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New Injectable Hydrogel Can Mitigate Damage to the Heart

A 3D model of a human heart.
Credit: jesse orrico / Unsplash.
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An injectable hydrogel can mitigate damage to the right ventricle of the heart with chronic pressure overload, according to a new study published March 6 in Journals of the American College of Cardiology: Basic to Translational Science.

The study, by a research team from the University of California San Diego, Georgia Institute of Technology and Emory University, was conducted in rodents. In 2019, this same hydrogel was shown to be safe in humans through an FDA-approved Phase 1 trial in people who suffered a heart attack. As a result of the new preclinical study, the FDA approved an investigational new drug application for the Emory and Georgia Tech researchers to start a clinical trial with the hydrogel in pediatric patients in the coming months, once institutional approvals are received.

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In this case, the injectable hydrogel is intended for children born with a condition that leaves them with an underdeveloped, nonfunctional left ventricle. The disorder, known as hypoplastic left heart syndrome, comprises less than 4 percent of congenital heart defects. But it is responsible for 40 percent of deaths associated with heart defects in newborns. Patients with the disorder have a 35 percent survival rate. 

Positive results

Preclinically, the treament’s effects were first seen two weeks after injection.

Researchers in Christman’s lab prepared the hydrogel with tissue from both the right and left ventricles of the pig hearts. Interestingly, tissues on each side of the heart differ vastly.

Hydrogels from either side of the heart improved systolic function–the heart’s ability to pump blood. They also reduced heart muscle growth and scaring while prompting arteriole formation and growth. But overall, hydrogel derived from left-ventricle tissue was more effective. That’s likely because the hydrogel derived from right-ventricle tissue is richer in type 1 collagen, which may have led to the enhanced inflammatory response seen in the RV hydrogel treated group.

The injected hydrogel also affected gene expression, specifically pathways related to cardiac repair, including the development of the circulatory system, muscle structure and vasculature, as well as regulation of immune response and cellular response to oxygen-containing compounds.

Next, Children's Healthcare of Atlanta, the children's hospital collaborating with Georgia Tech and Emory will start recruiting for a clinical trial investigating the treatment’s efficacy in newborns with hypoplastic left heart syndrome. 

Reference: Hunter JD, Mesfin JM, Ahmed T, et al. Myocardial Matrix Hydrogels Mitigate Negative Remodeling and Improve Function in Right Heart Failure Model. JACC: Basic to Translat Sci. 2024:S2452302X2400010X. doi: 10.1016/j.jacbts.2024.01.006

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