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...
Main Authors: | , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-08-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/22/17/9226 |
id |
doaj-24f11522d6ae47d8bf99bb5df416dd98 |
---|---|
record_format |
Article |
spelling |
doaj-24f11522d6ae47d8bf99bb5df416dd982021-09-09T13:47:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-01229226922610.3390/ijms22179226Cardiac Extracellular Matrix Hydrogel Enriched with Polyethylene Glycol Presents Improved Gelation Time and Increased On-Target Site Retention of Extracellular VesiclesLidia Gómez-Cid0María Luisa López-Donaire1Diego Velasco2Víctor Marín3María Isabel González4Beatriz Salinas5Lorena Cussó6Ángel García7Susana Belén Bravo8María Eugenia Fernández-Santos9Carlos Elvira10Johanna Sierra11Ester Arroba12Rafael Bañares13Lilian Grigorian-Shamagian14Francisco Fernández-Avilés15Department of Cardiology, Hospital General Universitario Gregorio Marañón, 28009 Madrid, SpainDepartamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, 28911 Leganés, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Hospital Gregorio Marañón, 28009 Madrid, SpainDepartment of Cardiology, Hospital General Universitario Gregorio Marañón, 28009 Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Hospital Gregorio Marañón, 28009 Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Hospital Gregorio Marañón, 28009 Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Hospital Gregorio Marañón, 28009 Madrid, SpainInstituto de Investigación Sanitaria de Santiago de Compostela (IDIS), 15706 Santiago de Compostela, SpainInstituto de Investigación Sanitaria de Santiago de Compostela (IDIS), 15706 Santiago de Compostela, SpainDepartment of Cardiology, Hospital General Universitario Gregorio Marañón, 28009 Madrid, SpainInstitute of Polymer Science and Technology, CSIC, Juan de la Cierva 3, 28006 Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Hospital Gregorio Marañón, 28009 Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Hospital Gregorio Marañón, 28009 Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Hospital Gregorio Marañón, 28009 Madrid, SpainDepartment of Cardiology, Hospital General Universitario Gregorio Marañón, 28009 Madrid, SpainDepartment of Cardiology, Hospital General Universitario Gregorio Marañón, 28009 Madrid, SpainStem-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, <i>p</i> < 0.001, and threefold increase in storage modulus, <i>p</i> < 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, <i>p</i> < 0.001, similar to EVs and cECMH alone) and increased on-site retention in vivo (fourfold increase vs. EVs alone, <i>p</i> < 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.https://www.mdpi.com/1422-0067/22/17/9226extracellular vesicleshydrogelextracellular matrixdrug deliverypolyethylene glycolcardiac regenerative therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lidia Gómez-Cid María Luisa López-Donaire Diego Velasco Víctor Marín María Isabel González Beatriz Salinas Lorena Cussó Ángel García Susana Belén Bravo María Eugenia Fernández-Santos Carlos Elvira Johanna Sierra Ester Arroba Rafael Bañares Lilian Grigorian-Shamagian Francisco Fernández-Avilés |
spellingShingle |
Lidia Gómez-Cid María Luisa López-Donaire Diego Velasco Víctor Marín María Isabel González Beatriz Salinas Lorena Cussó Ángel García Susana Belén Bravo María Eugenia Fernández-Santos Carlos Elvira Johanna Sierra Ester Arroba Rafael Bañares Lilian Grigorian-Shamagian Francisco Fernández-Avilés 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 extracellular vesicles hydrogel extracellular matrix drug delivery polyethylene glycol cardiac regenerative therapy |
author_facet |
