Perfusable Vessel-on-a-Chip for Antiangiogenic Drug Screening with Coaxial Bioprinting

Zeming Gu^1,2, Mingjun Xie^1,2, Shang Lv^1,2, Nian Liu^1,2, Jing He^1,2, Yuanrong Li^1,2, Yuanbo Zhu^1,2, Jianzhong Fu^1,2, Hui Lin³, Chaoqi Xie^1,2*, 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

IJB 2022, 8(4), 619 https://doi.org/10.18063/ijb.v8i4.619

Received: 28 June 2022 | Accepted: 1 August 2022 | Published online: 22 September 2022

(This article belongs to the Special Issue 3D Bioprinting with Photocurable Bioinks--Call for Papers )

© 2022 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

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

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