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End date: 2019 × Start date: 2010 × DDC: 570 × WGL Institute: IPF ×

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Now showing 1 - 10 of 27
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    A hyperbranched dopamine-containing PEG-based polymer for the inhibition of α-synuclein fibrillation
    (Orlando, Fla. : Academic Press, 2015) Breydo, Leonid; Newland, Ben; Zhang, Hong; Rosser, Anne; Werner, Carsten; Uversky, Vladimir N.; Wang, Wenxin
    Aggregation of α-synuclein is believed to play an important role in Parkinson's disease and in other neurodegenerative maladies. Small molecule inhibitors of this process are among the most promising drug candidates for neurodegenerative diseases. Dendrimers have also been studied for anti-fibrillation applications but they can be difficult and expensive to synthetize. Here we show that RAFT polymerization can be used to produce a hyperbranched polyethylene glycol structure via a one-pot reaction. This polymer included a dopamine moiety, a known inhibitor of α-synuclein fibril formation. Dopamine within the polymer structure was capable of aggregation inhibition, although not to the same degree as free dopamine. This result opens up new avenues for the use of controlled radical polymerizations as a means of preparing hyperbranched polymers for anti-fibrillation activity, but shows that the incorporation of functional groups from known small molecules within polymers may alter their biological activity.
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    PH-Responsive Biohybrid Carrier Material for Phenol Decontamination in Wastewater
    (Columbus, Ohio : American Chemical Soc., 2018) Pretscher, Martin; Pineda-Contreras, Beatriz A.; Kaiser, Patrick; Reich, Steffen; Schöbel, Judith; Kuttner, Christian; Freitag, Ruth; Fery, Andreas; Schmalz, Holger; Agarwal, Seema
    Smart polymers are a valuable platform to protect and control the activity of biological agents over a wide range of conditions, such as low pH, by proper encapsulation. Such conditions are present in olive oil mill wastewater with phenol as one of the most problematic constituents. We show that elastic and pH-responsive diblock copolymer fibers are a suitable carrier for Corynebacterium glutamicum, i.e., bacteria which are known for their ability to degrade phenol. Free C. glutamicum does not survive low pH conditions and fails to degrade phenol at low pH conditions. Our tea-bag like biohybrid system, where the pH-responsive diblock copolymer acts as a protecting outer shell for the embedded bacteria, allows phenol degradation even at low pH. Utilizing a two-step encapsulation process, planktonic cells were first encapsulated in poly(vinyl alcohol) to protect the bacteria against the organic solvents used in the second step employing coaxial electrospinning.
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    A customizable microfluidic platform for medium-throughput modeling of neuromuscular circuits
    (Amsterdam [u.a.] : Elsevier Science, 2019) Bellmann, Jessica; Goswami, Ruchi Y.; Girardo, Salvatore; Rein, Nelly; Hosseinzadeh, Zohreh; Hicks, Michael R.; Busskamp, Volker; Pyle, April D.; Werner, Carsten; Sterneckert, Jared
    Neuromuscular circuits (NMCs) are vital for voluntary movement, and effective models of NMCs are needed to understand the pathogenesis of, as well as to identify effective treatments for, multiple diseases, including Duchenne's muscular dystrophy and amyotrophic lateral sclerosis. Microfluidics are ideal for recapitulating the central and peripheral compartments of NMCs, but myotubes often detach before functional NMCs are formed. In addition, microfluidic systems are often limited to a single experimental unit, which significantly limits their application in disease modeling and drug discovery. Here, we developed a microfluidic platform (MFP) containing over 100 experimental units, making it suitable for medium-throughput applications. To overcome detachment, we incorporated a reactive polymer surface allowing customization of the environment to culture different cell types. Using this approach, we identified conditions that enable long-term co-culture of human motor neurons and myotubes differentiated from human induced pluripotent stem cells inside our MFP. Optogenetics demonstrated the formation of functional NMCs. Furthermore, we developed a novel application of the rabies tracing assay to efficiently identify NMCs in our MFP. Therefore, our MFP enables large-scale generation and quantification of functional NMCs for disease modeling and pharmacological drug targeting. © 2019 The Authors
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    Probing carbonyl-water hydrogen-bond interactions in thin polyoxazoline brushes
    (Melville, NY : AIP Publishing, 2016) Kroning, Annika; Furchner, Andreas; Adam, Stefan; Uhlmann, Petra; Hinrichs, Karsten
    Temperature-responsive oxazoline-based polymer brushes have gained increased attention as biocompatible surfaces. In aqueous environment, they can be tuned between hydrophilic and hydrophobic behavior triggered by a temperature stimulus. This transition is connected with changes in molecule–solvent interactions and results in a switching of the brushes between swollen and collapsed states. This work studies the temperature-dependent interactions between poly(2-oxazoline) brushes and water. In detail, thermoresponsive poly(2-cyclopropyl-2-oxazoline), nonresponsive hydrophilic poly(2-methyl-2-oxazoline), as well as a copolymer of the two were investigated with in situ infrared ellipsometry. Focus was put on interactions of the brushes' carbonyl groups with water molecules. Different polymer–water interactions could be observed and assigned to hydrogen bonding between C=O groups and water molecules. The switching behavior of the brushes in the range of 20–45 °C was identified by frequency shifts and intensity changes of the amide I band.
