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  -