, we developed a software tool MIMA (MS-IMS-Mapper), which can computationally generate analyte layers for MCC/IMS spectra by using the corresponding GC/MSD data. We demonstrate the power of our method by successfully identifying the analytes of a seven-component mixture. In conclusion, the main contribution of MIMA is a fast and easy computational method for assigning analyte names to yet un-assigned signals in MCC/IMS data. We believe that this will greatly impact modern MCC/IMS-based biomarker research by 'giving a name' to previously detected disease-specific molecules.
Online measurement of drug concentrations in patient's breath is a promising approach for individualized dosage. A direct transfer from breath- to blood-concentrations is not possible. Measured exhaled concentrations are following the blood-concentration with a delay in non-steady-state situations. Therefore, it is necessary to integrate the breath-concentration into a pharmacological model. Two different approaches for pharmacokinetic modelling are presented. Usually a 3-compartment model is used for pharmacokinetic calculations of blood concentrations. This 3-compartment model is extended with a 2-compartment model based on the first compartment of the 3-compartment model and a new lung compartment. The second approach is to calculate a time delay of changes in the concentration of the first compartment to describe the lung-concentration. Exemplarily both approaches are used for modelling of exhaled propofol. Based on time series of exhaled propofol measurements using an ion-mobility-spectrometer every minute for 346 min a correlation of calculated plasma and the breath concentration was used for modelling to deliver R2 = 0.99 interdependencies. Including the time delay modelling approach the new compartment coefficient ke0lung was calculated to ke0lung = 0.27 min−1 with R2 = 0.96. The described models are not limited to propofol. They could be used for any kind of drugs, which are measurable in patient's breath.
Die Ionenmobilitätsspektrometrie ist eine gasanalytische Methode, die analytisch zwischen Sensoren auf der einen Seite und Spektrometern auf der anderen angesiedelt ist. Ihre Vorteile liegen darin, auch komplexere Gasgemische als Sensoren erfolgreich vor Ort und online sowie bettseitig im Krankenhaus analysieren zu können. Beispiele als dem Bereich Bio- und Prozessanalytik sollen die jeweiligen Ansätze und das Potential von der Fragestellung über die jeweils spezifische Lösung bis hin zum Ergebnis am Prozess exemplarisch zusammenstellen. Hierbei werden sowohl die analytische Sicht als auch die Marktsicht thematisiert.
Scanning Near-Field Optical Microscopy (SNOM) has developed during recent decades into a valuable tool to optically image the surface topology of materials with super-resolution. With aperture-based SNOM systems, the resolution scales with the size of the aperture, but also limits the sensitivity of the detection and thus the application for spectroscopic techniques like Raman SNOM. In this paper we report the extension of solid immersion lens (SIL) technology to Raman SNOM. The hemispherical SIL with a tip on the bottom acts as an apertureless dielectric nanoprobe for simultaneously acquiring topographic and spectroscopic information. The SIL is placed between the sample and the microscope objective of a confocal Raman microscope. The lateral resolution in the Raman mode is validated with a cross section of a semiconductor layer system and, at approximately 180 nm, is beyond the classical diffraction limit of Abbe.
Background: Multicapillary column ion-mobility spectrometry (MCC-IMS) may identify volatile components in exhaled gas. The authors therefore used MCC-IMS to evaluate exhaled gas in a rat model of sepsis, inflammation, and hemorrhagic shock.
Methods: Male Sprague-Dawley rats were anesthetized and ventilated via tracheostomy for 10 h or until death. Sepsis was induced by cecal ligation and incision in 10 rats; a sham operation was performed in 10 others. In 10 other rats, endotoxemia was induced by intravenous administration of 10 mg/kg lipopolysaccharide. In a final 10 rats, hemorrhagic shock was induced to a mean arterial pressure of 35 +/- 5 mmHg. Exhaled gas was analyzed with MCC-IMS, and volatile compounds were identified using the BS-MCC/IMS-analytes database (Version 1209; B&S Analytik, Dortmund, Germany).