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    Preparation of Polymer Electrolyte Membranes via Radiation-Induced Graft Copolymerization on Poly(ethylene-alt-tetrafluoroethylene) (ETFE) Using the Crosslinker N,N′-Methylenebis(acrylamide)
    (Basel : MDPI, 2018) Ke, Xi; Drache, Marco; Gohs, Uwe; Kunz, Ulrich; Beuermann, Sabine
    Polymer electrolyte membranes (PEM) prepared by radiation-induced graft copolymerization are investigated. For this purpose, commercial poly(ethylene-alt-tetrafluoroethylene) (ETFE) films were activated by electron beam treatment and subsequently grafted with the monomers glycidyl methacrylate (GMA), hydroxyethyl methacrylate (HEMA) and N,N′-methylenebis(acrylamide) (MBAA) as crosslinker. The target is to achieve a high degree of grafting (DG) and high proton conductivity. To evaluate the electrochemical performance, the PEMs were tested in a fuel cell and in a vanadium redox-flow battery (VRFB). High power densities of 134 mW∙cm−2 and 474 mW∙cm−2 were observed, respectively.
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    Thermo-responsive cell culture carrier: Effects on macrophage functionality and detachment efficiency
    (London : Sage, 2017) Rennert, Knut; Nitschke, Mirko; Wallert, Maria; Keune, Natalie; Raasch, Martin; Lorkowski, Stefan; Mosig, Alexander S.
    Harvesting cultivated macrophages for tissue engineering purposes by enzymatic digestion of cell adhesion molecules can potentially result in unintended activation, altered function, or behavior of these cells. Thermo-responsive polymer is a promising tool that allows for gentle macrophage detachment without artificial activation prior to subculture within engineered tissue constructs. We therefore characterized different species of thermo-responsive polymers for their suitability as cell substrate and to mediate gentle macrophage detachment by temperature shift. Primary human monocyte- and THP-1-derived macrophages were cultured on thermo-responsive polymers and characterized for phagocytosis and cytokine secretion in response to lipopolysaccharide stimulation. We found that both cell types differentially respond in dependence of culture and stimulation on thermo-responsive polymers. In contrast to THP-1 macrophages, primary monocyte–derived macrophages showed no signs of impaired viability, artificial activation, or altered functionality due to culture on thermo-responsive polymers compared to conventional cell culture. Our study demonstrates that along with commercially available UpCell carriers, two other thermo-responsive polymers based on poly(vinyl methyl ether) blends are attractive candidates for differentiation and gentle detachment of primary monocyte–derived macrophages. In summary, we observed similar functionality and viability of primary monocyte–derived macrophages cultured on thermo-responsive polymers compared to standard cell culture surfaces. While this first generation of custom-made thermo-responsive polymers does not yet outperform standard culture approaches, our results are very promising and provide the basis for exploiting the unique advantages offered by custom-made thermo-responsive polymers to further improve macrophage culture and recovery in the future, including the covalent binding of signaling molecules and the reduction of centrifugation and washing steps. Optimizing these and other benefits of thermo-responsive polymers could greatly improve the culture of macrophages for tissue engineering applications.
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    Treatment of Focal Cartilage Defects in Minipigs with Zonal Chondrocyte/Mesenchymal Progenitor Cell Constructs
    (Basel : Molecular Diversity Preservation International, 2019) Bothe, Friederike; Deubel, Anne-Kathrin; Hesse, Eliane; Lotz, Benedict; Groll, Jürgen; Werner, Carsten; Richter, Wiltrud; Hagmann, Sebastien
    Despite advances in cartilage repair strategies, treatment of focal chondral lesions remains an important challenge to prevent osteoarthritis. Articular cartilage is organized into several layers and lack of zonal organization of current grafts is held responsible for insufficient biomechanical and biochemical quality of repair-tissue. The aim was to develop a zonal approach for cartilage regeneration to determine whether the outcome can be improved compared to a non-zonal strategy. Hydrogel-filled polycaprolactone (PCL)-constructs with a chondrocyte-seeded upper-layer deemed to induce hyaline cartilage and a mesenchymal stromal cell (MSC)-containing bottom-layer deemed to induce calcified cartilage were compared to chondrocyte-based non-zonal grafts in a minipig model. Grafts showed comparable hardness at implantation and did not cause visible signs of inflammation. After 6 months, X-ray microtomography (_CT)-analysis revealed significant bone-loss in both treatment groups compared to empty controls. PCL-enforcement and some hydrogel-remnants were retained in all defects, but most implants were pressed into the subchondral bone. Despite important heterogeneities, both treatments reached a significantly lower modified O’Driscoll-score compared to empty controls. Thus, PCL may have induced bone-erosion during joint loading and misplacement of grafts in vivo precluding adequate permanent orientation of zones compared to surrounding native cartilage. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
