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dc.contributor.authorKelly, Danielen
dc.contributor.authorBuckley, Conoren
dc.date.accessioned2013-08-21T14:05:42Z
dc.date.available2013-08-21T14:05:42Z
dc.date.issued2012en
dc.date.submitted2012en
dc.identifier.citationBuckley CT, Meyer EG, Kelly DJ, The influence of construct scale on the composition and functional properties of cartilaginous tissues engineered using bone marrow-derived mesenchymal stem cells., Tissue engineering. Part A, 18, 3-4, 2012, 382-396en
dc.identifier.issn1937-3341en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/67190
dc.descriptionPUBLISHEDen
dc.description.abstractEngineering cartilaginous tissue of a scale necessary to treat defects observed clinically is a well-documented challenge in the field of cartilage tissue engineering. The objective of this study was to determine how the composition and mechanical properties of cartilaginous tissues that are engineered by using bone marrow-derived mesenchymal stem cells (MSCs) depend on the scale of the construct. Porcine bone marrow-derived MSCs were encapsulated in agarose hydrogels, and constructs of different cylindrical geometries (?4?1.5 mm; ?5?3 mm; ?6?4.5 mm; ?8?4.5?mm) were fabricated and maintained in a chemically defined serum-free medium supplemented with transforming growth factor-?3 for 42 days. Total sulfated glycosaminoglycan (sGAG) accumulation by day 42 increased from 0.14% w/w to 0.88% w/w as the construct geometry increased from ?4?1.5 to ?8?4.5?mm, with collagen accumulation increasing from 0.31% w/w to 1.62% w/w. This led to an increase in the dynamic modulus from 90.81 to 327.51?kPa as the engineered tissue increased in scale from ?4?1.5 to ?8?4.5?mm. By decreasing the external oxygen tension from 20% to 5%, it was possible to achieve these higher levels of mechanical functionality in the smaller engineered tissues. Constructs were then sectioned into smaller subregions to quantify the spatial accumulation of extracellular matrix components, and a model of oxygen diffusion and consumption was used to predict spatial gradients in oxygen concentration throughout the construct. sGAG accumulation was always highest in regions where oxygen concentration was predicted to be lowest. In addition, as the size of the engineered construct increased, different regions of the construct preferentially supported either sGAG or collagen accumulation, thus suggesting that gradients in regulatory factors other than oxygen were playing a role in determining levels of collagen synthesis. The identification of such factors and the means to control their spatial concentration within developing tissues represents a central challenge in engineering large cartilaginous grafts.en
dc.description.sponsorshipSFI 08/Y15/B1336en
dc.format.extent382-396en
dc.language.isoenen
dc.relation.ispartofseriesTissue engineering. Part Aen
dc.relation.ispartofseries18en
dc.relation.ispartofseries3-4en
dc.rightsYen
dc.subjectspatial concentrationen
dc.subject.lcshspatial concentrationen
dc.titleThe influence of construct scale on the composition and functional properties of cartilaginous tissues engineered using bone marrow-derived mesenchymal stem cells.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/kellyd9en
dc.identifier.peoplefinderurlhttp://people.tcd.ie/cbuckleen
dc.identifier.rssinternalid81530en
dc.identifier.doihttp://dx.doi.org/10.1089/ten.tea.2011.0145en
dc.subject.TCDThemeNext Generation Medical Devicesen
dc.identifier.orcid_id0000-0003-4091-0992en


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