Microfluidics: Tissue Chips and Microphysiological Systems

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "B:Biology and Biomedicine".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 21463

Special Issue Editors


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Guest Editor
Departments of Medicine and Biomedical Engineering, School of Engineering and School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Interests: microfluidics; bioMEMS; tissue engineering; tissue chips; microphysiological systems
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Guest Editor
Department of Mechanical Engineering and McMaster School of Biomedical Engineering, McMaster University, Hamilton, ON L8S 4L7, Canada
Interests: micro/nanofabrication; bioprinting; biomedical microdevices; microelectromechanical systems; microfluidics; medical and environmental sensors; smart textiles; biomaterials; artificial organs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Regulatory approval of a single drug using the current drug discovery process costs ~ $800 million and takes ~ 15 years. A major limitation is the translation of results from animal models to patients. Nearly 30% of drugs are found to be toxic in humans despite being found to be safe in animal models wheras another 60% of drugs fail due to lack of efficacy due to interspecies differences in drug metabolizing enzymes. Therefore, there is significant interest in developing human models of human disease to overcome shortcomings with animal models. In the past few years, several major funding agencies including the NIH, DoD, NSF and CASIS have pushed for the development of Human Tissue Chip (TC) models that utilize either primary human cells or human induced pluripotent stem cell (hiPSC) derived cells. Physiologically relevant 3D TCs closely mimic organ/tissue -like structural organization, along with critical aspects of the native tissue environment to replicate in-vivo function. The ultimate goal is to combine multiple TCs together to form complex Microphysiological Systems (MPS) for drug screening and disease modeling. Microfluidic techniques provide unique tools to engineer complex tissue, providing opportunities to incorporate perfusion networks at the capillary scale, scaffolds for organization of complex 3D tissue architectures and incorporation of on-chip sensors/detectors for non-destructive readouts. Microfluidic networks can also enable communication between multiple TCs within a circulatory network. This special edition solicits original research articles, reviews, and opinions focused on the use of microfluidic technologies to construct TCs and /or integrate multiple TCs within a MPS.

Prof. Dr. Palaniappan Sethu
Prof. P. Ravi Selvaganapathy
Guest Editors

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Keywords

  • Tissue Chips
  • Microphysiological Systems
  • Microfluidics
  • In-vitro Models

Published Papers (5 papers)