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    Viscoelastic Behavior of Embroidered Scaffolds for ACL Tissue Engineering Made of PLA and P(LA-CL) After In Vitro Degradation
    (Basel : Molecular Diversity Preservation International, 2019) Hahn, Judith; Schulze-Tanzil, Schulze-Tanzil; Schröpfer, Michaela; Meyer, Michael; Gögele, Clemens; Hoyer, Mariann; Spickenheuer, Axel; Heinrich, Gert; Breier, Annette
    A rupture of the anterior cruciate ligament (ACL) is the most common knee ligament injury. Current applied reconstruction methods have limitations in terms of graft availability and mechanical properties. A new approach could be the use of a tissue engineering construct that temporarily reflects the mechanical properties of native ligament tissues and acts as a carrier structure for cell seeding. In this study, embroidered scaffolds composed of polylactic acid (PLA) and poly(lactic-co-"-caprolactone) (P(LA-CL)) threads were tested mechanically for their viscoelastic behavior under in vitro degradation. The relaxation behavior of both scaffold types (moco: mono-component scaffold made of PLA threads, bico: bi-component scaffold made of PLA and P(LA-CL) threads) was comparable to native lapine ACL. Most of the lapine ACL cells survived 32 days of cell culture and grew along the fibers. Cell vitality was comparable for moco and bico scaffolds. Lapine ACL cells were able to adhere to the polymer surfaces and spread along the threads throughout the scaffold. The mechanical behavior of degrading matrices with and without cells showed no significant differences. These results demonstrate the potential of embroidered scaffolds as an ACL tissue engineering approach. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
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    Thermo-responsive polymer brushes with side graft chains: Relationship between molecular architecture and underwater adherence
    (Basel : Molecular Diversity Preservation International, 2019) Sidoli, Ugo; Tee, Hisaschi T.; Raguzin, Ivan; Mühldorfer, Jakob; Wurm, Frederik R.; Synytska, Alla
    During the last few decades, wet adhesives have been developed for applications in various fields. Nonetheless, key questions such as the most suitable polymer architecture as well as the most suitable chemical composition remain open. In this article, we investigate the underwater adhesion properties of novel responsive polymer brushes with side graft chain architecture prepared using “grafting through” approach on flat surfaces. The incorporation in the backbone of thermo-responsive poly(N-isopropylacrylamide) (PNIPAm) allowed us to obtain LCST behavior in the final layers. PNIPAm is co-polymerized with poly(methyl ethylene phosphate) (PMEP), a poloyphosphoester. The final materials are characterized studying the surface-grafted polymer as well as the polymer from the bulk solution, and pure PNIPAm brush is used as reference. PNIPAm-g-PMEP copolymers retain the responsive behavior of PNIPAm: when T > LCST, a clear switching of properties is observed. More specifically, all layers above the critical temperature show collapse of the chains, increased hydrophobicity and variation of the surface charge even if no ionizable groups are present. Secondly, effect of adhesion parameters such as debonding rate and contact time is studied. Thirdly, the reversibility of the adhesive properties is confirmed by performing adhesion cycles. Finally, the adhesive properties of the layers are studied below and above the LCST against hydrophilic and hydrophobic substrates. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
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    Thermoresponsive Catechol Based-Polyelectrolyte Complex Coatings for Controlled Release of Bortezomib
    (Basel : Molecular Diversity Preservation International, 2019) Reis, Berthold; Vehlow, David; Rust, Tarik; Kuckling, Dirk; Müller, Martin
    To overcome the high relapse rate of multiple myeloma (MM), a drug delivery coating for functionalization of bone substitution materials (BSM) is reported based on adhesive, catechol-containing and stimuli-responsive polyelectrolyte complexes (PECs). This system is designed to deliver the MM drug bortezomib (BZM) directly to the anatomical site of action. To establish a gradual BZM release, the naturally occurring caffeic acid (CA) is coupled oxidatively to form poly(caffeic acid) (PCA), which is used as a polyanion for complexation. The catechol functionalities within the PCA are particularly suitable to form esters with the boronic acid group of the BZM, which are then cleaved in the body fluid to administer the drug. To achieve a more thorough control of the release, the thermoresponsive poly(N-isoproplyacrylamide-co-dimethylaminoethylmethacrylate) (P(NIPAM-co-DMAEMA)) was used as a polycation. Using turbidity measurements, it was proven that the lower critical solution temperature (LCST) character of this polymer was transferred to the PECs. Further special temperature dependent attenuated total reflection infrared spectroscopy (ATR-FTIR) showed that coatings formed by PEC immobilization exhibit a similar thermoresponsive performance. By loading the coatings with BZM and studying the release in a model system, via UV/Vis it was observed, that both aims, the retardation and the stimuli control of the release, were achieved. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.