Monguió Tortajada, MartaPrat Vidal, CristinaMoron Font, MiriamClos Sansalvador, MartaCalle, AlexandraGastelurrutia, PalomaCserkoova, AdrianaMorancho, AnnaRamírez, Miguel ÁngelRosell, AnnaBayés Genís, AntoniGálvez Montón, CarolinaBorràs i Serres, Francesc EnricRoura, Santiago2021-09-032021-09-032021-07-01https://hdl.handle.net/2445/179846The administration of extracellular vesicles (EV) from mesenchymal stromal cells (MSC) is a promising cell-free nanotherapy for tissue repair after myocardial infarction (MI). However, the optimal EV delivery strategy remains undetermined. Here, we designed a novel MSC-EV delivery, using 3D scaffolds engineered from decellularised cardiac tissue as a cell-free product for cardiac repair. EV from porcine cardiac adipose tissue-derived MSC (cATMSC) were purified by size exclusion chromatography (SEC), functionally analysed and loaded to scaffolds. cATMSC-EV markedly reduced polyclonal proliferation and pro-inflammatory cytokines production (IFNγ, TNFα, IL12p40) of allogeneic PBMC. Moreover, cATMSC-EV recruited outgrowth endothelial cells (OEC) and allogeneic MSC, and promoted angiogenesis. Fluorescently labelled cATMSC-EV were mixed with peptide hydrogel, and were successfully retained in decellularised scaffolds. Then, cATMSC-EV-embedded pericardial scaffolds were administered in vivo over the ischemic myocardium in a pig model of MI. Six days from implantation, the engineered scaffold efficiently integrated into the post-infarcted myocardium. cATMSC-EV were detected within the construct and MI core, and promoted an increase in vascular density and reduction in macrophage and T cell infiltration within the damaged myocardium. The confined administration of multifunctional MSC-EV within an engineered pericardial scaffold ensures local EV dosage and release, and generates a vascularised bioactive niche for cell recruitment, engraftment and modulation of short-term post-ischemic inflammation.14 p.application/pdfengcc by-nc-nd (c) Monguió Tortajada, Marta et al., 2021http://creativecommons.org/licenses/by-nc-nd/3.0/es/Enginyeria de teixitsInfart de miocardiTissue engineeringMyocardial infarctioninfo:eu-repo/semantics/article2021-07-29info:eu-repo/semantics/openAccess33778207