Adaptable Microfluidic Vessel-on-a-Chip Platform for Investigating Tumor Metastatic Transport in Bloodstream

Abstract

Cancer metastasis counts for 90% of cancer fatalities, and its development process is still a mystery. The dynamic process of tumor metastatic transport in the blood vessel is not well understood, in which some biomechanical factors, such as shear stress and various flow patterns, may have significant impacts. Here, we report a microfluidic vessel-on-achip platform for recapitulating several key metastatic steps of tumor cells in blood vessels on the same chip, including intravasation, circulating tumor cell (CTC) vascular adhesion, and extravasation. Due to its excellent adaptability, our system can reproduce various microenvironments to investigate the specific interactions between CTCs and blood vessels. On the basis of this platform, effects of important biomechanical factors on CTC adhesion such as vascular surface properties and vessel geometry-dependent hemodynamics were specifically inspected. We demonstrated that CTC adhesion is more likely to occur under certain mechano-physiological situations, such as vessels with vascular glycocalyx (VGCX) shedding and hemodynamic disturbances. Finally, computational models of both the fluidic dynamics in vessels and CTC adhesion were established based on the confocal scanned 3D images. The modeling results are believed to provide insights into exploring tumor metastasis progression and inspire new ideas for anticancer therapy development.

Application of microfluidic chips in the simulation of the urinary system microenvironment

“…In recent years, considerable progress has been achieved in utilizing microfluidic technology in the research of urinary tumor drug screening, tumor metastasis, and glomerulus-on-chip development [ [127] , [128] , [129] , [130] ]. Microfluidic models of the urinary systems have enriched the understanding of microenvironments from single-cell cultures to co-culture involving two types of cells based on membranes to multicellular co-culture based on microcolumns or 3D biological printing technology.…”

Microfluidic vascular models of tumor cell extravasation

“…Recently, a two-step seeding method was developed to generate perfusable MVNs with physiological-like small diameters, where tumor cell clusters (containing 2-4 cells) were trapped and tracked to monitor extravasation (91). Another vessel-on-a-chip platform was developed to study CTC and endothelium interactions (43). Prostate cancer (PC3) single cells or clusters were perfused through an EC-coated channel with a diameter over 200 µm and extravasated under HGF stimulation.…”

Hierarchical Vessel Network-Supported Tumor Model-on-a-Chip Constructed by Induced Spontaneous Anastomosis

“…The first method builds blood vessels using endothelial cells to line the constructed channels with desired geometries in the hydrogel. With this method, vessels with diameters ranging from a few hundred micrometers to a few millimeters can be achieved. − For example, Kinstlinger et al used sacrificial materials to build millimeter-scale channels in the hydrogel with 3D printing technology. After seeding the human umbilical vein endothelial cells (HUVECs) to fully cover the channel inner surface, a perfusable dendritic vascular network was constructed in vitro.…”

“…After template removal and cell seeding, the patient-derived vessel model could be rapidly reconstituted in vitro for personalized medicine study . These models not only realized 3D vessel–tissue interface but also make it possible to study the vessel–tissue interaction at the cellular level. ,− However, due to the limited resolution of the fabrication technology and the difficulty of perfusing cells into thin channels, it is difficult to construct capillary vessels with complicated structures and diameters below 100 μm …”