@article{KadeOttoLuxenhoferetal.2021, author = {Kade, Juliane C. and Otto, Paul F. and Luxenhofer, Robert and Dalton, Paul D.}, title = {Melt electrowriting of poly(vinylidene difluoride) using a heated collector}, series = {Polymers for Advanced Technologies}, volume = {32}, journal = {Polymers for Advanced Technologies}, number = {12}, issn = {1042-7147}, doi = {10.1002/pat.5463}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318493}, pages = {4951 -- 4955}, year = {2021}, abstract = {Previous research on the melt electrowriting (MEW) of poly(vinylidene difluoride) (PVDF) resulted in electroactive fibers, however, printing more than five layers is challenging. Here, we investigate the influence of a heated collector to adjust the solidification rate of the PVDF jet so that it adheres sufficiently to each layer. A collector temperature of 110°C is required to improve fiber processing, resulting in a total of 20 fiber layers. For higher temperatures and higher layers, an interesting phenomenon occurred, where the intersection points of the fibers coalesced into periodic spheres of diameter 206 ± 52 μm (26G, 150°C collector temperature, 2000 mm/min, 10 layers in x- and y-direction).The heated collector is an important component of a MEW printer that allows polymers with a high melting point to be processable with increased layers.}, language = {en} } @article{WielandStrisselSchorleetal.2021, author = {Wieland, Annalena and Strissel, Pamela L. and Schorle, Hannah and Bakirci, Ezgi and Janzen, Dieter and Beckmann, Matthias W. and Eckstein, Markus and Dalton, Paul D. and Strick, Reiner}, title = {Brain and breast cancer cells with PTEN loss of function reveal enhanced durotaxis and RHOB dependent amoeboid migration utilizing 3D scaffolds and aligned microfiber tracts}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {20}, issn = {2072-6694}, doi = {10.3390/cancers13205144}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248443}, year = {2021}, abstract = {Background: Glioblastoma multiforme (GBM) and metastatic triple-negative breast cancer (TNBC) with PTEN mutations often lead to brain dissemination with poor patient outcome, thus new therapeutic targets are needed. To understand signaling, controlling the dynamics and mechanics of brain tumor cell migration, we implemented GBM and TNBC cell lines and designed 3D aligned microfibers and scaffolds mimicking brain structures. Methods: 3D microfibers and scaffolds were printed using melt electrowriting. GBM and TNBC cell lines with opposing PTEN genotypes were analyzed with RHO-ROCK-PTEN inhibitors and PTEN rescue using live-cell imaging. RNA-sequencing and qPCR of tumor cells in 3D with microfibers were performed, while scanning electron microscopy and confocal microscopy addressed cell morphology. Results: In contrast to the PTEN wildtype, GBM and TNBC cells with PTEN loss of function yielded enhanced durotaxis, topotaxis, adhesion, amoeboid migration on 3D microfibers and significant high RHOB expression. Functional studies concerning RHOB-ROCK-PTEN signaling confirmed the essential role for the above cellular processes. Conclusions: This study demonstrates a significant role of the PTEN genotype and RHOB expression for durotaxis, adhesion and migration dependent on 3D. GBM and TNBC cells with PTEN loss of function have an affinity for stiff brain structures promoting metastasis. 3D microfibers represent an important tool to model brain metastasizing tumor cells, where RHO-inhibitors could play an essential role for improved therapy.}, language = {en} } @article{KadeTandonWeichholdetal.2021, author = {Kade, Juliane C. and Tandon, Biranche and Weichhold, Jan and Pisignano, Dario and Persano, Luana and Luxenhofer, Robert and Dalton, Paul D.}, title = {Melt electrowriting of poly(vinylidene fluoride-co-trifluoroethylene)}, series = {Polymer International}, volume = {70}, journal = {Polymer International}, number = {12}, doi = {10.1002/pi.6272}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257654}, pages = {1725-1732}, year = {2021}, abstract = {Poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-co-TrFE)) is an electroactive polymer with growing interest for applications in biomedical materials and flexible electronics. In this study, a solvent-free additive manufacturing technique called melt electrowriting (MEW) has been utilized to fabricate well-defined microperiodic structures of the copolymer (P(VDF-co-TrFE)). MEW of the highly viscous polymer melt was initiated using a heated collector at temperatures above 120 °C and required remarkably slow collector speeds below 100 mm min\(^{-1}\). The fiber surface morphology was affected by the collector speed and an increase in β-phase was observed for scaffolds compared to the unprocessed powder. Videography shows vibrations of the P(VDF-co-TrFE) jet previously unseen during MEW, probably due to repeated charge buildup and discharge. Furthermore, piezo-force microscopy measurements demonstrated the electromechanical response of MEW-fabricated fibers. This research therefore achieves the melt electrohydrodynamic processing of fibers with micrometer resolution into defined structures with an important electroactive polymer.