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

Despite the systemic spread of cancer, the ventricular myocardium remains one of the least common sites of metastasis—a phenomenon that remains poorly understood. 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. Overall, this platform provides a new approach for uncovering organ-specific drivers of metastasis and cardiac resistance to metastasis, paving the way for future discovery of metastasis-inhibiting therapies.