TY  - JOUR
A1  - Janzen, Dieter
A1  - Bakirci, Ezgi
A1  - Faber, Jessica
A1  - Andrade Mier, Mateo
A1  - Hauptstein, Julia
A1  - Pal, Arindam
A1  - Forster, Leonard
A1  - Hazur, Jonas
A1  - Boccaccini, Aldo R.
A1  - Detsch, Rainer
A1  - Teßmar, Jörg
A1  - Budday, Silvia
A1  - Blunk, Torsten
A1  - Dalton, Paul D.
A1  - Villmann, Carmen
T1  - Reinforced Hyaluronic Acid-Based Matrices Promote 3D Neuronal Network Formation
JF  - Advanced Healthcare Materials
N2  - 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.
KW  - 3D model systems
KW  - melt electrowriting
KW  - cortical neurons
KW  - astrocytes
KW  - Ca\(^{2+}\)-Imaging
KW  - hyaluronic acid
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318682
VL  - 11
IS  - 21
ER  - 
TY  - JOUR
A1  - Ryma, Matthias
A1  - Genç, Hatice
A1  - Nadernezhad, Ali
A1  - Paulus, Ilona
A1  - Schneidereit, Dominik
A1  - Friedrich, Oliver
A1  - Andelovic, Kristina
A1  - Lyer, Stefan
A1  - Alexiou, Christoph
A1  - Cicha, Iwona
A1  - Groll, Jürgen
T1  - A Print-and-Fuse Strategy for Sacrificial Filaments Enables Biomimetically Structured Perfusable Microvascular Networks with Functional Endothelium Inside 3D Hydrogels
JF  - Advanced Materials
N2  - A facile and flexible approach for the integration of biomimetically branched microvasculature within bulk hydrogels is presented. For this, sacrificial scaffolds of thermoresponsive poly(2-cyclopropyl-2-oxazoline) (PcycloPrOx) are created using melt electrowriting (MEW) in an optimized and predictable way and subsequently placed into a customized bioreactor system, which is then filled with a hydrogel precursor solution. The aqueous environment above the lower critical solution temperature (LCST) of PcycloPrOx at 25 °C swells the polymer without dissolving it, resulting in fusion of filaments that are deposited onto each other (print-and-fuse approach). Accordingly, an adequate printing pathway design results in generating physiological-like branchings and channel volumes that approximate Murray's law in the geometrical ratio between parent and daughter vessels. After gel formation, a temperature decrease below the LCST produces interconnected microchannels with distinct inlet and outlet regions. Initial placement of the sacrificial scaffolds in the bioreactors in a pre-defined manner directly yields perfusable structures via leakage-free fluid connections in a reproducible one-step procedure. Using this approach, rapid formation of a tight and biologically functional endothelial layer, as assessed not only through fluorescent dye diffusion, but also by tumor necrosis factor alpha (TNF-α) stimulation, is obtained within three days.
KW  - hydrogels
KW  - microvasculature
KW  - melt electrowriting
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318532
VL  - 34
IS  - 28
ER  - 
TY  - JOUR
A1  - Haag, Hannah
A1  - Sonnleitner, David
A1  - Lang, Gregor
A1  - Dalton, Paul D.
T1  - Melt electrowriting to produce microfiber fragments
JF  - Polymers for Advanced Technologies
KW  - melt electrowriting
KW  - medical-grade poly(ε-caprolactone)
KW  - fiber
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318465
SN  - 1042-7147
VL  - 33
IS  - 6
SP  - 1989
EP  - 1992
ER  - 
TY  - JOUR
A1  - Kade, Juliane C.
A1  - Otto, Paul F.
A1  - Luxenhofer, Robert
A1  - Dalton, Paul D.
T1  - Melt electrowriting of poly(vinylidene difluoride) using a heated collector
JF  - Polymers for Advanced Technologies
N2  - 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.
KW  - additive manufacturing
KW  - polymer processing
KW  - melt electrowriting
KW  - electroactive
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318493
SN  - 1042-7147
VL  - 32
IS  - 12
SP  - 4951
EP  - 4955
ER  - 
TY  - JOUR
A1  - Bakirci, Ezgi
A1  - Frank, Andreas
A1  - Gumbel, Simon
A1  - Otto, Paul F.
A1  - Fürsattel, Eva
A1  - Tessmer, Ingrid
A1  - Schmidt, Hans‐Werner
A1  - Dalton, Paul D.
T1  - Melt Electrowriting of Amphiphilic Physically Crosslinked Segmented Copolymers
JF  - Macromolecular Chemistry and Physics
N2  - 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.
KW  - melt electrowriting
KW  - 3D printing
KW  - additive manufacturing
KW  - electrohydrodynamics
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257572
VL  - 222
IS  - 22
ER  - 
TY  - JOUR
A1  - Ryma, Matthias
A1  - Tylek, Tina
A1  - Liebscher, Julia
A1  - Blum, Carina
A1  - Fernandez, Robin
A1  - Böhm, Christoph
A1  - Kastenmüller, Wolfgang
A1  - Gasteiger, Georg
A1  - Groll, Jürgen
T1  - Translation of collagen ultrastructure to biomaterial fabrication for material-independent but highly efficient topographic immunomodulation
JF  - Advanced materials
N2  - Supplement-free induction of cellular differentiation and polarization solely through the topography of materials is an auspicious strategy but has so far significantly lagged behind the efficiency and intensity of media-supplementation-based protocols. Consistent with the idea that 3D structural motifs in the extracellular matrix possess immunomodulatory capacity as part of the natural healing process, it is found in this study that human-monocyte-derived macrophages show a strong M2a-like prohealing polarization when cultured on type I rat-tail collagen fibers but not on collagen I films. Therefore, it is hypothesized that highly aligned nanofibrils also of synthetic polymers, if packed into larger bundles in 3D topographical biomimetic similarity to native collagen I, would induce a localized macrophage polarization. For the automated fabrication of such bundles in a 3D printing manner, the strategy of “melt electrofibrillation” is pioneered by the integration of flow-directed polymer phase separation into melt electrowriting and subsequent selective dissolution of the matrix polymer postprocessing. This process yields nanofiber bundles with a remarkable structural similarity to native collagen I fibers, particularly for medical-grade poly(ε-caprolactone). These biomimetic fibrillar structures indeed induce a pronounced elongation of human-monocyte-derived macrophages and unprecedentedly trigger their M2-like polarization similar in efficacy as interleukin-4 treatment.
