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Advances in Organ-on-Chip

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 10360

Special Issue Editor


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Guest Editor
Department of Biomedical Engineering, Korea University, Seoul 02481, Republic of Korea
Interests: organ on a chip; intervertebral disc (IVD) degeneration; photobiomodulation; electroceuticals; vagus nerve stimulation (VNS)
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Special Issue Information

Dear Colleagues,

Since the intricacy of the physiological environment cannot be replicated in 2D on in vitro cell culture platforms similar to Petri dishes or microplates, they provide an inaccurate depiction of human or animal physiology. The extracellular matrix, neighbouring cells and mechanical stimuli generated by flow, concentration gradients, and movement all contribute molecular signals to the cellular microenvironment that cells are highly attuned to. When cultures are kept stationary in well plates, the mechanical and biological cues nearly completely disappear. The 3D environment can be recreated by seeding cells more densely on scaffolds. This increased cell density, however, necessitates the careful consideration of food and oxygen delivery, especially for long-term culture experiments. Media flow can be included to overcome this restriction, but it makes the design of the cell culture chamber much more complicated, so that flow-induced stress can be predicted and controlled. When dealing with flow systems, it is also important to address practical concerns, such as preventing leaks and obstructions. The addition of flow enables the coupling of numerous chambers, allowing for more complex coculture models and studies of crosstalk between different tissues to be built.

For this Special Issue, we are looking for submissions that fit the following theme: any type of cell that can be used in a novel approach using 3D environment models to overcome limitations of 2D in vitro cell culture platforms.

Prof. Dr. Hyuk William Choi
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • organ-on-chip
  • 3D cultures on scaffolds
  • high-throughput screening
  • organoids
  • coculturing cells
  • in vitro human tissue model
  • nanopatterned substrates
  • 3D bioprinting
  • induced pluripotent stem cells
  • drug discovery

Published Papers (4 papers)

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Research

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15 pages, 3646 KiB  
Article
Engineered Human Intervertebral Disc Model Inducing Degenerative Microglial Proinflammation
by Min-Ho Hwang, You Jung Kang, Hyeong-Guk Son, Hansang Cho and Hyuk Choi
Int. J. Mol. Sci. 2022, 23(20), 12216; https://doi.org/10.3390/ijms232012216 - 13 Oct 2022
Viewed by 1593
Abstract
Degeneration of the intervertebral disc (IVD) is a major contributor to low back pain (LBP). IVD degeneration is characterized by abnormal production of inflammatory cytokines secreted by IVD cells. Although the underlying molecular mechanisms of LBP have not been elucidated, increasing evidence suggests [...] Read more.
Degeneration of the intervertebral disc (IVD) is a major contributor to low back pain (LBP). IVD degeneration is characterized by abnormal production of inflammatory cytokines secreted by IVD cells. Although the underlying molecular mechanisms of LBP have not been elucidated, increasing evidence suggests that LBP is associated particularly with microglia in IVD tissues and the peridiscal space, aggravating the cascade of degenerative events. In this study, we implemented our microfluidic chemotaxis platform to investigate microglial inflammation in response to our reconstituted degenerative IVD models. The IVD models were constructed by stimulating human nucleus pulposus (NP) cells with interleukin-1β and producing interleukin-6 (129.93 folds), interleukin-8 (18.31 folds), C-C motif chemokine ligand-2 (CCL-2) (6.12 folds), and CCL-5 (5.68 folds). We measured microglial chemotaxis (p < 0.05) toward the conditioned media of the IVD models. In addition, we observed considerable activation of neurodegenerative and deactivation of protective microglia via upregulated expression of CD11b (p < 0.001) and down-regulation of CD206 protein (p < 0.001) by soluble factors from IVD models. This, in turn, enhances the inflammatory milieu in IVD tissues, causing matrix degradation and cellular damage. Our findings indicate that degenerative IVD may induce degenerative microglial proinflammation, leading to LBP development. Full article
(This article belongs to the Special Issue Advances in Organ-on-Chip)
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14 pages, 4326 KiB  
Article
Microfluidic Electroceuticals Platform for Therapeutic Strategies of Intervertebral Disc Degeneration: Effects of Electrical Stimulation on Human Nucleus Pulposus Cells under Inflammatory Conditions
by Tae-Won Kim, An-Gi Kim, Kwang-Ho Lee, Min-Ho Hwang and Hyuk Choi
Int. J. Mol. Sci. 2022, 23(17), 10122; https://doi.org/10.3390/ijms231710122 - 4 Sep 2022
Cited by 2 | Viewed by 1861
Abstract
The degeneration of an intervertebral disc (IVD) is a major cause of lower back pain. IVD degeneration is characterized by the abnormal expression of inflammatory cytokines and matrix degradation enzymes secreted by IVD cells. In addition, macrophage-mediated inflammation is strongly associated with IVD [...] Read more.
The degeneration of an intervertebral disc (IVD) is a major cause of lower back pain. IVD degeneration is characterized by the abnormal expression of inflammatory cytokines and matrix degradation enzymes secreted by IVD cells. In addition, macrophage-mediated inflammation is strongly associated with IVD degeneration. However, the precise pathomechanisms of macrophage-mediated inflammation in IVD are still unknown. In this study, we developed a microfluidic platform integrated with an electrical stimulation (ES) array to investigate macrophage-mediated inflammation in human nucleus pulposus (NP). This platform provides multiple cocultures of different cell types with ES. We observed macrophage-mediated inflammation and considerable migration properties via upregulated expression of interleukin (IL)-6 (p < 0.001), IL-8 (p < 0.05), matrix metalloproteinase (MMP)-1 (p < 0.05), and MMP-3 (p < 0.05) in human NP cells cocultured with macrophages. We also confirmed the inhibitory effects of ES at 10 μA due to the production of IL-6 (p < 0.05) and IL-8 (p < 0.01) under these conditions. Our findings indicate that ES positively affects degenerative inflammation in diverse diseases. Accordingly, the microfluidic electroceutical platform can serve as a degenerative IVD inflammation in vitro model and provide a therapeutic strategy for electroceuticals. Full article
(This article belongs to the Special Issue Advances in Organ-on-Chip)
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Review

