When a person has a heart attack, clots or narrowed arteries block blood flow, harming or killing cells within the tissue. After the initial pain subsides, the heart's walls thin out, the organ becomes enlarged and scar tissue forms — all of which can lead to eventual heart failure. A team of scientists has been working to find a way to shore up the heart's weakened areas, and it looks like they've done it.
The American Heart Association reports that 750,000 people each year in the United States suffer heart attacks. Even more alarmingly, 5 million U.S. residents experience symptoms of heart failure, which can range from fatigue and shortness of breath to eventual death. "Heart failure is a huge problem, and few therapies are available for these patients," says Jason A. Burdick, PhD, leader of the study.
Treatment includes lifestyle changes, medication, implants or heart transplants. Burdick, who is at the University of Pennsylvania, explains that these options either don't work well or, in the case of transplants, are hard to come by.
Researchers at other institutions have done animal studies in which they injected cells into the damaged section of the heart to try to repair damage. To prevent the cells from leaking out, those researchers embedded them in biodegradable hydrogels — water-swollen networks of polymer chains with a consistency similar to Jell-O. But these scientists noticed something odd when they injected the hydrogel without the added cells in control experiments. Some of the animals' hearts still showed improvement compared with untreated animals.
As a result of those initial experiments, a few labs are now testing out hydrogel treatments, including two materials that are in clinical trials. Neither is from Burdick's lab, but he believes it's important for everyone to keep moving forward to figure out how the therapy could be used to help patients, "It's different from any current treatment," says Burdick, adding that different types of hydrogels could also suit different patients' needs.
Some experimental heart attack treatments require opening up the chest, but the two hydrogel materials already in clinical trials are injected into the damaged tissue through a long catheter inserted through the skin — eliminating the need for open-chest surgery.
Burdick and his graduate student Christopher B. Rodell, in collaboration with Robert C. Gorman, MD, also at Penn, are using this same minimally invasive technique in their own work. But his team has designed hydrogels with very specific properties. One of the hydrogels that Burdick and his team developed forms additional crosslinks between polymer chains after injection. The resulting material is stiffer and lasts longer than a gel without these additional crosslinks and the gels in clinical trials.
In fact, Burdick's hydrogel is unique because it provides mechanical support to stabilize the damaged area. In sheep studies, this gel limits formation of scar tissue, thinning of the heart's walls and enlargement of the heart. By preserving the organ's size, the gels also reduce leakage of blood through the mitral valve. Together, these benefits maintain the heart's blood-pumping ability and could stave off heart failure.
The team's materials are based on hyaluronic acid (HA), a type of sugar molecule that occurs naturally in the body. The researchers modified the HA molecules by attaching adamantane and cyclodextrin groups to allow the gels to flow through catheters, and they added thiol and methacrylate groups to enable post-injection cross-linking to stiffen the hydrogel. Once the researchers finalize the hydrogel formulation and delivery method, they hope to partner with a catheter firm to bring a product to market.
Burdick's team and other research groups are also designing hydrogels that contain drugs or cells that can repair heart tissue.
The researchers presented their work at the 252nd National Meeting & Exposition of the American Chemical Society (ACS).