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dc.contributor.authorMiller, Rachel Elizabeth
dc.contributor.authorMroszczyk, Keri A.
dc.contributor.authorLee, Richard T.
dc.contributor.authorPatwari, Parth
dc.contributor.authorGrodzinsky, Alan J.
dc.contributor.authorFlorine, Emily Marie
dc.contributor.authorLiebesny, Paul Hancock
dc.date.accessioned2015-03-04T16:05:05Z
dc.date.available2015-03-04T16:05:05Z
dc.date.issued2014-10
dc.date.submitted2013-11
dc.identifier.issn1937-3341
dc.identifier.issn1937-335X
dc.identifier.urihttp://hdl.handle.net/1721.1/95793
dc.description.abstractHeparin-binding insulin-like growth factor 1 (HB-IGF-1) is a fusion protein of IGF-1 with the HB domain of heparin-binding epidermal growth factor-like growth factor. A single dose of HB-IGF-1 has been shown to bind specifically to cartilage and to promote sustained upregulation of proteoglycan synthesis in cartilage explants. Achieving strong integration between native cartilage and tissue-engineered cartilage remains challenging. We hypothesize that if a growth factor delivered by the tissue engineering scaffold could stimulate enhanced matrix synthesis by both the cells within the scaffold and the adjacent native cartilage, integration could be enhanced. In this work, we investigated methods for adsorbing HB-IGF-1 to self-assembling peptide hydrogels to deliver the growth factor to encapsulated chondrocytes and cartilage explants cultured with growth factor-loaded hydrogels. We tested multiple methods for adsorbing HB-IGF-1 in self-assembling peptide hydrogels, including adsorption prior to peptide assembly, following peptide assembly, and with/without heparan sulfate (HS, a potential linker between peptide molecules and HB-IGF-1). We found that HB-IGF-1 and HS were retained in the peptide for all tested conditions. A subset of these conditions was then studied for their ability to stimulate increased matrix production by gel-encapsulated chondrocytes and by chondrocytes within adjacent native cartilage. Adsorbing HB-IGF-1 or IGF-1 prior to peptide assembly was found to stimulate increased sulfated glycosaminoglycan per DNA and hydroxyproline content of chondrocyte-seeded hydrogels compared with basal controls at day 10. Cartilage explants cultured adjacent to functionalized hydrogels had increased proteoglycan synthesis at day 10 when HB-IGF-1 was adsorbed, but not IGF-1. We conclude that delivery of HB-IGF-1 to focal defects in cartilage using self-assembling peptide hydrogels is a promising technique that could aid cartilage repair via enhanced matrix production and integration with native tissue.en_US
dc.description.sponsorshipNational Science Foundation (U.S.). Graduate Research Fellowship Programen_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant EB003805)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant AR060331)en_US
dc.description.sponsorshipWhitaker Health Sciences Fund Fellowshipen_US
dc.description.sponsorshipMassachusetts Life Sciences Centeren_US
dc.description.sponsorshipBiomeasure, Inc.en_US
dc.language.isoen_US
dc.publisherMary Ann Liebert, Inc.en_US
dc.relation.isversionofhttp://dx.doi.org/10.1089/ten.TEA.2013.0679en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceMary Ann Lieberten_US
dc.titleDelivering Heparin-Binding Insulin-Like Growth Factor 1 with Self-Assembling Peptide Hydrogelsen_US
dc.typeArticleen_US
dc.identifier.citationFlorine, Emily M., Rachel E. Miller, Paul H. Liebesny, Keri A. Mroszczyk, Richard T. Lee, Parth Patwari, and Alan J. Grodzinsky. “Delivering Heparin-Binding Insulin-Like Growth Factor 1 with Self-Assembling Peptide Hydrogels.” Tissue Engineering Part A 21, no. 3–4 (February 2015): 637–646. © 2014 Mary Ann Liebert, Inc.en_US
dc.contributor.departmentLincoln Laboratoryen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.mitauthorFlorine, Emily Marieen_US
dc.contributor.mitauthorLiebesny, Paul Hancocken_US
dc.contributor.mitauthorMroszczyk, Keri A.en_US
dc.contributor.mitauthorGrodzinsky, Alan J.en_US
dc.relation.journalTissue Engineering. Part Aen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsFlorine, Emily M.; Miller, Rachel E.; Liebesny, Paul H.; Mroszczyk, Keri A.; Lee, Richard T.; Patwari, Parth; Grodzinsky, Alan J.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-4942-3456
dc.identifier.orcidhttps://orcid.org/0000-0002-4121-8183
dc.identifier.orcidhttps://orcid.org/0000-0002-5770-838X
mit.licensePUBLISHER_POLICYen_US


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