# Amnion membrane organ-on-chip for modeling intra-amniotic infection

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $218,387

## Abstract

Project Summary
Intra-amniotic infection, also referred to as chorioamnionitis, is a major etiological factor of preterm premature
rupture of the membranes (pPROM), leading to preterm birth. Despite its prevalence and grave consequences,
the pathology of intra-amniotic infection has yet to be completely understood due to a lack of tractable human-
relevant models. Even though animal models of preterm birth have been successfully developed for testing
medical interventions of intra-amniotic infection, they remain suboptimal for quantitative studies of dynamic
bacterium-amnion interactions in the intrauterine cavity. The scarcity of preterm human amnion samples,
especially from early/mid-gestation stages, also prevents these human tissues as experimental models for
studying intra-amniotic infection and its functional link to pPROM. Altogether, there is a critical need for
quantitative, tractable, human-relevant amnion membrane models for advancing fundamental understanding of
intra-amniotic infection.
 The primary goal of this NIH R21 project is to specifically address this significant technological need, by
developing a human-relevant amnion membrane model that can faithfully recapitulate the interaction between
bacteria and amnion membrane tissues, and at the same time, allow high-resolution, quantitative experiments
to study mechanisms underlying bacterial invasion of the amniotic cavity. In our preliminary study, we have
unexpectedly discovered the amniogenic differentiation potency of human pluripotent stem cells (hPSCs) and
successfully developed an hPSC-based, synthetic microfluidic embryogenesis platform in which key
developmental landmarks during early human post-implantation development can be recapitulated
successively in a highly controllable and scalable fashion. Importantly, we also observed sensitive
inflammatory response of hPSC-derived amniotic cells to bacterial infection. Thus, in this research we propose
to leverage the amnion differentiation potential of hPSCs, in conjunction with innovative microfluidics, to
develop the first-of-its-kind human amnion membrane organ-on-chip system. We will further apply this tractable
experimental system to quantitatively study the dynamics of bacterial invasion of the amniotic cavity and to
elucidate the functional connection between inflammation-induced amniotic membrane remodeling and intra-
amniotic bacterial trafficking. Successful accomplishment of this proposed research will lead to innovative
technologies and methodologies for controllable, reproducible, and scalable manufacturing of human amnion
membrane tissues, offering a tractable experimental system for studying related pregnancy complications,
including intra-amniotic infection. The reproducibility and scalability of the human amnion membrane organ-on-
chip system will make it a promising screening platform to explore complex interactions between the human
amnion membrane, bacterial pathogens, drugs and toxic substances.

## Key facts

- **NIH application ID:** 10372321
- **Project number:** 1R21HD105192-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jianping Fu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $218,387
- **Award type:** 1
- **Project period:** 2022-06-21 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10372321

## Citation

> US National Institutes of Health, RePORTER application 10372321, Amnion membrane organ-on-chip for modeling intra-amniotic infection (1R21HD105192-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10372321. Licensed CC0.

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