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RESEARCH ARTICLE

A Systematic Thermal Analysis for Accurately

Predicting the Extrusion Printability of

Alginate–Gelatin-Based Hydrogel Bioinks

Qi Li 1,2† , Bin Zhang 1,2† , Qian Xue , Chunxiao Zhao , Yichen Luo , Hongzhao Zhou *,
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1,2
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Liang Ma *, Huayong Yang , Dapeng Bai 1,2
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1 State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou, 310058, People’s
Republic of China
2 School of Mechanical Engineering, Zhejiang University, Hangzhou, 310058, People’s Republic of China
† These authors contributed equally to this work
Abstract: Three-dimensional (3D) bioprinting has significant potential for addressing the global problem of organ shortages.
Extrusion printing is a versatile 3D bioprinting technique, but its low accuracy currently limits the solution. This lack of
precision is attributed largely to the complex thermal and dynamic properties of bioinks and makes it difficult to provide
accurate estimations of the printed results. It is necessary to understand the relationship between printing temperature and
materials’ printability to address this issue. This paper proposes a quantitative thermal model incorporating a system’s printing
temperatures (syringe, ambient, and bioink) to facilitate accurate estimations of the printing outcomes. A physical model
was established to reveal the relationship between temperature, pressure, and velocity in guiding the printing of sodium
alginate–gelatin composite hydrogel (a popular bioink) to optimize its extrusion-based printability. The model considered
the phenomenon of bioink die swells after extrusion. A series of extrusion experiments confirmed that the proposed model
offers enhanced printing outcome estimations compared with conventional models. Two types of nozzles (32- and 23-gauge)
were used to print several sets of lines with a linewidth step of 50 μm by regulating the extrudate’s temperature, pressure,
and velocity separately. The study confirmed the potential for establishing a reasonable, accurate open-loop linewidth control
based on the proposed optimization method to expand the application of extrusion-based bioprinting further.

Keywords: 3D bioprinting; Pneumatic extrusion; Thermal effects; Temperature control; Printability

*Correspondence to: Hongzhao Zhou, State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou,
310058, People’s Republic of China; hz_zhou@zju.edu.cn; Liang Ma,State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang

University, Hangzhou, 310058, People’s Republic of China; liangma@zju.edu.cn

Received: May 13, 2021; Accepted: May 26, 2021; Published Online: June 22, 2021
(This article belongs to the Special Section: Bioprinting of 3D Functional Tissue Constructs)

Citation: Li Q, Zhang B, Xue Q, et al., 2021, A Systematic Thermal Analysis for Accurately Predicting the Extrusion
Printability of Alginate–Gelatin-Based Hydrogel Bioinks. Int J Bioprint, 7(3):394. http://doi.org/10.18063/ijb.v7i3.394

1. Introduction efficiency, accuracy , and ability to fabricate scaffolds
[3]
that provide 3D microenvironments, thereby avoiding the
The three-dimensional (3D) bioprinting technique has the drawbacks associated with traditional two-dimensional
potential for creating functional tissues and organs in vitro, monolayer cell culture . In extrusion-based printing [5-10] ,
[4]
which could address the global shortage of human tissue/ syringes and pistons are used to extrude bioinks with
organ donation in the context of rising transplantation viscosities of 30 – 10 mPa·s from nozzles to form
7
demands [1,2] . Over recent years, 3D bioprinting has complex 3D architectures that offer various benefits in cell
[11]
become the focus of increasing attention due to its high culture . The technique allows the low-cost and high-
© 2021 Li, 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.
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