@article{JanzenBakirciFaberetal.2022,
  author    = {Janzen, Dieter and Bakirci, Ezgi and Faber, Jessica and Andrade Mier, Mateo and Hauptstein, Julia and Pal, Arindam and Forster, Leonard and Hazur, Jonas and Boccaccini, Aldo R. and Detsch, Rainer and Teßmar, J{\"o}rg and Budday, Silvia and Blunk, Torsten and Dalton, Paul D. and Villmann, Carmen},
  title     = {Reinforced Hyaluronic Acid-Based Matrices Promote 3D Neuronal Network Formation},
  series = {Advanced Healthcare Materials},
  volume    = {11},
  journal   = {Advanced Healthcare Materials},
  number    = {21},
  doi       = {10.1002/adhm.202201826},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318682},
  year      = {2022},
  abstract  = {3D neuronal cultures attempt to better replicate the in vivo environment to study neurological/neurodegenerative diseases compared to 2D models. A challenge to establish 3D neuron culture models is the low elastic modulus (30-500 Pa) of the native brain. Here, an ultra-soft matrix based on thiolated hyaluronic acid (HA-SH) reinforced with a microfiber frame is formulated and used. Hyaluronic acid represents an essential component of the brain extracellular matrix (ECM). Box-shaped frames with a microfiber spacing of 200 µm composed of 10-layers of poly(ɛ-caprolactone) (PCL) microfibers (9.7 ± 0.2 µm) made via melt electrowriting (MEW) are used to reinforce the HA-SH matrix which has an elastic modulus of 95 Pa. The neuronal viability is low in pure HA-SH matrix, however, when astrocytes are pre-seeded below this reinforced construct, they significantly support neuronal survival, network formation quantified by neurite length, and neuronal firing shown by Ca\(^{2+}\) imaging. The astrocyte-seeded HA-SH matrix is able to match the neuronal viability to the level of Matrigel, a gold standard matrix for neuronal culture for over two decades. Thus, this 3D MEW frame reinforced HA-SH composite with neurons and astrocytes constitutes a reliable and reproducible system to further study brain diseases.},
  language  = {en}
}
@article{KadeBakirciTandonetal.2022,
  author    = {Kade, Juliane C. and Bakirci, Ezgi and Tandon, Biranche and Gorgol, Danila and Mrlik, Miroslav and Luxenhofer, Robert and Dalton, Paul D.},
  title     = {The Impact of Including Carbonyl Iron Particles on the Melt Electrowriting Process},
  series = {Macromolecular Materials and Engineering},
  volume    = {307},
  journal   = {Macromolecular Materials and Engineering},
  number    = {12},
  issn      = {1438-7492},
  doi       = {10.1002/mame.202200478},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318482},
  year      = {2022},
  abstract  = {Melt electrowriting, a high-resolution additive manufacturing technique, is used in this study to process a magnetic polymer-based blend for the first time. Carbonyl iron (CI) particles homogenously distribute into poly(vinylidene fluoride) (PVDF) melts to result in well-defined, highly porous structures or scaffolds comprised of fibers ranging from 30 to 50 µm in diameter. This study observes that CI particle incorporation is possible up to 30 wt\% without nozzle clogging, albeit that the highest concentration results in heterogeneous fiber morphologies. In contrast, the direct writing of homogeneous PVDF fibers with up to 15 wt\% CI is possible. The fibers can be readily displaced using magnets at concentrations of 1 wt\% and above. Combined with good viability of L929 CC1 cells using Live/Dead imaging on scaffolds for all CI concentrations indicates that these formulations have potential for the usage in stimuli-responsive applications such as 4D printing.},
  language  = {en}
}
@article{HaagSonnleitnerLangetal.2022,
  author    = {Haag, Hannah and Sonnleitner, David and Lang, Gregor and Dalton, Paul D.},
  title     = {Melt electrowriting to produce microfiber fragments},
  series = {Polymers for Advanced Technologies},
  volume    = {33},
  journal   = {Polymers for Advanced Technologies},
  number    = {6},
  issn      = {1042-7147},
  doi       = {10.1002/pat.5641},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318465},
  pages     = {1989 -- 1992},
  year      = {2022},
  language  = {en}
}
@article{BoehmTandonHrynevichetal.2022,
  author    = {B{\"o}hm, Christoph and Tandon, Biranche and Hrynevich, Andrei and Teßmar, J{\"o}rg and Dalton, Paul D.},
  title     = {Processing of Poly(lactic-co-glycolic acid) Microfibers via Melt Electrowriting},
