MInD: Multi-organ Invasion Device incorporating a 3D printed granular elastomer reveals cardiac resistance to cancer metastasis

To investigate this, we developed the Multi-organ Invasion Device (MInD), a dynamic organ-on-a-chip platform that enables multi-organ culture under flow. Organ compartments are connected in MInD using PermeoTubes—3D-printed conduits with multi-scale fractal porosity fabricated from a granular poly(octamethylene maleate (anhydride) citrate) (POMaC) ink to impart viscoelasticity and ECM-mimetic permeability that supported cancer cell intravasation, migration, and extravasation.

Highly aggressive breast cancer cells preferentially invaded hepatic tissue, while invasion into cardiac tissue was markedly suppressed in both co- and tri-organ culture. Cytokine profiling and RNA sequencing revealed that cardiac co-culture downregulated pro-metastatic and immunosuppressive cytokines and upregulated immune-activating and anti-invasive genes. In contrast, hepatic co-culture promoted matrix remodeling, angiogenesis, and immune suppression.