# Bioprinting A Physiologically Aligned, Thick Cardiac Tissue for Regenerative Medicine

> **NIH NIH F31** · HARVARD UNIVERSITY · 2021 · $34,938

## Abstract

PROJECT SUMMARY
Each year 750,000 American experience a heart attack, many of whom progress to heart failure. Heart failure,
which accounts for 10% of annual deaths in the United States, is characterized by insufficient pumping
that restricts the blood supply to peripheral organs. Current treatments cannot mitigate this decline as they
do not address the fundamental problem of cell loss. Stem cell derived cardiomyocytes represent an
unlimited, personalized therapy with demonstrated potential to regenerate this contractile function.
Recently, the transplantation of stem cell derived cardiomyocytes restored heart function in rhesus
monkeys with surgically induced heart attacks. The dramatic improvement in this highly translational model is
attributed at least in part to the contractile force generated by the transplanted cells. Despite this improvement
in function, only ~5% of cells survived after 4 weeks. Tissue engineering represents one approach to
improve the re-muscularization strategy by replicating the cellular and extracellular matrix composition of the
heart.
In the heart, cells are oriented in a double helical, three-dimensional architecture. This orientation generates
twist akin to wringing a wet rag. This twist helps scale a cardiomyocyte’s 15% shortening and 8% thickening to
a 65% ejection fraction. Towards generating a personalized therapy capable of adapting to the size and position
of an individual’s heart attack, we aim to recapitulate the architecture and torsional function of myocardium. The
central hypothesis of this proposal are: 1) replicating the physiological twist of myocardium is necessary for
cardiac re-muscularization, and 2) 3D bioprinting aligned cardiac sheets with physiologically relative changes in
orientation will generate twist. Importantly, this approach is complementary to previously developed, 3D printed
vascularization strategies and enables a scalable and tailorable approach. Overall, this project aims to generate
a more physiological tissue that can be used to study physiological indicators of contractile function, which will
inform in vivo studies that aim to re-muscularize the heart. In addition, such tissue may help elucidate disease
mechanisms previously unidentifiable with simpler in vitro models.
Aim 1: Generate a printable bioink composed of aligned, anisotropic cardiac μtissues.
Aim 2: 3D bioprint μtissue-laden inks into uniaxially aligned cardiac tissue sheets.
Aim 3: Determine how relative alignment between 3D bioprinted layers impacts parameters of twist.

## Key facts

- **NIH application ID:** 10245085
- **Project number:** 5F31HL144043-03
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** JOHN AHRENS
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $34,938
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10245085

## Citation

> US National Institutes of Health, RePORTER application 10245085, Bioprinting A Physiologically Aligned, Thick Cardiac Tissue for Regenerative Medicine (5F31HL144043-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10245085. Licensed CC0.

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