Decellularized myocardial patch functionalized with stem cell-derived exosomes improves cardiac healing after infarction

Masoumeh Sepehri; Jafar Ai; Neda Bayat; Naghmeh Bahrami; Nasrin Lotfibakhshaiesh; Ali Mohammad; Hosein Ghanbari; Amir Nahanmoghadam; Majid Sharifi; Resa Naser; Mohsen Abedini Esfahlani; Shahram Rabbani; Somayeh Ebrahimi-Barough

doi:10.1016/j.tice.2026.103737

Decellularized myocardial patch functionalized with stem cell-derived exosomes improves cardiac healing after infarction

Tissue Cell. 2026 Jun 26:103:103737. doi: 10.1016/j.tice.2026.103737. Online ahead of print.

Affiliations

¹ Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
² Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, Iran.
³ Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN, USA.
⁴ Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
⁶ Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
⁷ Research Center for Advanced Technologies in Cardiovascular Medicine, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: sh-rabbani@tums.ac.ir.
⁸ Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA. Electronic address: ebrahimi_s@sina.tums.ac.ir.

PMID: 42372499
DOI: 10.1016/j.tice.2026.103737

Abstract

Acute myocardial infarction (AMI) leads to irreversible cardiomyocyte loss, extracellular matrix (ECM) disruption, and progressive ventricular remodeling, for which effective regenerative therapies remain limited. While cell-based cardiac patches have shown promise, their clinical translation is hindered by poor graft survival, immune incompatibility, and safety concerns. Acellular ECM-based scaffolds offer a safer alternative but lack sufficient biological activity to drive robust repair. To address these limitations, we developed a novel exosome-loaded acellular myocardial patch (EXO-AMP) that combines the structural advantages of decellularized myocardium with the potent paracrine activity of human endometrial mesenchymal stem cell-derived exosomes (hEnMSC-EXOs) delivered via a fibrin hydrogel. Rat left ventricular myocardium was decellularized using Triton X-100 and SDS, producing scaffolds with preserved ultrastructure, negligible residual DNA (∼3.83 ng/mg), and favorable mechanical properties in the hydrated state. hEnMSCs displayed strong adhesion and proliferation on the acellular myocardial patches (AMPs), confirming excellent cytocompatibility. Exosomes were incorporated into a fibrin hydrogel layer and loaded onto AMPs to create EXO-AMPs. In a rat model of acute MI, EXO-AMPs were implanted immediately after LAD ligation and evaluated over 30 days. EXO-AMP treatment significantly improved cardiac function compared with AMP-only and untreated MI groups, as demonstrated by higher LVEF, reduced LV dilation, and improved systolic performance. Histological analyses revealed thicker infarct walls, reduced fibrosis, increased viable myocardium, and robust angiogenesis, confirmed by elevated CD31 expression. These findings suggest that EXO-AMPs provide synergistic mechanical reinforcement and sustained paracrine signaling, creating a pro-regenerative microenvironment that attenuates post-infarction remodeling. Overall, EXO-AMPs represent a promising next-generation biomaterial that integrates structural ECM support with biologically active exosome therapy, offering a powerful platform for myocardial repair with strong translational potential.

Keywords: Acellular heart patch; Acute myocardial infarction; Endometrial stem cells; Exosome; Heart regeneration.