TY - JOUR A1 - Zhang, Quanchao A1 - Rudolph, Tobias A1 - Benitez, Alejandro J. A1 - Gould, Oliver E. C. A1 - Behl, Marc A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Temperature-controlled reversible pore size change of electrospun fibrous shape-memory polymer actuator based meshes JF - Smart materials and structures N2 - Fibrous membranes capable of dynamically responding to external stimuli are highly desirable in textiles and biomedical materials, where adaptive behavior is required to accommodate complex environmental changes. For example, the creation of fabrics with temperature-dependent moisture permeability or self-regulating membranes for air filtration is dependent on the development of materials that exhibit a reversible stimuli-responsive pore size change. Here, by imbuing covalently crosslinked poly(ε-caprolactone) (cPCL) fibrous meshes with a reversible bidirectional shape-memory polymer actuation (rbSMPA) we create a material capable of temperature-controlled changes in porosity. Cyclic thermomechanical testing was used to characterize the mechanical properties of the meshes, which were composed of randomly arranged microfibers with diameters of 2.3 ± 0.6 μm giving an average pore size of approx. 10 μm. When subjected to programming strains of εm = 300% and 100% reversible strain changes of εʹrev = 22% ± 1% and 6% ± 1% were measured, with switching temperature ranges of 10 °C–30 °C and 45 °C–60 °C for heating and cooling, respectively. The rbSMPA of cPCL fibrous meshes generated a microscale reversible pore size change of 11% ± 3% (an average of 1.5 ± 0.6 μm), as measured by scanning electron microscopy. The incorporation of a two-way shape-memory actuation capability into fibrous meshes is anticipated to advance the development and application of smart membrane materials, creating commercially viable textiles and devices with enhanced performance and novel functionality. KW - reversible shape-memory effect KW - fiber meshes KW - electrospinning Y1 - 2019 U6 - https://doi.org/10.1088/1361-665X/ab10a1 SN - 0964-1726 SN - 1361-665X VL - 28 IS - 5 PB - IOP Publ. Ltd. CY - Bristol ER - TY - GEN A1 - Randall, Matthew J. A1 - Jüngel, Astrid A1 - Rimann, Markus A1 - Wuertz-Kozak, Karin T1 - Advances in the biofabrication of 3D skin in vitro BT - healthy and pathological models T2 - Postprints der Universität Potsdam : Humanwissenschaftliche Reihe N2 - The relevance for in vitro three-dimensional (3D) tissue culture of skin has been present for almost a century. From using skin biopsies in organ culture, to vascularized organotypic full-thickness reconstructed human skin equivalents, in vitro tissue regeneration of 3D skin has reached a golden era. However, the reconstruction of 3D skin still has room to grow and develop. The need for reproducible methodology, physiological structures and tissue architecture, and perfusable vasculature are only recently becoming a reality, though the addition of more complex structures such as glands and tactile corpuscles require advanced technologies. In this review, we will discuss the current methodology for biofabrication of 3D skin models and highlight the advantages and disadvantages of the existing systems as well as emphasize how new techniques can aid in the production of a truly physiologically relevant skin construct for preclinical innovation. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 680 KW - 3D tissue model KW - skin KW - in vitro KW - bioprinting KW - electrospinning KW - skin disease KW - biofabrication KW - preclinical testing Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-468844 SN - 1866-8364 IS - 680 ER - TY - JOUR A1 - Hommes-Schattmann, Paul J. A1 - Neffe, Axel T. A1 - Ahmad, Bilal A1 - Williams, Gareth R. A1 - Vanneaux, Valerie A1 - Menasche, Philippe A1 - Kalfa, David A1 - Lendlein, Andreas T1 - RGD constructs with physical anchor groups as polymer co-electrospinnable cell adhesives JF - Polymers for advanced technologies N2 - The tissue integration of synthetic polymers can be promoted by displaying RGD peptides at the biointerface with the objective of enhancing colonization of the material by endogenous cells. A firm but flexible attachment of the peptide to the polymer matrix, still allowing interaction with receptors, is therefore of interest. Here, the covalent coupling of flexible physical anchor groups, allowing for temporary