Advances in Organs-on-a-Chip Engineering

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Biofabrication and Biomanufacturing".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 10304

Special Issue Editors


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Guest Editor
Associate Professor, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
Interests: organ-on-a-chip; microphysiological system; microfluidics; organoid; drug-screening; disease modeling

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Guest Editor
Professor, Laboratory of Biomaterials and Translational Medicine, Sun Yat-sen University, Guangzhou 510630, China
Interests: biomaterials; controlled-release; microphysiological system; microfluidics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Advances in microfabrication, stem cell technology, tissue engineering, and mathematical modeling have created unprecedented in vitro models—organs-on-a-chip (OOC) systems—to predict risk and efficacy of drugs candidates, and accelerate their steps to the market. Another critical advantage of OOC is its potential to replace, reduce, and refine animal testing. Most recently, the FDA’s alternative methods working group have proposed OOC and microphyisological systems (MPSs) as official models to evaluate drug candidates for IND application and to build disease models. Currently, OOC and MPS have been defined as consisting of engineered miniaturized physiological environments to mimic tissue microenvironments. Micro-tissue units, e.g., self-assembled, differentiated, 3D-printed or tissue-engineered units, were constructed within this microchip and microenvironment, and were engineered to recapitulate the specified/targeted tissue or organ responses. OOC and MPS have been applied in drug evaluation, personalized medicine, disease modeling, space medicine, and many other fields. Highly automated and AI-based OOC systems, integrating cell culture, imaging, and data analysis, are of great interest to OOC researchers and potential users. This Special Issue aims to provide selected contributions on advances in the fabrication, characterization, and application of organs-on-a-chip systems.

Potential topics include, but are not limited to, the following:

  • The development of materials for construction of tissue microenvironment;
  • Organs-on-a-chip system design and fabrication;
  • The development of novel in vitro tissue models;
  • Drug evaluation using OOC or MPS;
  • The development of in vitro disease models;
  • Database for organoid and OOC research;
  • AI-based OOC imaging and data analysis.

Dr. Zaozao Chen
Dr. Mingqiang Li
Guest Editors

Manuscript Submission Information

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Keywords

  • organs-on-a-chip
  • microphysiological system
  • microfluidics
  • organoid
  • drug screening
  • disease modeling

Published Papers (4 papers)

