Simultaneous Culturing of Cell Monolayers and Spheroids on a Single Microfluidic Device for Bridging the Gap between 2D and 3D Cell Assays in Drug Research

Abstract

(1 of 11)Two-dimensional (2D) cell cultures have been the primary screening tools to predict drug impacts in vitro for decades. However, owing to the lack of tissuespecific architecture of 2D cultures, secondary screening using three-dimensional (3D) cell culture models is often necessary. A microfluidic approach that facilitates side-by-side 2D and 3D cell culturing in a single microchannel and thus combines the benefits of both set-ups in drug screening; that is, the uniform spatiotemporal distributions of oxygen, nutrients, and metabolic wastes in 2D, and the tissuelike architecture, cell-cell, and cell-extracellular matrix interactions only achieved in 3D. The microfluidic platform is made from an organically modified ceramic material, which is inherently biocompatible and supports cell adhesion (2D culture) and metal adhesion (for integration of impedance electrodes to monitor cell proliferation). To induce 3D spheroid formation on another area, a single-step lithography process is used to fabricate concave microwells, which are made cellrepellant by nanofunctionalization (i.e., plasma porosification and hydrophobic coating). Thanks to the concave shape of the microwells, the spheroids produced on-chip can also be released, with the help of microfluidic flow, for further off-chip characterization after culturing. In this study, the methodology is evaluated for drug cytotoxicity assessment on human hepatocytes.

Biomedical Application of Functional Materials in Organ-on-a-Chip

“…Enhancements in cell adhesion, proliferation, and differentiation in response to clay nanoparticles have been observed in investigation into clay-cell interactions, suggesting the potential for the generation of multifunctional scaffolds for tissue engineering (Dawson and Oreffo, 2013). A UV-curable hybrid ceramic polymer Ormocomp is inherently biocompatible supporting cell adhesion without any additional coating and has been utilized as scaffolds for cell culture (Scheiwe et al, 2015;Järvinen et al, 2020). Ormocomp has excellent transparency for VIS and near UV down to 350 nm.…”

Recent Advances in Microfluidic Platforms for Programming Cell‐Based Living Materials

“…Reproduced under the terms of the Creative Commons CC BY license. [ 179 ] Copyright 2020, The Authors, published by Wiley‐VCH. b) Microfluidic extrusion‐based method for the fabrication of multiple cell layers with hydrogel scaffold.…”

“…Microchamber‐based microfluidic platforms have been used to program cell sheets without scaffolds taking advantage of their unique features for cell culture. Just loading cells into the microfluidic channels/chambers and culturing for a certain time, various cell sheets, such as Caco‐2 cells, [ 177 ] primary porcine aortic endothelial cells, [ 178 ] Huh7 human hepatoma cells, [ 179 ] could be prepared for diverse application. For example, Järvinen et al.…”

“…presented the preparation of cell monolayers and spheroids simultaneously in a microfluidic device with chambers and concave microwells for the assessment of drug cytotoxicity on human hepatocytes (Figure 7a). [ 179 ]…”

Three-Dimensional Cell Culture Models to Study Respiratory Virus Infections Including COVID-19

“…Microfluidic systems produce a high yield of identically sized spheroids in a limited amount of time and devoid of extensive labor [ 56 , 58 ]. They are compatible for use in high throughput screening and analysis and in combination with advances machines where they can be supplied with biosensors for immediate observation and imaging [ 59 ].…”