Organ Model: Digestive System

Synopsis

While Organ-on-a-Chip technology is increasingly being used to improve our understanding of human biology and advance drug development, it also offers new opportunities to better understand animal physiology, nutrition, and health.

In this on-demand webinar, Dr. Nicole Reisinger of dsm-firmenich shares the development and application of porcine Intestine-Chip and Liver-Chip models designed to investigate responses to deoxynivalenol (DON), a common mycotoxin in animal feed that can negatively affect livestock health and performance.

To investigate how DON affects different aspects of porcine physiology, the dsm-firmenich team applied Organ-on-a-Chip technology across both intestinal and liver models. Using Emulate’s Zoë® Culture Module, they established a porcine Intestine-Chip to evaluate effects on epithelial barrier function, inflammatory signaling, and cellular metabolism, as well as a porcine Liver-Chip to study hepatotoxicity and metabolic responses.

The team then transferred the Liver-Chip model to Emulate’s AVA Emulation System™, expanding the work onto a platform designed to support greater experimental scale and more integrated workflows. By applying the same Organ-Chip model across the complementary Zoë and AVA platforms, the work demonstrates how researchers can build on established biology while scaling studies to support broader applications in animal nutrition, health, and toxicology.

Dr. Reisinger also discusses ongoing efforts to expand these approaches into bovine models, highlighting the broader potential for Organ-on-a-Chip technology across livestock species and research applications.

Key Learning Points

• Discover how porcine Intestine-Chip and Liver-Chip models can recreate tissue-specific aspects of livestock biology under physiologically relevant conditions.
• Learn how these models were used to investigate intestinal and hepatic responses to the mycotoxin deoxynivalenol (DON).
• See how the porcine Liver-Chip model is being implemented on the AVA Emulation System™ to support integrated, scalable Organ-Chip experimentation.
• Explore how Organ-Chip approaches could expand the toolkit available for animal nutrition, health, and toxicology research across multiple livestock species.

With over 150 peer-reviewed publications across 35+ 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:

Endometrium

• Modeling human embryo adhesion using a microfluidic platform

Blood-Brain Barrier

• A human 3D BBB chip model of acute stroke simulating a reversible penumbra

PROTOCOL:

Lung (Tumor)

• Protocol for generation of a 3D humanized lung-tumor-on-a-chip model of immune-hot and immune-cold microenvironments

PRE-PRINT:

Intestine (Ileum)

• Discovery of a radiation countermeasure therapeutic for intestinal injury enabled by human organ chips combined with AI

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.

Organ Model: Intestine (Caco-2)

Applications: Immunology & Inflammation

Highlights

In this study, a human Gut-on-a-Chip was used to model gastrointestinal acute radiation syndrome (GI-ARS). Researchers exposed intestinal epithelial cells and/or the surrounding culture medium to gamma radiation, enabling them to distinguish the direct effects of radiation from indirect injury mediated by irradiated extracellular factors. The Gut-on-a-Chip revealed that prolonged exposure to irradiated medium drove oxidative stress, epithelial injury, and disruption of intestinal tissue architecture. Using this model, the authors demonstrated that a commercially available probiotic formulation reduced oxidative stress, protected epithelial structure, and preserved tissue integrity, supporting its potential as a medical countermeasure for radiation-induced intestinal injury.

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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: Mouth

Applications: Cancer

Highlights

This study presents a preliminary organ-on-a-chip model of oral dysplasia (OD-OoC) designed to better replicate the complex tissue interactions of precancerous lesions in the oral cavity. The microfluidic system integrates endothelial cells, gingival fibroblasts, and dysplastic oral keratinocytes across a collagen I–coated membrane, enabling organized three-dimensional cell–cell interactions under flow conditions. Imaging confirmed the presence and spatial organization of all cell types, as well as fibroblast migration across the membrane and dysplastic epithelial phenotypes distinct from healthy cells. This platform may provide a physiologically relevant in vitro tool to study epithelial transformation, cell migration, and early mechanisms involved in oral cancer development.

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Organ Model: Intestine (Colon)

Application: Immunology & Inflammation

How Organ-Chips Were Used: Patient-specific epithelial cells and stromal fibroblasts were isolated and cultured to establish healthy and IBD-specific Colon Intestine-Chips.

Key highlights:

• Colon Intestine-Chips replicated key hallmarks of IBD, including inflammation, compromised barrier function, reduced mucus accumulation, fibrosis, and increased cancer risk.
• Stromal fibroblasts from IBD patients were identified as primary drivers of intestinal barrier disruption and inflammation.
• Peristalsis-like mechanical deformations have a direct effect on mucus production, and they exacerbated inflammation and fibrosis in IBD Chips but not in healthy chips.
• Mechanical deformations also enhanced immune cell migration in IBD Chips.

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Organ Model: Intestine (Ileum)

Application: Immunology & Inflammation

Highlights

Researchers created a human Ileum-Chip model of acute radiation injury using patient-derived ileal epithelial cells cultured alongside intestinal microvascular endothelial cells under flow and peristalsis-like mechanical motion. When exposed to clinically relevant doses of gamma radiation, the model reproduced key features of intestinal radiation injury, including epithelial cell loss, villus blunting, barrier disruption, inflammation, and reduced mucus production, as well as the protective effects of the probiotic formulation VSL#3 observed in patients. Transcriptomic data generated from the Organ-Chips were then analyzed using the AI-based drug repurposing platform NeMoCAD, which identified the antifungal drug miconazole as a potential radiation countermeasure. Testing miconazole back in the Ileum-Chip confirmed its protective effects and provided insight into a potential MMP9-mediated mechanism, demonstrating how Organ-Chips can be paired with AI for both therapeutic discovery and human-relevant validation.

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Organ Model: Intestine

Applications: ADME

Highlights

This study directly compared three culture formats—organoids, Transwells, and intestine-on-chip systems—using the same hiPSC-derived intestinal epithelial cells to understand how culture context shapes biology. While all three models supported intestinal differentiation, the Intestine-Chip consistently reproduced the most mature, adult-like phenotype, with the strongest upregulation of genes involved in digestion, nutrient transport, and drug metabolism, including CYP enzymes. The dynamic flow and physiologically relevant microenvironment provided by the Organ-Chip drove functional maturation that static organoid and Transwell systems could not achieve. These findings highlight Organ-Chips as a more predictive platform for studying human intestinal function, drug absorption, and DDI risk.

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Organ Model: Intestine (Duodenum)

Applications: ADME

Highlights

Researchers used the Duodenum Intestine-Chip to enable more physiologically relevant measurements of drug permeability than conventional static or animal-based models. By benchmarking permeability of three model compounds against RRCK cells and correlating chip-derived values with clinical P_eff, the researchers demonstrated that Organ-Chip data can be integrated into PBPK platforms like Simcyp® and GastroPlus™ to improve predictions of human systemic exposure. This work highlights the potential of Organ-Chips to enhance drug absorption modeling and reduce reliance on less predictive preclinical systems.

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