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InVADE: Integrated Vasculature for Assessing Dynamic Events
Author(s) -
Lai Benjamin Fook Lun,
Huyer Locke Davenport,
Lu Rick Xing Ze,
Drecun Stasja,
Radisic Milica,
Zhang Boyang
Publication year - 2017
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201703524
Subject(s) - metastasis , crosstalk , perfusion , scaffold , biomedical engineering , cancer research , pathology , biology , materials science , cancer , medicine , physics , optics
Drug screening with simplified 2D cell culture and relevant animal testing fail to predict clinical outcomes. With the rising cost of drug development, predictive 3D tissue models with human cells are in urgent demand. Establishing vascular perfusion of 3D tissues has always been a challenge, but it is necessary to mimic drug transport and to capture complex interorgan crosstalk. Here, a versatile multiwell plate is presented empowered by built‐in microfabricated vascular scaffolds that define the vascular space and support self‐assembly of various parenchymal tissues. In this configuration, assembly and organ‐specific function of a metabolically active liver, a free‐contracting cardiac muscle, and a metastatic solid tumor are demonstrated, tracking organ function using noninvasive analysis techniques. By linking the 3D tumor and the liver tissue in series, it is demonstrated that the presence of liver tissue is crucial to correctly reveal the efficacy of a chemotherapeutic drug, Tegafur. Furthermore, the complete cancer metastasis cascade is demonstrated across multiple organs, where cancer cells escaping from the solid tumor can invade a distant liver tissue connected through a continuous vascular interface. This combinatory use of microfabricated scaffold onto a standard cell culturing platform can offer important insights into the mechanics of complex interorgan biological events.