Results: All sham animals survived the observation period, whereas mean survival time was 7.9 h in the septic animals, 9.1 h in endotoxemic animals, and 2.5 h in hemorrhagic shock. Volatile compounds showed statistically significant differences in septic and endotoxemic rats compared with sham rats for 3-pentanone and acetone. Endotoxic rats differed significantly from sham for 1-propanol, butanal, acetophenone, 1,2-butandiol, and 2-hexanone. Statistically significant differences were observed between septic and endotoxemic rats for butanal, 3-pentanone, and 2-hexanone. 2-Hexanone differed from all other groups in the rats with shock.
Conclusions: Breath analysis of expired organic compounds differed significantly in septic, inflammation, and sham rats. MCC-IMS of exhaled breath deserves additional study as a noninvasive approach for distinguishing sepsis from inflammation.
The analysis of exhaled metabolites has become a promising field of research in recent decades. Several volatile organic compounds reflecting metabolic disturbance and nutrition status have even been reported. These are particularly important for long-term measurements, as needed in medical research for detection of disease progression and therapeutic efficacy. In this context, it has become urgent to investigate the effect of fasting and glucose treatment for breath analysis. In the present study, we used amodel of ventilated rats that fasted for 12 h prior to the experiment. Ten rats per group were randomly assigned for continuous intravenous infusion without glucose or an infusion including 25 mg glucose per 100 g per hour during an observation period of 12 h. Exhaled gas was analysed using multicapillary column ion-mobility spectrometry. Analytes were identified by the BS-MCC/IMS database (version 1209; B & S Analytik, Dortmund, Germany). Glucose infusion led to a significant increase in blood glucose levels (p<0.05 at 4 h and thereafter) and cardiac output (p<0.05 at 4 h and thereafter). During the observation period, 39 peaks were found collectively. There were significant differences between groups in the concentration of ten volatile organic compounds: p<0.001 at 4 h and thereafter for isoprene, cyclohexanone, acetone, p-cymol, 2-hexanone, phenylacetylene, and one unknown compound, and p<0.001 at 8 h and thereafter for 1-pentanol, 1-propanol, and 2-heptanol. Our results indicate that for long-term measurement, fasting and the withholding of glucose could contribute to changes of volatile metabolites in exhaled air.
Perivascular cells are multilineage cells located around the vessel wall and important for wall stabilization. In this study, we evaluated a stem cell media and a perivascular cell-specific media for the culture of primary perivascular cells regarding their cell morphology, doubling time, stem cell properties, and expression of cell type-specific markers. When the two cell culture media were compared to each other, perivascular cells cultured in the stem cell medium had a more elongated morphology and a faster doubling rate and cells cultured in the pericyte medium had a more typical morphology, with several filopodia, and a slower doubling rate. To evaluate stem cell properties, perivascular cells, CD146 cells, and mesenchymal stem cells (MSCs) were differentiated into the adipogenic, osteogenic, and chondrogenic lineages. It was seen that perivascular cells, as well as CD146 cells and MSCs, cultured in stem cell medium showed greater differentiation than cells cultured in pericyte-specific medium. The expression of pericyte-specific markers CD146, neural/glial antigen 2 (NG2), platelet-derived growth factor receptor-β (PDGFR-β), myosin, and α-smooth muscle actin (α-SMA) could be found in both pericyte cultures, as well as to varying amounts in CD146 cells, MSCs, and endothelial cells. The here presented work shows that perivascular cells can adapt to their in vitro environment and cell culture conditions influence cell functionality, such as doubling rate or differentiation behavior. Pericyte-specific markers were shown to be expressed also from cells other than perivascular cells. We can further conclude that CD146⁺ perivascular cells are inhomogeneous cell population probably containing stem cell subpopulations, which are located perivascular around capillaries.
Critical size bone defects and non-union fractions are still challenging to treat. Cell-loaded bone substitutes have shown improved bone ingrowth and bone formation. However, a lack of methods for homogenously colonizing scaffolds limits the maximum volume of bone grafts. Additionally, therapy robustness is impaired by heterogeneous cell populations after graft generation. Our aim was to establish a technology for generating grafts with a size of 10.5 mm in diameter and 25 mm of height, and thus for grafts suited for treatment of critical size bone defects. Therefore, a novel tailor-made bioreactor system was developed, allowing standardized flow conditions in a porous poly(L-lactide co-caprolactone) material. Scaffolds were seeded with primary human mesenchymal stem cells derived from four different donors. In contrast to static experimental conditions, homogenous cell distributions were accomplished under dynamic culture. Additionally, culture in the bioreactor system allowed the induction of osteogenic lineage commitment after one week of culture without addition of soluble factors. This was demonstrated by quantitative analysis of calcification and gene expression markers related to osteogenic lineage. In conclusion, the novel bioreactor technology allows efficient and standardized conditions for generating bone substitutes that are suitable for the treatment of critical size defects in humans.
