New Penn-Designed Gel Allows for Targeted Therapy After Heart Attack

Combatting the tissue degrading enzymes that cause lasting damage following a heart attack is tricky. Each patient responds to a heart attack differently and damage can vary from one part of the heart muscle to another, but existing treatments can't be fine-tuned to deal with this variation.

University of Pennsylvania researchers have developed a way to address this problem via a material that can be applied directly to the damaged heart tissue. The potentially dangerous enzymes break down this gel-like material, releasing enzyme inhibitors contained within. This responsive, balancing approach is ideal for keeping enzymes at the right level to minimize the long-term damage that can lead to congestive heart failure.

The ability of this gel to deliver enzyme inhibitors as needed suggests that the researchers' technique might also find use in other inflammation-related disorders, such as osteoarthritis where the same enzymes degrade cartilage tissue.

A study demonstrating their design's efficacy was published in the journal Nature Materials. It was led by Jason Burdick, professor of bioengineering in Penn's School of Engineering and Applied Science, and Brendan Purcell, a post-doctoral researcher in his lab. Joseph Gorman and Robert Gorman of the Department of Surgery in Penn's Perelman School of Medicine contributed to the research. The Penn team collaborated with Francis G. Spinale of the University of South Carolina School of Medicine, along with members of his research group.

"For heart attack patients, the first priority is restoring blood flow to the heart," Burdick said. "What's neglected, however, are the secondary effects that occur after a heart attack, including what's known as ventricular remodeling."

Remodeling is a phenomenon that ultimately changes the overall shape and performance of the heart. After a heart attack, the body naturally releases enzymes as part of the inflammatory response to injury. But when this response is sustained too long, those enzymes begin to break up the extracellular matrix inside the muscle tissue that makes up the walls of the heart, making it thinner and weaker. The walls balloon out under the pressure of normal heart pumping, resulting in an enlarged heart that pumps less blood with each beat.

Synthetic or lab-grown versions of inhibitors to the tissue-degrading enzymes have been used in clinical trials, but only in a non-targeted fashion. Patients receive them intravenously or orally, with the hope that the inhibitor molecules make their way to the heart.

"As you can imagine, this type of delivery can lead to off-target problems," Burdick said. "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."

"That's where our approach came in," Purcell said. "We used injectable gels to deliver the inhibitors locally, rather than systemically. And to really fine-tune the targeting, the innovation with this material is that it releases the inhibitor in response to the activity level of the enzyme."