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- ItemKallikrein-Related Peptidase 6 Is Associated with the Tumour Microenvironment of Pancreatic Ductal Adenocarcinoma(Basel : MDPI, 2021) Candido, Juliana B; Maiques, Oscar; Boxberg, Melanie; Kast, Verena; Peerani, Eleonora; Tomás-Bort, Elena; Weichert, Wilko; Sananes, Amiram; Papo, Niv; Magdolen, Viktor; Sanz-Moreno, Victoria; Loessner, DanielaAs cancer-associated factors, kallikrein-related peptidases (KLKs) are components of the tumour microenvironment, which represents a rich substrate repertoire, and considered attractive targets for the development of novel treatments. Standard-of-care therapy of pancreatic cancer shows unsatisfactory results, indicating the need for alternative therapeutic approaches. We aimed to investigate the expression of KLKs in pancreatic cancer and to inhibit the function of KLK6 in pancreatic cancer cells. KLK6, KLK7, KLK8, KLK10 and KLK11 were coexpressed and upregulated in tissues from pancreatic cancer patients compared to normal pancreas. Their high expression levels correlated with each other and were linked to shorter survival compared to low KLK levels. We then validated KLK6 mRNA and protein expression in patient-derived tissues and pancreatic cancer cells. Coexpression of KLK6 with KRT19, αSMA or CD68 was independent of tumour stage, while KLK6 was coexpressed with KRT19 and CD68 in the invasive tumour area. High KLK6 levels in tumour and CD68+ cells were linked to shorter survival. KLK6 inhibition reduced KLK6 mRNA expression, cell metabolic activity and KLK6 secretion and increased the secretion of other serine and aspartic lysosomal proteases. The association of high KLK levels and poor prognosis suggests that inhibiting KLKs may be a therapeutic strategy for precision medicine.
- ItemPressure- and Temperature-Dependent Crystallization Kinetics of Isotactic Polypropylene under Process Relevant Conditions(Basel : MDPI, 2021) Spoerer, Yvonne; Boldt, Regine; Androsch, René; Kuehnert, InesIn this study, a non-nucleated homopolymer (HP) and random copolymer (RACO), as well as a nucleated HP and heterophasic copolymer (HECO) were investigated regarding their crystallization kinetics. Using pvT-measurements and fast scanning chip calorimetry (FSC), the crystallization behavior was analyzed as a function of pressure, cooling rate and temperature. It is shown that pressure and cooling rate have an opposite influence on the crystallization temperature of the materials. Furthermore, the addition of nucleating agents to the material has a significant effect on the maximum cooling rate at which the formation of α-crystals is still possible. The non-nucleated HP and RACO materials show significant differences that can be related to the sterically hindering effect of the comonomer units of RACO on crystallization, while the nucleated materials HP and HECO show similar crystallization kinetics despite their different structures. The pressure-dependent shift factor of the crystallization temperature is independent of the material. The results contribute to the description of the relationship between the crystallization kinetics of the material and the process parameters influencing the injection-molding induced morphology. This is required to realize process control in injection molding in order to produce pre-defined morphologies and to design material properties.
- ItemCruciate Ligament Cell Sheets Can Be Rapidly Produced on Thermoresponsive poly(glycidyl ether) Coating and Successfully Used for Colonization of Embroidered Scaffolds(Basel : MDPI, 2021) Zahn, Ingrid; Stöbener, Daniel David; Weinhart, Marie; Gögele, Clemens; Breier, Annette; Hahn, Judith; Schröpfer, Michaela; Meyer, Michael; Schulze-Tanzil, GundulaAnterior cruciate ligament (ACL) cell sheets combined with biomechanically competent scaffolds might facilitate ACL tissue engineering. Since thermoresponsive polymers allow a rapid enzyme-free detachment of cell sheets, we evaluated the applicability of a thermoresponsive poly(glycidyl ether) (PGE) coating for cruciate ligamentocyte sheet formation and its influence on ligamentocyte phenotype during sheet-mediated colonization of embroidered scaffolds. Ligamentocytes were seeded on surfaces either coated with PGE or without coating. Detached ligamentocyte sheets were cultured separately or wrapped around an embroidered scaffold made of polylactide acid (PLA) and poly(lactic-co-ε-caprolactone) (P(LA-CL)) threads functionalized by gas-phase fluorination and with collagen foam. Ligamentocyte viability, protein and gene expression were determined in sheets detached from surfaces with or without PGE coating, scaffolds seeded with sheets from PGE-coated plates and the respective monolayers. Stable and vital ligamentocyte sheets could be produced within 24 h with both surfaces, but more rapidly with PGE coating. PGE did not affect ligamentocyte phenotype. Scaffolds could be colonized with sheets associated with high cell survival, stable gene expression of ligament-related type I collagen, decorin, tenascin C and Mohawk after 14 d and extracellular matrix (ECM) deposition. PGE coating facilitates ligamentocyte sheet formation, and sheets colonizing the scaffolds displayed a ligament-related phenotype.