immobilization on polymeric surfaces via hydrophobic or dipole-dipole interactions, to a RGD peptide was investigated. For this purpose, a stearate or an oligo(ethylene glycol) (OEG) was attached to GRGDS in 51-69% yield. The obtained RGD linker constructs were characterized by NMR, IR and MALDI-ToF mass spectrometry, revealing that the commercially available OEG and stearate linkers are in fact mixtures of similar compounds. The RGD linker constructs were co-electrospun with poly(p-dioxanone) (PPDO). After electrospinning, nitrogen could be detected on the surface of the PPDO fibers by X-ray photoelectron spectroscopy. The nitrogen content exceeded the calculated value for the homogeneous material mixture suggesting a pronounced presentation of the peptide on the fiber surface. Increasing amounts of RGD linker constructs in the electrospinning solution did not lead to a detection of an increased amount of peptide on the scaffold surface, suggesting inhomogeneous distribution of the peptide on the PPDO fiber surface. Human adipose-derived stem cells cultured on the patches showed similar viability as when cultured on PPDO containing pristine RGD. The fully characterized RGD linker constructs could serve as valuable tools for the further development of tissue-integrating polymeric scaffolds. Copyright (c) 2016 John Wiley & Sons, Ltd. KW - electrospinning KW - RGD peptides KW - cell adhesion KW - biofunctionalization Y1 - 2017 U6 - https://doi.org/10.1002/pat.3963 SN - 1042-7147 SN - 1099-1581 VL - 28 SP - 1312 EP - 1317 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Thielke, Michael W. A1 - Secker, Christian A1 - Schlaad, Helmut A1 - Theato, Patrick T1 - Electrospinning of Crystallizable Polypeptoid Fibers JF - Macromolecular rapid communications N2 - A unique fabrication process of low molar mass, crystalline polypeptoid fibers is described. Thermoresponsive fiber mats are prepared by electrospinning a homogeneous blend of semicrystalline poly(N-(n-propyl) glycine) (PPGly; 4.1 kDa) with high molar mass poly(ethylene oxide) (PEO). Annealing of these fibers at approximate to 100 degrees C selectively removes the PEO and produces stable crystalline fiber mats of pure PPGly, which are insoluble in aqueous solution but can be redissolved in methanol or ethanol. The formation of water-stable polypeptoid fiber mats is an important step toward their utilization in biomedical applications such as tissue engineering or wound dressing. KW - biomaterials KW - crystallization KW - electrospinning KW - polypeptoids KW - thermoresponsive Y1 - 2016 U6 - https://doi.org/10.1002/marc.201500502 SN - 1022-1336 SN - 1521-3927 VL - 37 SP - 100 EP - 104 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Sauter, Tilman A1 - Geiger, Brett A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Encasement of metallic cardiovascular stents with endothelial cell-selective copolyetheresterurethane microfibers JF - Polymers for advanced technologies N2 - Cardiovascular metallic stents established in clinical application are typically coated by a thin polymeric layer on the stent struts to improve hemocompatibility, whereby often a drug is added to the coating to inhibit neointimal hyperplasia. Besides such thin film coatings recently nano/microfiber coated stents are investigated, whereby the fibrous coating was applied circumferential on stents. Here, we explored whether a thin fibrous encasement of metallic stents with preferentially longitudinal aligned fibers and different local fiber densities can be achieved by electrospinning. An elastic degradable copolyetheresterurethane, which is reported to selectively enhance the adhesion of endothelial cells, while simultaneously rejecting smooth muscle cells, was utilized for stent coating. The fibrous stent encasements were microscopically assessed regarding their single fiber diameters, fiber covered area and fiber alignment at three characteristic stent regions before and after stent expansion. Stent coatings with thicknesses in the range from 30 to 50 mu m were achieved via electrospinning with 1,1,1,3,3,3-hexafluoro-2-propanol (HFP)-based polymer solution, while a mixture of HFP and formic acid as solvent resulted in encasements with a thickness below 5 mu m comprising submicron sized single fibers. All polymeric encasements were mechanically stable during expansion, whereby the fibers