Osteochondral tissue regeneration through polymeric delivery of DNA encoding for the SOX trio and RUNX2

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dc.citation.firstpage4103en_US
dc.citation.issueNumber10en_US
dc.citation.journalTitleActa Biomaterialiaen_US
dc.citation.lastpage4112en_US
dc.citation.volumeNumber10en_US
dc.contributor.authorNeedham, Clark J.en_US
dc.contributor.authorShah, Sarita R.en_US
dc.contributor.authorDahlin, Rebecca L.en_US
dc.contributor.authorKinard, Lucas A.en_US
dc.contributor.authorLam, Johnnyen_US
dc.contributor.authorWatson, Brendan M.en_US
dc.contributor.authorLu, Stevenen_US
dc.contributor.authorKasper, F. Kurtisen_US
dc.contributor.authorMikos, Antonios G.en_US
dc.contributor.orgBioengineeringen_US
dc.date.accessioned2017-06-12T21:49:43Zen_US
dc.date.available2017-06-12T21:49:43Zen_US
dc.date.issued2014en_US
dc.description.abstractNative osteochondral repair is often inadequate owing to the inherent properties of the tissue, and current clinical repair strategies can result in healing with a limited lifespan and donor site morbidity. This work investigates the use of polymeric gene therapy to address this problem by delivering DNA encoding for transcription factors complexed with the branched poly(ethylenimine)–hyaluronic acid (bPEI–HA) delivery vector via a porous oligo[poly(ethylene glycol) fumarate] hydrogel scaffold. To evaluate the potential of this approach, a bilayered scaffold mimicking native osteochondral tissue organization was loaded with DNA/bPEI–HA complexes. Next, bilayered implants either unloaded or loaded in a spatial fashion with bPEI–HA and DNA encoding for either Runt-related transcription factor 2 (RUNX2) or SRY (sex determining region Y)-box 5, 6, and 9 (the SOX trio), to generate bone and cartilage tissues respectively, were fabricated and implanted in a rat osteochondral defect. At 6 weeks post-implantation, micro-computed tomography analysis and histological scoring were performed on the explants to evaluate the quality and quantity of tissue repair in each group. The incorporation of DNA encoding for RUNX2 in the bone layer of these scaffolds significantly increased bone growth. Additionally, a spatially loaded combination of RUNX2 and SOX trio DNA loading significantly improved healing relative to empty hydrogels or either factor alone. Finally, the results of this study suggest that subchondral bone formation is necessary for correct cartilage healing.en_US
dc.identifier.citationNeedham, Clark J., Shah, Sarita R., Dahlin, Rebecca L., et al.. "Osteochondral tissue regeneration through polymeric delivery of DNA encoding for the SOX trio and RUNX2." <i>Acta Biomaterialia,</i> 10, no. 10 (2014) Elsevier: 4103-4112. https://doi.org/10.1016/j.actbio.2014.05.011.en_US
dc.identifier.doihttps://doi.org/10.1016/j.actbio.2014.05.011en_US
dc.identifier.urihttps://hdl.handle.net/1911/94830en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.en_US
dc.subject.keywordOPFen_US
dc.subject.keywordPolymeric gene deliveryen_US
dc.subject.keywordRUNX-2en_US
dc.subject.keywordSOX trioen_US
dc.subject.keywordbPEI–HAen_US
dc.titleOsteochondral tissue regeneration through polymeric delivery of DNA encoding for the SOX trio and RUNX2en_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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