}, language = {en} } @article{BakirciFrankGumbeletal.2021, author = {Bakirci, Ezgi and Frank, Andreas and Gumbel, Simon and Otto, Paul F. and F{\"u}rsattel, Eva and Tessmer, Ingrid and Schmidt, Hans-Werner and Dalton, Paul D.}, title = {Melt Electrowriting of Amphiphilic Physically Crosslinked Segmented Copolymers}, series = {Macromolecular Chemistry and Physics}, volume = {222}, journal = {Macromolecular Chemistry and Physics}, number = {22}, doi = {10.1002/macp.202100259}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257572}, year = {2021}, abstract = {Various (AB)\(_{n}\) and (ABAC)\(_{n}\) segmented copolymers with hydrophilic and hydrophobic segments are processed via melt electrowriting (MEW). Two different (AB)\(_{n}\) segmented copolymers composed of bisurea segments and hydrophobic poly(dimethyl siloxane) (PDMS) or hydrophilic poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) (PPO-PEG-PPO) segments, while the amphiphilic (ABAC)\(_{n}\) segmented copolymers consist of bisurea segments in the combination of hydrophobic PDMS segments and hydrophilic PPO-PEG-PPO segments with different ratios, are explored. All copolymer compositions are processed using the same conditions, including nozzle temperature, applied voltage, and collector distance, while changes in applied pressure and collector speed altered the fiber diameter in the range of 7 and 60 µm. All copolymers showed excellent processability with MEW, well-controlled fiber stacking, and inter-layer bonding. Notably, the surfaces of all four copolymer fibers are very smooth when visualized using scanning electron microscopy. However, the fibers show different roughness demonstrated with atomic force microscopy. The non-cytotoxic copolymers increased L929 fibroblast attachment with increasing PDMS content while the different copolymer compositions result in a spectrum of physical properties.}, language = {en} } @article{HrynevichAchenbachJungstetal.2021, author = {Hrynevich, Andrei and Achenbach, Pascal and Jungst, Tomasz and Brook, Gary A. and Dalton, Paul D.}, title = {Design of Suspended Melt Electrowritten Fiber Arrays for Schwann Cell Migration and Neurite Outgrowth}, series = {Macromolecular Bioscience}, volume = {21}, journal = {Macromolecular Bioscience}, number = {7}, doi = {10.1002/mabi.202000439}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257535}, year = {2021}, abstract = {In this study, well-defined, 3D arrays of air-suspended melt electrowritten fibers are made from medical grade poly(ɛ-caprolactone) (PCL). Low processing temperatures, lower voltages, lower ambient temperature, increased collector distance, and high collector speeds all aid to direct-write suspended fibers that can span gaps of several millimeters between support structures. Such processing parameters are quantitatively determined using a "wedge-design" melt electrowritten test frame to identify the conditions that increase the suspension probability of long-distance fibers. All the measured parameters impact the probability that a fiber is suspended over multimillimeter distances. The height of the suspended fibers can be controlled by a concurrently fabricated fiber wall and the 3D suspended PCL fiber arrays investigated with early post-natal mouse dorsal root ganglion explants. The resulting Schwann cell and neurite outgrowth extends substantial distances by 21 d, following the orientation of the suspended fibers and the supporting walls, often generating circular whorls of high density Schwann cells between the suspended fibers. This research provides a design perspective and the fundamental parametric basis for suspending individual melt electrowritten fibers into a form that facilitates cell culture.}, language = {en} } @article{MieszczanekRobinsonDaltonetal.2021, author = {Mieszczanek, Pawel and Robinson, Thomas M. and Dalton, Paul D. and Hutmacher, Dietmar W.}, title = {Convergence of Machine Vision and Melt Electrowriting}, series = {Advanced Materials}, volume = {33}, journal = {Advanced Materials}, number = {29}, doi = {10.1002/adma.202100519}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256365}, year = {2021}, abstract = {Melt electrowriting (MEW) is a high-resolution additive manufacturing technology that balances multiple parametric variables to arrive at a stable fabrication process. The better understanding of this balance is underscored here using high-resolution camera vision of jet stability profiles in different electrical fields. Complementing this visual information are fiber-diameter measurements obtained at precise points, allowing the correlation to electrified jet properties. Two