Injected liquid forms a gel in damaged heart

A newly developed gel targets a damaged area (red) of the heart (green) after heart attack in a rat. Carlini et al., Nature Communications

Every 40 seconds, someone in the United States has a heart attack. A heart attack happens when the flow of oxygen-rich blood to a section of heart muscle becomes blocked and the heart can’t get oxygen. If blood flow isn’t restored quickly, the heart muscle begins to die. Early treatment for a heart attack can prevent or limit this damage. Limiting the amount of heart damage improves your chance for a better quality of life.

Previous studies have explored the use of protective or healing substances for tissue that’s harmed by inflammation after a heart attack. Inflammation can kill heart muscle cells. It can also damage the scaffold that holds cells together within heart tissue. Unfortunately, scars form after a heart attack that keep the heart from working as well as before.

In lab studies, researchers have shown that hydrogels can reduce scarring in the heart. They can also be used to help deliver drugs to the heart. But most gels are so thick and sticky that they can’t flow through the thin tube of a catheter. Catheters make it possible to inject solutions into the heart without invasive surgery.

Previously, a team of researchers led by Nathan C. Gianneschi at Northwestern University and Dr. Karen L. Christman at the University of California, San Diego, designed a solution of molecules called peptides that could be activated by the inflammatory substances produced during disease. The activation caused the peptide solution to form a scaffold.

For their current study, the team set out to develop a peptide solution that could be injected into heart muscle and form a gel only at the site of damage from a heart attack. The work was funded in part by an NIH Director’s Transformative Research Award and NIH’s National Heart, Lung, and Blood Institute (NHLBI). Results were published on April 15, 2019, in Nature Communications.

First, the team designed a solution of circular peptides that could gel on contact with diseased tissue. They showed that inflammation-related enzymes snipped the circular peptides, causing them to become flat and form a mesh or scaffold.

Next, the team showed that the peptide solution could flow through a catheter when kept at body temperature for an hour. This means that the liquid could be delivered to the heart without surgery. Additional tests using human heart cells and whole blood showed that the peptide solution wasn’t toxic and didn’t cause blood clots.

After that, the team tested whether the solution could safely form a gel at the site of heart damage within the body. One week after heart attacks in female rats, the team injected the cyclic peptide solution into the heart damage. The next day, the researchers analyzed the heart tissue and found the gel only at the site of injury. The gel didn’t kill heart cells, and the unwanted inflammatory response was no greater with peptide gel than with salt water.

“We inject a self-assembling peptide solution that seeks out a target—the heart’s damaged tissue—and the solution is then activated by the inflammatory environment itself and gels,” Gianneschi says. “The key is to have the material create a self-assembling framework, which can then be used as a base to deliver therapeutics to the heart.”

With further development, this approach might be useful for treating heart attacks as well as tissue damage caused by inflammation elsewhere in the body.

—by Geri Piazza