deposited on the struts remained their position. The observed changes in fiber density and diameter indicated diverse local deformation mechanisms of the microfibers at the different regions between the struts. Based on these results it can be anticipated that the presented fibrous encasement of stents might be a promising alternative to stents with polymeric strut coatings releasing anti-proliferative drugs. Copyright (c) 2015 John Wiley & Sons, Ltd. KW - multifunctional polymers KW - stent coatings KW - electrospinning KW - biomaterials KW - degradable polymers Y1 - 2015 U6 - https://doi.org/10.1002/pat.3583 SN - 1042-7147 SN - 1099-1581 VL - 26 IS - 10 SP - 1209 EP - 1216 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Schneider, Tobias A1 - Kohl, Benjamin A1 - Sauter, Tilman A1 - Kratz, Karl A1 - Lendlein, Andreas A1 - Ertel, Wolfgang A1 - Schulze-Tanzil, Gundula T1 - Influence of fiber orientation in electrospun polymer scaffolds on viability, adhesion and differentiation of articular chondrocytes JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Degradable polymers with a tailorable degradation rate might be promising candidate materials for biomaterial-based cartilage repair. In view of the poor intrinsic healing capability of cartilage, implantation of autologous chondrocytes seeded on a biocompatible slow degrading polymer might be an encouraging approach to improve cartilage repair in the future. This study was undertaken to test if the fiber orientation (random versus aligned) of two different degradable polymers and a polymer intended for long term applications could influence primary articular chondrocytes growth and ultrastructure. A degradable copoly(ether) esterurethane (PDC) was synthesized via co-condensation of poly(p-dioxanone) diol and poly(epsilon-caprolactone) diol using an aliphatic diisocyanate as linker. Poly(p-dioxanone) (PPDO) was applied as commercially available degradable polymer, while polyetherimide (PEI) was chosen as biomaterial enabling surface functionalization. The fibrous scaffolds of PDC and PPDO were obtained by electrospinning using 1,1,1,3,3,3 hexafluoro-2-propanol (HFP), while for PEI dimethyl acetamide (DMAc) was applied as solvent. Primary porcine articular chondrocytes were seeded at different cell densities on the fibrous polymer scaffolds and analyzed for viability (fluorescein diacetate/ethidiumbromide staining), for type II collagen synthesis (immunolabelling), ultrastructure and orientation on the fibers (SEM: scanning electron microscopy). Vital chondrocytes adhered on all electrospun scaffolds irrespective of random and aligned topologies. In addition, the chondrocytes produced the cartilage-specific type II collagen on all tested polymer topologies suggesting their differentiated functions. SEM revealed an almost flattened chondrocytes shape on scaffolds with random fiber orientation: whereby chondrocytes growth remained mainly restricted to the scaffold surface. On aligned fibers the chondrocytes exhibited a more spindle-shaped morphology with rougher cell surfaces but only a minority of the cells aligned according to the fibers. As a next step the reduction of the fiber diameter of electrospun scaffolds should be addressed as an important parameter to mimic cartilage ECM structure. KW - Chondrocytes KW - electrospinning KW - scaffold KW - differentiation KW - multiblock copolymer Y1 - 2012 U6 - https://doi.org/10.3233/CH-2012-1608 SN - 1386-0291 VL - 52 IS - 2-4 SP - 325 EP - 336 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Rüder, Constantin A1 - Sauter, Tilman A1 - Kratz, Karl A1 - Haase, Tobias A1 - Peter, Jan A1 - Jung, Friedrich A1 - Lendlein, Andreas A1 - Zohlnhöfer, Dietlind T1 - Influence of fibre diameter and orientation of electrospun copolyetheresterurethanes on smooth muscle and endothelial cell behaviour JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Polymers exhibiting cell-selective effects represent an extensive research field with high relevance for biomedical applications e.g. in the cardiovascular field supporting re-endothelialization while suppressing smooth muscle cell overgrowth. Such an endothelial cell-selective effect could be recently demonstrated for a copolyetheresterurethane (PDC) containing biodegradable poly(p-dioxanone) and poly(epsilon-caprolactone) segments, which selectively enhanced the adhesion of human umbilical