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14 pages, 1140 KiB  
Review
Towards a More Realistic In Vitro Meat: The Cross Talk between Adipose and Muscle Cells
by Margherita Pallaoro, Silvia Clotilde Modina, Andrea Fiorati, Lina Altomare, Giorgio Mirra, Paola Scocco and Alessia Di Giancamillo
Int. J. Mol. Sci. 2023, 24(7), 6630; https://doi.org/10.3390/ijms24076630 - 1 Apr 2023
Viewed by 2584
Abstract
According to statistics and future predictions, meat consumption will increase in the coming years. Considering both the environmental impact of intensive livestock farming and the importance of protecting animal welfare, the necessity of finding alternative strategies to satisfy the growing meat demand is [...] Read more.
According to statistics and future predictions, meat consumption will increase in the coming years. Considering both the environmental impact of intensive livestock farming and the importance of protecting animal welfare, the necessity of finding alternative strategies to satisfy the growing meat demand is compelling. Biotechnologies are responding to this demand by developing new strategies for producing meat in vitro. The manufacturing of cultured meat has faced criticism concerning, above all, the practical issues of culturing together different cell types typical of meat that are partly responsible for meat’s organoleptic characteristics. Indeed, the existence of a cross talk between adipose and muscle cells has critical effects on the outcome of the co-culture, leading to a general inhibition of myogenesis in favor of adipogenic differentiation. This review aims to clarify the main mechanisms and the key molecules involved in this cross talk and provide an overview of the most recent and successful meat culture 3D strategies for overcoming this challenge, focusing on the approaches based on farm-animal-derived cells. Full article
(This article belongs to the Special Issue Advances in Organ-on-Chip)
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27 pages, 55669 KiB  
Review
The Gut–Organ-Axis Concept: Advances the Application of Gut-on-Chip Technology
by Yuxi Guo, Xuefeng Chen, Pin Gong, Guoliang Li, Wenbo Yao and Wenjuan Yang
Int. J. Mol. Sci. 2023, 24(4), 4089; https://doi.org/10.3390/ijms24044089 - 17 Feb 2023
Cited by 20 | Viewed by 3918
Abstract
The intestine is considered to be a vital digestive organ to absorb nutrients and is the largest immune organ, while numerous microorganisms coexist with the host. It is well known that the complex interactions between the gut microbiota and the host’s immune system [...] Read more.
The intestine is considered to be a vital digestive organ to absorb nutrients and is the largest immune organ, while numerous microorganisms coexist with the host. It is well known that the complex interactions between the gut microbiota and the host’s immune system inevitably affect the function of other organs, creating an “axis” between them. During the past few years, a new technique based mainly on microfluidics and cell biology has been developed to emulate the structure, function, and microenvironment of the human gut, called the “gut-on-chip”. This microfluidic chip provides insight into key aspects of gut function in health and disease, such as the gut–brain axis, gut–liver axis, gut–kidney axis, and gut–lung axis. In this review, we first describe the basic theory of the gut axis and the various composition and parameter monitoring of the gut microarray systems, as well as summarize the development and emerging advances in the gut–organ-on-chip, with a focus on the host-gut flora and nutrient metabolism, and highlight their role in pathophysiological studies. In addition, this paper discusses the challenges and prospects for the current development and further use of the gut–organ-on-chip platform. Full article
(This article belongs to the Special Issue Advances in Organ-on-Chip)
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