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In this study, we developed the easily accessible engineered exosomes for treatment of DMD\u2010associated cardiomyopathy and explored the underlying mechanisms in Dmd\u03944 mice, a model harboring hot spot mutation in the dystrophin gene.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Dmd\u03944 mice and their cardiomyopathy phenotype were confirmed by Sanger sequencing, pathological staining, flow cytometry, immunoblotting, single\u2010cell sequencing and echocardiographic analysis. Engineered exosomes, exosomes\u2010 cardiac homing peptide (Exo\u2010CHP), were synthesised and characterised by click chemistry and miRNA sequence, separately. The targeted ability and the therapeutic effects of Exo\u2010CHP were studied in vitro and in vivo. Primary cardiomyocytes were used to study the underlying mechanism of Exo\u2010CHP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Dmd\u03944 mice showed an obvious cardiomyopathy\u2010associated phenotype. Exo\u2010CHP can target myocardium and mitigate pathological progression of cardiomyopathy in Dmd\u03944 mice. The therapeutic effects of intravenously delivered Exo\u2010CHP significantly reduced myocardial inflammation, fibrosis and improved the mice's cardiac function. The rescue effects were mediated through the regulation of gene expression at the transcriptomic level, prevention of dystrophin protein complex degradation, and inhibition of intracellular calcium influx and calpain protease activity. The miR\u201021 knockdown Exo\u2010CHP can counteract the protective effects of Exo\u2010CHP on the calcium content and membrane integrity of primary Dmd\u03944\u2010derived cardiomyocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study demonstrated the feasibility, efficacy and the possible mechanism of mesenchymal stromal cell\u2010derived engineered exosomes, positioning them as a potential cell\u2010free intervention for DMD\u2010associated cardiomyopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70751","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T12:34:16Z","timestamp":1785155656000},"source":"Crossref","is-referenced-by-count":0,"title":["Engineered exosomes improve myocardial cell membrane integrity and heart function in dystrophic cardiomyopathy"],"prefix":"10.1002","volume":"16","author":[{"given":"Qihong","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyuan","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics West China Hospital of Stomatology Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital Sichuan University  Chengdu 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