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dc.contributor.authorLarson, Benjamin
dc.contributor.authorYu, Sarah N.
dc.contributor.authorPark, Hyoungshin
dc.contributor.authorWu, Patrick B.
dc.contributor.authorLanger, Robert S
dc.contributor.authorFreed, Lisa E
dc.date.accessioned2020-08-25T15:37:44Z
dc.date.available2020-08-25T15:37:44Z
dc.date.issued2019-08
dc.identifier.issn1932-7005
dc.identifier.issn1932-6254
dc.identifier.urihttps://hdl.handle.net/1721.1/126797
dc.description.abstractThe development of mechanically functional cartilage and bone tissue constructs of clinically relevant size, as well as their integration with native tissues, remains an important challenge for regenerative medicine. The objective of this study was to assess adult human mesenchymal stem cells (MSCs) in large, three-dimensionally woven poly(ε-caprolactone; PCL) scaffolds in proximity to viable bone, both in a nude rat subcutaneous pouch model and under simulated conditions in vitro. In Study I, various scaffold permutations—PCL alone, PCL-bone, “point-of-care” seeded MSC-PCL-bone, and chondrogenically precultured Ch-MSC-PCL-bone constructs—were implanted in a dorsal, ectopic pouch in a nude rat. After 8 weeks, only cells in the Ch-MSC-PCL constructs exhibited both chondrogenic and osteogenic gene expression profiles. Notably, although both tissue profiles were present, constructs that had been chondrogenically precultured prior to implantation showed a loss of glycosaminoglycan (GAG) as well as the presence of mineralization along with the formation of trabecula-like structures. In Study II of the study, the GAG loss and mineralization observed in Study I in vivo were recapitulated in vitro by the presence of either nearby bone or osteogenic culture medium additives but were prevented by a continued presence of chondrogenic medium additives. These data suggest conditions under which adult human stem cells in combination with polymer scaffolds synthesize functional and phenotypically distinct tissues based on the environmental conditions and highlight the potential influence that paracrine factors from adjacent bone may have on MSC fate, once implanted in vivo for chondral or osteochondral repair.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grants R42 AR055404, P41 EB021911, P30 AR057235, P30 AR073752, OD10707))en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Grant P30CA014051)en_US
dc.language.isoen
dc.publisherWileyen_US
dc.relation.isversionof10.1002/TERM.2899en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.sourcePMCen_US
dc.titleChondrogenic, hypertrophic, and osteochondral differentiation of human mesenchymal stem cells on three‐dimensionally woven scaffoldsen_US
dc.typeArticleen_US
dc.identifier.citationLarson, Benjamin L. et al. “Chondrogenic, hypertrophic, and osteochondral differentiation of human mesenchymal stem cells on three‐dimensionally woven scaffolds.” Journal of Tissue Engineering and Regenerative Medicine, 13, 8 (August 2019): 1453–1465 © 2019 The Author(s)en_US
dc.contributor.departmentDavid H. Koch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentInstitute for Medical Engineering and Scienceen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.relation.journalJournal of Tissue Engineering and Regenerative Medicineen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2020-08-24T13:16:06Z
dspace.date.submission2020-08-24T13:16:08Z
mit.journal.volume13en_US
mit.journal.issue8en_US
mit.licenseOPEN_ACCESS_POLICY


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