Organ Model: Liver

With over 150 peer-reviewed publications across 30+ organ models, Emulate Organ-Chips are empowering researchers to make game-changing scientific breakthroughs! Download this digest to easily explore all publications related to your field of research, or to just learn more about how the technology itself is developing.

New this quarter:

Fallopian Tube

• Human fallopian tube-on-a-chip for preclinical testing of non-hormonal contraceptives with living human sperm

Intestine

• Probiotic intervention mitigates radiation-induced intestinal injury by alleviating oxidative stress in a human gut-on-a-chip

Lung (Airway)

• Development of an acute inhalation toxicity testing method based on a lung-on-a-chip

Lung (Alveolus)

• Enhanced lung delivery of an immunostimulatory duplex RNA augments the antitumor activity by reshaping systemic cytokine pharmacodynamics

Lung (Alveolus)

• Alveolus-on-a-Chip: A Novel Tool for Modeling Lung Transplant Cold Storage Ischemia/Reperfusion Injury

Placenta

• Simvastatin Restores Uteroplacental Hemodynamics and Trophoblast Function in Obstetric Antiphospholipid Syndrome in a Placenta-on-a-Chip Model

REVIEW ARTICLES:

Female Reproductive Tract

• Female Reproductive Tract Organ-on-Chips: Modeling Barrier Function and Drug Transport

Drug Development

• Human organ-on-a-chip technology as a catalyst for drug discovery

PUBLISHED FROM PRE-PRINT:

Intestine (Colon)

• Human inflammatory bowel disease-on-a-chip for modelling disease progression, cancer initiation and sex-specific effects

Lymph Node

• In vitro recapitulation of intramuscular mRNA vaccination with naive and recall antigens using a human lymphoid follicle chip platform

Vasculature

• Human coronary artery organ-chip with circulating immune cells recapitulates anti-inflammatory effect of pulsatile wall strain

Application: Drug Discovery

Highlights

This review highlights Organ-Chips as a more human-relevant preclinical platform that recreates key aspects of organ physiology—including tissue-tissue interfaces, dynamic fluid flow, mechanical forces, and immune interactions—to improve prediction of human drug responses. Unlike conventional cell cultures or animal models, Organ-Chips enable therapeutics to be evaluated using clinically relevant dosing routes and pharmacokinetic profiles, supporting more accurate assessment of efficacy, toxicity, and mechanisms of resistance. The authors also emphasize that combining Organ-Chips with high-throughput screening, functional genomics, and artificial intelligence could accelerate target identification and drug discovery while helping reduce the high rate of clinical trial failures. Although challenges remain around standardization and scalability, the review concludes that Organ-Chips are poised to become an increasingly important tool for drug development and regulatory safety assessment.

Synopsis

Organ-on-a-Chip technology is emerging as a powerful New Approach Methodology (NAM) for drug development, driven by the need for more human-relevant and scalable experimental models. As these systems move toward broader adoption, a key challenge remains: generating consistent, interpretable data that supports confident experimental and translational decision-making.

This webinar examines how imaging and AI-driven analysis workflows enable Organ-Chip studies to scale from innovation to routine application. Speakers begin with an overview of Organ-on-a-Chip technology and its role in addressing translational gaps in drug discovery, highlighting how Liver-Chips are being evaluated in collaboration with regulatory agencies for better prediction of drug-induced liver injury.

The session then explores how the newly released AVA™ Emulation System enables scalable Organ-Chip experimentation through an integrated system for incubation, microfluidic delivery, and routine imaging. Paired with AI-driven analysis, brightfield image data can be used to automate quality control by monitoring chip health, morphology, and assay performance over time across large studies.

To complete the workflow, post-study high-resolution imaging is applied to evaluate more complex biological markers, including toxicology-relevant endpoints and drug uptake. These datasets are paired with advanced analysis techniques that translate imaging data into quantitative, biologically meaningful insights.

Attendees will gain a practical understanding of how unified imaging and analysis strategies—spanning routine QC through advanced interrogation—support scalability, reproducibility, and alignment with evolving regulatory expectations for Organ-Chips and other NAM-based drug development.

Organ Model: Liver

Application: Toxicology

Highlights

The FDA used the Emulate Liver-Chip S1 to culture primary human hepatocytes and non-parenchymal liver cells under continuous perfusion, enabling extended drug exposure and collection of effluent for biomarker analysis. By identifying optimized ELISA- and chemistry-based methods, the study established standardized, reproducible approaches for measuring translational liver injury biomarkers in Organ-Chips, supporting their use in predictive toxicology and regulatory science.

Products Used In This Publication

Synopsis

Animal models have served as the default standard in preclinical research for decades, but their limited predictive value for human outcomes continues to slow drug development and contribute to high attrition rates. Recent regulatory milestones—including the FDA’s roadmap to reduce animal use, the NIH’s prioritization of human-relevant models, and Emulate’s own Liver-Chip S1 acceptance into the FDA ISTAND program—signal a decisive shift toward New Approach Methodologies (NAMs).

In this webinar, hosted in conjunction with the Physician’s Committee for Responsible Medicine, Emulate’s Dr. Daniel Levner, Chief Technology Officer, shares how the FDA’s ISTAND qualification of the Liver-Chip S1 represents a pivotal step for regulatory recognition and broader adoption of Organ-on-a-Chip technology. Attendees will gain insight into how this breakthrough aligns with global initiatives to reduce animal testing, the scientific validation underpinning the platform, and practical strategies for integrating Liver-Chip data into regulatory submissions.

