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

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.

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