# Extracellular Matrix Hydrogels for Treating Cardiomyopathy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $387,500

## Abstract

Summary
Despite recent advances in tissue engineering and regenerative medicine, heart failure (HF) continues to be
the leading cause of death in the U.S., and the rest of the western world. Therefore, our long-term goal is the
development of new, minimally invasive tissue-engineered therapies for the treatment of ischemic and
nonischemic cardiomyopathy. While cell therapies have been extensively studied for the treatment of MI and
HF, meta-analyses of initial cell therapy trials suggest only a modest effect on cardiac function. More recently
acellular biomaterials have shown great promise in providing similar or greater functional benefit without the
complications associated with cell delivery. Injectable biomaterials that stimulate endogenous repair are an
attractive alternative since potential therapies could still be delivered minimally invasively via catheter, yet
could be off the shelf and have significantly reduced costs compared to cell products. The PI's lab developed
the first cardiac specific injectable hydrogel, which is derived from decellularized porcine myocardial
extracellular matrix (ECM) and is deliverable via a transendocardial injection catheter. This material is liquid at
room temperature and forms a porous and fibrous scaffold upon injection, which we have shown promotes
endogenous cell infiltration and cardiac repair in subacute MI models (injection 1-2 weeks post-MI). This initial
work lead to the recent initiation of a clinical trial in post-MI patients. In pre-clinical studies, we showed that
injection of the material alone post-MI results in decreased borderzone cardiomyocyte (CM) apoptosis,
activation of potential endogenous progenitor cells, a pro-remodeling vs. pro-inflammatory environment,
increased neovascularization, reduced fibrosis, a shift in CM metabolism, and increased cardiac muscle,
yielding significant improvements in both regional and global cardiac function. Under our previous R01, we
were successful in beginning to decipher mechanism of action of this material as well as push forward with
translation into patients. In this renewal, we will continue to pursue both basic and translation research goals.
We propose to continue to better understand the mechanism of action of the material in the context of
subacute MI, specifically answering the remaining question of how the hydrogel increases cardiac muscle.
Given the strong need for therapies for acute MI, ischemic HF, and nonischemic HF, we are also proposing
studies to enable translation of this material into other patient populations. We hypothesize that the myocardial
matrix hydrogel, which contains cardiac specific cues, results in the generation of new cardiac muscle in the
context of MI, and that the material can be delivered alone to improve cardiac function in acute MI, as well as
ischemic and nonischemic HF.

## Key facts

- **NIH application ID:** 9839412
- **Project number:** 5R01HL113468-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Karen L Christman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,500
- **Award type:** 5
- **Project period:** 2012-07-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9839412

## Citation

> US National Institutes of Health, RePORTER application 9839412, Extracellular Matrix Hydrogels for Treating Cardiomyopathy (5R01HL113468-08). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9839412. Licensed CC0.

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