# Creating Hydrogel Tissue Mimics to Better Understand Congenital Heart Disease

> **NIH NIH F31** · UNIVERSITY OF FLORIDA · 2021 · $9,831

## Abstract

PROJECT SUMMARY/ABSTRACT
In this proposal, I aim to develop natural materials-based hydrogel cardiac tissue mimics that can serve
as in vitro test beds for congenital heart disease (CHD). The motivation for this work is the lack of three-
dimensional in vitro models for CHD that currently exist, and the little information known about the biophysical
inputs of disease progression.
CHD affects 1 percent of all live births worldwide. Numerous genetic mutations resulting in cardiac
maldevelopment exist, a common one of which is a mutation in the Nkx2-5 gene. Preliminary data in an Nkx2-5
mutant mouse model from collaborator Dr. Kasahara revealed that approximately 20 genes are downregulated
in the ventricles of diseased versus healthy hearts, two thirds of which are localized to the cell membrane or
extracellular space. As the extracellular matrix (ECM) has been shown to play a role in many cellular processes
such as migration, differentiation, and proliferation, this data warrants further exploration. Additionally, mutant
hearts were shown to have ventricular noncompaction, a phenotype in which the heart’s trabecular layer is
spongy rather than firm, limiting the heart’s capacity to pump blood effectively. Hence, the overall hypothesis
for this project is that the Nkx2-5 mutation influences the biophysical properties of embryonic cardiac tissue,
which in turn dynamically regulate developing cardiac cells.
Replicating this disease phenotype in vitro could provide an effective method for studying the mechanisms of
cardiac maldevelopment. An ECM component of interest in this project is hyaluronic acid (HA) because it is
found ubiquitously throughout the ECM of the body, including cardiac tissue, and provides an excellent base for
the development of hydrogel tissue mimics. The Schmidt lab has engineered HA-based hydrogels to mimic the
mechanical properties of various ECM landscapes, independent of composition. These techniques will be
applied to the creation of hydrogel scaffolds in this project. To this end, I propose 3 aims to accomplish the tasks
of creating my ECM-based hydrogel tissue mimics. In Aim 1, I will determine the biophysical properties of cardiac
tissue affected by the Nkx2-5 mutation. To do this I will assess ECM composition of healthy and diseased hearts
through tandem mass spectrometry and Western blotting, and mechanical properties through indentation. In Aim
2, I will develop ECM-based hydrogel scaffolds to mimic the biophysical properties of healthy and diseased
cardiac tissues and establish these scaffolds as 3D cell culture systems. To accomplish this, I will create HA-
based hydrogel scaffolds with ECM compositions and mechanical properties matched to those of diseased and
healthy heart tissue. In Aim 3, I will evaluate the biophysical properties that modify the fate of developing
myocardial cells. For these studies, cardiomyocytes isolated from healthy and diseased hearts will be cultured
in mutant and wild type test beds. The a...

## Key facts

- **NIH application ID:** 10108945
- **Project number:** 5F31HL150942-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Deanna Bousalis
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $9,831
- **Award type:** 5
- **Project period:** 2020-02-21 → 2021-05-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10108945

## Citation

> US National Institutes of Health, RePORTER application 10108945, Creating Hydrogel Tissue Mimics to Better Understand Congenital Heart Disease (5F31HL150942-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10108945. Licensed CC0.

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