vein endothelial cells (HUVEC) while suppressing the attachment of smooth muscle cells (SMC). In this study we investigated the influence of the fibre orientation (random and aligned) and fibre diameter (2 mu m and 500 nm) of electrospun PDC scaffolds on the adhesion, proliferation and apoptosis of HUVEC and SMC. Adhesion, viability and proliferation of HUVEC was diminished when the fibre diameter was reduced to a submicron scale, while the orientation of the microfibres did only slightly influence the cellular behaviour. In contrast, a submicron fibre diameter improved SMC viability. In conclusion, PDC scaffolds with micron-sized single fibres could be promising candidate materials for cell-selective stent coatings. KW - Endothelialization KW - drug eluting stent KW - degradable polymer KW - electrospinning KW - cell selectivity Y1 - 2013 U6 - https://doi.org/10.3233/CH-131787 SN - 1386-0291 SN - 1875-8622 VL - 55 IS - 4 SP - 513 EP - 522 PB - IOS Press CY - Amsterdam ER - TY - THES A1 - Gentsch, Rafael T1 - Complex bioactive fiber systems by means of electrospinning T1 - Komplexe Bioaktive Fasersysteme mittels Elektrospinnen N2 - Nanofibrous mats are interesting scaffold materials for biomedical applications like tissue engineering due to their interconnectivity and their size dimension which mimics the native cell environment. Electrospinning provides a simple route to access such fiber meshes. This thesis addresses the structural and functional control of electrospun fiber mats. In the first section, it is shown that fiber meshes with bimodal size distribution could be obtained in a single-step process by electrospinning. A standard single syringe set-up was used to spin concentrated poly(ε-caprolactone) (PCL) and poly(lactic-co-glycolic acid) (PLGA) solutions in chloroform and meshes with bimodal-sized fiber distribution could be directly obtained by reducing the spinning rate at elevated humidity. Scanning electron microscopy (SEM) and mercury porosity of the meshes suggested a suitable pore size distribution for effective cell infiltration. The bimodal fiber meshes together with unimodal fiber meshes were evaluated for cellular infiltration. While the micrometer fibers in the mixed meshes generate an open pore structure, the submicrometer fibers support cell adhesion and facilitate cell bridging on the large pores. This was revealed by initial cell penetration studies, showing superior ingrowth of epithelial cells into the bimodal meshes compared to a mesh composed of unimodal 1.5 μm fibers. The bimodal fiber meshes together with electrospun nano- and microfiber meshes were further used for the inorganic/organic hybrid fabrication of PCL with calcium carbonate or calcium phosphate, two biorelevant minerals. Such composite structures are attractive for the potential improvement of properties such as stiffness or bioactivity. It was possible to encapsulate nano and mixed sized plasma-treated PCL meshes to areas > 1 mm2 with calcium carbonate using three different mineralization methods including the use of poly(acrylic acid). The additive seemed to be useful in stabilizing amorphous calcium carbonate to effectively fill the space between the electrospun fibers resulting in composite structures. Micro-, nano- and mixed sized fiber meshes were successfully coated within hours by fiber directed crystallization of calcium phosphate using a ten-times concentrated simulated body fluid. It was shown that nanofibers accelerated the calcium phosphate crystallization, as compared to microfibers. In addition, crystallizations performed at static conditions led to hydroxyapatite formations whereas in dynamic conditions brushite coexisted. In the second section, nanofiber functionalization strategies are investigated. First, a one-step process was introduced where a peptide-polymer-conjugate (PLLA-b-CGGRGDS) was co-spun with PLGA in such a way that the peptide is enriched on the surface. It was shown that by adding methanol to the chloroform/blend solution, a dramatic increase of the peptide concentration at the fiber surface could be achieved as determined by X-ray photoelectron spectroscopy (XPS). Peptide accessibility was demonstrated via a contact angle comparison of pure PLGA and RGD-functionalized fiber meshes. In addition, the electrostatic attraction between a RGD-functionalized fiber and a silica bead at pH ~ 4 confirmed