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dc.contributor.authorNeedham, Clark J.
Shah, Sarita R.
Dahlin, Rebecca L.
Kinard, Lucas A.
Lam, Johnny
Watson, Brendan M.
Lu, Steven
Kasper, F. Kurtis
Mikos, Antonios G.
dc.date.accessioned 2017-06-12T21:49:43Z
dc.date.available 2017-06-12T21:49:43Z
dc.date.issued 2014
dc.identifier.citation Needham, 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." Acta Biomaterialia, 10, no. 10 (2014) Elsevier: 4103-4112. https://doi.org/10.1016/j.actbio.2014.05.011.
dc.identifier.urihttps://hdl.handle.net/1911/94830
dc.description.abstract Native 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.
dc.language.iso eng
dc.publisher Elsevier
dc.rights This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.
dc.title Osteochondral tissue regeneration through polymeric delivery of DNA encoding for the SOX trio and RUNX2
dc.type Journal article
dc.citation.journalTitle Acta Biomaterialia
dc.subject.keywordOPF
Polymeric gene delivery
RUNX-2
SOX trio
bPEI–HA
dc.citation.volumeNumber 10
dc.citation.issueNumber 10
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.1016/j.actbio.2014.05.011
dc.identifier.pmcid PMC4160371
dc.identifier.pmid 24854956
dc.type.publication post-print
dc.citation.firstpage 4103
dc.citation.lastpage 4112


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