Spheroid Engineering in Microfluidic Devices

Abstract

cell culture techniques are commonly employed to investigate biophysical and biochemical cellular responses. However, these culture methods, having monolayer cells, lack cell−cell and cell−extracellular matrix interactions, mimicking the cell microenvironment and multicellular organization. Three-dimensional (3D) cell culture methods enable equal transportation of nutrients, gas, and growth factors among cells and their microenvironment. Therefore, 3D cultures show similar cell proliferation, apoptosis, and differentiation properties to in vivo. A spheroid is defined as self-assembled 3D cell aggregates, and it closely mimics a cell microenvironment in vitro thanks to cell−cell/matrix interactions, which enables its use in several important applications in medical and clinical research. To fabricate a spheroid, conventional methods such as liquid overlay, hanging drop, and so forth are available. However, these labor-intensive methods result in low-throughput fabrication and uncontrollable spheroid sizes. On the other hand, microfluidic methods enable inexpensive and rapid fabrication of spheroids with high precision. Furthermore, fabricated spheroids can also be cultured in microfluidic devices for controllable cell perfusion, simulation of fluid shear effects, and mimicking of the microenvironment-like in vivo conditions. This review focuses on recent microfluidic spheroid fabrication techniques and also organ-on-a-chip applications of spheroids, which are used in different disease modeling and drug development studies.

Rocking- and diffusion-based culture of tumor spheroids-on-a-chip

“…In this regard, due to its simplicity, flexibility, versatility, and costeffectiveness the device configuration we proposed is potentially useful for further investigations toward both clinical and preclinical applications. [44][45][46][47][48][49]…”

Breaking the clean room barrier: exploring low-cost alternatives for microfluidic devices

“…Hydrogels are a versatile class of materials composed of cross-linked polymeric chains that have the remarkable ability to store a significant amount of water ( Sharma & Tiwari, 2020 ; Bento et al, 2023 ; Tevlek et al, 2023 ). One of their most notable characteristics is their high degree of porosity, which makes them highly responsive to external stimuli such as temperature, pH, and ionic strength ( García-Torres et al, 2022 ; Camman et al, 2023 ).…”

Twenty years of islet-on-a-chip: microfluidic tools for dissecting islet metabolism and function

“…Islet-ona-chip devices have been used to recreate multiple islet populations 37 and enhance the formation of stem cellderived islet organoids. [38][39][40][41] We now review the various isleton-a-chip platforms developed for manipulating the microenvironment to compare various treatments, 42 create glucose gradients, 43 reaggregate tissue, and generate stem cell-derived islet organoids. These devices were often designed with optical windows to simultaneously measure islet morphology and function by microscopic imaging.…”