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Research

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10 pages, 14821 KiB  
Article
Investigating the Function of Adult DRG Neuron Axons Using an In Vitro Microfluidic Culture System
by Rahul Atmaramani, Srivennela Veeramachaneni, Liz Valeria Mogas, Pratik Koppikar, Bryan J. Black, Audrey Hammack, Joseph J. Pancrazio and Rafael Granja-Vazquez
Micromachines 2021, 12(11), 1317; https://doi.org/10.3390/mi12111317 - 27 Oct 2021
Cited by 6 | Viewed by 3305
Abstract
A critical role of the peripheral axons of nociceptors of the dorsal root ganglion (DRG) is the conduction of all-or-nothing action potentials from peripheral nerve endings to the central nervous system for the perception of noxious stimuli. Plasticity along multiple sites along the [...] Read more.
A critical role of the peripheral axons of nociceptors of the dorsal root ganglion (DRG) is the conduction of all-or-nothing action potentials from peripheral nerve endings to the central nervous system for the perception of noxious stimuli. Plasticity along multiple sites along the pain axis has now been widely implicated in the maladaptive changes that occur in pathological pain states such as neuropathic and inflammatory pain. Notably, increasing evidence suggests that nociceptive axons actively participate through the local expression of ion channels, receptors, and signal transduction molecules through axonal mRNA translation machinery that is independent of the soma component. In this report, we explore the sensitization of sensory neurons through the treatment of compartmentalized axon-like structures spanning microchannels that have been treated with the cytokine IL-6 and, subsequently, capsaicin. These data demonstrate the utility of isolating DRG axon-like structures using microfluidic systems, laying the groundwork for constructing the complex in vitro models of cellular networks that are involved in pain signaling for targeted pharmacological and genetic perturbations. Full article
(This article belongs to the Special Issue Microfluidics: Tissue Chips and Microphysiological Systems)
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14 pages, 1422 KiB  
Article
Ultrasound-Based Scaffold-Free Core-Shell Multicellular Tumor Spheroid Formation
by Karl Olofsson, Valentina Carannante, Madoka Takai, Björn Önfelt and Martin Wiklund
Micromachines 2021, 12(3), 329; https://doi.org/10.3390/mi12030329 - 20 Mar 2021
Cited by 9 | Viewed by 3281
Abstract
In cancer research and drug screening, multicellular tumor spheroids (MCTSs) are a popular model to bridge the gap between in vitro and in vivo. However, the current techniques to culture mixed co-culture MCTSs do not mimic the structural architecture and cellular spatial distribution [...] Read more.
In cancer research and drug screening, multicellular tumor spheroids (MCTSs) are a popular model to bridge the gap between in vitro and in vivo. However, the current techniques to culture mixed co-culture MCTSs do not mimic the structural architecture and cellular spatial distribution in solid tumors. In this study we present an acoustic trapping-based core-shell MCTSs culture method using sequential seeding of the core and shell cells into microwells coated with a protein repellent coating. Scaffold-free core-shell ovarian cancer OVCAR-8 cell line MCTSs were cultured, stained, cleared and confocally imaged on-chip. Image analysis techniques were used to quantify the shell thickness (23.2 ± 1.8 µm) and shell coverage percentage (91.2 ± 2.8%). We also show that the shell thickness was evenly distributed over the MCTS cores with the exception of being slightly thinner close to the microwell bottom. This scaffold-free core-shell MCTSs formation technique and the analysis tools presented herein could be used as an internal migration assay within the MCTS or to form core-shell MCTS co-cultures to study therapy response or the interaction between tumor and stromal cells. Full article
(This article belongs to the Special Issue Microfluidics: Tissue Chips and Microphysiological Systems)
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11 pages, 13308 KiB  
Article
Patterning Biological Gels for 3D Cell Culture inside Microfluidic Devices by Local Surface Modification through Laminar Flow Patterning
by Joshua Loessberg-Zahl, Jelle Beumer, Albert van den Berg, Jan C. T. Eijkel and Andries D. van der Meer
Micromachines 2020, 11(12), 1112; https://doi.org/10.3390/mi11121112 - 16 Dec 2020
Cited by 9 | Viewed by 5463
Abstract
Microfluidic devices are used extensively in the development of new in vitro cell culture models like organs-on-chips. A typical feature of such devices is the patterning of biological hydrogels to offer cultured cells and tissues a controlled three-dimensional microenvironment. A key challenge of [...] Read more.
Microfluidic devices are used extensively in the development of new in vitro cell culture models like organs-on-chips. A typical feature of such devices is the patterning of biological hydrogels to offer cultured cells and tissues a controlled three-dimensional microenvironment. A key challenge of hydrogel patterning is ensuring geometrical confinement of the gel, which is generally solved by inclusion of micropillars or phaseguides in the channels. Both of these methods often require costly cleanroom fabrication, which needs to be repeated even when only small changes need be made to the gel geometry, and inadvertently expose cultured cells to non-physiological and mechanically stiff structures. Here, we present a technique for facile patterning of hydrogel geometries in microfluidic chips, but without the need for any confining geometry built into the channel. Core to the technique is the use of laminar flow patterning to create a hydrophilic path through an otherwise hydrophobic microfluidic channel. When a liquid hydrogel is injected into the hydrophilic region, it is confined to this path by the surrounding hydrophobic regions. The various surface patterns that are enabled by laminar flow patterning can thereby be rendered into three-dimensional hydrogel structures. We demonstrate that the technique can be used in many different channel geometries while still giving the user control of key geometric parameters of the final hydrogel. Moreover, we show that human umbilical vein endothelial cells can be cultured for multiple days inside the devices with the patterned hydrogels and that they can be stimulated to migrate into the gel under the influence of trans-gel flows. Finally, we demonstrate that the patterned gels can withstand trans-gel flow velocities in excess of physiological interstitial flow velocities without rupturing or detaching. This novel hydrogel-patterning technique addresses fundamental challenges of existing methods for hydrogel patterning inside microfluidic chips, and can therefore be applied to improve design time and the physiological realism of microfluidic cell culture assays and organs-on-chips. Full article
(This article belongs to the Special Issue Microfluidics: Tissue Chips and Microphysiological Systems)
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11 pages, 3535 KiB  
Article
Measuring Surface and Interfacial Tension In Situ in Microdripping Mode for Electrohydrodynamic Applications
by Karim I. Budhwani, Gerald M. Pekmezi and Mohamed M. Selim
Micromachines 2020, 11(7), 687; https://doi.org/10.3390/mi11070687 - 16 Jul 2020
Cited by 2 | Viewed by 2929
Abstract
Walking on water is made possible, at least for tiny insects, by molecular interaction at the interfaces of dissimilar materials. Impact of these interactions—surface tension (SFT) and, more broadly, interfacial tension (IFT)—is particularly evident at micro and nano sizescales. Thus, implications of walking [...] Read more.
Walking on water is made possible, at least for tiny insects, by molecular interaction at the interfaces of dissimilar materials. Impact of these interactions—surface tension (SFT) and, more broadly, interfacial tension (IFT)—is particularly evident at micro and nano sizescales. Thus, implications of walking on water can be significant for SFT or IFT (S/IFT)-driven nanofabrication technologies, such as electrohydrodynamic atomization (EHDA), in developing next generation biomimetic microphysiological systems (MPS) and drug delivery systems (DDS). However, current methods for estimating S/IFT, based on sessile drops or new surface formation on a ring or plate, are unsuitable for integration with EHDA assemblies used in electrospinning and electrospraying. Here, we show an in situ method for estimating S/IFT specifically devised for EHDA applications using signal processing algorithms that correlate the frequency and periodicity of liquid dispensed in EHDA microdripping mode with numerical solutions from computational fluid dynamics (CFD). Estimated S/IFT was generally in agreement with published ranges for water–air, 70% ethanol–air, chloroform–air, and chloroform–water. SFT for solutions with surfactants decreased with increasing concentrations of surfactant, but at relatively higher than published values. This was anticipated, considering that established methods measure SFT at boundaries with asymmetrically high concentrations of surfactants which lower SFT. Full article
(This article belongs to the Special Issue Microfluidics: Tissue Chips and Microphysiological Systems)
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Review