Key learning objectives

• Identify strategies for incorporating Liver-Chip data into IND submissions to increase confidence, improve predictability, and accelerate decision-making.
• Understand what FDA ISTAND acceptance means for the regulatory qualification of Organ-on-a-Chip technology and its impact on drug development.
• Learn how Emulate’s Liver-Chip S1 is poised to meet FDA expectations for context of use, building on strong scientific evidence and cross-industry collaboration.
• Explore the FDA’s roadmap to reduce animal usage and how Organ-on-a-Chip technology can future-proof your pipeline against evolving regulatory standards.

This recording was originally presented on September 10, 2025.

Organ Model: Liver

Application: Toxicology

Highlights

Researchers from AbbVie built rat and dog quad-culture Liver-Chips (hepatocytes + sinusoidal endothelial, Kupffer, and stellate cells) under physiological flow, validated one week of experimental window stability (monitoring albumin, LDH/AST, CYPs/FMO), and then dosed ABT-288. The chips reproduced in vivo, species-specific metabolism: dog chips showed much higher FMO-mediated N-oxide formation and modestly greater toxicity signals (↓albumin, ↑ALT/AST/LDH) than rat—differences that were not seen in liver microsomes or 2D hepatocytes.

Significance: animal-cell MPS models can capture species differences in metabolism-driven hepatotoxicity that conventional in vitro systems miss, providing a translational bridge that both builds confidence in human MPS readouts and can help interpret preclinical safety signals (potentially reducing animal use and de-risking First in Human decisions).

Products Used In This Publication

Organ Model: Liver

Application: Toxicology

Highlights

In this study, researchers used the Emulate Quad-Culture Liver-Chip to evaluate the hepatotoxicity of four phytocannabinoids—CBD, CBN, CBC, and CBG—by continuously dosing chips for 7 days and assessing markers of liver injury. The Liver-Chip revealed compound-specific toxicity profiles, with CBC showing the most pronounced hepatotoxic effects, and provided mechanistic insights into oxidative stress and mitochondrial dysfunction in both hepatocytes and non-parenchymal cells. These findings highlight the Liver-Chip as a human-relevant alternative for liver toxicity screening of cannabinoids.

Products Used In This Publication

Originally presented at the MPS World Summit 2025 Annual Meeting in Brussels, Belgium.

Authors

Randy S. Daughters¹*, Anthony R. Heng¹, Adriana Cespedes¹, Max Winkelman¹, Sushma Jadalannagari¹, Taehee Lee¹, Gabrielle Fortes¹, Jake Chaff¹, Josiah Sliz¹, Lorna Ewart¹

¹ Emulate, Inc., 27 Drydock Avenue, Boston, MA, 02210, USA

Abstract

Emulate’s new Chip-R1™ Rigid Chip is a minimally drug-absorbing Organ-Chip consumable designed for improved in vitro toxicology. It incorporates minimally drug absorbing thermoplastics along with a new porous, cell culture-treated membrane that reduce small lipophilic drug absorption. Validated with a quad culture liver model consisting of human primary hepatocytes, liver sinusoidal endothelial cells, Kupffer cells, and stellate cells, Chip-R1 supports physiological features of the liver, including albumin production and small molecule metabolism. Its reduced drug absorption enhances reproducibility and sensitivity in detecting toxicity versus PDMS-based chips. This significant improvement enables more accurate prediction of small molecule toxicity and metabolism in a human-relevant liver model, advancing drug development workflows.

Organ Model: Liver

Application: Toxicology

Highlights

Researchers used the Emulate Liver-Chip S1 Quad-Culture BioKit containing primary human hepatocytes, endothelial cells, stellate cells, and Kupffer cells to model radiation-induced liver disease (RILD). Radiation exposure on the chip reproduced key features of RILD—including DNA damage, cellular senescence, metabolic and endothelial dysfunction, inflammation, and stellate cell activation—and enabled discovery of molecular pathways involved. The chip was further used to test N-acetylcysteine amide (NACA), which reduced radiation-associated damage and supported identification of potential biomarkers for radiation response and treatment efficacy.

Products Used In This Publication

Article Type: Perspective

Organ Models: Liver

Application: Toxicology

Abstract: Predicting which drugs might have the potential to cause drug-induced liver injury (DILI) is highly complex and the current methods, 2D cell-based models and animal tests, are not sensitive enough to prevent some costly failures in clinical trials or to avoid all patient safety concerns for DILI post-market. Animal-based methods are hampered by important species differences in metabolism and adaptive immunity compared to humans and the standard 2D in vitro approaches have limited metabolic functionality and complexity. On 24 April 2023 the Alliance for Human Relevant Science hosted a workshop at the Royal Society, London entitled Drug-Induced Liver Injury (DILI): Can Human-Focused Testing Improve Clinical Translation? The conclusion was that complex in vitro models (CIVMs) provide a significant step forward in the safety testing paradigm. This perspective article, written by the participants, builds on those discussions to provide a ‘state of play’ on liver CIVMs with recommendations for how to encourage their greater uptake by the pharmaceutical industry.