Cell-Based Microfluidic Device Utilizing Cell Sheet Technology.

Katsuhisa Sakaguchi,Tatsuya Shimizu,Shinjiro Umezu,Masanori Takaira,Ryu-Ichiro Tanaka,Kei Akimoto

doi:10.34133/2022/9758187

Abstract

The development of microelectromechanical systems has resulted in the rapid development of polydimethylpolysiloxane (PDMS) microfluidic devices for drug screening models. Various cell functions, such as the response of endothelial cells to fluids, have been elucidated using microfluidic devices. Additionally, organ-on-a-chip systems that include organs that are important for biological circulation, such as the heart, liver, pancreas, kidneys, and brain, have been developed. These organs realize the biological circulation system in a manner that cannot be reproduced by artificial organs; however, the flow channels between the organs are often artificially created by PDMS. In this study, we developed a microfluidic device consisting only of cells, by combining cell sheet technology with microtitanium wires. Microwires were placed between stacked fibroblast cell sheets, and the cell sheets adhered to each other, after which the microwires were removed leaving a luminal structure with a size approximately equal to the arteriolar size. The lumen structure was constructed using wires with diameters of 50, 100, 150, and 200 μm, which were approximations of the arteriole diameters. Furthermore, using a perfusion device, we successfully perfused the luminal structure created inside the cell sheets. The results revealed that a culture solution can be supplied to a cell sheet with a very high cell density. The biofabrication technology proposed in this study can contribute to the development of organ-on-a-chip systems.

Highlights

Microfluidic devices, such as organ-on-a-chip systems, are rapidly being developed to identify drug effects and obtain biological knowledge in vitro, without conducting animal experiments [1, 2]
Many of the microfluidic devices used as drug screening models are made of PDMS, with the channel elasticity and permeability of the culture solution differing from those in vivo
These images confirm that a luminal structure was created where the titanium wire was pinched

Summary

Introduction

Microfluidic devices, such as organ-on-a-chip systems, are rapidly being developed to identify drug effects and obtain biological knowledge in vitro, without conducting animal experiments [1, 2]. By using the drug discovery model in organ-on-chip systems, an environment closer to the living body can be created by passing the drug through blood vessels constructed by cells before reaching the target organ. It improves vascular function such as fibroblasts and endothelial cells lined with pericyte and secrete cytokines and antithrombotic proteins to maintain target organ function [9, 10]. This study investigated whether a microchannel device consisting only of cells can be created using cell sheet technology This is a tissue engineering technique wherein cells are transformed into a sheet using a culture dish, onto which a polymer whose affinity for water changes in response to temperature is grafted.

Methods

Discussion

Conclusion