# Image Guided Delivery of Bioresponsive Hydrogels

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $793,000

## Abstract

Summary
 Myocardial infarction (MI) causes regional dysfunction placing remote areas of the heart at a
mechanical disadvantage resulting in long term adverse left ventricular (LV) remodeling and complicating
congestive heart failure (CHF), which remains a leading cause of morbidity and death in the Western world.
The current project will focus on evaluating and modulating the critical balance of matrix metalloproteinases
(MMP) and tissue inhibitors of matrix metalloproteinases (TIMP) which is known to play an important role
during remodeling post-MI. A number of pharmacological and surgical therapies have been proposed to limit
post-MI remodeling, including; the intramyocardial administration of biomaterials. These polymeric therapies
have demonstrated mixed success in reducing infarct size, increasing angiogenesis, improving regional
function, and limiting post-MI remodeling in pre-clinical studies, and have been recently translated to patients.
We have established novel noninvasive hybrid SPECT/CT approaches for evaluation of changes in regional
myocardial perfusion, angiogenesis, MMP activation, along with echocardiographic imaging approaches for
quantitative evaluation of regional myocardial strain and ventricular remodeling. The current multi-PI proposal
will focus on; 1) development of a novel imageable MMP-responsive theranostic hydrogel for post-MI therapy
and tracking delivery and serial evaluation of hydrogel retention, 2) application of multimodality non-invasive
anatomical, physiological and molecular imaging approaches for directing and evaluating the percutaneous
intramyocardial delivery of MMP-responsive hydrogels, and 3) the evaluation of the mechanisms by which
these injectable MMP-responsive hydrogels that release local TIMP alter myocardial mechanics and limit post-
MI remodeling. We hypothesize that the intramyocardial delivery of MMP-responsive hydrogels that locally
release TIMP-3 early post-MI will result in; 1) modulation of the local MMP-TIMP balance and the inflammatory
response within the MI, 2) alteration of regional and global myocardial mechanics, 3) improvement in
angiogenesis and myocardial perfusion, and 4) a reduction of adverse global post-MI remodeling. We also
hypothesize that our multimodality imaging approach will facilitate optimal delivery of a theranostic hydrogel,
and allow tracking of critical anatomical, physiological and molecular events, along with therapeutic efficacy.
Accordingly, we propose to specifically: 1) development an imageable MMP-responsive theranostic hydrogels
for post-MI therapy, 2) apply multimodality imaging to direct and evaluate percutaneous image-guided
intramyocardial delivery these hydrogels using clinically relevant porcine models of post-MI remodeling, and 3)
evaluate the mechanisms of therapeutic efficacy. The diagnostic and therapeutic approaches developed in the
proposed project will be directly translatable to the management of patients following MI.

## Key facts

- **NIH application ID:** 9838794
- **Project number:** 5R01HL137365-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Jason A Burdick
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $793,000
- **Award type:** 5
- **Project period:** 2017-12-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9838794

## Citation

> US National Institutes of Health, RePORTER application 9838794, Image Guided Delivery of Bioresponsive Hydrogels (5R01HL137365-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9838794. Licensed CC0.

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