# A Novel Shear Thinning Hydrogel System for Advanced Cellular Therapy in Ischemic Heart Disease

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $481,642

## Abstract

Project Summary
Cardiovascular disease is the leading cause of death in the United States. Clinical therapies
currently available for heart failure are limited and do not provide a viable strategy to restore blood
flow to a large group of patients. Consequently, the survival in this patient population is severely
limited. Experimental therapies have attempted to restore circulation to threatened heart muscle
using stem cells to regenerate micro-circulation. While this strategy demonstrated promise in
experimental settings, translation to clinical therapy has been limited by a lack of significant
benefit, due to cell death and a lack of retention (<1%). The therapeutic benefit of stem cells
appears to be largely related to paracrine mechanisms (the proteins secreted by the cells) rather
than the cells themselves. Exosomes appear to be at the center of paracrine signaling.
Exosomes are vesicles secreted by the cells that contain cell signaling molecules that play an
important role in cell survival, replication, and formation of vessels. They are particularly attractive
for therapy, when compared to cells, in that they are easily harvested in large quantities, can be
frozen and stored indefinitely, and rapidly prepared for therapy. Unfortunately, retaining the
exosomes in the heart with just injection is a challenge. In order to overcome these limitations,
we have developed a novel shear thinning hydrogel to allow delivery and retention of exosomes
in the heart. This novel hydrogel is able to liquefy under shear forces, enabling injection through
a syringe, and immediately reforming upon elimination of the shear stress. The properties of the
gel facilitate optimal exosome delivery (98%) with minimal loss. We hypothesize that delivery of
exosomes within the shear thinning hydrogel will enable efficient delivery to compromised heart
muscle with excellent retention. We will identify factors secreted by the exosomes and gain an
understanding of the pathways involved in therapy. We will also evaluate optimal timing, relative
to myocardial infarction (heart attack) for delivery of the exosomes. Additionally, we will translate
therapy to a sheep model of heart failure, as a preclinical assessment.

## Key facts

- **NIH application ID:** 9964883
- **Project number:** 5R01HL135090-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** PAVAN ATLURI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $481,642
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964883

## Citation

> US National Institutes of Health, RePORTER application 9964883, A Novel Shear Thinning Hydrogel System for Advanced Cellular Therapy in Ischemic Heart Disease (5R01HL135090-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9964883. Licensed CC0.

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