The ability to create three-dimensional (3D) models of brain tissue from patient-derived cells, would open new possibilities in studying the neuropathology of disorders such as epilepsy and schizophrenia. While organoid culture has provided impressive examples of patient-specific models, the generation of organised 3D structures remains a challenge. 3D bioprinting is a rapidly developing technology where living cells, encapsulated in suitable bioink matrices, are printed to form 3D structures. 3D bioprinting may provide the capability to organise neuronal populations in 3D, through layer-by-layer deposition, and thereby recapitulate the complexity of neural tissue. However, printing neuron cells raises particular challenges since the biomaterial environment must be of appropriate softness to allow for the neurite extension, properties which are anathema to building self-supporting 3D structures. Here, we review the topic of 3D bioprinting of neurons, including critical discussions of hardware and bio-ink formulation requirements.
Melt electrowriting (MEW) is an electrohydrodynamic process capable of producing organized patterns of micrometer‐scale polymer fibers. Integrating MEW with other additive manufacturing technologies, such as extrusion‐printing or bioprinting, offers tantalizing possibilities for multi‐scale biofabrication of anatomically shaped scaffolds. However, introducing 3D structures onto the conventionally flat collector plate significantly complicates the MEW process because these objects perturb the electrostatic field. Here, the systematic investigation of how simple 3D objects (hemispheres) distort MEW patterns printed in their vicinity is reported. The authors assess the influence of a series of parameters on fiber deflection including: distance from the hemisphere, hemisphere size and material composition, height of the nozzle, translation speed, applied voltage, and applied pressure. In light of these data, a model which captures the basic physics behind the deflection phenomenon is derived. An optimization algorithm to calculate tool‐paths which pre‐emptively account for these deviations is also introduced. Finally, the authors validate how G‐code produced by this algorithm effectively corrects the distortion effect, restoring the ability to create well‐defined MEW patterns in the vicinity of 3D objects. This study suggests a foundation for understanding the complexities of MEW on non‐planar collectors, and towards multitechnology biofabrication.
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