Microneedle Patch Loaded with Exosomes Containing MicroRNA‐29b Prevents Cardiac Fibrosis after Myocardial Infarction

Abstract

Myocardial infarction (MI) is a cardiovascular disease that poses a serious threat to human health. Uncontrolled and excessive cardiac fibrosis after MI has been recognized as a primary contributor to mortality by heart failure. Thus, prevention of fibrosis or alleviation of fibrosis progression is important for cardiac repair. To this end, a biocompatible microneedle (MN) patch based on gelatin is fabricated to load exosomes containing microRNA-29b (miR-29b) mimics with antifibrotic activity to prevent excessive cardiac fibrosis after MI. Exosomes are isolated from human umbilical cord mesenchymal stem cells and loaded with miR-29b mimics via electroporation, which can be internalized effectively in cardiac fibroblasts to upregulate the expression of miR-29b and downregulate the expression of fibrosis-related proteins. After being implanted in the infarcted heart of a mouse MI model, the MN patch can increase the retention of loaded exosomes in the infarcted myocardium, leading to alleviation of inflammation, reduction of the infarct size, inhibition of fibrosis, and improvement of cardiac function. This design explored the MN patch as a suitable platform to deliver exosomes containing antifibrotic biomolecules locally for the prevention of cardiac fibrosis, showing the potential for MI treatment in clinical applications.

Application of stem cells in regeneration medicine

“…MN is a promising new technology that can be used to provide multiple drugs for the treatment of ischemic cardiomyopathy. By encapsulating cardiac stromal cells in fibrin gels and inoculating them on the MN matrix, polymeric MNs create “channels” between MNs and the host myocardium, allowing them to deliver regenerative factors to the damaged myocardium thereby accelerating cardiac repair 287,288 . The activation of hair follicle stem cells (HFSCs) can accelerate the regeneration of hair follicles, but difficulties remain in improving and managing them effectively.…”

Microneedle systems: cell, exosome, and nucleic acid based strategies

“…71 Yuan et al successfully prevented cardiac fibrosis after myocardial infarction by delivering microRNA-29b-loaded exosomes via gelatin MN patches. 72…”

“…71 Yuan et al successfully prevented cardiac fibrosis after myocardial infarction by delivering microRNA-29b-loaded exosomes via gelatin MN patches. 72 To further enhance the effectiveness of exosome-mediated delivery, researchers have combined nanomotors with MN systems to drive the movement of exosomes using self-propelled forces generated through chemical reactions with the surrounding environment (Fig. 12).…”

Mesenchymal Stem Cell-Derived Exosomes for Myocardial Infarction Treatment

“…Inflammation and subsequent fibrosis are important pathological reactions that result in scar formation post-MI. Human umbilical cord MSCs-EXO containing miR-29b have been shown to prevent cardiac fibrosis following MI, leading to a reduction in infarct size and improved cardiac function in a mouse model of MI [86]. Moreover, miR-671 carried by adipose-derived MSC-EXO has been proven to also reduce myocardial fibrosis and inflammation both in vitro and in vivo [77].…”