Injectable hydrogel with miR-222-engineered extracellular vesicles ameliorates myocardial ischemic reperfusion injury via mechanotransduction

Cell Reports Medicine, 2025 · DOI: https://doi.org/10.1016/j.xcrm.2025.101987 · Published: March 18, 2025

Cardiovascular Science Regenerative Medicine Biomedical

Simple Explanation

This research introduces a new method for treating heart damage after a heart attack, called myocardial ischemic reperfusion injury (IRI). The method involves injecting a special gel (hydrogel) containing tiny sacs (extracellular vesicles) that are engineered to deliver a specific molecule (miR-222) to the damaged heart tissue. The injection of this gel helps to improve heart function and reduce the amount of damage caused by IRI.

Study Duration

3 weeks

Participants

Male C57BL/6 mice

Evidence Level

Not specified

Key Findings

1
Targeting miR-222-engineered EVs are incorporated in mechanical GEL hydrogels
2
Mechanical GEL-TeEV patches attenuate cardiac IRI remodeling
3
Improvements are linked to adhesion, force, and mechanotransduction preservation

Research Summary

The study develops injectable GelMA hydrogels with controlled mechanical properties containing targeting miR-222-engineered extracellular vesicles (TeEVs). These injectable patches facilitate the precise targeting of TeEVs for the efﬁcient rescue of damaged cells, alleviating acute IRI and mitigating remodeling post IRI. The improvements are linked to focal adhesion activation, cytoskeleton force enhancement, and nuclear force-sensing preservation, paving the way for force-sensing approaches to cardiac therapy using bio-engineered therapeutic patches.

Practical Implications

Minimally Invasive Cardiac Repair

The injectable hydrogel patch offers a less invasive method for delivering therapeutics directly to the heart, potentially reducing the risks associated with open-chest surgery.

Targeted Drug Delivery

The use of targeting peptides and engineered extracellular vesicles allows for precise delivery of miR-222 to damaged cardiomyocytes, enhancing therapeutic efficacy.

Improved Cardiac Function

The study demonstrates that the GEL-TeEV patch can effectively mitigate cardiac dysfunction and remodeling post-IRI, suggesting a potential treatment for heart failure.

Study Limitations

1
Non-human primate models were not performed.
2
Long-term TeEV retention effect (over three weeks) is not executed due to the degradability of mechanical hydrogel model.
3
Potential off-targeting effects of TeEVs may partially occur in non-cardiac cells.

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