Heal Damage

For people who survive a heart attack, the days immediately following the event are critical for their longevity and long-term healing of the heart’s tissue. Now researchers at Northwestern University and University of California, San Diego (UC San Diego) have design a minimally invasive platform to deliver a nanomaterial that turns the body’s inflammatory response into a signal to heal rather than a means of scarring following a heart attack.
Tissue engineering strategies to replace or supplement the extracellular matrix that degrades following a heart attack are not new, but most promising hydrogels cannot be deliver to the heart using minimally invasive catheter delivery because they clog the tube. The Northwestern-UC San Diego team has demonstrate a novel way to deliver a bioactivated, biodegradable, regenerative substance through a noninvasive catheter without clogging.

Peptide base approach

They sought to create a peptide base approach because the compounds form nano fibers that look and mechanically act very similar to native extracellular matrix. The compounds also are biodegradable and biocompatible,” said first author Andrea Carlini. They now a postdoctoral fellow in the lab of John Rogers; hence in Northwestern’s department of materials science and engineering.

Most pre clinical strategies have relied on direct injections into the heart; but because this is not a feasible option for humans, they sought to develop a platform that be deliver via intracoronary or transendocardial catheter,” said Carlini, who was a graduate student in Gianneschi’s lab when the study was conducted.

Peptides are short chains of amino acids instrumental for healing. The team’s approach relies on a catheter to deliver self-assembling peptides and eventually a therapeutic to the heart following myocardial infarction, or heart attack. What we’ve create is a targeting-and-response type of material,” said Gianneschi; hence associate director of Northwestern’s International Institute of Nanotechnology and a member of the Simpson Querrey Institute.
They inject a self assembling peptide solution that seeks out a target the heart’s damage; so extracellular matrix and the solution is then activate by the inflammatory environment itself and gels,” they said. “The key is to have the material create a self-assembling framework; which mimics the natural scaffold that holds cells and tissues together.”

Proof of concept tests

The team’s preclinical research was conduct in rats and segment into two proof-of-concept tests. The first test establish that the material could be fed through a catheter; so without clogging and without interacting with human blood. The second determine whether the self-assembling peptides could find their way to the damage tissue, bypassing healthy heart tissue.
Researchers now know that when they remove the florescent tag and replace it with a therapeutic; so the self-assembling peptides will locate to the affect 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 area where Christman’s lab at UC San Diego has deep knowledge. If the research team can prove their approach to be efficacious; so then there is “a fairly clear path” in terms of progressing toward a clinical trial, Gianneschi said. The process, however, would take several years.

Having demonstrated the platform’s ability to activate in the presence of specific disease associated enzymes; so Gianneschi’s lab also has validated analogous approaches in peripheral artery disease and in metastatic cancer; hence each of which produce similar chemical and biological inflammatory responses. The Nature Communications paper is titled “Enzyme-responsive progelator cyclic peptides for minimally invasive delivery to the heart post-myocardial infarction.”