Lidia Gómez-Cid María Luisa López-Donaire Diego Velasco Víctor Marín María Isabel González Beatriz Salinas Lorena Cussó Ángel García Susana Belén Bravo María Eugenia Fernández-Santos Carlos Elvira Johanna Sierra Ester Arroba Rafael Bañares Lilian Grigorian-Shamagian Francisco Fernández-Avilés |
author_sort |
Lidia Gómez-Cid |
title |
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_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 |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-08-01 |
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, <i>p</i> < 0.001, and threefold increase in storage modulus, <i>p</i> < 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, <i>p</i> < 0.001, similar to EVs and cECMH alone) and increased on-site retention in vivo (fourfold increase vs. EVs alone, <i>p</i> < 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. |
topic |
extracellular vesicles hydrogel extracellular matrix drug delivery polyethylene glycol cardiac regenerative therapy |
url |
https://www.mdpi.com/1422-0067/22/17/9226 |
work_keys_str_mv |
AT lidiagomezcid cardiacextracellularmatrixhydrogelenrichedwithpolyethyleneglycolpresentsimprovedgelationtimeandincreasedontargetsiteretentionofextracellularvesicles AT marialuisalopezdonaire cardiacextracellularmatrixhydrogelenrichedwithpolyethyleneglycolpresentsimprovedgelationtimeandincreasedontargetsiteretentionofextracellularvesicles AT diegovelasco cardiacextracellularmatrixhydrogelenrichedwithpolyethyleneglycolpresentsimprovedgelationtimeandincreasedontargetsiteretentionofextracellularvesicles AT victormarin cardiacextracellularmatrixhydrogelenrichedwithpolyethyleneglycolpresentsimprovedgelationtimeandincreasedontargetsiteretentionofextracellularvesicles AT mariaisabelgonzalez cardiacextracellularmatrixhydrogelenrichedwithpolyethyleneglycolpresentsimprovedgelationtimeandincreasedontargetsiteretentionofextracellularvesicles AT beatrizsalinas cardiacextracellularmatrixhydrogelenrichedwithpolyethyleneglycolpresentsimprovedgelationtimeandincreasedontargetsiteretentionofextracellularvesicles AT lorenacusso cardiacextracellularmatrixhydrogelenrichedwithpolyethyleneglycolpresentsimprovedgelationtimeandincreasedontargetsiteretentionofextracellularvesicles AT angelgarcia cardiacextracellularmatrixhydrogelenrichedwithpolyethyleneglycolpresentsimprovedgelationtimeandincreasedontargetsiteretentionofextracellularvesicles AT susanabelenbravo cardiacextracellularmatrixhydrogelenrichedwithpolyethyleneglycolpresentsimprovedgelationtimeandincreasedontargetsiteretentionofextracellularvesicles AT mariaeugeniafernandezsantos cardiacextracellularmatrixhydrogelenrichedwithpolyethyleneglycolpresentsimprovedgelationtimeandincreasedontargetsiteretentionofextracellularvesicles AT carloselvira cardiacextracellularmatrixhydrogelenrichedwithpolyethyleneglycolpresentsimprovedgelationtimeandincreasedontargetsiteretentionofextracellularvesicles AT johannasierra cardiacextracellularmatrixhydrogelenrichedwithpolyethyleneglycolpresentsimprovedgelationtimeandincreasedontargetsiteretentionofextracellularvesicles AT esterarroba cardiacextracellularmatrixhydrogelenrichedwithpolyethyleneglycolpresentsimprovedgelationtimeandincreasedontargetsiteretentionofextracellularvesicles AT rafaelbanares cardiacextracellularmatrixhydrogelenrichedwithpolyethyleneglycolpresentsimprovedgelationtimeandincreasedontargetsiteretentionofextracellularvesicles AT liliangrigorianshamagian cardiacextracellularmatrixhydrogelenrichedwithpolyethyleneglycolpresentsimprovedgelationtimeandincreasedontargetsiteretentionofextracellularvesicles AT franciscofernandezaviles cardiacextracellularmatrixhydrogelenrichedwithpolyethyleneglycolpresentsimprovedgelationtimeandincreasedontargetsiteretentionofextracellularvesicles |
_version_ |
1717760153669861376 |