ArticleEuropean journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V2015
Chip-based human liver-intestine and liver-skin co-cultures--A first step toward systemic repeated dose substance testing in vitro.
Article in European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
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Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 211 citations in OpenAlex.
- Advances in Engineering Human Tissue Models.Frontiers in bioengineering and biotechnology · 2020Pooled it
- Introduction to the 3RsC's cross-platform microphysiological systems evaluation for drug-induced liver injury in collaboration with FDA-CDER.Regulatory toxicology and pharmacology : RTP · 2026Article
- Modeling of lung-liver interaction during infection in a human fluidic organ-on-a-chip.Scientific reports · 2025Article
- Exosomes From Intestinal Epithelial Cells Promote Hepatic Differentiation of Liver Progenitor Cells in Gut-Liver-on-a-Chip Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Aging on Chip: Harnessing the Potential of Microfluidic Technologies in Aging and Rejuvenation Research.Advanced healthcare materials · 2025Review
- The Application of Microfluidic Chips in Primary Urological Cancer: Recent Advances and Future Perspectives.Smart medicine · 2025Review
- An eighteen-organ microphysiological system coupling a vascular network and excretion system for drug discovery.Microsystems & nanoengineering · 2025Article
- Organ-on-a-Chip Applications in Microfluidic Platforms.Micromachines · 2025Review
- A human skin-on-a-chip platform for microneedling-driven skin cancer treatment.Materials today. Bio · 2025Article
- Combination of Low-Dose Sulforaphane and Docetaxel on Mitochondrial Function and Metabolic Reprogramming in Prostate Cancer Cell Lines.International journal of molecular sciences · 2025Article
- Digital twin-enhanced three-organ microphysiological system for studying drug pharmacokinetics in pregnant women.Frontiers in pharmacology · 2025Article
- Environmentally Controlled Microfluidic System Enabling Immune Cell Flow and Activation in an Endothelialised Skin-On-Chip.Advanced healthcare materials · 2024Article
- Targeted Cancer Therapy-on-A-Chip.Advanced healthcare materials · 2024Review
- Dynamic microphysiological system chip platform for high-throughput, customizable, and multi-dimensional drug screening.Bioactive materials · 2024Article
- Advances and challenges in organ-on-chip technology: toward mimicking human physiology and disease in vitro.Medical & biological engineering & computing · 2024Review
- Reducing Inert Materials for Optimal Cell-Cell and Cell-Matrix Interactions within Microphysiological Systems.Biomimetics (Basel, Switzerland) · 2024Article
- Vascularized 3D Human Skin Models in the Forefront of Dermatological Research.Advanced healthcare materials · 2024Review
- Vascular organs-on-chip made with patient-derived endothelial cells: technologies to transform drug discovery and disease modeling.Expert opinion on drug discovery · 2024Review
- Applying new approach methodologies to assess next-generation tobacco and nicotine products.Frontiers in toxicology · 2024Review
- Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called "human-on-a-chip" concepts are aiming to replace respective animals and humans in substance evaluation with miniaturized functional human organisms. The major technical hurdle toward success in this field is the life-like combination of human barrier organ models, such as intestine, lung or skin, with parenchymal organ equivalents, such as liver, at the smallest biologically acceptable scale. Here, we report on a reproducible homeostatic long-term co-culture of human liver equivalents with either a reconstructed human intestinal barrier model or a human skin biopsy applying a microphysiological system. We used a multi-organ chip (MOC) platform, which provides pulsatile fluid flow within physiological ranges at low media-to-tissue ratios. The MOC supports submerse cultivation of an intact intestinal barrier model and an air-liquid interface for the skin model during their co-culture with the liver equivalents respectively at (1)/100.000 the scale of their human counterparts in vivo. To increase the degree of organismal emulation, microfluidic channels of the liver-skin co-culture could be successfully covered with human endothelial cells, thus mimicking human vasculature, for the first time. Finally, exposure routes emulating oral and systemic administration in humans have been qualified by applying a repeated dose administration of a model substance - troglitazone - to the chip-based co-cultures.
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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.