Page 75 - IJB-7-3

RESEARCH ARTICLE

3D Printing of Layered Gradient Pore Structure of

Brain-like Tissue

Na Pei ,Zhiyan Hao , Sen Wang , Binglei Pan , Ao Fang , Jianfeng Kang , Dichen Li ,
1,2
1,2
1,2
1,2
3
1,2
1,2
Jiankang He , Ling Wang *
1,2
1,2
1 State Key Laboratory for Manufacturing System Engineering, Xi’an Jiaotong University, 710054, Xi’an, Shaanxi, China
2 School of Mechanical Engineering, Xi’an Jiaotong University, 710054, Xi’an, ShanXi, China
3 Jihua Laboratory, Foshan, 528000, Guangdong, China
Abstract: The pathological research and drug development of brain diseases require appropriate brain models. Given the
complex, layered structure of the cerebral cortex, as well as the constraints on the medical ethics and the inaccuracy of animal
models, it is necessary to construct a brain-like model in vitro. In this study, we designed and built integrated three-dimensional
(3D) printing equipment for cell printing/culture, which can guarantee cell viability in the printing process and provide the
equipment foundation for manufacturing the layered structures with gradient distribution of pore size. Based on this printing
equipment, to achieve the purpose of printing the layered structures with multiple materials, we conducted research on the
performance of bio-inks with different compositions and optimized the printing process. By extruding and stacking materials,
we can print the layered structure with the uniform distribution of cells and the gradient distribution of pore sizes. Finally, we
can accurately print a structure with 30 layers. The line width (resolution) of the printed monolayer structure was about 478
μm, the forming accuracy can reach 97.24%, and the viability of cells in the printed structure is as high as 94.5%.
Keywords: Brain-like model; Layered gradient structure; Integrated cell printing/culture equipment; 3D bio-printing

*Correspondence to: Ling Wang, State Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong University, Xi’an 710054,
Shaanxi, China; menlwang@mail.xjtu.edu.cn

Received: March 22, 2021; Accepted: April 20, 2021; Published Online: June 15, 2021
(This article belongs to the Special Section: Bioprinting of 3D Functional Tissue Constructs)
Citation: Pei N, Hao Z, Wang S, et al., 2021, 3D Printing of Layered Gradient Pore Structure of Brain-like Tissue. Int J
Bioprint, 7(3):359. http://doi.org/10.18063/ijb.v7i3.359

1. Introduction Compared with the traditional tissue engineering
methods, 3D bioprinting technology can be used to
According to the statistics from the World Health manufacture biomimetic tissue with complex structure
Organization, the burden of brain diseases throughout through a highly automated manufacturing platform.
the world has exceeded that of cardiovascular diseases Three-dimensional (3D) bioprinting technology has high
and cancer, accounting for 28% . At present, the precision and repeatability, which has great potential
[1]
models used for brain pathology research and new drug in achieving the envisioned goal of tissue-specific
development are mainly derived from animal models , composition and localization of simulated cells and
[2]
which not only have long cycles but also display huge extracellular components . The 3D bioprinting processes
[7]
differences as compared to the human brain tissue , can be classified into five main categories: (i) Extrusion
[3]
leading to a failure rate of drug development as high bioprinting [8,9] , (ii) stereolithography bioprinting , (iii)
[10]
as 95%. In addition, the two-dimensional (2D) cell inkjet bioprinting , (iv) laser-assisted bioprinting ,
[11]
[12]
model is the main approach for pathological research, and (v) microvalve-based bioprinting . Extrusion-
[13]
but due to lacking the interactions of cell-cell and cell- based bioprinting technology is the most commonly used
extracellular matrix (ECM), the neurons cultured on bioprinting method because of its fast printing speed and
2D cell culture dishes show significant deficiency [4-6] . a wide variety of bio-inks that can be printed.
© 2021 Pei, et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/
licenses/by/4.0/), permitting distribution and reproduction in any medium, provided the original work is cited.
71