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35 pages, 7508 KiB  
Review
Tissue Chips and Microphysiological Systems for Disease Modeling and Drug Testing
by Leslie Donoghue, Khanh T. Nguyen, Caleb Graham and Palaniappan Sethu
Micromachines 2021, 12(2), 139; https://doi.org/10.3390/mi12020139 - 28 Jan 2021
Cited by 11 | Viewed by 5683
Abstract
Tissue chips (TCs) and microphysiological systems (MPSs) that incorporate human cells are novel platforms to model disease and screen drugs and provide an alternative to traditional animal studies. This review highlights the basic definitions of TCs and MPSs, examines four major organs/tissues, identifies [...] Read more.
Tissue chips (TCs) and microphysiological systems (MPSs) that incorporate human cells are novel platforms to model disease and screen drugs and provide an alternative to traditional animal studies. This review highlights the basic definitions of TCs and MPSs, examines four major organs/tissues, identifies critical parameters for organization and function (tissue organization, blood flow, and physical stresses), reviews current microfluidic approaches to recreate tissues, and discusses current shortcomings and future directions for the development and application of these technologies. The organs emphasized are those involved in the metabolism or excretion of drugs (hepatic and renal systems) and organs sensitive to drug toxicity (cardiovascular system). This article examines the microfluidic/microfabrication approaches for each organ individually and identifies specific examples of TCs. This review will provide an excellent starting point for understanding, designing, and constructing novel TCs for possible integration within MPS. Full article
(This article belongs to the Special Issue Microfluidics: Tissue Chips and Microphysiological Systems)
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