# Engineering thick human cardiac tissue constructs with patterned, perfusable microvessels for treatment of myocardial infarction

> **NIH NIH F31** · UNIVERSITY OF WASHINGTON · 2022 · $6,653

## Abstract

PROJECT SUMMARY
 Causing the death of more than 17 million people every year, cardiovascular disease is the leading cause
of death worldwide. Progressive heart failure caused by myocardial infarction, or death of cardiac tissue due to
a blockage in the coronary vasculature, is a major contributor to this burden. During a heart attack, up to 25% of
the left ventricle’s contractile cells may be lost, leading to a remodeling response that leaves the heart wall thin
and scarred and greatly reduces cardiac function. Besides whole heart transplantation, available treatment
options can only slow the progression of disease and provide palliative care. As such, there is a great clinical
need for therapies that prevent or treat the ruinous aftermath of myocardial infarction by restoring both the muscle
tissue and the complex vasculature that is needed to support the muscle tissue. Implantable cellularized cardiac
patches have emerged as a potential approach to treat myocardial infarction because complex tissues can be
created by tuning architecture and allowing the tissues to mature. Although advances in tissue engineering and
pluripotent stem cell technology have resulted in cardiac tissues that show promise for improving heart function,
current implantable cellularized cardiac patches remain insufficiently thin due to inadequate nutrient supply.
Previous approaches of vascularizing cardiac tissues have heavily relied on self-assembly of endothelial
networks, leaving them minimally perfusable, or utilize scaffold materials that inadequately balance the stiffness
required for vascular integrity with the remodeling capacity needed support cardiomyocyte coupling and rapid
host vascular infiltration needed for efficient perfusion in vivo. To address this need, we propose to engineer
thick, densely cellularized cardiac patches by incorporating a patterned, perfusable vasculature into a
collagen scaffold for implantation onto infarcted hearts. Our group has previously developed a technique
incorporating injection molding and soft lithography to generate perfusable vasculatures embedded within
collagen matrices and demonstrated that endothelial cells will readily remodel the matrix while the perfusable
vasculature remains intact. In this proposal, we will utilize this technique to generate cardiac tissues containing
stem cell-derived cardiomyocytes and perfusable networks of stem cell-derived endothelial cells. We
hypothesize that incorporating patterned, perfusable endothelial networks into cardiac tissues will
enhance cardiomyocyte survival and function in vitro as well as promote rapid host vascular integration
and tissue survival after implantation. To test this hypothesis, we will utilize a multilayer stacking technique
to generate 3-mm thick cardiac tissues with a three-dimensional vascular network to enable greater tissue
perfusion. We will assess tissue survival, maturation, and function in these tissues and similar tissues without
perfusable vascular ne...

## Key facts

- **NIH application ID:** 10540305
- **Project number:** 5F31HL158061-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Nicole Zeinstra
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $6,653
- **Award type:** 5
- **Project period:** 2021-04-01 → 2022-06-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10540305

## Citation

> US National Institutes of Health, RePORTER application 10540305, Engineering thick human cardiac tissue constructs with patterned, perfusable microvessels for treatment of myocardial infarction (5F31HL158061-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10540305. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*