  series = {Macromolecular Chemistry and Physics},
  volume    = {223},
  journal   = {Macromolecular Chemistry and Physics},
  number    = {5},
  doi       = {10.1002/macp.202100417},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318444},
  year      = {2022},
  abstract  = {Polymers sensitive to thermal degradation include poly(lactic-co-glycolic acid) (PLGA), which is not yet processed via melt electrowriting (MEW). After an initial period of instability where mean fiber diameters increase from 20.56 to 27.37 µm in 3.5 h, processing stabilizes through to 24 h. The jet speed, determined using critical translation speed measurements, also reduces slightly in this 3.5 h period from 500 to 433 mm min\(^{-1}\) but generally remains constant. Acetyl triethyl citrate (ATEC) as an additive decreases the glass transition temperature of PLGA from 49 to 4 °C, and the printed ATEC/PLGA fibers exhibits elastomeric behavior upon handling. Fiber bundles tested in cyclic mechanical testing display increased elasticity with increasing ATEC concentration. The processing temperature of PLGA also reduces from 165 to 143 °C with increase in ATEC concentration. This initial window of unstable direct writing seen with neat PLGA can also be impacted through the addition of 10-wt\% ATEC, producing fiber diameters of 14.13 ± 1.69 µm for the first 3.5 h of heating. The investigation shows that the initial changes to the PLGA direct-writing outcomes seen in the first 3.5 h are temporary and that longer times result in a more stable MEW process.},
  language  = {en}
}
@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{BoehmStahlhutWeichholdetal.2022,
  author    = {B{\"o}hm, Christoph and Stahlhut, Philipp and Weichhold, Jan and Hrynevich, Andrei and Teßmar, J{\"o}rg and Dalton, Paul D.},
  title     = {The Multiweek Thermal Stability of Medical-Grade Poly(ε-caprolactone) During Melt Electrowriting},
  series = {Small},
  volume    = {18},
  journal   = {Small},
  number    = {3},
  doi       = {10.1002/smll.202104193},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257741},
  year      = {2022},
  abstract  = {Melt electrowriting (MEW) is a high-resolution additive manufacturing technology that places unique constraints on the processing of thermally degradable polymers. With a single nozzle, MEW operates at low throughput and in this study, medical-grade poly(ε-caprolactone) (PCL) is heated for 25 d at three different temperatures (75, 85, and 95 °C), collecting daily samples. There is an initial increase in the fiber diameter and decrease in the jet speed over the first 5 d, then the MEW process remains stable for the 75 and 85 °C groups. When the collector speed is fixed to a value at least 10\% above the jet speed, the diameter remains constant for 25 d at 75 °C and only increases with time for 85 and 95 °C. Fiber fusion at increased layer height is observed for 85 and 95 °C, while the surface morphology of single fibers remain similar for all temperatures. The properties of the prints are assessed with no observable changes in the degree of crystallinity or the Young's modulus, while the yield strength decreases in later phases only for 95 °C. After the initial 5-d period, the MEW processing of PCL at 75 °C is extraordinarily stable with overall fiber diameters averaging 13.5 ± 1.0 µm over the entire 25-d period.},
  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}
}
@unpublished{SchaeferJanzenBakircietal.2019,
  author    = {Schaefer, Natascha and Janzen, Dieter and Bakirci, Ezgi and Hrynevich, Andrei and Dalton, Paul D. and Villmann, Carmen},
  title     = {3D Electrophysiological Measurements on Cells Embedded within Fiber-Reinforced Matrigel},
  series = {Advanced Healthcare Materials},
  journal   = {Advanced Healthcare Materials},
  doi       = {10.1002/adhm.201801226},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244194},
  year      = {2019},
