Variable Tumor Microenvironment-on-a-chip with Temporal Angiogenic Switching System by Diffusion Control

Abstract

Organ-on-a-chip has the potential to replace preclinical trials which have been problematic for decades due to unaffordable cost and time. The performance of in vitro tumor-on-a-chip depends on how accurately the system represents analogous tumor-microenvironment (TME) and TME associated phenomena. In this study, we have focused on angiogenesis, one of the most significant features of TME for tumor growth and metastasis. Angiogenesis in TME is triggered through cascaded interactions among TME associated neighboring cells including immune cells, tumor cells, and fibroblast cells [1]. Therefore, temporally-controlled TME-on-achip is desired for an accurate representation of angiogenesis. However, conventional microfluidic devices cannot temporarily manipulate the condition of interacting cells and secreted signal molecules. Here, we proposed a hydrogel-based variable TME-on- a-chip with diffusion switch channels. The channels between hydrogel walls enable temporal diffusion control by controlling inflow. The diffusion control was observed in diffusion experiment with a fluorescent dye. Furthermore, experiment of HUVEC's migration toward diffused VEGF also confirmed that TME-on-a-chip is capable of reproducing an angiogenic switch triggering through temporal diffusion control. Due to a simple fabrication procedure, the design of the microfluidic device can be easily modified to represent more complex variable TME models.