Injectable hydrogels can reduce damage to the right ventricle caused by chronic pressure overload, according to a new study published March 6. Journal of the American College of Cardiology: From basic science to translational science.

The study was conducted in rodents by a research team from the University of California, San Diego, Georgia Institute of Technology, and Emory University. In 2019, this same hydrogel was shown to be safe for humans through an FDA-approved Phase 1 trial in people who had suffered a heart attack. As a result of new preclinical research, the FDA has approved an investigational new drug application by researchers at Emory Technological Institute and Georgia Tech, allowing hydrogels to be used in pediatric patients in the coming months upon institutional approval. The company plans to begin clinical trials of the drug.

In this case, the injectable hydrogel is intended for children born with an underdeveloped and non-functioning left ventricle. This disorder, known as hypoplastic left heart syndrome, accounts for less than 4% of congenital heart defects. However, 40% of deaths related to heart defects in newborns are caused by the heart. The survival rate for patients with this disorder is 35%.

Current treatment consists of a series of three open-heart surgeries performed before the patient’s fifth year of life to reroute the oxygenated blood supply to the right ventricle. Pediatric patients who survive into childhood after surgery also receive medication, physical therapy, and special diets. However, this palliative surgery is expensive. In a healthy heart, the right ventricle’s job is to pump blood to the lungs. The job involves handling blood at lower pressures and in smaller volumes. The need for the right ventricle to pump blood throughout the body results in several maladaptive characteristics, such as excessively large muscles and scarring. Eventually, the right ventricle fails and the patient requires a heart transplant.

”To our knowledge, this is the first time that an injectable biomaterial therapy has been evaluated as effective in alleviating right ventricular heart failure. ” “It’s important to understand that this is the case,” said study lead author Gervaun D. Hunter, a Ph.D. from Port Gibson, Mississippi. He received his Ph.D. from the Xu Cheng Jean Lei Department of Biotechnology at the University of California, San Diego.

In rodent studies, injecting the hydrogel into the right ventricle improved function, allowing the heart to withstand increases in blood pressure and volume. The treatment also slowed the rate of tissue scarring and maladaptive muscle growth. Hydrogel injections are expected to increase the amount of time a patient’s heart can function.

Although this is not a cure, our goal is to extend the patient’s life. ”

Karen Christman, professor of bioengineering at the University of California, San Diego, and corresponding author of the paper

This treatment dramatically improves patients’ quality of life and may also allow for better cognitive function and growth.

”You may be able to wait until you are on the adult heart transplant list.” said Michael E. Davis, one of the paper’s senior authors, director of the Pediatric Heart Research and Outcomes (HeRO) Center at Children’s Medical Center Atlanta, and professor of biomedical engineering at Georgia Tech and Emory University School of Medicine. Stated.

The hydrogel is made from cardiac extracellular matrix from which cellular contents have been removed through a washing process. Dry and crush into powder. It is then liquefied into a liquid that can be easily injected into the heart. Once body temperature and pH are reached, the liquid transforms into a semi-solid, porous gel that encourages the patient’s own cells to repopulate areas of damaged heart tissue and improve heart function.

positive results

Preclinically, the effects of the treatment were first seen two weeks after injection.

Researchers in Christman’s lab prepared the hydrogel using tissue taken from both the right and left ventricles of pig hearts. Interestingly, the tissues on both sides of the heart are very different.

The hydrogel from both sides of the heart improved contractile function, or the heart’s ability to pump blood. It also reduced myocardial growth and fear while promoting arteriole formation and growth. However, hydrogels derived from left ventricular tissue were more effective overall. This is likely because the hydrogel derived from RV tissue is enriched with type 1 collagen, which may have led to the enhanced inflammatory response seen in the RV hydrogel treatment group.

The injected hydrogels also affected gene expression, particularly pathways related to cardiac repair, such as the circulatory system, muscle structure, vasculature development, and regulation of immune and cellular responses to oxygen-containing compounds. .

Next, Children’s Healthcare of Atlanta, a children’s hospital affiliated with Georgia Tech and Emory, will begin recruiting for a clinical trial investigating the treatment’s effects on newborns with hypoplastic left heart syndrome.

Funding for the study was provided in part by the National Heart, Lung, and Blood Institute of the National Institutes of Health.