Injectable Hydrogel Prevents Damage to Heart’s Right Ventricle Due To Chronic Pressure Overload

Hypoplastic left heart syndrome is a serious pediatric condition where the left ventricle is underdeveloped and nonfunctional, accounting for less than 4% of congenital heart defects yet resulting in 40% of newborn heart defect-related deaths. This syndrome has a survival rate of only 35%. Current treatment involves three major open-heart surgeries before age five, aiming to redirect oxygenated blood to the right ventricle. Post-surgery, pediatric patients also require medication, physical therapy, and a specialized diet. However, this treatment burdens the right ventricle, which is typically responsible for pumping blood at lower pressure and volume to the lungs. Over time, this unnatural workload causes the right ventricle to enlarge and scar, eventually leading to heart failure and necessitating a transplant. Now, a new study has led to the development of an injectable hydrogel that can mitigate damage to the right ventricle of the heart with chronic pressure overload.

A research team that included investigators from University of California San Diego (La Jolla, CA, USA) conducted the study in rodents. In 2019, this same hydrogel was demonstrated to be safe for human use through an FDA-approved Phase 1 trial in people who suffered a heart attack. In this case, the injectable hydrogel is intended for children born with hypoplastic left heart syndrome. The hydrogel is made from the cardiac extracellular matrix, which undergoes a process to remove cellular content, is then dried, ground into powder, and liquefied for injection. Upon contact with body temperature and pH, it transforms into a semi-solid, porous gel that promotes cardiac tissue repair and enhances functionality by encouraging the patient’s cells to repopulate damaged areas.

In the rodent study, hydrogels prepared from both the left and right ventricular tissues of pig hearts showed different effects due to inherent tissue differences. The injection into the right ventricle improved heart function, tolerating elevated blood pressure and volume, and reduced tissue scarring and maladaptive muscle growth. While hydrogels from both heart sides improved systolic function, the left-ventricle-derived hydrogel was more effective, potentially due to lower type 1 collagen levels compared to right-ventricle tissue, which showed a heightened inflammatory response.

The hydrogel also influenced gene expression, particularly pathways related to cardiac repair, such as circulatory system development, muscle structure, and vascular regulation, along with immune response and response to oxygen-containing compounds. Based on these preclinical findings, the FDA has authorized an investigational new drug application to begin a clinical trial in pediatric patients following institutional approvals. This trial will examine the hydrogel’s effectiveness in newborns with hypoplastic left heart syndrome with the aim of extending the functional period of the patient’s heart, significantly improving their quality of life, cognitive function, and growth.

“To the best of our knowledge, it’s the first time that an injectable biomaterial therapy has been evaluated to mitigate right ventricular heart failure,” said Jervaughn D. Hunter from UC San Diego.

“This isn’t a cure, but our goal is to prolong a patient’s life,” added Karen Christman, a bioengineering professor at UC San Diego.

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