Exploring New Ways to Fix a Broken Heart

A novel strategy and dynamic material could heal damage from a myocardial infarction. (Image: via   pixabay  /  CC0 1.0)
A novel strategy and dynamic material could heal damage from a myocardial infarction. (Image: via pixabay / CC0 1.0)

Scientists have designed a minimally invasive platform that turns the body’s inflammatory response into a signal to heal, rather than a means of scarring the heart following myocardial infarction.

Although tissue engineering strategies to replace or supplement the degrading extracellular matrix (ECM) following a heart attack are not new, researchers — led by co-principal investigators Nathan Gianneschi, chemistry, biomedical engineering and materials science and engineering; and Karen Christman at the University of California, San Diego — have demonstrated a novel way to deliver a bioactivated, biodegradable, regenerative substance through a noninvasive catheter. The research was published in Nature Communications.

Andrea Carlini, a postdoctoral fellow in the lab of John Rogers, materials science and engineering, who is the paper’s first author, said:

Peptides are short chains of amino acids instrumental for healing. The team’s approach relies on a catheter to deliver self-assembling peptides (SAP) — and a therapeutic — to the heart following myocardial infarction. Gianneschi, a member of Northwestern’s Simpson Querrey Institute as well as its International Institute of Nanotechnology, said:

When a person has a heart attack, the matrix is stripped away and scar tissue often forms in its place, decreasing the heart’s functionality. Because of this, most heart attack survivors have some degree of heart disease, the largest killer in America. The team’s preclinical research was conducted in rats and segmented into two proof of concept tests.

The first test established that the material could be fed through a catheter without clogging and without interacting with human blood. The second determined whether the SAPs could find their way to the damaged tissue, bypassing healthy heart tissue.

Researchers created a fluorescent tag for the SAPs to carry and then imaged the heart to see where the peptides eventually settled. Carlini said:

Researchers now know that when they remove the fluorescent tag and replace it with a drug, the SAP will locate to the affected area of the heart. One hurdle is that catheter delivery in a rodent model is far more complicated — because of the animal’s much smaller body — than the same procedure in a human. This is one aspect where Christman’s lab at UC-San Diego has immense knowledge.

If the team can prove the approach to be efficacious, there is then “a fairly clear path” in terms of progressing toward a clinical trial, says Gianneschi. The process, however, would take several years. Carlini added:

By programming in a spring-like switch, Carlini was able to unfurl these naturally circular compounds to create a flat substance with much more surface area and greater stickiness. The process creates conditions for the peptides to better self-assemble, or stack, atop one another and form the scaffold that so closely resembles the native ECM.

Having demonstrated the platform’s ability to activate in the presence of specific disease-associated enzymes, Gianneschi’s lab has also validated analogous approaches in peripheral artery disease and in metastatic cancer, each of which produces similar chemical and biological inflammatory responses. He added:

Provided by: Northwestern University [Note: Materials may be edited for content and length.]

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