AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB025260245
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RESEARCH ARTICLE

Inkjet bioprinting of NE-4C neural progenitor cells with enhanced neuronal differentiation via retinoic acid treatment

Xinda Li1,2† ,  Xiaolei Guo3,4† ,  Jinzhou Feng1 ,  Lihua Chen1 ,  Huan X Xiong1 ,  Ruxiang Xu1* ,  Tao Xu1,2,5*
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1 Department of Neurosurgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
2 Department of Mechanical Engineering, School of Mechanical Engineering, Tsinghua University, Beijing, China
3 Center for Medical Device Evaluation, National Medical Products Administration, Beijing, China
4 State Key Laboratory of Tribology, Department of Mechanical Engineering, School of Mechanical Engineering, Tsinghua University, Beijing, China
5 Center for Bio-intelligent Manufacturing and Living Matter Bioprinting, Research Institute of Tsinghua University in Shenzhen, Tsinghua University, Shenzhen, Guangdong, China
†These authors contributed equally to this work.
IJB, 025260245 https://doi.org/10.36922/IJB025260245
Received: 24 June 2025 | Accepted: 25 July 2025 | Published online: 25 July 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

During inkjet bioprinting, cells are subjected to direct shear stress as they pass through the nozzles, causing reversible deformation of the cell membranes and potentially triggering subcellular changes, such as activation of molecular pathways, leading to beneficial o utcomes. I n t his s tudy, n eural p rogenitor NE-4C c ells were printed through 30μm thermal inkjet nozzles. Compared to manually pipetted cells (control group), bioprinted cells (inkjet group) exhibited several distinct changes, such as reduced cell proliferation during the first four days after bioprinting, increased tolerance to high-concentration retinoic acid, and significantly elevated expression of the early neuronal marker class III β-tubulin, indicating enhanced neuronal differentiation. Furthermore, RNA sequencing and enrichment analysis further revealed upregulation of cell metabolism pathways in the bioprinted group. Collectively, these findings suggest that inkjet bioprinting may be a promising strategy to accelerate neural tissue formation, warranting further studies.

Graphical abstract
Keywords
Inkjet bioprinting
Neural differentiation
Neural progenitor cells
Funding
This research is supported by the National Natural Science Foundation of China (Grant No.52075285), the Applied Basic Research Project of Sichuan Province (Grant No.2021YJ0563), and the Natural Science Foundation of Sichuan Province (Grant No. 2023NSFSC0851).
Conflict of interest
The authors declare they have no competing interests.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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