@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{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{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{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{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{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{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{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} } @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{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{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{KotzRischArnoldetal.2019, author = {Kotz, Frederik and Risch, Patrick and Arnold, Karl and Sevim, Semih and Puigmart{\´i}-Luis, Josep and Quick, Alexander and Thiel, Michael and Hrynevich, Andrei and Dalton, Paul D. and Helmer, Dorothea and Rapp, Bastian E.}, title = {Fabrication of arbitrary three-dimensional suspended hollow microstructures in transparent fused silica glass}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, doi = {10.1038/s41467-019-09497-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224787}, year = {2019}, abstract = {Fused silica glass is the preferred material for applications which require long-term chemical and mechanical stability as well as excellent optical properties. The manufacturing of complex hollow microstructures within transparent fused silica glass is of particular interest for, among others, the miniaturization of chemical synthesis towards more versatile, configurable and environmentally friendly flow-through chemistry as well as high-quality optical waveguides or capillaries. However, microstructuring of such complex three-dimensional structures in glass has proven evasive due to its high thermal and chemical stability as well as mechanical hardness. Here we present an approach for the generation of hollow microstructures in fused silica glass with high precision and freedom of three-dimensional designs. The process combines the concept of sacrificial template replication with a room-temperature molding process for fused silica glass. The fabricated glass chips are versatile tools for, among other, the advance of miniaturization in chemical synthesis on chip.}, language = {en} } @article{CastilhoHochleitnerWilsonetal.2018, author = {Castilho, Miguel and Hochleitner, Gernot and Wilson, Wouter and van Rietbergen, Bert and Dalton, Paul D. and Groll, J{\"u}rgen and Malda, Jos and Ito, Keita}, title = {Mechanical behavior of a soft hydrogel reinforced with three-dimensional printed microfibre scaffolds}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, doi = {10.1038/s41598-018-19502-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222280}, year = {2018}, abstract = {Reinforcing hydrogels with micro-fibre scaffolds obtained by a Melt-Electrospinning Writing (MEW) process has demonstrated great promise for developing tissue engineered (TE) constructs with mechanical properties compatible to native tissues. However, the mechanical performance and reinforcement mechanism of the micro-fibre reinforced hydrogels is not yet fully understood. In this study, FE models, implementing material properties measured experimentally, were used to explore the reinforcement mechanism of fibre-hydrogel composites. First, a continuum FE model based on idealized scaffold geometry was used to capture reinforcement effects related to the suppression of lateral gel expansion by the scaffold, while a second micro-FE model based on micro-CT images of the real construct geometry during compaction captured the effects of load transfer through the scaffold interconnections. Results demonstrate that the reinforcement mechanism at higher scaffold volume fractions was dominated by the load carrying-ability of the fibre scaffold interconnections, which was much higher than expected based on testing scaffolds alone because the hydrogel provides resistance against buckling of the scaffold. We propose that the theoretical understanding presented in this work will assist the design of more effective composite constructs with potential applications in a wide range of TE conditions.}, language = {en} } @article{TylekBlumHrynevichetal.2020, author = {Tylek, Tina and Blum, Carina and Hrynevich, Andrei and Schlegelmilch, Katrin and Schilling, Tatjana and Dalton, Paul D and Groll, J{\"u}rgen}, title = {Precisely defined fiber scaffolds with 40 μm porosity induce elongation driven M2-like polarization of human macrophages}, series = {Biofabrication}, volume = {12}, journal = {Biofabrication}, number = {2}, doi = {10.1088/1758-5090/ab5f4e}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254012}, year = {2020}, abstract = {Macrophages are key players of the innate immune system that can roughly be divided into the pro-inflammatory M1 type and the anti-inflammatory, pro-healing M2 type. While a transient initial pro-inflammatory state is helpful, a prolonged inflammation deteriorates a proper healing and subsequent regeneration. One promising strategy to drive macrophage polarization by biomaterials is precise control over biomaterial geometry. For regenerative approaches, it is of particular interest to identify geometrical parameters that direct human macrophage polarization. For this purpose, we advanced melt electrowriting (MEW) towards the fabrication of fibrous scaffolds with box-shaped pores and precise inter-fiber spacing from 100 μm down to only 40 μm. These scaffolds facilitate primary human macrophage elongation accompanied by differentiation towards the M2 type, which was most pronounced for the smallest pore size of 40 μm. These new findings can be important in helping to design new biomaterials with an enhanced positive impact on tissue regeneration.}, language = {en} }