Bone homeostasis is maintained by osteoblasts (bone formation) and osteoclasts (bone resorption). While there have been numerous studies investigating mesenchymal stem cells and their potential to differentiate into osteoblasts as well as their interaction with different bone substitute materials, there is only limited knowledge concerning in vitro generated osteoclasts. Due to the increasing development of degradable bone-grafting materials and the need of sophisticated in vitro test methods, it is essential to gain deeper insight into the process of osteoclastogenesis and the resorption functionality of human osteoclasts. Therefore, we focused on the comparison of osteoclastogenesis and resorption activity on tissue culture polystyrene (TCPS) and bovine extracellular bone matrices (BMs). Cortical bone slices were used as two-dimensional (2D) substrates, whereas a thermally treated cancellous bone matrix was used for three-dimensional (3D) experiments. We isolated primary human monocytes and induced osteoclastogenesis by medium supplementation. Subsequently, the expression of the vitronectin receptor (αVβ3) and cathepsin K as well as the characteristic actin formation on TCPS and the two BMs were examined. The cell area of human osteoclasts was analyzed on TCPS and on BMs, whereas significantly larger osteoclasts could be detected on BMs. Additionally, we compared the diameter of the sealing zones with the measured diameter of the resorption pits on the BMs and revealed similar diameters of the sealing zones and the resorption pits. We conclude that using TCPS as culture substrate does not affect the expression of osteoclast-specific markers. The analysis of resorption activity can successfully be conducted on cortical as well as on cancellous bone matrices. For new in vitro test systems concerning bone resorption, we suggest the establishment of a 2D assay for high throughput screening of new degradable bone substitute materials with osteoclasts.
In the current study the in vitro outcome of a degradable magnesium alloy (AZ91D) and standard titanium modified by nanostructured-hydroxyapatite (n-HA) coatings concerning cell adhesion and osteogenic differentiation was investigated by direct cell culture. The n-HA modification was prepared via radio-frequency magnetron sputtering deposition and proven by field emission scanning electron microscopy and X-ray powder diffraction patterns revealing a homogenous surface coating. Human mesenchymal stem cell (hMSCs) adhesion was examined after one and 14 days displaying an enhanced initial cell adhesion on the n-HA modified samples. The osteogenic lineage commitment of the cells was determined by alkaline phosphatase (ALP) quantification. On day one n-HA coated AZ91D exhibited a comparable ALP expression to standard tissue culture polystyrene samples. However, after 14 days solely little DNA and ALP amounts were measurable on n-HA coated AZ91D due to the lack of adherent cells. Titanium displayed excellent cell adhesion properties and ALP was detectable after 14 days. An increased pH of the culture was measured for AZ91D as well as for n-HA coated AZ91D. We conclude that n-HA modification improves initial cell attachment on AZ91D within the first 24 h. However, the effect does not ersist for 14 days in in vitro conditions.
Thin radio-frequency magnetron sputter deposited nano-hydroxyapatite (HA) films were prepared on the surface of a Fe-tricalcium phosphate (Fe-TCP) bioceramic composite, which was obtained using a conventional powder injection moulding technique. The obtained nano-hydroxyapatite coated Fe-TCP biocomposites (nano HA-Fe-TCP) were studied with respect to their chemical and phase composition, surface morphology, water contact angle, surface free energy and hysteresis. The deposition process resulted in a homogeneous, single-phase HA coating. The ability of the surface to support adhesion and the proliferation of human mesenchymal stem cells (hMSCs) was studied using biological short-term tests in vitro. The surface of the uncoated Fe-TCP bioceramic composite showed an initial cell attachment after 24 h of seeding, but adhesion, proliferation and growth did not persist during 14 days of culture.However, the HA-Fe-TCP surfaces allowed cell adhesion, and proliferation during 14 days. The deposition of the nano-HA films on the Fe-TCP surface resulted in higher surface energy, improved hydrophilicity and biocompatibility compared with the surface of the uncoated Fe-TCP. Furthermore, it is suggested that an increase in the polar component of the surface energy was responsible for the enhanced cell adhesion and proliferation in the case of the nano-HA Fe-TCP biocomposites.
