# Peptides derived from soluble extracellular matrix for promoting improved healing following myocardial infarction

> **NIH NIH R56** · TUFTS UNIVERSITY MEDFORD · 2022 · $384,697

## Abstract

Summary: Cardiovascular disease is the leading cause of death in the United States and there are limited
treatments options available for preventing the functional decline to heart failure following a significant myocardial
infarction (MI). One more recent promising approach is the use of acellular biomaterials to alter the remodeling
response by mechanical means, biochemical means, or both. One specific biological material that has shown
great promise in pre-clinical studies is adult porcine ventricular cardiac extracellular matrix (ECM) which recently
successfully completed Phase I clinical trials. However, sourcing of the porcine hearts to generate the material
can be difficult and maintaining consistency in a product as complex as cardiac ECM is challenging. Further, we,
and others, have demonstrated that ECM derived from earlier developmental time points is more regenerative
than ECM derived from adult tissues, but supply issues are even greater for younger hearts at the scale
necessary to generate a therapeutic. Recent work form our group suggests that the specific beneficial effects of
solubilized ECM may be traced to a smaller set of specific ECM proteins or peptides present in the soluble matrix.
Identification and characterization of the set of specific peptides in soluble ECM that promote better healing post-
myocardial infarction could lead to a more consistent and reliable therapeutic option for treating remodeling post-
MI. Our hypotheses, based on significant preliminary data from our own group and others, are 1) that specific
peptides present in early developmental age cardiac ECM will promote a more regenerative healing response in
adult injury than solubilized adult ventricular ECM and 2) that by identifying these peptides and developing
delivery methods that promote their persistence while aiding in neo-tissue formation, we will more effectively
repair the heart following MI. To test this hypotheses, we will carry out three aims. In the first aim we will assess
whether ECM derived from fetal porcine hearts promotes improved healing and functional repair to a greater
extent than adult porcine cardiac extracellular matrix. We will induce MI through ischemia-reperfusion injury and
compare cardiac remodeling and function between injections of adult or fetal cardiac ECM. In the second aim,
we will isolate and characterize specific peptides derived from cardiac ECM that promote regenerative
phenotypes in cells relevant to cardiac healing and repair. We will carry out a novel blot culture method previously
developed by our lab to identify and characterize peptides in solubilized ECM that promote specific cell
responses, synthesize them and assess the mechanism of action for identified fragments. In the third aim we
will develop a biomaterial delivery system for delivering soluble cardiac ECM or peptide derivatives of cardiac
ECM to enhance persistence of the regenerative effects and promote neo-tissue formation, utilizing silk as the
...

## Key facts

- **NIH application ID:** 10705333
- **Project number:** 1R56HL153984-01A1
- **Recipient organization:** TUFTS UNIVERSITY MEDFORD
- **Principal Investigator:** Lauren D. Black III
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $384,697
- **Award type:** 1
- **Project period:** 2022-09-22 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10705333

## Citation

> US National Institutes of Health, RePORTER application 10705333, Peptides derived from soluble extracellular matrix for promoting improved healing following myocardial infarction (1R56HL153984-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10705333. Licensed CC0.

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