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  - Kade, Juliane C.
A1  - Bakirci, Ezgi
A1  - Tandon, Biranche
A1  - Gorgol, Danila
A1  - Mrlik, Miroslav
A1  - Luxenhofer, Robert
A1  - Dalton, Paul D.
T1  - The Impact of Including Carbonyl Iron Particles on the Melt Electrowriting Process
JF  - Macromolecular Materials and Engineering
N2  - 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.
KW  - additive manufacturing
KW  - melt electrospinning writing
KW  - magnetoactive materials
KW  - electroactive polymers
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318482
SN  - 1438-7492
VL  - 307
IS  - 12
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  - Weigl, Franziska
A1  - Blum, Carina
A1  - Sancho, Ana
A1  - Groll, Jürgen
T1  - Correlative Analysis of Intra– Versus Extracellular Cell Detachment Events via the Alignment of Optical Imaging and Detachment Force Quantification
JF  - Advanced Materials Technologies
N2  - In recent decades, hybrid characterization systems have become pillars in the study of cellular biomechanics. Especially, Atomic Force Microscopy (AFM) is combined with a variety of optical microscopy techniques to discover new aspects of cell adhesion. AFM, however, is limited to the early-stage of cell adhesion, so that the forces of mature cell contacts cannot be addressed. Even though the invention of Fluidic Force Microscopy (FluidFM) overcomes these limitations by combining the precise force-control of AFM with microfluidics, the correlative investigation of detachment forces arising from spread mammalian cells has been barely achieved. Here, a novel multifunctional device integrating Fluorescence Microscopy (FL) into FluidFM technology (FL-FluidFM) is introduced, enabling real-time optical tracking of entire cell detachment processes in parallel to the undisturbed acquisition of force-distance curves. This setup, thus, allows for entailing two pieces of information at once. As proof-of-principle experiment, this method is applied to fluorescently labeled rat embryonic fibroblast (REF52) cells, demonstrating a precise matching between identified force-jumps and visualized cellular unbinding steps. This study, thus, presents a novel characterization tool for the correlated evaluation of mature cell adhesion, which has great relevance, for instance, in the development of biomaterials or the fight against diseases such as cancer.
KW  - Fluorescence Microscopy
KW  - FluidFM technology
KW  - detachment force quantification
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318544
SN  - 2365-709X
VL  - 7
IS  - 11
ER  - 
TY  - JOUR
A1  - Pien, Nele
A1  - Bartolf–Kopp, Michael
A1  - Parmentier, Laurens
A1  - Delaey, Jasper
A1  - de Vos, Lobke
A1  - Mantovani, Diego
A1  - van Vlierberghe, Sandra
A1  - Dubruel, Peter
A1  - Jungst, Tomasz
T1  - Melt Electrowriting of a Photo–Crosslinkable Poly(ε–caprolactone)–Based Material into Tubular Constructs with Predefined Architecture and Tunable Mechanical Properties
JF  - Macromolecular Materials and Engineering
N2  - Melt electrowriting (MEW) is an additive manufacturing process that produces highly defined constructs with elements in the micrometer range. A specific configuration of MEW enables printing tubular constructs to create small-diameter tubular structures. The small pool of processable materials poses a bottleneck for wider application in biomedicine. To alleviate this obstacle, an acrylate-endcapped urethane-based polymer (AUP), using a poly(ε-caprolactone) (PCL) (molar mass: 20 000 g mol\(^{−1}\)) (AUP PCL20k) as backbone material, is synthesized and utilized for MEW. Spectroscopic analysis confirms the successful modification of the PCL backbone with photo-crosslinkable acrylate endgroups. Printing experiments of AUP PCL20k reveal limited printability but the photo-crosslinking ability is preserved post-printing. To improve printability and to tune the mechanical properties of printed constructs, the AUP-material is blended with commercially available PCL (AUP PCL20k:PCL in ratios 80:20, 60:40, 50:50). Print fidelity improves for 60:40 and 50:50 blends. Blending enables modification of the constructs' mechanical properties to approximate the range of blood vessels for transplantation surgeries. The crosslinking-ability of the material allows pure AUP to be manipulated post-printing and illustrates significant differences in mechanical properties of 80:20 blends after crosslinking. An in vitro cell compatibility assay using human umbilical vein endothelial cells also demonstrates the material's non-cytotoxicity.
KW  - acrylate-endcapped urethane-based polymer (AUP)
KW  - tubular constructs
KW  - physicochemical characterization
KW  - photo-crosslinking
KW  - melt electrowriting (MEW)
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318524
SN  - 1438-7492
VL  - 307
IS  - 7
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  - Böhm, Christoph
A1  - Tandon, Biranche
A1  - Hrynevich, Andrei
A1  - Teßmar, Jörg
A1  - Dalton, Paul D.
T1  - Processing of Poly(lactic–co–glycolic acid) Microfibers via Melt Electrowriting
JF  - Macromolecular Chemistry and Physics
N2  - 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.
KW  - poly(lactide-co-glycolide)
KW  - 3D printing
KW  - additive manufacturing
KW  - electrohydrodynamics
KW  - melt electrospinning writing
KW  - plasticizers
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318444
VL  - 223
IS  - 5
ER  - 
TY  - JOUR
A1  - Brand, Jessica S.
