In preclinical neurodegenerative disease research, mimicking the shape and function of three-dimensional (3D) brain tissues within a high throughput platform that allows for the non-invasive collection of electrophysiological data remains a challenge. A general lack of such platforms could provide a rationale for the failure of a large percentage of novel drug candidates entering later-stage clinical trials. Therefore, with the added positional benefit of being able to produce in-house innovative microelectrode arrays (MEA) for electrophysiological recording - we have set out to tackle this challenge and develop the so-called Nerve-on-a-chip systems to fill the scientific gap.
The MEA integrated neuro-microphysiological system that arose from this initiative has been published in Biofabrication – here, we demonstrate how its sensitive multimodal nature; the ability of the platform to (noninvasively) measure electrophysiological inputs from 3D neural networks whilst simultaneously providing the opportunity to interrogate detailed morphology – sets it apart from other on-chip models.
Furthermore, we are currently building out the applicability of the platform in modeling specific neurodegenerative phenotypes by tailoring key features towards, for instance, effective incorporation of microglia (essential immune effector cells of the CNS), Alzheimer’s/Parkinson’s related constructs (Aβ-seeding), and 3D brain organoids.
Funding: Eurostars: "Neurochip"; Go-Bio Initiative: "Neurobot"; H2020-MSCA-ITN: "BonePain II"; Baden Württemberg Foundation; IMI (Innovative Medicines Initiative; EU):; German Federal Ministry of Education and Research (BMBF): ; NC3Rs; Volkswagen Foundation;
Publications
B. Molina-Martínez, L.-V. Jentsch, F. Ersoy, M. van der Moolen, S. Donato, T. V. Ness, P. Heutink, P. D. Jones, P. Cesare
A multimodal 3D neuro-microphysiological system with neurite-trapping microelectrodes
Biofabrication, 2022, 14, 025004, https://doi.org/10.1088/1758-5090/ac463b
M. van der Moolen, A. Lovera, F. Ersoy, S. Mommo, P. Loskill, P. Cesare
Cancer-mediated axonal guidance of sensory neurons in a microelectrode-based innervation MPS
Biofabrication, 2024, 16, 025013, https://doi.org/10.1088/1758-5090/ad218a