  abstract  = {2D electrophysiology is often used to determine the electrical properties of neurons, while in the brain, neurons form extensive 3D networks. Thus, performing electrophysiology in a 3D environment provides a closer situation to the physiological condition and serves as a useful tool for various applications in the field of neuroscience. In this study, we established 3D electrophysiology within a fiber-reinforced matrix to enable fast readouts from transfected cells, which are often used as model systems for 2D electrophysiology. Using melt electrowriting (MEW) of scaffolds to reinforce Matrigel, we performed 3D electrophysiology on a glycine receptor-transfected Ltk-11 mouse fibroblast cell line. The glycine receptor is an inhibitory ion channel associated when mutated with impaired neuromotor behaviour. The average thickness of the MEW scaffold was 141.4 ± 5.7µm, using 9.7 ± 0.2µm diameter fibers, and square pore spacings of 100 µm, 200 µm and 400 µm. We demonstrate, for the first time, the electrophysiological characterization of glycine receptor-transfected cells with respect to agonist efficacy and potency in a 3D matrix. With the MEW scaffold reinforcement not interfering with the electrophysiology measurement, this approach can now be further adapted and developed for different kinds of neuronal cultures to study and understand pathological mechanisms under disease conditions.},
  language  = {en}
}
@article{WangSarwatWangetal.2020,
  author    = {Wang, Shuang and Sarwat, Mariah and Wang, Peng and Surrao, Denver C. and Harkin, Damien G. and St John, James A. and Bolle, Eleonore C. L. and Forget, Aurelien and Dalton, Paul D. and Dargaville, Tim R.},
  title     = {Hydrogels with Cell Adhesion Peptide-Decorated Channel Walls for Cell Guidance},
  series = {Macromolecular Rapid Communications},
  volume    = {41},
  journal   = {Macromolecular Rapid Communications},
  number    = {15},
  doi       = {10.1002/marc.202000295},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218031},
  year      = {2020},
  abstract  = {A method is reported for making hollow channels within hydrogels decorated with cell-adhesion peptides exclusively at the channel surface. Sacrificial fibers of different diameters are used to introduce channels within poly(ethylene glycol) hydrogels crosslinked with maleimide-thiol chemistry, which are backfilled with a cysteine-containing peptide solution which is conjugated to the lumen with good spatial efficiency. This allows for peptide patterning in only the areas of the hydrogel where they are needed when used as cell-guides, reducing the amount of required peptide 20-fold when compared to bulk functionalization. The power of this approach is highlighted by successfully using these patterned hydrogels without active perfusion to guide fibroblasts and olfactory ensheathing cells—the latter having unique potential in neural repair therapies.},
  language  = {en}
}
@article{LiashenkoHrynevichDalton2020,
  author    = {Liashenko, Ievgenii and Hrynevich, Andrei and Dalton, Paul D.},
  title     = {Designing Outside the Box: Unlocking the Geometric Freedom of Melt Electrowriting using Microscale Layer Shifting},
  series = {Advanced Materials},
  volume    = {32},
  journal   = {Advanced Materials},
  number    = {28},
  doi       = {10.1002/adma.202001874},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217974},
  year      = {2020},
  abstract  = {Melt electrowriting, a high-resolution additive manufacturing technology, has so far been developed with vertical stacking of fiber layers, with a printing trajectory that is constant for each layer. In this work, microscale layer shifting is introduced through deliberately offsetting the printing trajectory for each printed layer. Inaccuracies during the printing of sinusoidal walls are corrected via layer shifting, resulting in accurate control of their geometry and mechanical properties. Furthermore, more substantial layer shifting allows stacking of fiber layers in a horizontal manner, overcoming the electrostatic autofocusing effect that favors vertical layer stacking. Novel nonlinear geometries, such as overhangs, wall texturing and branching, and smooth and abrupt changes in printing trajectory are presented, demonstrating the flexibility of the layer shifting approach beyond the state-of-the-art. The practice of microscale layer shifting for melt electrowriting enables more complex geometries that promise to have a profound impact on the development of products in a broad range of applications.},
  language  = {en}
}
@article{JanzenBakirciWielandetal.2020,
  author    = {Janzen, Dieter and Bakirci, Ezgi and Wieland, Annalena and Martin, Corinna and Dalton, Paul D. and Villmann, Carmen},
  title     = {Cortical Neurons form a Functional Neuronal Network in a 3D Printed Reinforced Matrix},
  series = {Advanced Healthcare Materials},
  volume    = {9},
  journal   = {Advanced Healthcare Materials},
  number    = {9},