Reflectometry is known since long as an interferometric method which can be used to characterize surfaces and thin films regarding their structure and,to a certain degree,composition as well.Properties like layer structures,layer thickness,density,and interface roughness can be determined by fitting the obtained reflectivity data with an appropriate model using a recursive fitting routine. However,one major drawback of the reflectometric method is its restriction to planar surfaces.In this article we demonstrate an approach to apply X-ray and neutron reflectometry to curved surfaces by means of the example of bent bare and coated glass slides.We prove the possibility to observe all features like Fresnel decay,Kiessig fringes,Bragg peaks and off-specular scattering and are able to interpret the data using common fitting software and to derive quantitative results about roughness,layer thickness and internal structure. The proposed method has become practical due to the availability of high quality 2D-detectors. It opens up the option to explore many kinds and shapes of samples,which,due to their geometry,have not been in the focus of reflectometry techniques until now.
Block-copolyesters of polyethylene terephthalate (PET) and polyethylene naphthalate (PEN) were synthesized via reactive extrusion. The influence of processing parameters on the material properties on a molecular scale like degree of trans-esterification, block length, and degree of randomness were investigated. The varied process factors were extrusion temperature and rotational speed. The effects of process parameter variation were investigated by 1H-NMR-spectroscopy. The experimental results show a clear dependence of the molecular properties on the processing conditions. By using statistical experimental design (DoE), it was possible to prepare defined copolyesters from PET and PEN without addition of further chemicals. With a degree of randomness between 0.05 and 0.5, the presence of an actual copolyester was confirmed when appropriate extrusion conditions were applied. The reactive extrusion process was confirmed to be suitable to produce defined block-copolyesters in a predictable and reproducible way. It was possible to produce designed sequence lengths, which could be adjusted within a range of 11–136 repeating units in the case of PET and, in the case of PEN, of 2.5–26. The produced materials can be used as barrier materials or barrier coatings to protect substrates against molecular oxygen and water vapour, e.g., in organic photovoltaic applications or food packaging. The described method is a one-pot alternative method to the previously described chemical recycling pathway.
The interfacial compatibility between polymers and nanoclay fillers as well as the thermostability of both components are important characteristics for processing them into polymer composites. While the polymer component is often grafted using common polymerization reactions, the nanoclay component is usually surface modified by surfactant treatment to improve compatibility. In the present study, the polymer ethylene vinyl alcohol and a nanoclay filler based on natural bentonite are both surface modified by different silanes, 3-glycidoxypropyltrimethoxysilane and methacryloxymethyltrimethoxysilane and their interfacial properties are investigated by inverse gas chromatography. The silane-modified samples had improved interfacial properties as reflected by a significant increase in dispersive and specific surface energies. Lewis acidities were determined using chloroform and 1,4-dioxane as polar probes and showed a good match between polymer and nanofiller interfaces. Lewis acidity was generally lower after silane-modification. Silanization yielded increased thermal stability of the treated samples. Thus, silanization led to improved compatibility and enhanced thermal stability which facilitates further processing.
The physiology of vascular cells depends on stimulating mechanical forces caused by pulsatile flow. Thus, mechano-transduction processes and responses of primary human endothelial cells (ECs) and smooth muscle cells (SMCs) have been studied to reveal cell-type specific differences which may contribute to vascular tissue integrity. Here, we investigate the dynamic reorientation response of ECs and SMCs cultured on elastic membranes over a range of stretch frequencies from 0.01 to 1 Hz. ECs and SMCs show different cell shape adaptation responses (reorientation) dependent on the frequency. ECs reveal a specific threshold frequency (0.01 Hz) below which no responses is detectable while the threshold frequency for SMCs could not be determined and is speculated to be above 1 Hz. Interestingly, the reorganization of the actin cytoskeleton and focal adhesions system, as well as changes in the focal adhesion area, can be observed for both cell types and is dependent on the frequency. RhoA and Rac1 activities are increased for ECs but not for SMCs upon application of a uniaxial cyclic tensile strain. Analysis of membrane protrusions revealed that the spatial protrusion activity of ECs and SMCs is independent of the application of a uniaxial cyclic tensile strain of 1 Hz while the total number of protrusions is increased for ECs only. Our study indicates differences in the reorientation response and the reaction times of the two cell types in dependence of the stretching frequency, with matching data for actin cytoskeleton, focal adhesion realignment, RhoA/Rac1 activities, and membrane protrusion activity. These are promising results which may allow cell-type specific activation of vascular cells by frequency selective mechanical stretching. This specific activation of different vascular cell types might be helpful in improving strategies in regenerative medicine.
