Sound-based assembly of a microcapillary network in a saturn-like tumor model for drug testing

The tumor microenvironment (TME), consisting of extracellular matrix, proteins, stromal cells, and a vascular system, is reported to have a key role in cancer progression and prognosis. Thereby, the interaction between the vascular network and tumor mass is an important feature of the TME since the anticancer agents which are delivered to the TME can trigger the vascular response and influence the therapeutic outcome of the treatment. To identify and develop new therapeutic strategies, 3D in vitro models that recapitulate the complexity of the TME are urgently needed. Among them, vascularized tumor models are a promising approach, allowing to target tumor angiogenesis and reduce tumor growth. By using sound patterning, cells can be condensed locally into highly reproducible patterns through the action of mild hydrodynamic forces. Here, we use a soundwave-driven cell assembly approach to create a ring-shaped microcapillary network in fibrin hydrogel. Then, we generate a 3D vascularized tumor model by combining a tumor heterotypic spheroid, consisting of fibroblasts and Malignant Pleural Mesothelioma (MPM) cells, with the surrounding vascular ring. Based on its shape, we name it Saturn-like vascularized Tumor Model (STM). The growth of the microcapillary network is monitored over time by fluorescence imaging. The area covered by the microcapillary network, and its continuous increase in presence of the heterotypic tumor spheroid was monitored. Interestingly, this effect is enhanced when treating the STM with the anticancer agent Cisplatin. Overall, we show the use of sound patterning as a fast and cell-friendly approach to spatially organize and condense cells, to generate a 3D in vitro platform from which simple readouts of drug tests can be extracted by image analysis, with the potential to provide a model system for tailored tumor therapy.