KW  - biofabrication
KW  - extracellular matrix
KW  - immunomodulation
KW  - macrophages
KW  - melt electrofibrillation
KW  - melt electrowriting
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256381
VL  - 33
IS  - 33
ER  - 
TY  - JOUR
A1  - Diloksumpan, Paweena
A1  - de Ruijter, Mylène
A1  - Castilho, Miguel
A1  - Gbureck, Uwe
A1  - Vermonden, Tina
A1  - van Weeren, P René
A1  - Malda, Jos
A1  - Levato, Riccardo
T1  - Combining multi-scale 3D printing technologies to engineer reinforced hydrogel-ceramic interfaces
JF  - Biofabrication
N2  - Multi-material 3D printing technologies that resolve features at different lengths down to the microscale open new avenues for regenerative medicine, particularly in the engineering of tissue interfaces. Herein, extrusion printing of a bone-biomimetic ceramic ink and melt electrowriting (MEW) of spatially organized polymeric microfibres are integrated for the biofabrication of an osteochondral plug, with a mechanically reinforced bone-to-cartilage interface. A printable physiological temperature-setting bioceramic, based on α-tricalcium phosphate, nanohydroxyapatite and a custom-synthesized biodegradable and crosslinkable poloxamer, was developed as bone support. The mild setting reaction of the bone ink enabled us to print directly within melt electrowritten polycaprolactone meshes, preserving their micro-architecture. Ceramic-integrated MEW meshes protruded into the cartilage region of the composite plug, and were embedded with mechanically soft gelatin-based hydrogels, laden with articular cartilage chondroprogenitor cells. Such interlocking design enhanced the hydrogel-to-ceramic adhesion strength >6.5-fold, compared with non-interlocking fibre architectures, enabling structural stability during handling and surgical implantation in osteochondral defects ex vivo. Furthermore, the MEW meshes endowed the chondral compartment with compressive properties approaching those of native cartilage (20-fold reinforcement versus pristine hydrogel). The osteal and chondral compartment supported osteogenesis and cartilage matrix deposition in vitro, and the neo-synthesized cartilage matrix further contributed to the mechanical reinforcement at the ceramic-hydrogel interface. This multi-material, multi-scale 3D printing approach provides a promising strategy for engineering advanced composite constructs for the regeneration of musculoskeletal and connective tissue interfaces.
KW  - biofabrication
KW  - melt electrowriting
KW  - bioinspired interface
KW  - bone and cartilage tissue engineering
KW  - microfibres
KW  - ceramics
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254005
VL  - 12
IS  - 2
ER  - 
TY  - JOUR
A1  - Mechau, Jannik
A1  - Frank, Andreas
A1  - Bakirci, Ezgi
A1  - Gumbel, Simon
A1  - Jungst, Tomasz
A1  - Giesa, Reiner
A1  - Groll, Jürgen
A1  - Dalton, Paul D.
A1  - Schmidt, Hans‐Werner
T1  - Hydrophilic (AB)\(_{n}\) Segmented Copolymers for Melt Extrusion‐Based Additive Manufacturing
JF  - Macromolecular Chemistry and Physics
N2  - 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.
KW  - 3D printing
KW  - (AB)\(_{n}\) segmented copolymers
KW  - biocompatibility
KW  - melt electrowriting
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224513
VL  - 222
IS  - 1
ER  - 
TY  - JOUR
A1  - Wang, Shuang
A1  - Sarwat, Mariah
A1  - Wang, Peng
A1  - Surrao, Denver C.
A1  - Harkin, Damien G.
A1  - St John, James A.
A1  - Bolle, Eleonore C. L.
A1  - Forget, Aurelien
A1  - Dalton, Paul D.
A1  - Dargaville, Tim R.
T1  - Hydrogels with Cell Adhesion Peptide‐Decorated Channel Walls for Cell Guidance
JF  - Macromolecular Rapid Communications
N2  - 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.
KW  - 3D printing
KW  - cell guidance
KW  - cell transplantation
KW  - melt electrowriting
KW  - synthetic hydrogels
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218031
VL  - 41
IS  - 15
ER  - 
TY  - JOUR
A1  - Janzen, Dieter
A1  - Bakirci, Ezgi
A1  - Wieland, Annalena
A1  - Martin, Corinna
A1  - Dalton, Paul D.
A1  - Villmann, Carmen
T1  - Cortical Neurons form a Functional Neuronal Network in a 3D Printed Reinforced Matrix
JF  - Advanced Healthcare Materials
N2  - 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.
KW  - 3D electrophysiology
KW  - 3D neuronal networks
KW  - cortical neurons
KW  - melt electrowriting
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215400
VL  - 9
IS  - 9
ER  -