# Development of a 3D hepatic-placental tandem organ-on-a-chip for toxicological screening

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2024 · $239,850

## Abstract

ABSTRACT
Ninety percent of pregnant U.S. women have simultaneously over 50 different chemicals in their bodies. With
over 70,000 chemicals registered with the U.S. Environmental Protection Agency and with many of which not
yet evaluated for reproductive toxicity, understanding the effects of chemical exposure on placental function is
much warranted. This is significant as many of these chemicals have the potential to alter placental function and
the health of the placenta is critical to a healthy pregnancy as well as fetal and maternal well-being. However,
studying the effects of chemical exposure on human placental function in vivo is filled with challenges, including
ethical concerns, inadequacy of animal models to recapitulate human trophoblast cell invasion, and difficulty of
working with limited primary cells that cannot be passaged many times. To advance the field of placental
toxicology, suitable in vitro human models capable of mimicking in vivo conditions and enabling dynamic drug
delivery in higher-throughput screening formats are urgently needed. Key limitations of available models include
low throughput and chemical hepatic biotransformation that occurs in vivo. In this proposal, we plan to develop
a high throughput system to test placental cell invasion using a 3D placental microtissue coupled with hepatic
liver biotransformation. This first-of-its-kind hepatic-placenta organ-tandem on a chip will simulate the liver
metabolism that chemicals undergo in vivo prior to reaching the placental bed. This state-of-the-art in vitro
platform will be the first step towards incorporating organism-level organization into reproductive risk assessment
using a non-animal-based approach. We anticipate that this new platform will be a key tool to be incorporated in
the development of adverse outcome pathways for future placental risk assessment.

## Key facts

- **NIH application ID:** 10829042
- **Project number:** 1R21ES035204-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Salman R Khetani
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $239,850
- **Award type:** 1
- **Project period:** 2024-03-21 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829042

## Citation

> US National Institutes of Health, RePORTER application 10829042, Development of a 3D hepatic-placental tandem organ-on-a-chip for toxicological screening (1R21ES035204-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10829042. Licensed CC0.

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