Development of a Hybrid Polymer-Based Microfluidic Platform for Culturing Hepatocytes towards Liver-on-a-Chip Applications.

Gulsim Kulsharova,Akbota Kurmangaliyeva,Elvira Darbayeva,Galiya Toxeitova,Luis Rojas-Solórzano

doi:10.3390/polym13193215

Abstract

The drug development process can greatly benefit from liver-on-a-chip platforms aiming to recapitulate the physiology, mechanisms, and functionalities of liver cells in an in vitro environment. The liver is the most important organ in drug metabolism investigation. Here, we report the development of a hybrid cyclic olefin copolymer (COC) and polydimethylsiloxane (PDMS) microfluidic (HCP) platform to culture a Huh7 hepatoma cell line in dynamic conditions towards the development of a liver-on-a-chip system. The microfluidic platform is comprised of a COC bottom layer with a microchannel and PDMS-based flat top layer sandwiched together. The HCP device was applied for culturing Huh7 cells grown on a collagen-coated microchannel. A computational fluid dynamics modeling study was conducted for the HCP device design revealing the presence of air volume fraction in the chamber and methods for optimizing experimental handling of the device. The functionality and metabolic activity of perfusion culture were assessed by the secretion rates of albumin, urea, and cell viability visualization. The HCP device hepatic culture remained functional and intact for 24 h, as assessed by resulting levels of biomarkers similar to published studies on other in vitro and 2D cell models. The present results provide a proof-of-concept demonstration of the hybrid COC–PDMS microfluidic chip for successfully culturing a Huh7 hepatoma cell line, thus paving the path towards developing a liver-on-a-chip platform.

Highlights

Microphysiological platforms such as liver-on-a-chip (LOC) devices have the potential to reduce the costs of drug testing and the number of animal models used in drug development [1]
Since in this work we focus on cell functionality and growth in the developed hybrid cyclic olefin copolymer (COC)–PDMS device and not on drug metabolism studies, the Huh7 cultured COC–PDMS platform holds great potential for developing a robust and reproducible liver-on-a-chip that can be applied to other types of cells for drug metabolism studies
Liver-on-a-chip (LOC) microfluidic platforms recapitulating certain organ characteristics can help accelerate the drug development field and reduce animal models used in drug testing

Summary

Introduction

Microphysiological platforms such as liver-on-a-chip (LOC) devices have the potential to reduce the costs of drug testing and the number of animal models used in drug development [1]. Perfusion in LOC platforms aims to emulate the in vivo dynamic flow environment in the liver It can stimulate liver cell functions, including protein synthesis, carbohydrate transformations, detoxification, and hormone production in the human body [2]. One of the most commonly used materials in microfluidics and microphysiological platforms is polydimethylsiloxane (PDMS) It is low-cost, easy to use in soft lithography, optically transparent, highly elastic, gas permeable, and suitable for long-term cell culture in closed chambers [4]. Its disadvantages, such as hydrophobicity and drug metabolites’ absorbance, have been well established [5]

Methods

Results

Conclusion