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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

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dc.affiliation.dptoUC3M. Departamento de Bioingenieríaes
dc.affiliation.grupoinvUC3M. Grupo de Investigación: Tissue Engineering and Regenerative Medicine (TERMeG)es
dc.contributor.authorGomez Cid, Lidia
dc.contributor.authorLópez-Donaire, María Luisa
dc.contributor.authorVelasco Bayón, Diego
dc.contributor.authorMarín Calahorrano, Víctor-Jesús
dc.contributor.authorGonzález, María Isabel
dc.contributor.authorSalinas Rodríguez, Beatriz
dc.contributor.authorCusso Mula, Lorena
dc.contributor.authorGarcía, Ángel
dc.contributor.authorBravo, Susana Belén
dc.contributor.authorFernández-Santos, María Eugenia
dc.contributor.authorElvira, Carlos
dc.contributor.authorSierra, Johanna
dc.contributor.authorArroba, Ester
dc.contributor.authorBañares, Rafael
dc.contributor.authorGrigorian-Shamagian, Lilian
dc.contributor.authorFernández-Avilés, Francisco
dc.date.accessioned2021-09-30T11:58:17Z
dc.date.available2021-09-30T11:58:17Z
dc.date.issued2021-09-01
dc.descriptionThis article belongs to the Special Issue Extracellular Matrix in Development and Disease 3.0en
dc.description.abstractStem-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.en
dc.description.sponsorshipThis 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".en
dc.format.extent18
dc.identifier.bibliographicCitationInternational Journal of Molecular Sciences, 22(17), 9226.en
dc.identifier.doihttps://doi.org/10.3390/ijms22179226
dc.identifier.issn1422-0067
dc.identifier.publicationfirstpage9226
dc.identifier.publicationissue17
dc.identifier.publicationtitleInternational Journal of Molecular Sciencesen
dc.identifier.publicationvolume22
dc.identifier.urihttps://hdl.handle.net/10016/33348
dc.identifier.uxxiAR/0000028401
dc.language.isoeng
dc.publisherMDPI
dc.rights© 2021 by the authors. 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.en
dc.rightsAtribución 3.0 España*
dc.rights.accessRightsopen accessen
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subject.ecienciaBiología y Biomedicinaes
dc.subject.otherExtracellular vesiclesen
dc.subject.otherHydrogelen
dc.subject.otherExtracellular matrixen
dc.subject.otherDrug deliveryen
dc.subject.otherPolyethylene glycolen
dc.subject.otherCardiac regenerative therapyen
dc.titleCardiac extracellular matrix hydrogel enriched with polyethylene glycol presents improved gelation time and increased on-target site retention of extracellular vesiclesen
dc.typeresearch article*
dc.type.hasVersionVoR*
dspace.entity.typePublication
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