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International

Journal of Bioprinting

RESEARCH ARTICLE
Multiscale vascularized tumor-on-a-chip via

bioprinting for drug research

Jing Liu 1 id , Ying Zhao 1 id , Bihan Ren 1 id , Dingming Li 1 id , Tianma He 1 id ,
Haizhongshi Zhang 1 id , Zhenlei Zhang 1 id , and Haochen Liu *
2 id
1 Department of Biological Engineering, School of Biology, Food and Environment, Hefei University,
Hefei, Anhui, China
2 Department of Cardiovascular Surgery, Xi’an Children’s Hospital, Xi’an, Shaanxi, China

Abstract

Current in vitro tumor models often fail to recapitulate the hierarchical vascular
architecture and dynamic interactions of the tumor microenvironment (TME),
limiting their utility in cancer research. In this study, we present a multiscale
vascularized tumor model integrating coaxial bioprinting, inkjet printing, and fused
deposition modeling (FDM) to address this challenge. Firstly, coaxial bioprinting
enabled the fabrication of dual-layered vasculature with an endothelium layer and
a smooth muscle layer. Secondly, tumor spheroids with precise size control (±10
μm) were generated via inkjet printing by modulating Methacrylate Gelatin (GelMA)
concentration and valve actuation time. An FDM-printed chip was designed to co-
culture these components under perfusion, facilitating the self-organization of a
microvascular network around tumor spheroids. After 11 days of dynamic culture,
*Corresponding author: the model demonstrated tumor-driven angiogenic sprouting and early metastatic
Haochen Liu behavior, validated by the upregulation of metastasis-related genes (CD44, MMP2,
(haochen1010@163.com) N-cadherin) in vascularized cohorts. Drug testing with paclitaxel revealed dose-
Citation: Liu J, Zhao Y, Ren B, dependent suppression of tumor proliferation and invasion. This platform not only
et al. Multiscale vascularized mimics the structural and functional complexity of the TME but also provides a
tumor-on-a-chip via bioprinting scalable, physiologically relevant tool for investigating tumor–vascular crosstalk and
for drug research.
Int J Bioprint. 2025;11(4):378-391. evaluating anti-cancer therapeutics.
doi: 10.36922/IJB025180180
Received: May 1, 2025 Keywords: 3D bioprinting; Coaxial printing; Drug research; Inkjet printing;
1st revised: June 11, 2025
2nd revised: June 24, 2025 Tumor-on-a-chip; Vascularized tumor model
3rd revised: June 26, 2025
Accepted: June 26, 2025
Published online: June 26, 2025
Copyright: © 2025 Author(s). 1. Introduction
This is an Open Access article
distributed under the terms of the Cancer is currently the second leading cause of death worldwide, following cardiovascular
Creative Commons Attribution diseases. According to the World Health Organization, nearly 10 million cancer-related
License, permitting distribution
and reproduction in any medium, deaths were reported globally in 2022, accounting for one-sixth of total mortality, with
provided the original work is a rising prevalence in underdeveloped regions. Despite significant advances in cancer
1
properly cited. research, the molecular mechanisms underlying tumorigenesis and progression remain
Publisher’s Note: AccScience poorly understood, contributing to the high failure rate and exorbitant costs of anti-cancer
Publishing remains neutral with drug development. A major challenge lies in the lack of in vitro models that accurately
2
regard to jurisdictional claims in
published maps and institutional replicate the human tumor microenvironment (TME), leading to discrepancies between
3
affiliations. preclinical drug testing and clinical outcomes. The TME is a highly dynamic ecosystem,

Volume 11 Issue 4 (2025) 378 doi: 10.36922/IJB025180180