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dc.contributor.authorMartínez Ledo, Adriana
dc.contributor.authorVining, Kyle H.
dc.contributor.authorAlonso Fernández, María José
dc.contributor.authorGarcía Fuentes, Marcos
dc.contributor.authorMooney, David J.
dc.date.accessioned2020-09-01T06:32:14Z
dc.date.available2022-05-15T01:00:09Z
dc.date.issued2020
dc.identifier.citationActa Biomaterialia. Volume 110, 1 July 2020, Pages 153-163
dc.identifier.issn1742-7061
dc.identifier.urihttp://hdl.handle.net/10347/23246
dc.description.abstractGene delivery within hydrogel matrices can potentially direct mesenchymal stem cells (MSCs) towards a chondrogenic fate to promote regeneration of cartilage. Here, we investigated whether the mechanical properties of the hydrogel containing the gene delivery systems could enhance transfection and chondrogenic programming of primary human bone marrow-derived MSCs. We developed collagen-I-alginate interpenetrating polymer network hydrogels with tunable stiffness and adhesion properties. The hydrogels were activated with nanocomplexed SOX9 polynucleotides to direct chondrogenic differentiation of MSCs. MSCs transfected within the hydrogels showed higher expression of chondrogenic markers compared to MSCs transfected in 2D prior to encapsulation. The nanocomplex uptake and resulting expression of transfected SOX9 were jointly enhanced by increased stiffness and cell-adhesion ligand density in the hydrogels. Further, transfection of SOX9 effectively induced MSCs chondrogenesis and reduced markers of hypertrophy compared to control matrices. These findings highlight the importance of matrix stiffness and adhesion as design parameters in gene- activated matrices for regenerative medicine.
dc.description.sponsorshipThis work has been funded by Ministerio de Economía y Competitividad (MINECO-RETOS, Grant MAT2017-84361-R, Feder Funds), Fundación BBVA 2014-PO0110, Xunta de Galicia (Grupos de Referencia Competitiva, Feder Funds) and the National Institute of Dental and Craniofacial Research of the National Institutes of Health under Award Number R01DE013033 (D.J.M.). A. M. L. was supported by a FPU fellowship from the Spanish Ministry of Education (FPU12/05528). K. H. V. was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under Award Number K08DE025292
dc.language.isoeng
dc.publisherElsevier
dc.rights© 2020 Acta Materialia Inc. Published by Elsevier Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectGAMs
dc.subjectIPNs
dc.subject3D transfection
dc.subjectSOX9
dc.subjectTissue engineering
dc.titleExtracellular matrix mechanics regulate transfection and SOX9-directed differentiation of mesenchymal stem cells
dc.typeinfo:eu-repo/semantics/article
dc.identifier.DOI10.1016/j.actbio.2020.04.027
dc.relation.publisherversionhttps://doi.org/10.1016/j.actbio.2020.04.027
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.rights.accessrightsinfo:eu-repo/semantics/embargoedAccess
dc.contributor.affiliationUniversidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas
dc.contributor.affiliationUniversidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica
dc.description.peerreviewedSI


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© 2020 Acta Materialia Inc. Published by Elsevier Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Except where otherwise noted, this item's license is described as  © 2020 Acta Materialia Inc. Published by Elsevier Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license (http://creativecommons.org/licenses/by-nc-nd/4.0/)





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