Engineering of large vascularized adipose tissue constructs is still a challenge for the treatment of extensive high-graded burns or the replacement of tissue after tumor removal. Communication between mature adipocytes and endothelial cells is important for homeostasis and the maintenance of adipose tissue mass but, to date, is mainly neglected in tissue engineering strategies. Thus, new coculture strategies are needed to integrate adipocytes and endothelial cells successfully into a functional construct. This review focuses on the cross-talk of mature adipocytes and endothelial cells and considers their influence on fatty acid metabolism and vascular tone. In addition, the properties and challenges with regard to these two cell types for vascularized tissue engineering are highlighted.
Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammatory disease characterized by incompletely reversible airway obstruction. This clinically heterogeneous group of patients is characterized by different phenotypes. Spirometry and clinical parameters, such as severity of dyspnea and exacerbation frequency, are used to diagnose and assess the severity of COPD. The purpose of this study was to investigate whether volatile organic compounds (VOCs) could be detected in the exhaled breath of patients with COPD and whether these VOCs could distinguish COPD patients from healthy subjects. Moreover, we aimed to investigate whether VOCs could be used as biomarkers for classifying patients into different subgroups of the disease. Ion mobility spectrometry was used to detect VOCs in the exhaled breath of COPD patients. One hundred and thirty-seven peaks were found to have a statistically significant difference between the COPD group and the combined healthy smokers and nonsmoker group. Six of these VOCs were found to correctly discriminate COPD patients from healthy controls with an accuracy of 70%. Only 15 peaks were found to be statistically different between healthy smokers and healthy nonsmokers. Furthermore, by determining the cutoff levels for each VOC peak, it was possible to classify the COPD patients into breathprint subgroups. Forced expiratory volume in 1 second, body mass index, and C-reactive protein seem to play a role in the discrepancies observed in the different breathprint subgroups.
Computational breath analysis is a growing research area aiming at identifying volatile organic compounds (VOCs) in human breath to assist medical diagnostics of the next generation. While inexpensive and non-invasive bioanalytical technologies for metabolite detection in exhaled air and bacterial/fungal vapor exist and the first studies on the power of supervised machine learning methods for profiling of the resulting data were conducted, we lack methods to extract hidden data features emerging from confounding factors. Here, we present Carotta, a new cluster analysis framework dedicated to uncovering such hidden substructures by sophisticated unsupervised statistical learning methods. We study the power of transitivity clustering and hierarchical clustering to identify groups of VOCs with similar expression behavior over most patient breath samples and/or groups of patients with a similar VOC intensity pattern. This enables the discovery of dependencies between metabolites. On the one hand, this allows us to eliminate the effect of potential confounding factors hindering disease classification, such as smoking. On the other hand, we may also identify VOCs associated with disease subtypes or concomitant diseases. Carotta is an open source software with an intuitive graphical user interface promoting data handling, analysis and visualization. The back-end is designed to be modular, allowing for easy extensions with plugins in the future, such as new clustering methods and statistics. It does not require much prior knowledge or technical skills to operate. We demonstrate its power and applicability by means of one artificial dataset. We also apply Carotta exemplarily to a real-world example dataset on chronic obstructive pulmonary disease (COPD). While the artificial data are utilized as a proof of concept, we will demonstrate how Carotta finds candidate markers in our real dataset associated with confounders rather than the primary disease (COPD) and bronchial carcinoma (BC). Carotta is publicly available at http://carotta.compbio.sdu.dk.