  doi       = {10.1002/adhm.201901630},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215400},
  year      = {2020},
  abstract  = {Impairments in neuronal circuits underly multiple neurodevelopmental and neurodegenerative disorders. 3D cell culture models enhance the complexity of in vitro systems and provide a microenvironment closer to the native situation than with 2D cultures. Such novel model systems will allow the assessment of neuronal network formation and their dysfunction under disease conditions. Here, mouse cortical neurons are cultured from embryonic day E17 within in a fiber-reinforced matrix. A soft Matrigel with a shear modulus of 31 ± 5.6 Pa is reinforced with scaffolds created by melt electrowriting, improving its mechanical properties and facilitating the handling. Cortical neurons display enhance cell viability and the neuronal network maturation in 3D, estimated by staining of dendrites and synapses over 21 days in vitro, is faster in 3D compared to 2D cultures. Using functional readouts with electrophysiological recordings, different firing patterns of action potentials are observed, which are absent in the presence of the sodium channel blocker, tetrodotoxin. Voltage-gated sodium currents display a current-voltage relationship with a maximum peak current at -25 mV. With its high customizability in terms of scaffold reinforcement and soft matrix formulation, this approach represents a new tool to study neuronal networks in 3D under normal and, potentially, disease conditions.},
  language  = {en}
}
@article{RobinsonHutmacherDalton2019,
  author    = {Robinson, Thomas M. and Hutmacher, Dietmar W. and Dalton, Paul D.},
  title     = {The next frontier in melt electrospinning: taming the jet},
  series = {Advanced Functional Materials},
  volume    = {29},
  journal   = {Advanced Functional Materials},
  doi       = {10.1002/adfm.201904664},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204819},
  pages     = {1904664},
  year      = {2019},
  abstract  = {There is a specialized niche for the electrohydrodynamic jetting of melts, from biomedical products to filtration and soft matter applications. The next frontier includes optics, microfluidics, flexible electronic devices, and soft network composites in biomaterial science and soft robotics. The recent emphasis on reproducibly direct-writing continual molten jets has enabled a spectrum of contemporary microscale 3D objects to be fabricated. One strong suit of melt processing is the capacity for the jet to solidify rapidly into a fiber, thus fixing a particular structure into position. The ability to direct-write complex and multiscaled architectures and structures has greatly contributed to a large number of recent studies, explicitly, toward fiber-hydrogel composites and fugitive inks, and has expanded into several biomedical applications such as cartilage, skin, periosteum, and cardiovascular tissue engineering. Following the footsteps of a publication that summarized melt electrowriting literature up to 2015, the most recent literature from then until now is reviewed to provide a continuous and comprehensive timeline that demonstrates the latest advances as well as new perspectives for this emerging technology.},
  language  = {en}
}
@article{WeigandBoosTasbihietal.2016,
  author    = {Weigand, Annika and Boos, Anja M. and Tasbihi, Kereshmeh and Beier, Justus P. and Dalton, Paul D. and Schrauder, Michael and Horch, Raymund E. and Beckmann, Matthias W. and Strissel, Pamela L. and Strick, Reiner},
  title     = {Selective isolation and characterization of primary cells from normal breast and tumors reveal plasticity of adipose derived stem cells},
  series = {Breast Cancer Research},
  volume    = {18},
  journal   = {Breast Cancer Research},
  number    = {32},
  doi       = {10.1186/s13058-016-0688-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164759},
  year      = {2016},