the accessibility of the peptide. The bioactivity of these RGD-functionalized fiber meshes was demonstrated using blends containing 18 wt% bioconjugate. These meshes promoted adhesion behavior of fibroblast compared to pure PLGA meshes. In a second functionalization approach, a modular strategy was investigated. In a single step, reactive fiber meshes were fabricated and then functionalized with bioactive molecules. While the electrospinning of the pure reactive polymer poly(pentafluorophenyl methacrylate) (PPFPMA) was feasible, the inherent brittleness of PPFPMA required to spin a PCL blend. Blends and pure PPFPMA showed a two-step functionalization kinetics. An initial fast reaction of the pentafluorophenyl esters with aminoethanol as a model substance was followed by a slow conversion upon further hydrophilization. This was analysed by UV/Vis-spectroscopy of the pentaflurorophenol release upon nucleophilic substitution with the amines. The conversion was confirmed by increased hydrophilicity of the resulting meshes. The PCL/PPFPMA fiber meshes were then used for functionalization with more complex molecules such as saccharides. Aminofunctionalized D-Mannose or D-Galactose was reacted with the active pentafluorophenyl esters as followed by UV/Vis spectroscopy and XPS. The functionality was shown to be bioactive using macrophage cell culture. The meshes functionalized with D-Mannose specifically stimulated the cytokine production of macrophages when lipopolysaccharides were added. This was in contrast to D-Galactose- or aminoethanol-functionalized and unfunctionalized PCL/PPFPMA fiber mats. N2 - Biofunktionale Materialien gewinnen immer größere Bedeutung in biomedizinischen Anwendungen wie dem künstlichen Ersatz von Knochen oder Blutgefässe. Weiterhin können diese Stoffe nützlich sein, um die Wechselwirkung zwischen Biomaterialien und biologischen Systemen wie Zellen oder Organismen weiter zu erforschen. In diversen Studien konnten Größen wie dreidimensionaler Strukturaufbau, Oberflächentopographie, Mechanik und die Funktionalisierung mit bioaktiven Substanzen als Einflussfaktoren identifiziert werden, welche auf verschiedenen Größenskalen von makroskopisch bis nanoskopisch untersucht wurden und gegenwärtig erforscht werden. Bioinspiriert von Kollagenfasern, die als Strukturmotiv an verschieden Orten im menschlichen Körper vorkommen (z.B. extrazelluläre Matrix) konnte gezeigt werden, dass Fasermatten, die eine ähnliche Größendimensionen wie die vorher erwähnten Kollagenfasern (Ø ~ 500 nm) aufweisen, eine aussichtsreiche Gerüstmatrix darstellen. Eine einfache Methode Fasermatten in diesen Dimensionen herzustellen ist Elektrospinning, wobei typischerweise eine viskose Polymerlösung durch anlegen eines Hochspannungsfeldes verstreckt wird. Obwohl auf diese Weise hergestellte Fasermatten für gewisse Zelllinien eine ideale Zellwechselwirkung aufweisen, ist die Zellbesiedelung solcher Netzwerke, bedingt auch durch die kleinen Porendurchmesser, problematisch und bedarf meistens weiterer Prozessierungsschritte. Diese Arbeit beschäftigt sich mit der einfachen Herstellung von strukturel und funktional kontrollierten Fasersystem mittels Elektrospinning. Der erste Teil behandelt ein Einschrittverfahren zum Elektrospinnen von bimodalen Fasermatten bestehend aus Nano- und Mikrofasern. In Zellstudien mit Epithelzellen konnte gezeigt werden, dass solche Netzwerke tiefer besiedelt werden als Matten bestehend aus unimodalen 1.5 μm dicken Fasern. Des Weiteren wurden diese Fasermatten für fasergerichtete Kristallisation von Kalziumcarbonat und – phosphat benutzt. In einem zweiten Teil wurden 2 Strategien für die Faserfunktionalisierung mit Peptiden und Zuckermolekülen entwickelt. Zum einen wurde gezeigt, dass funktionale Peptidfasern durch Verspinnung einer Mischung von einem Peptid-Polymer-Konjugat mit einem kommerziellen Polymer hergestellt werden konnten. Zusätzlich wurde ein modularer Ansatz für die Herstellung von reaktiven Fasern ausgearbeitet, die anschließend mit Peptiden oder Zuckern funktionalisiert wurden. Die Bioaktivität der Zucker funktionalisierten Fasern konnte durch Zellversuche erfolgreich bestätigt werden. KW - Elektrospinnen KW - Faser KW - bioaktiv KW - funktional KW - Struktur KW - electrospinning KW - fiber KW - bioactive KW - functional KW - structure Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-44900 ER -