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Cardiac Extracellular Matrix Hydrogel Enriched with Polyethylene Glycol Presents Improved Gelation Time and Increased On-Target Site Retention of Extracellular Vesicles

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 mate...

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Autores principales: Gómez-Cid, Lidia, López-Donaire, María Luisa, Velasco, Diego, Marín, Víctor, González, María Isabel, Salinas, Beatriz, Cussó, Lorena, García, Ángel, Bravo, Susana Belén, Fernández-Santos, María Eugenia, Elvira, Carlos, Sierra, Johanna, Arroba, Ester, Bañares, Rafael, Grigorian-Shamagian, Lilian, Fernández-Avilés, Francisco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431142/
https://www.ncbi.nlm.nih.gov/pubmed/34502146
http://dx.doi.org/10.3390/ijms22179226
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author Gómez-Cid, Lidia
López-Donaire, María Luisa
Velasco, Diego
Marín, Víctor
González, María Isabel
Salinas, Beatriz
Cussó, Lorena
García, Ángel
Bravo, Susana Belén
Fernández-Santos, María Eugenia
Elvira, Carlos
Sierra, Johanna
Arroba, Ester
Bañares, Rafael
Grigorian-Shamagian, Lilian
Fernández-Avilés, Francisco
author_facet Gómez-Cid, Lidia
López-Donaire, María Luisa
Velasco, Diego
Marín, Víctor
González, María Isabel
Salinas, Beatriz
Cussó, Lorena
García, Ángel
Bravo, Susana Belén
Fernández-Santos, María Eugenia
Elvira, Carlos
Sierra, Johanna
Arroba, Ester
Bañares, Rafael
Grigorian-Shamagian, Lilian
Fernández-Avilés, Francisco
author_sort Gómez-Cid, Lidia
collection PubMed
description 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.
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spelling pubmed-84311422021-09-11 Cardiac Extracellular Matrix Hydrogel Enriched with Polyethylene Glycol Presents Improved Gelation Time and Increased On-Target Site Retention of Extracellular Vesicles Gómez-Cid, Lidia López-Donaire, María Luisa Velasco, Diego Marín, Víctor González, María Isabel Salinas, Beatriz Cussó, Lorena García, Ángel Bravo, Susana Belén Fernández-Santos, María Eugenia Elvira, Carlos Sierra, Johanna Arroba, Ester Bañares, Rafael Grigorian-Shamagian, Lilian Fernández-Avilés, Francisco Int J Mol Sci Article 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. MDPI 2021-08-26 /pmc/articles/PMC8431142/ /pubmed/34502146 http://dx.doi.org/10.3390/ijms22179226 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gómez-Cid, Lidia
López-Donaire, María Luisa
Velasco, Diego
Marín, Víctor
González, María Isabel
Salinas, Beatriz
Cussó, Lorena
García, Ángel
Bravo, Susana Belén
Fernández-Santos, María Eugenia
Elvira, Carlos
Sierra, Johanna
Arroba, Ester
Bañares, Rafael
Grigorian-Shamagian, Lilian
Fernández-Avilés, Francisco
Cardiac Extracellular Matrix Hydrogel Enriched with Polyethylene Glycol Presents Improved Gelation Time and Increased On-Target Site Retention of Extracellular Vesicles
title Cardiac Extracellular Matrix Hydrogel Enriched with Polyethylene Glycol Presents Improved Gelation Time and Increased On-Target Site Retention of Extracellular Vesicles
title_full Cardiac Extracellular Matrix Hydrogel Enriched with Polyethylene Glycol Presents Improved Gelation Time and Increased On-Target Site Retention of Extracellular Vesicles
title_fullStr Cardiac Extracellular Matrix Hydrogel Enriched with Polyethylene Glycol Presents Improved Gelation Time and Increased On-Target Site Retention of Extracellular Vesicles
title_full_unstemmed Cardiac Extracellular Matrix Hydrogel Enriched with Polyethylene Glycol Presents Improved Gelation Time and Increased On-Target Site Retention of Extracellular Vesicles
title_short Cardiac Extracellular Matrix Hydrogel Enriched with Polyethylene Glycol Presents Improved Gelation Time and Increased On-Target Site Retention of Extracellular Vesicles
title_sort cardiac extracellular matrix hydrogel enriched with polyethylene glycol presents improved gelation time and increased on-target site retention of extracellular vesicles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431142/
https://www.ncbi.nlm.nih.gov/pubmed/34502146
http://dx.doi.org/10.3390/ijms22179226
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