process signatures—the jet angle and for the first time, the Taylor cone area—are monitored and analyzed with a machine vision system, while SEM imaging for diameter measurement correlates real-time information. This information, in turn, allows the detection and correction of fiber pulsing for accurate jet placement on the collector, and the in-process assessment of the fiber diameter. Improved process control is used to successfully fabricate collapsible MEW tubes; structures that require exceptional accuracy and printing stability. Using a precise winding angle of 60° and 300 layers, the resulting 12 mm-thick tubular structures have elastic snap-through instabilities associated with mechanical metamaterials. This study provides a detailed analysis of the fiber pulsing occurrence in MEW and highlights the importance of real-time monitoring of the Taylor cone volume to better understand, control, and predict printing instabilities.}, language = {en} } @article{FischhaberFaberBakircietal.2021, author = {Fischhaber, Natalie and Faber, Jessica and Bakirci, Ezgi and Dalton, Paul D. and Budday, Silvia and Villmann, Carmen and Schaefer, Natascha}, title = {Spinal Cord Neuronal Network Formation in a 3D Printed Reinforced Matrix-A Model System to Study Disease Mechanisms}, series = {Advanced Healthcare Materials}, volume = {10}, journal = {Advanced Healthcare Materials}, number = {19}, doi = {10.1002/adhm.202100830}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256353}, year = {2021}, abstract = {3D cell cultures allow a better mimicry of the biological and mechanical environment of cells in vivo compared to 2D cultures. However, 3D cell cultures have been challenging for ultrasoft tissues such as the brain. The present study uses a microfiber reinforcement approach combining mouse primary spinal cord neurons in Matrigel with melt electrowritten (MEW) frames. Within these 3D constructs, neuronal network development is followed for 21 days in vitro. To evaluate neuronal development in 3D constructs, the maturation of inhibitory glycinergic synapses is analyzed using protein expression, the complex mechanical properties by assessing nonlinearity, conditioning, and stress relaxation, and calcium imaging as readouts. Following adaptation to the 3D matrix-frame, mature inhibitory synapse formation is faster than in 2D demonstrated by a steep increase in glycine receptor expression between days 3 and 10. The 3D expression pattern of marker proteins at the inhibitory synapse and the mechanical properties resemble the situation in native spinal cord tissue. Moreover, 3D spinal cord neuronal networks exhibit intensive neuronal activity after 14 days in culture. The spinal cord cell culture model using ultrasoft matrix reinforced by MEW fibers provides a promising tool to study and understand biomechanical mechanisms in health and disease.}, language = {en} } @article{MechauFrankBakircietal.2021, author = {Mechau, Jannik and Frank, Andreas and Bakirci, Ezgi and Gumbel, Simon and Jungst, Tomasz and Giesa, Reiner and Groll, J{\"u}rgen and Dalton, Paul D. and Schmidt, Hans-Werner}, title = {Hydrophilic (AB)\(_{n}\) Segmented Copolymers for Melt Extrusion-Based Additive Manufacturing}, series = {Macromolecular Chemistry and Physics}, volume = {222}, journal = {Macromolecular Chemistry and Physics}, number = {1}, doi = {10.1002/macp.202000265}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224513}, year = {2021}, abstract = {Several manufacturing technologies beneficially involve processing from the melt, including extrusion-based printing, electrospinning, and electrohydrodynamic jetting. In this study, (AB)\(_{n}\) segmented copolymers are tailored for melt-processing to form physically crosslinked hydrogels after swelling. The copolymers are composed of hydrophilic poly(ethylene glycol)-based segments and hydrophobic bisurea segments, which form physical crosslinks via hydrogen bonds. The degree of polymerization was adjusted to match the melt viscosity to the different melt-processing techniques. Using extrusion-based printing, a width of approximately 260 µm is printed into 3D constructs, with excellent interlayer bonding at fiber junctions, due to hydrogen bonding between the layers. For melt electrospinning, much thinner fibers in the range of about 1-15 µm are obtained and produced in a typical nonwoven morphology. With melt electrowriting, fibers are deposited in a controlled way to well-defined 3D constructs. In this case, multiple fiber layers fuse together enabling constructs with line width in the range of 70 to 160 µm. If exposed to water the printed constructs swell and form physically crosslinked hydrogels that slowly disintegrate, which is a feature for soluble inks within biofabrication strategies. In this context, cytotoxicity tests confirm the viability of cells and thus demonstrating biocompatibility of this class of copolymers.}, language = {en} }