Inkjet bioprinting of neural progenitor NE-4C cells with promoted neuronal differentiation efficiency under retinoic acid treatment

During inkjet bioprinting, cells are subjected to shear stress directly while passing through the nozzles, which would cause reversible deformation on cell membranes. Moreover, other subcellular-level changes such as activation of gene pathways might also occur during inkjet bioprinting, leading to beneficial results. In this study, neural progenitor NE-4C cells were printed through 30μm thermal inkjet nozzles. Compared with manually pipetted cells (control group), a series of changes have occured on inkjet-bioprinted cells (inkjet group): Cell proliferation was down-regulated during the initial 4 days after bioprinting. Meanwhile, inkjet group exhibited stronger tolerance to high-concentration retinoic acid (RA). Most importantly, the expression level of early neuron marker tuj-1 was significantly higher in inkjet group, indicating the promotion of neuronal differentiation efficiency. Furthermore, RNA sequence and enrichment analysis was performed which had shown that cell-metabolism pathways were upregulated in inkjet group. These beneficial effects collectively suggested that inkjet bioprinting might be a promising strategy to accelerate neural tissue formation while further studies are performed.