ArticleBiotechnology and bioengineering2020
Progressive hypoxia-on-a-chip: An in vitro oxygen gradient model for capturing the effects of hypoxia on primary hepatocytes in health and disease.
Article in Biotechnology and bioengineering, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 51 citations in OpenAlex.
- Review
- Organ-on-a-chip systems for modeling tumor and normal tissue microenvironments in radiotherapy research.Trends in biotechnology · 2026Review
- Estrogen and obesity synergistically suppress protein S via HIF1α, enhancing thrombosis potential.The Journal of clinical investigation · 2025Article
- Design, fabrication, and characterization of a user-friendly microfluidic device for studying liver zonation-on-chip (ZoC).Biomedical microdevices · 2025Article
- Computational and experimental advances in liver-on-a-chip technology for cancer research: a systematic review.Biophysical reviews · 2025Review
- A closed-loop modular multiorgan-on-chips platform for self-sustaining and tightly controlled oxygenation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Chip collection of hepatocellular carcinoma based on ONature communications · 2024Article
- Microfluidic design for in-vitro liver zonation-a numerical analysis using COMSOL Multiphysics.Medical & biological engineering & computing · 2024Article
- p66Shc deficiency in CLL cells enhances PD-L1 expression and suppresses immune synapse formation.Frontiers in cell and developmental biology · 2024Article
- Development of an Induced Pluripotent Stem Cell-Based Liver-on-a-Chip Assessed with an Alzheimer's Disease Drug.ACS biomaterials science & engineering · 2023Article
- Construction of Bone Hypoxic Microenvironment Based on Bone-on-a-Chip Platforms.International journal of molecular sciences · 2023Review
- The Applications and Challenges of the Development ofCellular and molecular bioengineering · 2023Review
- Simulating the Effect of Gut Microbiome on Cancer Cell Growth Using a Microfluidic Device.Sensors (Basel, Switzerland) · 2023Article
- Article
- Review
- Hepatocyte cultures: From collagen gel sandwiches to microfluidic devices with integrated biosensors.APL bioengineering · 2021Review
- Oxygen-Releasing Biomaterials: Current Challenges and Future Applications.Trends in biotechnology · 2021Review
- Microphysiological systems to study tumor-stroma interactions in brain cancer.Brain research bulletin · 2021Review
- Physiologically relevant oxygen tensions differentially regulate hepatotoxic responses in HepG2 cells.Toxicology in vitro : an international journal published in association with BIBRA · 2021Article
- Oxygen Biosensors and Control in 3D Physiomimetic Experimental Models.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Oxygen is vital to the function of all tissues including the liver and lack of oxygen, that is, hypoxia can result in both acute and chronic injuries to the liver in vivo and ex vivo. Furthermore, a permanent oxygen gradient is naturally present along the liver sinusoid, which plays a role in the metabolic zonation and the pathophysiology of liver diseases. Accordingly, here, we introduce an in vitro microfluidic platform capable of actively creating a series of oxygen concentrations on a single continuous microtissue, ranging from normoxia to severe hypoxia. This range approximately captures both the physiologically relevant oxygen gradient generated from the portal vein to the central vein in the liver, and the severe hypoxia occurring in ischemia and liver diseases. Primary rat hepatocytes cultured in this microfluidic platform were exposed to an oxygen gradient of 0.3-6.9%. The establishment of an ascending hypoxia gradient in hepatocytes was confirmed in response to the decreasing oxygen supply. The hepatocyte viability in this platform decreased to approximately 80% along the hypoxia gradient. Simultaneously, a progressive increase in accumulation of reactive oxygen species and expression of hypoxia-inducible factor 1α was observed with increasing hypoxia. These results demonstrate the induction of distinct metabolic and genetic responses in hepatocytes upon exposure to an oxygen (/hypoxia) gradient. This progressive hypoxia-on-a-chip platform can be used to study the role of oxygen and hypoxia-associated molecules in modeling healthy and injured liver tissues. Its use can be further expanded to the study of other hypoxic tissues such as tumors as well as the investigation of drug toxicity and efficacy under oxygen-limited conditions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.