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

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.

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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