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RESEARCH ARTICLE

Perfusable Vessel-on-a-Chip for Antiangiogenic Drug

Screening with Coaxial Bioprinting

Zeming Gu , Mingjun Xie , Shang Lv , Nian Liu , Jing He , Yuanrong Li , Yuanbo Zhu ,
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Jianzhong Fu , Hui Lin , Chaoqi Xie *, Yong He 1,4,5 *
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1 State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University,
Hangzhou 310027, China
2 Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang
University, Hangzhou 310027, China
3 Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310058,
China
4 Cancer Center, Zhejiang University, Hangzhou 310058, China
5 Key Laboratory of Materials Processing and Mold, Zhengzhou University, Zhengzhou 450002, China
Abstract: Vessel-on-a-chips, which can be used to study microscale fluid dynamics, tissue-level biological molecules
delivery and intercellular communication under favorable three-dimensional (3D) extracellular matrix microenvironment,
are increasingly gaining traction. However, not many of them can allow for long-term perfusion and easy observation of
angiogenesis process. Since angiogenesis is necessary for the expansion of tumor, antiangiogenic drugs play a significant role
in cancer treatment. In this study, we established an innovative and reliable antiangiogenic drug screening chip that was highly
modularly integrated for long-term perfusion (up to 10 days depending on the hydrogel formula) and real-time monitoring. To
maintain an unobstructed flow of cell-laden tubes for subsequent perfusion culture on the premise of excellent bioactivities, a
polycaprolactone stent inspired by coronary artery stents was introduced to hold up the tubular lumen from the inside, while the
perfusion chip was also elaborately designed to allow for convenient observation. After 3 days of perfusion screening, distinct
differences in human umbilical vein endothelial cell sprouting were observed for a gradient of concentrations of bevacizumab,
which pointed to the effectiveness and reliability of the drug screening perfusion system. Overall, a perfusion system for
antiangiogenic drug screening was developed, which can not only conduct drug evaluation, but also be potentially useful
in other vessel-mimicking scenarios in the area of tissue engineering, drug screening, pharmacokinetics, and regenerative
medicine.
Keywords: Coaxial bioprinting; Gelatin methacryloyl; Vessel-on-a-chip; Perfusion culture; Drug screening model

*Correspondence to: Chaoqi Xie, State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang
University, Hangzhou 310027, China; 342247006@qq.com; Yong He, State Key Laboratory of Fluid Power and Mechatronic Systems, School of
Mechanical Engineering, Zhejiang University, Hangzhou 310027, China; yongqin@zju.edu.cn
Received: June 28, 2022; Accepted: August 1, 2022; Published Online: September 22, 2022
(This article belongs to the Special Issue: 3D Bioprinting with Photocurable Bioinks)

Citation: Gu Z, Xie M, Lv S, et al., 2022, Perfusable Vessel-on-a-chip for Antiangiogenic Drug Screening with Coaxial Bioprinting. Int J
Bioprint, 8(4):619. DOI: http://doi.org/10.18063/ijb.v8i4.619

1. Introduction restenosis [1,2] . In the treatment of cancer, antiangiogenic
Angiogenesis, the generation of new blood vessels, drugs, which are often used to target angiogenesis in
[3]
plays a key role in various disease states, such as cancer, combination with other drugs , play significant roles,
diabetic retinopathy, age-related macular degeneration, since angiogenesis is necessary for the expansion of
rheumatoid arthritis, psoriasis, atherosclerosis, and tumor. Many studies concerning antiangiogenic drug

© 2022 Author(s). This is an Open-Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution and
reproduction in any medium, provided the original work is properly cited.
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