3D spheroid-microvasculature-on-a-chip for tumor-endothelium mechanobiology interplay

Abstract

In the final step of cancer metastasis, tumor cells become lodged in a distant capillary bed, where they can undergo extravasation and form a secondary tumor. While increasing evidence suggests blood/lymphatic flow and shear stress play a critical role in the tumor extravasation process, there is a lack of systematic and biomechanical approaches to recapitulate sophisticated 3D microtissue interactions within the controllable hydrodynamic microenvironment. Here, we report a simple-to-use 3D spheroid-microvasculature-on-a-chip (SMAC) model. Under static and controlled flow conditions, the SMAC recapitulates the biomechanical crosstalk between heterogeneous tumor spheroids and the endothelium in a high-throughput and quantitative manners. As an in vitro metastasis mechanobiology model, we discover 3D spheroid-induced endothelial compression and cell-cell junction degradation in the process of tumor migration and expansion. Lastly, we examine the shear stress effects on the endothelial orientation, polarization as well as the tumor spheroid expansion. Taken together, our SMAC model offers a miniaturized, cost-efficient and versatile platform for future investigation on metastasis mechanobiology, enhanced permeability and retention effect and even personalized therapeutic evaluation.

Microvasculature‐on‐a‐Post Chip That Recapitulates Prothrombotic Vascular Geometries and 3D Flow Disturbance

“…[10] Aditionally, we analyzed the orientation of the endothelium in response to shear flow, defined by the angle between the flow direction and the longest axis of an endothelial cell. [11] Under static condition, the endothelial cells in both straight, large and small post regions orientated and polarized randomly, and the addition of flow culture transformed the endothelial alignment parallel to the flow direction (Figure 3A,B; Figure S2A,B, Supporting Information). Compared to the static condition, the proportion of parallelly aligned endothelial cells in the straight region and on the large and small post increased significantly to 94.5%, 66.7%, and 72.4% respectively (Figure 3A,B,G).…”

A microfluidic approach for early prediction of thrombosis in patients with cancer

“…This model offers a controlled hydrodynamic microenvironment and physiologically relevant parameters to study the mechanobiology interplay between tumor spheroids and the endothelium during metastasis. 4 Such techniques provide a valuable platform for investigating cancer-associated interventions with procoagulant properties.…”

“…Microfluidics offers accessible modification and testing of these factors. Platforms such as droplet blood tests, 5 , 6 image-based vessel reconstruction models, 3 and endothelialized microchips 4 , 7 simplify and personalize testing procedures and have the potential for translation into user-friendly products. The success of point-of-care testing (POCT) in the commercialization of COVID-19 rapid antigen testing demonstrates the impact of POCT on healthcare delivery.…”