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: Gómez-Cid, L., López-Donaire, M. L., Velasco, Diego, Marín, V., González, M. I., Salinas, B., Cussó, Lorena, García, Á., Bravo, S. B., Fernández-Santos, María Eugenia, Elvira, Carlos, Sierra, J., Arroba, E., Bañares, Rafael, Grigorian-Shamagian, L., Fernández-Avilés, Francisco
Formato: artículo
Fecha de publicación:2021
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/253650
Acesso em linha:http://hdl.handle.net/10261/253650
Access Level:acceso abierto
Palavra-chave:Extracellular vesicles
Hydrogel
Extracellular matrix
Drug delivery
Polyethylene glycol
Cardiac regenerative therap
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spelling Cardiac extracellular matrix hydrogel enriched with polyethylene glycol presents improved gelation time and increased on-target site retention of extracellular vesiclesGómez-Cid, L.López-Donaire, M. L.Velasco, DiegoMarín, V.González, M. I.Salinas, B.Cussó, LorenaGarcía, Á.Bravo, S. B.Fernández-Santos, María EugeniaElvira, CarlosSierra, J.Arroba, E.Bañares, RafaelGrigorian-Shamagian, L.Fernández-Avilés, FranciscoExtracellular vesiclesHydrogelExtracellular matrixDrug deliveryPolyethylene glycolCardiac regenerative therapStem-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.This study was supported by the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Spain. PI16/01123; PI19/00161; Red de Terapia Celular (RD16.0011.0029) and CIBERCV CB16.11.00292). It has also been partially supported by Comunidad de Madrid, projects S2017/BMD- 3867 and EXOHEP-CM S2017/BMD-3727, co-funded by European Structural and Investment Fund, FSE, to RB and by Instituto de Salud Carlos III through the project PT20/00044, co-funded by European Regional Development Fund “A way to make Europe.Molecular Diversity Preservation InternationalInstituto de Salud Carlos IIIEuropean CommissionMinisterio de Ciencia, Innovación y Universidades (España)Comunidad de MadridConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120212021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/253650reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.3390/ijms22179226Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2536502026-05-22T06:33:51Z
dc.title.none.fl_str_mv 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
spellingShingle Cardiac extracellular matrix hydrogel enriched with polyethylene glycol presents improved gelation time and increased on-target site retention of extracellular vesicles
Gómez-Cid, L.
Extracellular vesicles
Hydrogel
Extracellular matrix
Drug delivery
Polyethylene glycol
Cardiac regenerative therap
title_short 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_sort Cardiac extracellular matrix hydrogel enriched with polyethylene glycol presents improved gelation time and increased on-target site retention of extracellular vesicles
dc.creator.none.fl_str_mv Gómez-Cid, L.
López-Donaire, M. L.
Velasco, Diego
Marín, V.
González, M. I.
Salinas, B.
Cussó, Lorena
García, Á.
Bravo, S. B.
Fernández-Santos, María Eugenia
Elvira, Carlos
Sierra, J.
Arroba, E.
Bañares, Rafael
Grigorian-Shamagian, L.
Fernández-Avilés, Francisco
author Gómez-Cid, L.
author_facet Gómez-Cid, L.
López-Donaire, M. L.
Velasco, Diego
Marín, V.
González, M. I.
Salinas, B.
Cussó, Lorena
García, Á.
Bravo, S. B.
Fernández-Santos, María Eugenia
Elvira, Carlos
Sierra, J.
Arroba, E.
Bañares, Rafael
Grigorian-Shamagian, L.
Fernández-Avilés, Francisco
author_role author
author2 López-Donaire, M. L.
Velasco, Diego
Marín, V.
González, M. I.
Salinas, B.
Cussó, Lorena
García, Á.
Bravo, S. B.
Fernández-Santos, María Eugenia
Elvira, Carlos
Sierra, J.
Arroba, E.
Bañares, Rafael
Grigorian-Shamagian, L.
Fernández-Avilés, Francisco
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
European Commission
Ministerio de Ciencia, Innovación y Universidades (España)
Comunidad de Madrid
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Extracellular vesicles
Hydrogel
Extracellular matrix
Drug delivery
Polyethylene glycol
Cardiac regenerative therap
topic Extracellular vesicles
Hydrogel
Extracellular matrix
Drug delivery
Polyethylene glycol
Cardiac regenerative therap
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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/253650
url http://hdl.handle.net/10261/253650
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.3390/ijms22179226
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.198674

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