AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB025180180
RESEARCH ARTICLE

Multiscale vascularized tumor-on-a-chip via bioprinting for drug research

Jing Liu1 Ying Zhao1 Bihan Ren1 Dingming Li1 Tianma He1 Haizhongshi Zhang1 Zhenlei Zhang1 Haochen Liu2*
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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
Received: 1 May 2025 | Accepted: 26 June 2025 | Published online: 26 June 2025
© 2025 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/ )
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, the model demonstrated tumor-driven angiogenic sprouting and early metastatic behavior, validated by the upregulation of metastasis-related genes (CD44, MMP2, N-cadherin) in vascularized cohorts. Drug testing with paclitaxel revealed dose-dependent suppression of tumor proliferation and invasion. This platform not only mimics the structural and functional complexity of the TME but also provides a scalable, physiologically relevant tool for investigating tumor–vascular crosstalk and evaluating anti-cancer therapeutics.  

Graphical abstract
Keywords
3D bioprinting
Coaxial printing
Drug research
Inkjet printing
Tumor-on-a-chip
Vascularized tumor model
Funding
This research was funded by the University Natural Science Research Project of Anhui Province (grant number: 2024AH051533), the Talent Research Foundation of Hefei University (grant number: 21-22RC26), the Natural Science Foundation of Hubei Province (grant number: 2023AFB411), and the Talent Research Foundation of Hefei University (grant number: 20RC40).
Conflict of interest
The authors declare that they have no financial and personal relationships with other people or organizations that can inappropriately influence the study. They also have no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in, or the review of, the article.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing