# Tissue Chip Models for Cardiovascular Development and Disease

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $425,212

## Abstract

PROJECT SUMMARY
Human Tissue Chips that accurately mimic organ-level structure and function are essential building blocks for
fully functional Human Microphysiological Systems (MPS) to recreate complex system-level interactions between
various organs and tissues. Human MPS have great potential to revolutionize basic and translational research
and provide platforms for drug testing and disease modeling with direct relevance to humans. Cardiac Tissue
Chips are of particular importance as they can not only be used to model cardiovascular disease but also
represent an essential component of any MPS platform used for drug discovery as drug induced cardiotoxicity
(arrhythmia risk) is a major reason for pharmaceutical withdrawal of FDA approved drugs. Development of
physiologically relevant models of the human myocardium is challenging due to the lack of appropriate human
cell types and culture systems. Recent breakthroughs in stem cell research have resulted in human induced
pluripotent stem cell derived cardiomyocytes (hiPS-CM) but these cells are immature in phenotype and differ
from human adult cardiomyocytes in terms of electrophysiological function, calcium handling, metabolism, and
contractile function. The heart is a dynamic organ responsible for maintaining systemic circulation and platforms
to culture engineered tissue need to recreate pressure-volume changes associated with physiological or
pathophysiological heart (pump) function. To address shortcomings with current Cardiac Tissue Chip platforms,
we developed a biomimetic cardiac tissue model (BCTM) that can subject engineered 3D cardiac tissue to
pressure-volume changes associated with the ventricular chamber. Using the BCTM, we generated new data
that demonstrates our ability to: (1) recreate pressure-volume changes associated with embryonic heart
development to accomplish early maturation of hiPS-CMs and (2) recreate pathological tissue remodeling
associated with pressure and volume overload. To establish the BCTM as a powerful Cardiac Tissue Chip Model
that can either be used independently as a model of cardiovascular development and disease, or integrated
within MPS for drug discovery and testing, we hypothesize: “Establishment of physiologically relevant
Human Cardiac Tissue Chip Models that can replicate in vivo –like structural remodeling and functional
adaptation as seen during heart development, normal function, and disease requires culture of
engineered cardiac tissue under pressure-volume changes associated with each of these conditions”.
To test this hypothesis, we propose three independent aims that focus on differentiation and maturation of hiPS-
CMs as a model of congenital heart disease, device-based approach to mitigate pathological cardiac tissue
remodeling and evaluate the cardiomyocyte circadian clock in development and disease. Successful completion
of this project will validate the BCTM as a relevant model of the human ventricle for cardiovascular disease
modeling and...

## Key facts

- **NIH application ID:** 9907698
- **Project number:** 1R01HL148462-01A1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Palaniappan Sethu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $425,212
- **Award type:** 1
- **Project period:** 2020-02-20 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9907698

## Citation

> US National Institutes of Health, RePORTER application 9907698, Tissue Chip Models for Cardiovascular Development and Disease (1R01HL148462-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9907698. Licensed CC0.

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