# ECM Shrink Wrapped Human Cardiomyocytes and Endothelial Cells to Accelerate Myocardial Regeneration

> **NIH NIH R21** · CARNEGIE-MELLON UNIVERSITY · 2020 · $176,743

## Abstract

Myocardial infarction (MI) is a major cause of cardiac-related death in the US and those fortunate to survive the
acute event suffer from chronic risk of arrhythmia, stroke and congestive heart failure. Repairing the heart is
difficult because cardiomyocytes are post-mitotic and cannot proliferate in order to regenerate damaged tissue.
Recent work has demonstrated that human cardiomyocytes can be derived from embryonic stem (ES) and
induced pluripotent stem (iPS) cells, as well as transdifferentiated from other cells. However, survival and
functional integration of these cardiomyocytes into stereotypical vascularized myocardium is still a major and
unresolved challenge. This proposal describes a breakthrough towards therapeutic cell delivery by wrapping
each cell in a nanostructured extracellular matrix (ECM) scaffold tailor made for enhancing survival,
myogenesis and integration into infarcted myocardium. The key innovation in our approach is the ability to
engineer 50-100 nm thick sheets of ECM with defined protein composition and shape and wrap this around
individual cells or small cell ensembles. This is an improvement over current encapsulation technology
because we can build the ECM around cardiomyocytes and endothelial cells to mimic the ECM that naturally
surrounds these cells in the healthy heart. This is critical, because the ECM is a primary regulator of integrin
binding, growth factor sequestration and mechanotransduction. Our preliminary results demonstrate that our
novel surface-initiated assembly technique can build an ECM nano-scaffold from a range of matrix proteins
and shrink wrap cardiomyocytes and endothelials cells. Further, we have shown using corneal endothelial cells
that we can effectively delivery cells in vivo. This proposal will build upon these results by achieving three
primary aims. One, develop the ECM nano-scaffold technology to shrink wrap cardiomyocytes and endothelial
cells in engineered layers of fibronectin, laminin and collagen type IV that match the matrix in the native
myocardium. Two, interrogate the role of ECM nano-scaffold composition, size and cell population on
maximizing muscle formation, pre-vascularization and contractility in 3D tissue. Looking forward, achieving
these aims will result in an injectable cell delivery technology that has enhanced capability to promote the
retention, survival, integration, myogenesis and vascularization of cardiomyocytes and endothelial cells into the
injured heart. This would have profound consequences by leading towards clinically-relevant therapeutic
strategies to decrease morbidity and mortality in MI and cardiovascular disease patients

## Key facts

- **NIH application ID:** 9924688
- **Project number:** 5R21HL144235-02
- **Recipient organization:** CARNEGIE-MELLON UNIVERSITY
- **Principal Investigator:** Adam Walter Feinberg
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $176,743
- **Award type:** 5
- **Project period:** 2019-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9924688

## Citation

> US National Institutes of Health, RePORTER application 9924688, ECM Shrink Wrapped Human Cardiomyocytes and Endothelial Cells to Accelerate Myocardial Regeneration (5R21HL144235-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9924688. Licensed CC0.

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