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. 2021 Jun 15;7(3):359.
doi: 10.18063/ijb.v7i3.359. eCollection 2021.

3D Printing of Layered Gradient Pore Structure of Brain-like Tissue

Na Pei  1   2 , Zhiyan Hao  1   2 , Sen Wang  1   2 , Binglei Pan  1   2 , Ao Fang  1   2 , Jianfeng Kang  3 , Dichen Li  1   2 , Jiankang He  1   2 , Ling Wang  1   2
Affiliations

3D Printing of Layered Gradient Pore Structure of Brain-like Tissue

Na Pei et al. Int J Bioprint. .

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 mm, the forming accuracy can reach 97.24%, and the viability of cells in the printed structure is as high as 94.5%.

Keywords: 3D bio-printing; Brain-like model; Integrated cell printing/culture equipment; Layered gradient structure.

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Conflict of interest statement

We have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in, or the review of, this article.

Figures

Figure 1
Figure 1
The integrated cell printing/culture equipment.
Figure 2
Figure 2
Printing a layered gradient structure that mimics the cortex. (A) Schematic diagram of the layered gradient brain-like model\designed in the current study. (B) The printing principle of the layered gradient brain-like structure.
Figure 3
Figure 3
Configuration process of the bio-ink.
Figure 4
Figure 4
Effect of different pre-cooling time at 4°C on the performance of the G6A1C1 bio-inks. (A) Curve of viscosity and shear rate of the mixed bio-inks. (B) Outflow state of the bio-inks. (C) The micro-morphology of the printed structures printed by the bio-inks with different pre-cooling time.
Figure 5
Figure 5
Effect of multi-layer structure printing with optimized single-layer printing parameters.
Figure 6
Figure 6
The use of different printing parameters to print the structure with different collagen concentrations in the ink.
Figure 7
Figure 7
Effect of the concentration of Ca2+ on the performance of the printed structure. (A-D) scanning electron microscope image of the morphology of the internal pore of the printed structure. (E) The size of the internal pore of the printed structure. (F) Compression modulus of the printed structure when treated with the different concentration of Ca2+ solution.
Figure 8
Figure 8
The macro and micro characteristics of the layered structure. (A) The macro-morphology of the layered structure. (B) The stress-strain diagram. (C) The scanning electron microscope image of the cross-section of the layered structure.
Figure 9
Figure 9
(A) The morphology of the layered structure and the distribution of cells inside of the layered structure which was cultured in a cell incubator for 1 day. (B) The macro morphology of the layered structure when cultured for 7 days. (C-E) The viability of cells in the layered structure when the structure was cultured for 1 day, 3 days, and 7 days, respectively. Green and red fluorescence denote living cells and dead cells, respectively.
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