Glue for a broken heart
For people who have suffered a myocardial infarction, the first days after the acute phase of the disease are critical in terms of life expectancy and long-term healing of heart tissue. American researchers at Northwestern University and the University of California at San Diego, led by Professor Nathan C. Gianneschi and Dr. Karen Christman, have developed a minimally invasive platform for introducing nanomaterial into the infarction zone, transforming the inflammatory reaction leading to scarring into the process of normal healing of injuries.
In myocardial infarction, the extracellular matrix is destroyed, in place of which scar tissue is formed, which reduces the functionality of the heart. For this reason, almost all people who have suffered a myocardial infarction have some degree of heart failure.
Tissue engineering strategies involving replacement or replenishment of the extracellular matrix after myocardial infarction are not new for specialists, however, it is impossible to introduce the most suitable hydrogels into the heart tissue with the help of minimally invasive catheters, since they clog the lumen.
The authors propose to solve this problem with the help of biodegradable and biocompatible oligopeptides – short amino acid chains that are activated under inflammatory conditions and form a gel-like material, very similar in appearance and mechanical properties to the extracellular matrix. The introduction of such a material into the area of damage will contribute to the preservation of the integrity of the tissue and its more complete restoration.
Work on the creation of such peptides began in 2012, and the researchers had to make great efforts to obtain a simple material from the point of view of synthesis that responds appropriately to the inflammatory environment. A decisive breakthrough was the production of spatially limited cyclic peptides that freely pass through the catheter and rapidly form hydrogels after contact with inflammation-associated enzymes. In the course of further experiments, linear analogues of these compounds with a larger surface area and higher stickiness were obtained. These properties allow peptides to form a gel framework that is close to the extracellular matrix in properties.
Most of the previously proposed preclinical strategies involved the direct introduction of an artificial extracellular matrix into the heart, but this approach is unacceptable for clinical practice. The authors suggested replacing it with the use of an intracoronary or transendocardial catheter.
At the first stage of their work, they demonstrated in laboratory conditions that therapeutic material can pass through a catheter without clogging its lumen and without interacting with human blood. The experiments of the second stage were devoted to the study of the ability of self-assembling peptides to find their way into damaged tissue, bypassing the preserved areas of the heart muscle. To do this, the researchers synthesized a fluorescent label and attached it to self-assembling peptides that were injected into the heart of mice using a syringe. Subsequent visualization of the heart tissue demonstrated the presence of large hydrogel conglomerates in the areas of damage.
Peptides react to biochemical signals inside the tissue of the post-infarction heart (green), spontaneously forming a gel-like material (red) that promotes healing. The hydrogel attached to the tissue is formed from nanofibers that self-assemble into a volumetric structure (bottom right).
Now experts are confident that peptides, to which a drug will be attached in the future instead of a fluorescent label, will fall precisely into the damaged area of the myocardium. The main problem standing in the way of further research is due to the difficulty of introducing a catheter to rodents due to their small size. However, this task is solvable, and the authors hope to complete preclinical studies within a few years and move on to the clinical stage of developing a new method of therapy.
Article by Andrea S. Carlini et al. Enzyme-responsive progelator cyclic peptides for minimally invasive delivery to the heart post-myocardial infarction is published in the journal Nature Communications.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on materials from Northwestern University: Fixing a broken heart: Exploring new ways to heal damage after a heart attack.