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Research

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21 pages, 6713 KiB  
Article
Multilayer In Vitro Human Skin Tissue Platforms for Quantitative Burn Injury Investigation
by Sean Brocklehurst, Neda Ghousifam, Kameel Zuniga, Danielle Stolley and Marissa Nichole Rylander
Bioengineering 2023, 10(2), 265; https://doi.org/10.3390/bioengineering10020265 - 17 Feb 2023
Cited by 1 | Viewed by 1928
Abstract
This study presents a multilayer in vitro human skin platform to quantitatively relate predicted spatial time–temperature history with measured tissue injury response. This information is needed to elucidate high-temperature, short-duration burn injury kinetics and enables determination of relevant input parameters for computational models [...] Read more.
This study presents a multilayer in vitro human skin platform to quantitatively relate predicted spatial time–temperature history with measured tissue injury response. This information is needed to elucidate high-temperature, short-duration burn injury kinetics and enables determination of relevant input parameters for computational models to facilitate treatment planning. Multilayer in vitro skin platforms were constructed using human dermal keratinocytes and fibroblasts embedded in collagen I hydrogels. After three seconds of contact with a 50–100 °C burn tip, ablation, cell death, apoptosis, and HSP70 expression were spatially measured using immunofluorescence confocal microscopy. Finite element modeling was performed using the measured thermal characteristics of skin platforms to determine the temperature distribution within platforms over time. The process coefficients for the Arrhenius thermal injury model describing tissue ablation and cell death were determined such that the predictions calculated from the time–temperature histories fit the experimental burn results. The activation energy for thermal collagen ablation and cell death was found to be significantly lower for short-duration, high-temperature burns than those found for long-duration, low-temperature burns. Analysis of results suggests that different injury mechanisms dominate at higher temperatures, necessitating burn research in the temperature ranges of interest and demonstrating the practicality of the proposed skin platform for this purpose. Full article
(This article belongs to the Special Issue Advances in Organs-on-a-Chip Engineering)
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15 pages, 3024 KiB  
Article
Evaluation of AMG510 Therapy on KRAS-Mutant Non–Small Cell Lung Cancer and Colorectal Cancer Cell Using a 3D Invasive Tumor Spheroid System under Normoxia and Hypoxia
by Meng Huang, Wei Hou, Jing Zhang, Menglan Li, Zilin Zhang, Xiaoran Li, Zaozao Chen, Cailian Wang and Lihua Yang
Bioengineering 2022, 9(12), 792; https://doi.org/10.3390/bioengineering9120792 - 12 Dec 2022
Cited by 3 | Viewed by 1995
Abstract
A 3D tumor spheroid has been increasingly applied in pharmaceutical development for its simulation of the tumor structure and microenvironment. The embedded-culture of a tumor spheroid within a hydrogel microenvironment could help to improve the mimicking of in vivo cell growth and the [...] Read more.
A 3D tumor spheroid has been increasingly applied in pharmaceutical development for its simulation of the tumor structure and microenvironment. The embedded-culture of a tumor spheroid within a hydrogel microenvironment could help to improve the mimicking of in vivo cell growth and the development of 3D models for tumor invasiveness evaluation, which could enhance its drug efficiency prediction together with cell viability detection. NCI-H23 spheroids and CT-26 spheroids, from a non–small cell lung cancer and colorectal cancer cell line, respectively, together with extracellular matrix were generated for evaluating their sensitivity to AMG510 (a KRASG12C inhibitor) under normoxia and hypoxia conditions, which were created by an on-stage environmental chamber. Results demonstrated that NCI-H23, the KRASG12C moderate expression cell line, only mildly responded to AMG510 treatment in normal 2D and 3D cultures and could be clearly evaluated by our system in hypoxia conditions, while the negative control CT-26 (G12D-mutant) spheroid exhibited no significant response to AMG510 treatment. In summary, our system, together with a controlled microenvironment and imaging methodology, provided an easily assessable and effective methodology for 3D in vitro drug efficiency testing and screenings. Full article
(This article belongs to the Special Issue Advances in Organs-on-a-Chip Engineering)
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19 pages, 5402 KiB  
Article
Addition of ROCK Inhibitors Alleviates Prostaglandin-Induced Inhibition of Adipogenesis in 3T3L-1 Spheroids
by Yosuke Ida, Tatsuya Sato, Araya Umetsu, Megumi Watanabe, Masato Furuhashi, Fumihito Hikage and Hiroshi Ohguro
Bioengineering 2022, 9(11), 702; https://doi.org/10.3390/bioengineering9110702 - 17 Nov 2022
Cited by 3 | Viewed by 1437
Abstract
To elucidate the additive effects of the ROCK inhibitors (ROCK-i), ripasudil (Rip) and Y27632 on bimatoprost acid (BIM-A), a prostaglandin analog (PG), on adipose tissue, two- and three-dimensional (2D or 3D) cultures of 3T3-L1 cells, the most well characterized cells in the field [...] Read more.
To elucidate the additive effects of the ROCK inhibitors (ROCK-i), ripasudil (Rip) and Y27632 on bimatoprost acid (BIM-A), a prostaglandin analog (PG), on adipose tissue, two- and three-dimensional (2D or 3D) cultures of 3T3-L1 cells, the most well characterized cells in the field of lipid research, were used. The cells were subjected to a variety of analyses including lipid staining, real-time cellular metabolic analysis, the mRNA expressions of genes related to adipogenesis and extracellular matrices (ECMs) as well as the sizes and physical properties of the 3D spheroids by a micro-squeezer. BIM-A induced strong inhibitory effects on most of the adipogenesis-related changes in the 2D and 3D cultured 3T3-L1 cells, including (1) the enlargement and softening of the 3D spheroids, (2) a dramatic enhancement in lipid staining and the expression of adipogenesis-related genes, and (3) a decrease in mitochondrial and glycolytic metabolic function. By adding ROCK-i to the BIM-A, most of these BIM-A-induced effects were cancelled. The collective findings reported herein suggest that ROCK-i eliminated the PG-induced suppression of adipogenesis in the 3T3-L1 cells, accompanied by the formation of enlarged 3D spheroids. Such effects of adding ROCK-i to a PG in preadipocytes on cellular properties appear to be associated with the suppression of PG-induced adverse effects, and provide additional insight into our understanding of lipid-related research. Full article
(This article belongs to the Special Issue Advances in Organs-on-a-Chip Engineering)
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Review

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22 pages, 36435 KiB  
Review
Organ-On-A-Chip Database Revealed—Achieving the Human Avatar in Silicon
by Lincao Jiang, Qiwei Li, Weicheng Liang, Xuan Du, Yi Yang, Zilin Zhang, Lili Xu, Jing Zhang, Jian Li, Zaozao Chen and Zhongze Gu
Bioengineering 2022, 9(11), 685; https://doi.org/10.3390/bioengineering9110685 - 12 Nov 2022
Cited by 3 | Viewed by 4224
Abstract
Organ-on-a-chip (OOC) provides microphysiological conditions on a microfluidic chip, which makes up for the shortcomings of traditional in vitro cellular culture models and animal models. It has broad application prospects in drug development and screening, toxicological mechanism research, and precision medicine. A large [...] Read more.
Organ-on-a-chip (OOC) provides microphysiological conditions on a microfluidic chip, which makes up for the shortcomings of traditional in vitro cellular culture models and animal models. It has broad application prospects in drug development and screening, toxicological mechanism research, and precision medicine. A large amount of data could be generated through its applications, including image data, measurement data from sensors, ~omics data, etc. A database with proper architecture is required to help scholars in this field design experiments, organize inputted data, perform analysis, and promote the future development of novel OOC systems. In this review, we overview existing OOC databases that have been developed, including the BioSystics Analytics Platform (BAP) developed by the University of Pittsburgh, which supports study design as well as data uploading, storage, visualization, analysis, etc., and the organ-on-a-chip database (Ocdb) developed by Southeast University, which has collected a large amount of literature and patents as well as relevant toxicological and pharmaceutical data and provides other major functions. We used examples to overview how the BAP database has contributed to the development and applications of OOC technology in the United States for the MPS consortium and how the Ocdb has supported researchers in the Chinese Organoid and Organs-On-A-Chip society. Lastly, the characteristics, advantages, and limitations of these two databases were discussed. Full article
(This article belongs to the Special Issue Advances in Organs-on-a-Chip Engineering)
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