Penn-designed gel soothes hearts after attack

Surviving a heart attack means coping with the damage it leaves behind. Even if blood flow to muscle tissue in the heart is promptly restored, the injury causes an inflammation response, and the accompanying enzymes can wreak havoc that can persist for months and even years.

This lasting damage can be as serious as the immediate threat posed by a heart attack, often leading to congestive heart failure as the muscle tissue is weakened and less able to pump blood.

An interdisciplinary Penn team has come up with a new material that addresses this problem in a personalized way. They have designed a drug-delivering gel that dissolves in the presence of the damaging enzymes, releasing enzyme inhibitors in the process.

The team was led by Jason Burdick, a professor of bioengineering in the School of Engineering and Applied Science, and Brendan Purcell, a post-doc in his lab. They collaborated with Joseph Gorman and Robert Gorman of the Perelman School of Medicine, as well as researchers from the University of South Carolina School of Medicine.

Post-heart attack therapies involving enzyme inhibitors have been tried in the past, but without a delivery mechanism to get them only to the heart—specifically, the parts where enzymes are overactive—they can do more harm than good.

“In other tissues where enzymes and inhibitors are in balance, these extra inhibitors can throw that balance off. This can cause the stiffening of joints, for example,” Burdick says.

To tailor the release of inhibitors to the presence of the enzyme activity they quell, the researchers encapsulated them in a material known as a hydrogel. Not only did this squishy network of sugars mimic how inhibitors are retained within the body’s tissues, it allowed the team to add custom cross-linking chemistry to hold the gel together and give it its responsive properties.

By choosing cross-linking bonds that the heart tissue-damaging enzyme could break down, the gel is able to remain stable for weeks, keeping its therapeutic molecules locked away until needed.

“Once we add the enzymes,” Burdick says, “we can make the gel degrade away within a few hours. We also showed that the level of enzyme correlates very nicely with how fast the gel degrades away and releases the inhibitor.”

The researchers are hopeful that these results will pave the way toward clinical use in human patients, where the gel would be applied to hearts via a catheter after the acute danger of a heart attack has passed. They believe this approach—preventing further damage rather than trying to regenerate lost tissue—will ultimately be more effective in preventing the onset of congestive heart failure.

Heart Attack Gel