Show simple item record

dc.contributor.authorThorpe, SDen_US
dc.contributor.authorNagel, Ten_US
dc.contributor.authorCarroll, SFen_US
dc.contributor.authorKelly, DJen_US
dc.date.accessioned2016-07-22T12:52:33Z
dc.date.available2013-03-02en_US
dc.date.issued2013en_US
dc.date.submitted2016-05-26T17:10:31.241Z
dc.identifier.other10.1371/journal.pone.0060764
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/13628
dc.descriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.description.abstractEngineering organs and tissues with the spatial composition and organisation of their native equivalents remains a major challenge. One approach to engineer such spatial complexity is to recapitulate the gradients in regulatory signals that during development and maturation are believed to drive spatial changes in stem cell differentiation. Mesenchymal stem cell (MSC) differentiation is known to be influenced by both soluble factors and mechanical cues present in the local microenvironment. The objective of this study was to engineer a cartilaginous tissue with a native zonal composition by modulating both the oxygen tension and mechanical environment thorough the depth of MSC seeded hydrogels. To this end, constructs were radially confined to half their thickness and subjected to dynamic compression (DC). Confinement reduced oxygen levels in the bottom of the construct and with the application of DC, increased strains across the top of the construct. These spatial changes correlated with increased glycosaminoglycan accumulation in the bottom of constructs, increased collagen accumulation in the top of constructs, and a suppression of hypertrophy and calcification throughout the construct. Matrix accumulation increased for higher hydrogel cell seeding densities; with DC further enhancing both glycosaminoglycan accumulation and construct stiffness. The combination of spatial confinement and DC was also found to increase proteoglycan-4 (lubricin) deposition toward the top surface of these tissues. In conclusion, by modulating the environment through the depth of developing constructs, it is possible to suppress MSC endochondral progression and to engineer tissues with zonal gradients mimicking certain aspects of articular cartilage.en_US
dc.description.sponsorshipFunding was provided by Science Foundation Ireland (President of Ireland Young Researcher Award: 08/Y15/B1336) and the European Research Council (StemRepair – Project number 258463).en_US
dc.format.extente60764 - ?en_US
dc.languageengen_US
dc.language.isoenen_US
dc.relation.ispartofPLoS Oneen_US
dc.subjectAnimalsen_US
dc.subjectCartilage, Articularen_US
dc.subjectCells, Cultureden_US
dc.subjectGlycosaminoglycansen_US
dc.subjectHydrogelsen_US
dc.subjectImmunohistochemistryen_US
dc.subjectMesenchymal Stem Cellsen_US
dc.subjectModels, Theoreticalen_US
dc.subjectProteoglycansen_US
dc.subjectSwineen_US
dc.titleModulating gradients in regulatory signals within mesenchymal stem cell seeded hydrogels: a novel strategy to engineer zonal articular cartilage.en_US
dc.typeArticle
dc.rights.holder2013. Thorpe at al
dc.identifier.doi10.1371/journal.pone.0060764en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/23613745en_US
pubs.issue4en_US
pubs.notesNot knownen_US
pubs.notesInitial upload not completed by author, 26/05/2016; completed on behalf of the author, 14/07/2016, SMen_US
pubs.publication-statusPublished onlineen_US
pubs.volume8en_US
dcterms.dateAccepted2013-03-02en_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record