Parkinson's disease (PD) is a progressive neurological disorder that affects movement. It is associated with lost dopaminergic (DA) neurons in the substantia nigra, a process that is not yet fully understood. To understand this deleterious disorder, there is an immense need to develop efficient in vitro three-dimensional (3D) models that can recapitulate complex organs such as the brain. However, due to the complexity of neurons, selecting suitable biomaterials to accommodate them is challenging. Here, we report on the fabrication of functional DA neuronal 3D models using ultrashort self-assembling tetrapeptide scaffolds. Our peptide-based models demonstrate biocompatibility both for primary mouse embryonic DA neurons and for human DA neurons derived from human embryonic stem cells. DA neurons encapsulated in these scaffolds responded to 6-hydroxydopamine, a neurotoxin that selectively induces loss of DA neurons. Using multi-electrode arrays, we recorded spontaneous activity in DA neurons encapsulated within these 3D peptide scaffolds for more than 1 month without decrease of signal intensity. Additionally, vascularization of our 3D models in a co-culture with endothelial cells greatly promoted neurite outgrowth, leading to denser network formation. This increase of neuronal networks through vascularization was observed for both primary mouse DA and cortical neurons. Furthermore, we present a 3D bioprinted model of DA neurons inspired by the mouse brain and created with an extrusion-based 3D robotic bioprinting system that was developed during previous studies and is optimized with time-dependent pulsing by microfluidic pumps. We employed a hybrid fabrication strategy that relies on an external mold of the mouse brain construct that complements the shape and size of the desired bioprinted model to offer better support during printing. We hope that our 3D model provides a platform for studies of the pathogenesis of PD and other neurodegenerative disorders that may lead to better understanding and more efficient treatment strategies.
Bibliographical noteFunding Information:
King Abdullah University of Science and Technology (KAUST) supported this work financially. We would like to acknowledge Hepi Hari Susapto for performing the SEM and TEM imaging for the peptides. We are grateful to our colleague Dr Leena Ali Ibrahim from KAUST for providing primary mouse neurons. Walaa F. Alsanie would like to acknowledge Taif university for support No. TURSP (2020/53).
© 2022 The Author(s). Published by IOP Publishing Ltd.
- 3D robotic bioprinting
- neuronal scaffolds
- Parkinson's disease
- Parkinson's in vitro models
- ultrashort self-assembling peptides
- ventral midbrain dopaminergic neurons
ASJC Scopus subject areas
- Biomedical Engineering