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Updated: May 24, 2025
Intramyocardial Transplantation of MSC-Loading Injectable Hydrogels after Myocardial Infarction in a Murine Model
Published on: September 20, 2020
Injectable hydrogel with miR-222-engineered extracellular vesicles ameliorates myocardial ischemic reperfusion injury
Yongtao Wang1, Danni Meng1, Xiaohui Shi1
1Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Science, Shanghai University, Nantong 226011, China; Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education), School of Life Science, Shanghai University, Shanghai 200444, China.
Abstract:
Cardiac ischemic reperfusion injury (IRI) significantly exacerbates cardiac dysfunction and heart failure, causing high mortality. Despite the severity of IRI, effective therapeutic strategies remain elusive. Acellular cardiac patches have shown considerable efficacy in delivering therapeutics directly to cardiac tissues. Herein, we develop injectable GelMA (GEL) hydrogels with controlled mechanical properties. Targeting miR-222-engineered extracellular vesicles (TeEVs), tailored with cardiac-ischemia-targeting peptides (CTPs), are developed as ischemic TeEV therapeutics. These TeEVs are encapsulated within mechanical hydrogels to create injectable TeEV-loaded cardiac patches, enabling minimal invasiveness to attenuate IRI. The injectable patches facilitate the precise targeting of TeEVs for the efficient rescue of damaged cells. Persistent delivery of TeEVs into the infarcted region alleviates acute IRI and mitigated remodeling post IRI. This is linked to focal adhesion activation, cytoskeleton force enhancement, and nuclear force-sensing preservation. These findings may pave the way for force-sensing approaches to cardiac therapy using bioengineered therapeutic patches.
