A heart-implanted patch that delivers time-controlled medication could offer a novel approach to post-infarction repair, preclinical research suggests.
The Temporal Intervention with Microparticle Encapsulation and Delivery (TIMED) programmed release system could allow drugs to be delivered at optimal times during recovery.
Using the hydrogel patch containing the time-release drugs halved the amount of damaged heart tissue in a rat model and significantly improve cardiac function, according to the study published in Cell Biomaterials.
The researchers hope that one day they will be able to incorporate the materials into stents, which could be inserted during angioplasty.
“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,” explained researcher Ana Jaklenec, PhD, at MIT.
“Our goal is to restore that function and help people regain a stronger, more resilient heart after a myocardial infarction.”
To improve recovery after a heart attack, Jaklenec and team created a hydrogel patch embedded with microparticles that could provide sequential drug release. The drugs are contained within poly(lactic-co-glycolic acid), or PLGA, polymer capsules with “lids.” Altering the molecular weight of the polymer lids controls the speed at which they were broken down, enabling the particles to be released in a controlled manner.
The current study included capsules that broke down at one to three days, seven to nine days, and 12 to 14 days after implantation.
Particles were created that initially released the growth factor neuregulin-1, which helps prevent cell death. This was followed by particles that release vascular endothelial growth factor (VEGF), which promotes cardiac blood growth.
Lastly, particles released the small molecule drug called GW788388, which inhibits the formation of scar tissue that can occur following a heart attack but has currently only been tested in animals.
The researchers tested the system in spheres of heart tissue that included cardiomyocytes generated from induced pluripotent stem cells, endothelial cells, and human ventricular cardiac fibroblasts.
These were exposed to a low-oxygen environment to simulate conditions after myocardial infarction and the patches then placed over them, resulting in blood vessel growth, better cell survival, and reduced fibrosis.
In a rat model of myocardial infarction, the patch resulted in a third higher survival compared with intravenous injection of the same drugs or intravenous injection, as well as reducing damaged tissue and improving cardiac output.
“The programmable design of the TIMED system allows incorporation of alternative therapeutic agents and tailored release schedules to better reflect human repair biology and emerging clinical strategies,” the researchers concluded.
They added: “Collectively, these engineering advancements position TIMED as a scalable and versatile platform, with the potential to transform sequential treatment across a broad spectrum of complex diseases.”