- ItemField-Induced Transversely Isotropic Shear Response of Ellipsoidal Magnetoactive Elastomers(Basel : MDPI, 2021) Chougale, Sanket; Romeis, Dirk; Saphiannikova, MarinaMagnetoactive elastomers (MAEs) claim a vital place in the class of field-controllable materials due to their tunable stiffness and the ability to change their macroscopic shape in the presence of an external magnetic field. In the present work, three principal geometries of shear deformation were investigated with respect to the applied magnetic field. The physical model that considers dipole-dipole interactions between magnetized particles was used to study the stress-strain behavior of ellipsoidal MAEs. The magneto-rheological effect for different shapes of the MAE sample ranging from disc-like (highly oblate) to rod-like (highly prolate) samples was investigated along and transverse to the field direction. The rotation of the MAE during the shear deformation leads to a non-symmetric Cauchy stress tensor due to a field-induced magnetic torque. We show that the external magnetic field induces a mechanical anisotropy along the field direction by determining the distinct magneto-mechanical behavior of MAEs with respect to the orientation of the magnetic field to shear deformation.
- ItemEffective Halogen-Free Flame-Retardant Additives for Crosslinked Rigid Polyisocyanurate Foams: Comparison of Chemical Structures(Basel : MDPI, 2022) Lenz, Johannes U.; Pospiech, Doris; Komber, Hartmut; Korwitz, Andreas; Kobsch, Oliver; Paven, Maxime; Albach, Rolf W.; Günther, Martin; Schartel, BernhardThe impact of phosphorus-containing flame retardants (FR) on rigid polyisocyanurate (PIR) foams is studied by systematic variation of the chemical structure of the FR, including non-NCO-reactive and NCO-reactive dibenzo[d,f][1,3,2]dioxaphosphepine 6-oxide (BPPO)- and 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO)-containing compounds, among them a number of compounds not reported so far. These PIR foams are compared with PIR foams without FR and with standard FRs with respect to foam properties, thermal decomposition, and fire behavior. Although BPPO and DOPO differ by just one oxygen atom, the impact on the FR properties is very significant: when the FR is a filler or a dangling (dead) end in the PIR polymer network, DOPO is more effective than BPPO. When the FR is a subunit of a diol and it is fully incorporated in the PIR network, BPPO delivers superior results.
- ItemMagneto-Mechanical Coupling in Magneto-Active Elastomers(Basel : MDPI, 2021) Metsch, Philipp; Romeis, Dirk; Kalina, Karl A.; Raßloff, Alexander; Saphiannikova, Marina; Kästner, MarkusIn the present work, the magneto-mechanical coupling in magneto-active elastomers is investigated from two different modeling perspectives: a micro-continuum and a particle–interaction approach. Since both strategies differ significantly in their basic assumptions and the resolution of the problem under investigation, they are introduced in a concise manner and their capabilities are illustrated by means of representative examples. To motivate the application of these strategies within a hybrid multiscale framework for magneto-active elastomers, their interchangeability is then examined in a systematic comparison of the model predictions with regard to the magneto-deformation of chain-like helical structures in an elastomer surrounding. The presented results show a remarkable agreement of both modeling approaches and help to provide an improved understanding of the interactions in magneto-active elastomers with chain-like microstructures.
- ItemThe Localization Behavior of Different CNTs in PC/SAN Blends Containing a Reactive Component(Basel : MDPI, 2021-3-1) Gültner, Marén; Boldt, Regine; Formanek, Petr; Fischer, Dieter; Simon, Frank; Pötschke, PetraCo-continuous blend systems of polycarbonate (PC), poly(styrene-co-acrylonitrile) (SAN), commercial non-functionalized multi-walled carbon nanotubes (MWCNTs) or various types of commercial and laboratory functionalized single-walled carbon nanotubes (SWCNTs), and a reactive component (RC, N-phenylmaleimide styrene maleic anhydride copolymer) were melt compounded in one step in a microcompounder. The blend system is immiscible, while the RC is miscible with SAN and contains maleic anhydride groups that have the potential to reactively couple with functional groups on the surface of the nanotubes. The influence of the RC on the localization of MWCNTs and SWCNTs (0.5 wt.%) was investigated by transmission electron microscopy (TEM) and energy-filtered TEM. In PC/SAN blends without RC, MWCNTs are localized in the PC component. In contrast, in PC/SAN-RC, the MWCNTs localize in the SAN-RC component, depending on the RC concentration. By adjusting the MWCNT/RC ratio, the localization of the MWCNTs can be tuned. The SWCNTs behave differently compared to the MWCNTs in PC/SAN-RC blends and their localization occurs either only in the PC or in both blend components, depending on the type of the SWCNTs. CNT defect concentration and surface functionalities seem to be responsible for the localization differences.
