<i>In vitro</i>nonalcoholic fatty liver disease model with cyclo-olefin-polymer-based microphysiological systems

Wen, Xiaopeng; Yamanaka, Makoto; Terada, Shiho; Kamei, Kazuhito

doi:10.1101/2020.12.28.424535

Cited by 3 publications

(3 citation statements)

References 38 publications

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“…Rennet et al reported a human liver model in a COC-based system with microfluidic flow conditions to study the influence of sepsis (severe inflammation) on hepatocellular dysfunction [ 9 ]. Wen et al modeled a nonalcoholic fatty liver disease model with a cyclo-olefin polymer-based device seeded with a HepaRG hepatoma cell line [ 11 ]. Reported platforms have all been made solely of COC.…”

Section: Introductionmentioning

confidence: 99%

Development of a Hybrid Polymer-Based Microfluidic Platform for Culturing Hepatocytes towards Liver-on-a-Chip Applications

et al. 2021

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The drug development process can greatly benefit from liver-on-a-chip platforms aiming to recapitulate the physiology, mechanisms, and functionalities of liver cells in an in vitro environment. The liver is the most important organ in drug metabolism investigation. Here, we report the development of a hybrid cyclic olefin copolymer (COC) and polydimethylsiloxane (PDMS) microfluidic (HCP) platform to culture a Huh7 hepatoma cell line in dynamic conditions towards the development of a liver-on-a-chip system. The microfluidic platform is comprised of a COC bottom layer with a microchannel and PDMS-based flat top layer sandwiched together. The HCP device was applied for culturing Huh7 cells grown on a collagen-coated microchannel. A computational fluid dynamics modeling study was conducted for the HCP device design revealing the presence of air volume fraction in the chamber and methods for optimizing experimental handling of the device. The functionality and metabolic activity of perfusion culture were assessed by the secretion rates of albumin, urea, and cell viability visualization. The HCP device hepatic culture remained functional and intact for 24 h, as assessed by resulting levels of biomarkers similar to published studies on other in vitro and 2D cell models. The present results provide a proof-of-concept demonstration of the hybrid COC–PDMS microfluidic chip for successfully culturing a Huh7 hepatoma cell line, thus paving the path towards developing a liver-on-a-chip platform.

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Section: Introductionmentioning

confidence: 99%

Development of a Hybrid Polymer-Based Microfluidic Platform for Culturing Hepatocytes towards Liver-on-a-Chip Applications

et al. 2021

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“…Furthermore, COC-based devices are also used to study illicit drug analysis and DNA amplification by performing a chip multiple displacement amplification reaction . Similarly, Wen et al demonstrated the use of COP for modeling a nonalcoholic fatty liver disease microphysiological system . The majority of microfluidic devices fabricated in laboratories required expensive equipment, which becomes difficult for all institutions to afford.…”

Section: Ooc Materialsmentioning

confidence: 99%

Advances in Organ-on-a-Chip Materials and Devices

Nahak¹,

Mishra²,

Preetam³

et al. 2022

ACS Appl. Bio Mater.

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The organ-on-a-chip (OoC) paves a way for biomedical applications ranging from preclinical to clinical translational precision. The current trends in the in vitro modeling is to reduce the complexity of human organ anatomy to the fundamental cellular microanatomy as an alternative of recreating the entire cell milieu that allows systematic analysis of medicinal absorption of compounds, metabolism, and mechanistic investigation. The OoC devices accurately represent human physiology in vitro; however, it is vital to choose the correct chip materials. The potential chip materials include inorganic, elastomeric, thermoplastic, natural, and hybrid materials. Despite the fact that polydimethylsiloxane is the most commonly utilized polymer for OoC and microphysiological systems, substitute materials have been continuously developed for its advanced applications. The evaluation of human physiological status can help to demonstrate using noninvasive OoC materials in real-time procedures. Therefore, this Review examines the materials used for fabricating OoC devices, the application-oriented pros and cons, possessions for device fabrication and biocompatibility, as well as their potential for downstream biochemical surface alteration and commercialization. The convergence of emerging approaches, such as advanced materials, artificial intelligence, machine learning, three-dimensional (3D) bioprinting, and genomics, have the potential to perform OoC technology at next generation. Thus, OoC technologies provide easy and precise methodologies in cost-effective clinical monitoring and treatment using standardized protocols, at even personalized levels. Because of the inherent utilization of the integrated materials, employing the OoC with biomedical approaches will be a promising methodology in the healthcare industry.

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“…Kamei et al developed a NAFLD model using a chip made of cyclo-olefin polymer (COP). 115 Hepatocytes were cultured on a chip made of PDMS and a chip made of COP, and the adsorption of AdipoRed lipid dye was compared. It was observed that the adsorption of lipid dyes was lower in the COP material.…”

Section: Liver Disease Modelsmentioning

confidence: 99%

Microtechnology-based in vitro models: Mimicking liver function and pathophysiology

et al. 2021

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The liver plays important roles in drug metabolism and homeostasis. The metabolism and biotransformation can not only affect the efficacy of drugs but also result in hepatotoxicity and drug-induced liver injury. Understanding the complex physiology of the liver and the pathogenetic mechanisms of liver diseases is essential for drug development. Conventional in vitro models have limitations in the ability to predict drug effects, due to the lack of physiological relevance. Recently, the liver-on-a-chip platform has been developed to reproduce the microarchitecture and in vivo environment of the liver. These efforts have improved the physiological relevance of the liver tissue used in the platform and have demonstrated its applicability to drug screening and disease models. In this review, we summarize the recent development of liver-on-a-chip models that closely mimic the in vivo liver environments and liver diseases.

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In vitrononalcoholic fatty liver disease model with cyclo-olefin-polymer-based microphysiological systems

Cited by 3 publications

References 38 publications

Development of a Hybrid Polymer-Based Microfluidic Platform for Culturing Hepatocytes towards Liver-on-a-Chip Applications

Development of a Hybrid Polymer-Based Microfluidic Platform for Culturing Hepatocytes towards Liver-on-a-Chip Applications

Advances in Organ-on-a-Chip Materials and Devices

Microtechnology-based in vitro models: Mimicking liver function and pathophysiology

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