  abstract  = {Background There is a need to establish more cell lines from breast tumors in contrast to immortalized cell lines from metastatic effusions in order to represent the primary tumor and not principally metastatic biology of breast cancer. This investigation describes the simultaneous isolation, characterization, growth and function of primary mammary epithelial cells (MEC), mesenchymal cells (MES) and adipose derived stem cells (ADSC) from four normal breasts, one inflammatory and one triple-negative ductal breast tumors. Methods A total of 17 cell lines were established and gene expression was analyzed for MEC and MES (n = 42) and ADSC (n = 48) and MUC1, pan-KRT, CD90 and GATA-3 by immunofluorescence. DNA fingerprinting to track cell line identity was performed between original primary tissues and isolates. Functional studies included ADSC differentiation, tumor MES and MEC invasion co-cultured with ADSC-conditioned media (CM) and MES adhesion and growth on 3D-printed scaffolds. Results Comparative analysis showed higher gene expression of EPCAM, CD49f, CDH1 and KRTs for normal MEC lines; MES lines e.g. Vimentin, CD10, ACTA2 and MMP9; and ADSC lines e.g. CD105, CD90, CDH2 and CDH11. Compared to the mean of all four normal breast cell lines, both breast tumor cell lines demonstrated significantly lower ADSC marker gene expression, but higher expression of mesenchymal and invasion gene markers like SNAI1 and MMP2. When compared with four normal ADSC differentiated lineages, both tumor ADSC showed impaired osteogenic and chondrogenic but enhanced adipogenic differentiation and endothelial-like structures, possibly due to high PDGFRB and CD34. Addressing a functional role for overproduction of adipocytes, we initiated 3D-invasion studies including different cell types from the same patient. CM from ADSC differentiating into adipocytes induced tumor MEC 3D-invasion via EMT and amoeboid phenotypes. Normal MES breast cells adhered and proliferated on 3D-printed scaffolds containing 20 fibers, but not on 2.5D-printed scaffolds with single fiber layers, important for tissue engineering. Conclusion Expression analyses confirmed successful simultaneous cell isolations of three different phenotypes from normal and tumor primary breast tissues. Our cell culture studies support that breast-tumor environment differentially regulates tumor ADSC plasticity as well as cell invasion and demonstrates applications for regenerative medicine.},
  language  = {en}
}
@article{ThibaudeauTaubenbergerHolzapfeletal.2014,
  author    = {Thibaudeau, Laure and Taubenberger, Anna V. and Holzapfel, Boris M. and Quent, Verena M. and Fuehrmann, Tobias and Hesami, Parisa and Brown, Toby D. and Dalton, Paul D. and Power, Carl A. and Hollier, Brett G. and Hutmacher, Dietmar W.},
  title     = {A tissue-engineered humanized xenograft model of human breast cancer metastasis to bone},
  series = {Disease Models \& Mechanisms},
  volume    = {7},
  journal   = {Disease Models \& Mechanisms},
  number    = {2},
  doi       = {10.1242/dmm.014076},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117466},
  pages     = {299-309},
  year      = {2014},
  abstract  = {The skeleton is a preferred homing site for breast cancer metastasis. To date, treatment options for patients with bone metastases are mostly palliative and the disease is still incurable. Indeed, key mechanisms involved in breast cancer osteotropism are still only partially understood due to the lack of suitable animal models to mimic metastasis of human tumor cells to a human bone microenvironment. In the presented study, we investigate the use of a human tissue-engineered bone construct to develop a humanized xenograft model of breast cancer-induced bone metastasis in a murine host. Primary human osteoblastic cell-seeded melt electrospun scaffolds in combination with recombinant human bone morphogenetic protein 7 were implanted subcutaneously in non-obese diabetic/severe combined immunodeficient mice. The tissue-engineered constructs led to the formation of a morphologically intact 'organ' bone incorporating a high amount of mineralized tissue, live osteocytes and bone marrow spaces. The newly formed bone was largely humanized, as indicated by the incorporation of human bone cells and human-derived matrix proteins. After intracardiac injection, the dissemination of luciferase-expressing human breast cancer cell lines to the humanized bone ossicles was detected by bioluminescent imaging. Histological analysis revealed the presence of metastases with clear osteolysis in the newly formed bone. Thus, human tissue-engineered bone constructs can be applied efficiently as a target tissue for human breast cancer cells injected into the blood circulation and replicate the osteolytic phenotype associated with breast cancer-induced bone lesions. In conclusion, we have developed an appropriate model for investigation of species-specific mechanisms of human breast cancer-related bone metastasis in vivo.},
  language  = {en}
}