A1  - Forster, Leonard
A1  - Böck, Thomas
A1  - Stahlhut, Philipp
A1  - Teßmar, Jörg
A1  - Groll, Jürgen
A1  - Albrecht, Krystyna
T1  - Covalently Cross-Linked Pig Gastric Mucin Hydrogels Prepared by Radical-Based Chain-Growth and Thiol-ene Mechanisms
JF  - Macromolecular Bioscience
N2  - Mucin, a high molecular mass hydrophilic glycoprotein, is the main component of mucus that coats every wet epithelium in animals. It is thus intrinsically biocompatible, and with its protein backbone and the o-glycosidic bound oligosaccharides, it contains a plethora of functional groups which can be used for further chemical modifications. Here, chain-growth and step-growth (thiol-ene) free-radical cross-linked hydrogels prepared from commercially available pig gastric mucin (PGM) are introduced and compared as cost-efficient and easily accessible alternative to the more broadly applied bovine submaxillary gland mucin. For this, PGM is functionalized with photoreactive acrylate groups or allyl ether moieties, respectively. Whereas homopolymerization of acrylate-functionalized polymers is performed, for thiol-ene cross-linking, the allyl-ether-functionalized PGM is cross-linked with thiol-functionalized hyaluronic acid. Morphology, mechanical properties, and cell compatibility of both kinds of PGM hydrogels are characterized and compared. Furthermore, the biocompatibility of these hydrogels can be evaluated in cell culture experiments.
KW  - click chemistry
KW  - photopolymerization
KW  - hydrogels
KW  - mucin
KW  - thiol-ene
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318453
VL  - 22
IS  - 4
ER  - 
TY  - JOUR
A1  - An, Ran
A1  - Strissel, Pamela L.
A1  - Al-Abboodi, Majida
A1  - Robering, Jan W.
A1  - Supachai, Reakasame
A1  - Eckstein, Markus
A1  - Peddi, Ajay
A1  - Hauck, Theresa
A1  - Bäuerle, Tobias
A1  - Boccaccini, Aldo R.
A1  - Youssef, Almoatazbellah
A1  - Sun, Jiaming
A1  - Strick, Reiner
A1  - Horch, Raymund E.
A1  - Boos, Anja M.
A1  - Kengelbach-Weigand, Annika
T1  - An innovative arteriovenous (AV) loop breast cancer model tailored for cancer research
JF  - Bioengineering
N2  - Animal models are important tools to investigate the pathogenesis and develop treatment strategies for breast cancer in humans. In this study, we developed a new three-dimensional in vivo arteriovenous loop model of human breast cancer with the aid of biodegradable materials, including fibrin, alginate, and polycaprolactone. We examined the in vivo effects of various matrices on the growth of breast cancer cells by imaging and immunohistochemistry evaluation. Our findings clearly demonstrate that vascularized breast cancer microtissues could be engineered and recapitulate the in vivo situation and tumor-stromal interaction within an isolated environment in an in vivo organism. Alginate–fibrin hybrid matrices were considered as a highly powerful material for breast tumor engineering based on its stability and biocompatibility. We propose that the novel tumor model may not only serve as an invaluable platform for analyzing and understanding the molecular mechanisms and pattern of oncologic diseases, but also be tailored for individual therapy via transplantation of breast cancer patient-derived tumors.
KW  - arteriovenous loop
KW  - breast cancer
KW  - animal model
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-278919
SN  - 2306-5354
VL  - 9
IS  - 7
ER  - 
TY  - JOUR
A1  - Karakaya, Emine
A1  - Bider, Faina
A1  - Frank, Andreas
A1  - Teßmar, Jörg
A1  - Schöbel, Lisa
A1  - Forster, Leonard
A1  - Schrüfer, Stefan
A1  - Schmidt, Hans-Werner
A1  - Schubert, Dirk Wolfram
A1  - Blaeser, Andreas
A1  - Boccaccini, Aldo R.
A1  - Detsch, Rainer
T1  - Targeted printing of cells: evaluation of ADA-PEG bioinks for drop on demand approaches
JF  - Gels
N2  - A novel approach, in the context of bioprinting, is the targeted printing of a defined number of cells at desired positions in predefined locations, which thereby opens up new perspectives for life science engineering. One major challenge in this application is to realize the targeted printing of cells onto a gel substrate with high cell survival rates in advanced bioinks. For this purpose, different alginate-dialdehyde—polyethylene glycol (ADA-PEG) inks with different PEG modifications and chain lengths (1–8 kDa) were characterized to evaluate their application as bioinks for drop on demand (DoD) printing. The biochemical properties of the inks, printing process, NIH/3T3 fibroblast cell distribution within a droplet and shear forces during printing were analyzed. Finally, different hydrogels were evaluated as a printing substrate. By analysing different PEG chain lengths with covalently crosslinked and non-crosslinked ADA-PEG inks, it was shown that the influence of Schiff's bases on the viscosity of the corresponding materials is very low. Furthermore, it was shown that longer polymer chains resulted in less stable hydrogels, leading to fast degradation rates. Several bioinks highly exhibit biocompatibility, while the calculated nozzle shear stress increased from approx. 1.3 and 2.3 kPa. Moreover, we determined the number of cells for printed droplets depending on the initial cell concentration, which is crucially needed for targeted cell printing approaches.
KW  - bioprinting
KW  - drop on demand
KW  - sodium alginate
KW  - polyethylene glycol
KW  - shear stress
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-267317
SN  - 2310-2861
VL  - 8
IS  - 4
ER  -