Injecting Self-Assembling Artificial Extracellular Matrix into a Damaged Heart

A number of approaches to tissue engineering and regenerative medicine have focused on providing a supporting structure for native cells, to steer their behavior towards regrowth rather than scarring or inactivity. The results here are an example of one class of minimally invasive approach, in which an artificial extracellular matrix material can be injected rather than implanted. In addition to providing a structure that cells favor, this sort of material can be laden with a mix of signal molecules that will aid cell survival and activity. Better repair following damage such as that of a heart attack is a poor second best to preventing the heart attack from occurring in the first place, but it is an incremental improvement over the present state of affairs.

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 delivered to the heart using minimally invasive catheter delivery because they clog the tube. Researchers have now demonstrated a novel way to deliver a bioactivated, biodegradable, regenerative substance through a noninvasive catheter without clogging.

When a person has a heart attack, the extracellular matrix is stripped away and scar tissue forms in its place, decreasing the heart's functionality. Because of this, most heart attack survivors have some degree of heart disease, the leading cause of death in America. "We sought to create a peptide-based approach because the compounds form nanofibers that look and mechanically act very similar to native extracellular matrix. The compounds also are biodegradable and biocompatible. Most preclinical strategies have relied on direct injections into the heart, but because this is not a feasible option for humans, we sought to develop a platform that could be delivered via intracoronary or transendocardial catheter."

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. 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 self-assembling peptides could find their way to the damaged tissue, bypassing healthy heart tissue. Researchers created and attached a fluorescent tag to the self-assembling peptides and then imaged the heart to see where the peptides eventually settled. "In previous work with responsive nanoparticles, we produced speckled fluorescence in the heart attack region, but in this case, we were able to see large continuous hydrogel assemblies throughout the tissue."



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