RT Journal Article T1 Cardiac Extracellular Matrix Hydrogel Enriched with Polyethylene Glycol Presents Improved Gelation Time and Increased On-Target Site Retention of Extracellular Vesicles A1 Gómez Cid, Lidia A1 López Donaire, María Luisa A1 Velasco, Diego A1 Marín, Víctor A1 González Tomé, María Isabel A1 Salinas, Beatriz A1 Cussó, Lorena A1 García, Ángel A1 Bravo, Susana Belén A1 Fernández Santos, María Eugenia A1 Elvira Martínez, Carlos María A1 Sierra, Johanna A1 Arroba, Ester A1 Bañares Cañizares, Rafael A1 Grigorian Shamagian, Lilian A1 Fernández-Avilés Díaz, Francisco Jesús AB Stem-cell-derived extracellular vesicles (EVs) have demonstrated multiple beneficial effects in preclinical models of cardiac diseases. However, poor retention at the target site may limit their therapeutic efficacy. Cardiac extracellular matrix hydrogels (cECMH) seem promising as drug-delivery materials and could improve the retention of EVs, but may be limited by their long gelation time and soft mechanical properties. Our objective was to develop and characterize an optimized product combining cECMH, polyethylene glycol (PEG), and EVs (EVs–PEG–cECMH) in an attempt to overcome their individual limitations: long gelation time of the cECMH and poor retention of the EVs. The new combined product presented improved physicochemical properties (60% reduction in half gelation time, p < 0.001, and threefold increase in storage modulus, p < 0.01, vs. cECMH alone), while preserving injectability and biodegradability. It also maintained in vitro bioactivity of its individual components (55% reduction in cellular senescence vs. serum-free medium, p < 0.001, similar to EVs and cECMH alone) and increased on-site retention in vivo (fourfold increase vs. EVs alone, p < 0.05). In conclusion, the combination of EVs–PEG–cECMH is a potential multipronged product with improved gelation time and mechanical properties, increased on-site retention, and maintained bioactivity that, all together, may translate into boosted therapeutic efficacy. PB MPDI SN 1422-0067 YR 2021 FD 2021-08-26 LK https://hdl.handle.net/20.500.14352/4842 UL https://hdl.handle.net/20.500.14352/4842 LA eng NO Gómez Cid, L., López Donaire, M. L., Velasco, D. et al. «Cardiac Extracellular Matrix Hydrogel Enriched with Polyethylene Glycol Presents Improved Gelation Time and Increased On-Target Site Retention of Extracellular Vesicles». International Journal of Molecular Sciences, vol. 22, n.o 17, agosto de 2021, p. 9226. DOI.org (Crossref), https://doi.org/10.3390/ijms22179226. NO Instituto de Salud Carlos III NO Comunidad de Madrid/Fondo Europeo de Desarrollo Regional NO Instituto de Salud Carlos III/Fondo Europeo de Desarrollo Regional DS Docta Complutense RD 9 abr 2025