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International
Journal of Bioprinting
REVIEW ARTICLE
Droplet-based bioprinting for fabrication of
tumor spheroids
Congying Liu, Yuhe Chen, Huawei Chen, and Pengfei Zhang *
School of Mechanical Engineering and Automation, Beihang University, Beijing, China
(This article belongs to the Special Issue: Bioprinting Process for Tumor Model Development)
Abstract
Cancer is now one of the leading causes of mortality worldwide, and the cancer
treatment development is still slow due to the lack of efficient in vitro tumor models
for studying tumorigenesis and facilitating drug development. Multicellular tumor
spheroids can recapitulate the critical properties of tumors in vivo, including
spatial organization, physiological responses, and metabolism, and are considered
powerful platform for disease study and drug screening. Although several spheroid
fabrication methods have been developed, most of them result in uncontrolled
cell aggregations, yielding spheroids of variable size and function. Droplet-based
bioprinting is capable of depositing cells in spatiotemporal manner so as to control
the composition and distribution of printed biological constructs, thereby facilitating
high-throughput fabrication of complicated and reproducible tumor spheroids.
In this review, we introduce the progress of droplet-based bioprinting technology
for the fabrication of tumor spheroids. First, different droplet-based bioprinting
technologies are compared in terms of their strengths and shortcomings, which
should be taken into account while fabricating tumor spheroids. Second, the latest
advances in modeling distinct types of cancers and the enabled applications with
tumor spheroids are summarized. Finally, we discuss the challenges and potentials
*Corresponding authors: revolving around the advances of bioprinting technology, improvement of spheroid
Pengfei Zhang quality, and integration of different technologies.
(zhangpf@buaa.edu.cn)
Citation: Liu C, Chen Y, Chen H, Keywords: Droplet-based bioprinting; Tumor spheroids; Tumor heterogeneity;
Zhang P. Droplet-based bioprinting
for fabrication of tumor spheroids. Diagnosis; Anti-cancer drug screening
Int J Bioprint. 2024;10(1):1214.
doi: 10.36922/ijb.1214
Received: June 30, 2023
Accepted: August 14, 2023 1. Introduction
Published Online: January 2, 2024
Cancer is a public health issue worldwide. According to the statistics from the
Copyright: © 2024 Author(s).
This is an Open Access article International Agency for Research on Cancer (IARC), there are 19.3 million new cancer
distributed under the terms of the cases and 10.0 million cancer deaths worldwide in 2020, and mortality rate is still
Creative Commons Attribution growing by 2023. Despite a deeper understanding of human genome and components
1-3
License, permitting distribution,
and reproduction in any medium, of tumor microenvironments, the development of more potent cancer treatment is still
4
provided the original work is a huge challenge even if various gene-targeting cancer therapies have been proposed.
properly cited. Anti-cancer drugs require rigorous in vitro and preclinical testings. However, due to the
Publisher’s Note: AccScience lack of precise testing models, drugs that have been screened on the existing models have
Publishing remains neutral with a very high failure rate, up to ~90%, in the clinical stage, and thus, a drug development
regard to jurisdictional claims in 5-7
published maps and institutional cycle can take up to 15 years and cost hundreds of millions of dollars. In addition
affiliations. to drug resistance in cancer, problems in drug development process such as long drug
Volume 10 Issue 1 (2024) 107 https://doi.org/10.36922/ijb.1214

