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  - Schmid, Rafael
A1  - Schmidt, Sonja K.
A1  - Hazur, Jonas
A1  - Detsch, Rainer
A1  - Maurer, Evelyn
A1  - Boccaccini, Aldo R.
A1  - Hauptstein, Julia
A1  - Teßmar, Jörg
A1  - Blunk, Torsten
A1  - Schrüfer, Stefan
A1  - Schubert, Dirk W.
A1  - Horch, Raymund E.
A1  - Bosserhoff, Anja K.
A1  - Arkudas, Andreas
A1  - Kengelbach-Weigand, Annika
T1  - Comparison of hydrogels for the development of well-defined 3D cancer models of breast cancer and melanoma
JF  - Cancers
N2  - Bioprinting offers the opportunity to fabricate precise 3D tumor models to study tumor pathophysiology and progression. However, the choice of the bioink used is important. In this study, cell behavior was studied in three mechanically and biologically different hydrogels (alginate, alginate dialdehyde crosslinked with gelatin (ADA–GEL), and thiol-modified hyaluronan (HA-SH crosslinked with PEGDA)) with cells from breast cancer (MDA-MB-231 and MCF-7) and melanoma (Mel Im and MV3), by analyzing survival, growth, and the amount of metabolically active, living cells via WST-8 labeling. Material characteristics were analyzed by dynamic mechanical analysis. Cell lines revealed significantly increased cell numbers in low-percentage alginate and HA-SH from day 1 to 14, while only Mel Im also revealed an increase in ADA–GEL. MCF-7 showed a preference for 1% alginate. Melanoma cells tended to proliferate better in ADA–GEL and HA-SH than mammary carcinoma cells. In 1% alginate, breast cancer cells showed equally good proliferation compared to melanoma cell lines. A smaller area was colonized in high-percentage alginate-based hydrogels. Moreover, 3% alginate was the stiffest material, and 2.5% ADA–GEL was the softest material. The other hydrogels were in the same range in between. Therefore, cellular responses were not only stiffness-dependent. With 1% alginate and HA-SH, we identified matrices that enable proliferation of all tested tumor cell lines while maintaining expected tumor heterogeneity. By adapting hydrogels, differences could be accentuated. This opens up the possibility of understanding and analyzing tumor heterogeneity by biofabrication.
KW  - breast cancer
KW  - melanoma
KW  - biofabrication
KW  - hydrogel
KW  - tumor heterogeneity
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211195
SN  - 2072-6694
VL  - 12
IS  - 8
ER  -