- ItemFabrication of Microfluidic Devices for Emulsion Formation by Microstereolithography(Basel : MDPI, 2021) Männel, Max J.; Baysak, Elif; Thiele, JulianDroplet microfluidics—the art and science of forming droplets—has been revolutionary for high-throughput screening, directed evolution, single-cell sequencing, and material design. However, traditional fabrication techniques for microfluidic devices suffer from several disadvantages, including multistep processing, expensive facilities, and limited three-dimensional (3D) design flexibility. High-resolution additive manufacturing—and in particular, projection micro-stereolithography (PµSL)—provides a promising path for overcoming these drawbacks. Similar to polydimethylsiloxane-based microfluidics 20 years ago, 3D printing methods, such as PµSL, have provided a path toward a new era of microfluidic device design. PµSL greatly simplifies the device fabrication process, especially the access to truly 3D geometries, is cost-effective, and it enables multimaterial processing. In this review, we discuss both the basics and recent innovations in PµSL; the material basis with emphasis on custom-made photopolymer formulations; multimaterial 3D printing; and, 3D-printed microfluidic devices for emulsion formation as our focus application. Our goal is to support researchers in setting up their own PµSL system to fabricate tailor-made microfluidics.
- ItemStraightforward Approach for Preparing Durable Antibacterial ZnO Nanoparticle Coatings on Flexible Substrates(Basel : MDPI, 2022) Šutka, Andris; Mežule, Linda; Denisova, Viktorija; Meier-Haack, Jochen; Kulkarni, Akshay; Bitina, Sanda; Smits, Krisjanis; Vihodceva, SvetlanaFlexible antibacterial materials have gained utmost importance in protection from the distribution of bacteria and viruses due to the exceptional variety of applications. Herein, we demonstrate a readily scalable and rapid single-step approach for producing durable ZnO nanoparticle antibacterial coating on flexible polymer substrates at room temperature. Substrates used are polystyrene, poly(ethylene-co-vinyl acetate) copolymer, poly(methyl methacrylate), polypropylene, high density polyethylene and a commercial acrylate type adhesive tape. The deposition was achieved by a spin-coating process using a slurry of ZnO nanoparticles in toluene. A stable modification layer was obtained when toluene was a solvent for the polymer substrates, namely polystyrene and poly(ethylene-co-vinyl acetate). These coatings show high antibacterial efficiency causing >5 log decrease in the viable counts of Gram-negative bacteria Escherichia. coli and Gram-positive bacteria Staphylococcus aureus in 120 min. Even after tapping these coated surfaces 500 times, the antibacterial properties remained unchanged, showing that the coating obtained by the presented method is very robust. In contrast to the above findings, the coatings are unstable when toluene is not a solvent for the substrate.
- ItemA Polymer for Application as a Matrix Phase in a Concept of In Situ Curable Bioresorbable Bioactive Load-Bearing Continuous Fiber Reinforced Composite Fracture Fixation Plates(Basel : MDPI, 2021) Plyusnin, Artem; He, Jingwei; Elschner, Cindy; Nakamura, Miho; Kulkova, Julia; Spickenheuer, Axel; Scheffler, Christina; Lassila, Lippo V. J.; Moritz, NikoThe use of bioresorbable fracture fixation plates made of aliphatic polyesters have good potential due to good biocompatibility, reduced risk of stress-shielding, and eliminated need for plate removal. However, polyesters are ductile, and their handling properties are limited. We suggested an alternative, PLAMA (PolyLActide functionalized with diMethAcrylate), for the use as the matrix phase for the novel concept of the in situ curable bioresorbable load-bearing composite plate to reduce the limitations of conventional polyesters. The purpose was to obtain a preliminary understanding of the chemical and physical properties and the biological safety of PLAMA from the prospective of the novel concept. Modifications with different molecular masses (PLAMA-500 and PLAMA-1000) were synthesized. The efficiency of curing was assessed by the degree of convergence (DC). The mechanical properties were obtained by tensile test and thermomechanical analysis. The bioresorbability was investigated by immersion in simulated body fluid. The biocompatibility was studied in cell morphology and viability tests. PLAMA-500 showed better DC and mechanical properties, and slower bioresorbability than PLAMA-1000. Both did not prevent proliferation and normal morphological development of cells. We concluded that PLAMA-500 has potential for the use as the matrix material for bioresorbable load-bearing composite fracture fixation plates.