[Image courtesy of the researchers]
The patch, placed on the heart after a heart attack, can help both heal and regenerate cardiac tissue. MIT said its engineers designed the patch to carry several different drugs capable of release at different times on a pre-programmed schedule.
In a study of rats, the researchers demonstrated that the treatment reduced the amount of damaged heart tissue by 50%. According to the MIT website, findings also included significantly improved cardiac function.
The researchers say that, if approved for use in humans, the patch could help heart attack victims recover more cardiac function than currently possible.
“When someone suffers a major heart attack, the damaged cardiac tissue doesn’t regenerate effectively, leading to a permanent loss of heart function. The tissue that was damaged doesn’t recover,” said Ana Jaklenec, a principal investigator at MIT’s Koch Institute for Integrative Cancer Research. “Our goal is to restore that function and help people regain a stronger, more resilient heart after a myocardial infarction.”
Jaklenec served as senior author for the new study alongside Robert Langer, the David H. Koch Institute Professor at MIT. Their findings appeared in Cell Biomaterials with former MIT postdoc Erika Wang is serving as lead author for the paper.
The aim of the MIT researchers
According to MIT, many patients have bypass surgery after a heart attack. This procedure improves blood flow but fails to repair the damaged cardiac tissue, according to the researchers. So, the MIT team set forth to create a patch capable of application to the heart at the same time as surgery.
The team sought to deliver drugs over an extended period of time as diseases such as heart conditions require phase-specific treatment. However, they say most available systems release drugs all at once. The researchers believed that timed delivery would better synchronize therapy and recovery.
“We wanted to see if it’s possible to deliver a precisely orchestrated therapeutic intervention to help heal the heart, right at the site of damage, while the surgeon is already performing open-heart surgery,” Jaklenec said.
The researchers sought to adapt drug delivery microparticles they already developed in previous efforts. MIT says these microparticles consist of capsules “similar to tiny coffee cups with lids.” The capsules are made from PLGA, a polymer, and can be sealed with a drug inside.
MIT said the researchers can change the molecular weight of the polymers used to form the lids to control how quickly they degrade. This enables them to program certain releases at specific times. To conduct the study, they designed particles that break down during days 1-3, 7-9 and 12-14 after implantation.
This method allowed for a regimen of three drugs that promote heart healing in different ways. The first set released neuregulin-1, a growth factor that helps to prevent cell death. Next, it released VEGF, a growth factor that promotes formation of blood vessels surrounding the heart. Finally, it released a small-molecule drug called GW788388, which inhibits the formation of scar tissue.
The researchers embedded rows of the particles into thin sheets of a hydrogel made from alginate and PEGDA. For the study, they created compact, miniature patches only a few millimeters across.
“We encapsulate arrays of these particles in a hydrogel patch, and then we can surgically implant this patch into the heart. In this way, we’re really programming the treatment into this material,” Wang says.
Testing the drug delivery patches
The researchers tested their patches on spheres of heart tissue including cardiomyocytes generated from induced pluripotent stem cells. These spheres included endothelial cells and human ventricular cardiac fibroblasts.
Mimicking the effects of a heart attack, the researchers exposed the tissue to low-oxygen conditions then applied the patches. According to MIT, they found that the patches promoted blood vessel growth, helped cell survival and reduced the amount of developed fibrosis.
Testing on a rat model of a heart attack, the researchers also saw significant improvements following treatment. Animals treated with the patch showed 33% higher survival rates than those with no treatment or IV injection of the same drugs. Researchers also saw a 50% reduction in the amount of damaged tissue and significantly increased cardiac output.
MIT said the researchers observed that the patches eventually dissolve over time. Eventually, they become a very thin layer over the course of a year without disrupting the heart’s mechanical function.
The patch requires surgical implantation. However, the researchers want to explore using the microparticles in stents for drug delivery on a programmed schedule.
“This is an important way to combine drug delivery and biomaterials to potentially new treatments for patients,” Langer said.
