NIH grant recipients to develop novel coronary heart disease treatment

Growth of blood vessels (red arrows) after the insertion of the implant. Credit: Christie ZhangAll Rights Reserved.

UNIVERSITY PARK, Pa. — The National Institutes of Health awarded Penn State and University of Akron researchers a $2 million grant to develop a novel implant patch that can release protein drugs as needed for improved treatment of coronary heart disease.

Coronary heart disease, or ischemic heart disease, includes heart problems caused by narrowed heart arteries, which in turn result in less blood and oxygen reaching the heart muscle. It can ultimately lead to a heart attack, known clinically as a myocardial infarction (MI). Coronary heart disease is the most common cardiovascular ailment, affecting approximately 15 million Americans and accounting for approximately 2,150 American deaths every day.

“In general, an initial therapy for acute MI is to restore blood delivery to tissues as quickly as possible,” said Yong Wang, professor of biomedical engineering at Penn State and co-principal investigator on the grant. “Thus, we can salvage as much of the endangered heart muscle as possible. This currently may be accomplished through medical or mechanical means, such as administration of clot-dissolving drugs, coronary angioplasty, coronary artery bypass graft surgery or any combination of these.”

The implant Wang’s lab is developing aims to improve on these treatments and has multiple functions — for example, angiogenesis. 

“Angiogenesis means the growth of new blood vessels,” Wang said. “The idea of angiogenesis is that we can create new vessels in the location where original blood vessels are blocked so that blood can flow through new vessels while the original ones are blocked. Thus, the heart still can get blood flow and the heart muscle still can survive and function.”

Angiogenesis would happen when angiogenic growth factors, specific proteins that incite growth of blood vessels, are introduced to the affected region of the heart. 

“The angiogenic factors stimulate the growth of endothelial cells and smooth muscle cells, which are key cells of our blood vessels,” Wang said. 

The controlled release of these therapies via the implant is carried out by a process that Wang’s lab developed, where aptamers, short strands of DNA that bind to the protein drug molecules, are incorporated into hydrogels, polymer chains which mimic the structure of tissue. 

“The proteins are released through diffusion coupled with molecular binding,” Wang said. “It is anticipated that aptamer-functionalized patches implanted in the heart would stably sequester therapeutic proteins in the implant and release them in a sustained manner.”

Wang describes the process as part of what his lab has coined “biomimetic intelligence.”

“Biomimetic intelligence refers to designing specific molecules, structures, materials, devices or even tissues that can resemble or exceed their natural counterparts in certain functions,” he said.

The researchers will test the functionality of the implant in rats. If everything goes well, they will test it in bigger animals and eventually enter clinical trials.

“The treatment of MI remains challenging today,” Wang said. "The ability to develop multifunctional implants for local delivery of therapeutic agents holds great potential to open a new and better avenue of treatment for the millions stricken with pulmonary heart disease.”

Christie Zhang, associate professor of biomedical engineering at the University of Akron, is co-principal investigator on the grant. Other researchers from Penn State include Lidya Abune, doctoral candidate in biomedical engineering, and Nan Zhao, graduate research assistant in biomedical engineering.

Last Updated July 31, 2020