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dc.contributor.authorGeiger, Brett Charles
dc.contributor.authorQuadir, Mohiuddin Abdul
dc.contributor.authorKrishnan, Yamini
dc.contributor.authorGrodzinsky, Alan J
dc.contributor.authorHammond, Paula T
dc.contributor.authorShah, Nisarg J.
dc.contributor.authorHyder, Md Nasim
dc.date.accessioned2018-09-14T16:00:52Z
dc.date.available2018-09-14T16:00:52Z
dc.date.issued2016-11
dc.date.submitted2016-10
dc.identifier.issn2380-6761
dc.identifier.urihttp://hdl.handle.net/1721.1/117760
dc.description.abstractThe efficient transport of biological therapeutic materials to target tissues within the body is critical to their efficacy. In cartilage tissue, the lack of blood vessels prevents the entry of systemically administered drugs at therapeutic levels. Within the articulating joint complex, the dense and highly charged extracellular matrix (ECM) hinders the transport of locally administered therapeutic molecules. Consequently, cartilage injury is difficult to treat and frequently results in debilitating osteoarthritis. Here we show a generalizable approach in which the electrostatic assembly of synthetic polypeptides and a protein, insulin-like growth factor-1 (IGF-1), can be used as an early interventional therapy to treat injury to the cartilage. We demonstrated that poly(glutamic acid) and poly(arginine) associated with the IGF-1 via electrostatic interactions, forming a net charged nanoscale polyelectrolyte complex (nanoplex). We observed that the nanoplex diffused into cartilage plugs in vitro and stimulated ECM production. In vivo, we monitored the transport, retention and therapeutic efficacy of the nanoplex in an established rat model of cartilage injury. A single therapeutic dose, when administered within 48 hours of the injury, conferred protection against cartilage degradation and controlled interleukin-1 (IL-1) mediated inflammation. IGF-1 contained in the nanoplex was detected in the joint space for up to 4 weeks following administration and retained bioactivity. The results indicate the potential of this approach as an early intervention therapy following joint injury to delay or even entirely prevent the onset of osteoarthritis. Keywords: compounds/materials; drug delivery; nanoparticles; regenerative medicine; osteoarthritisen_US
dc.description.sponsorshipUnited States. Department of Defense (Contract W81XWH-14-1-0544)en_US
dc.publisherWileyen_US
dc.relation.isversionofhttp://dx.doi.org/10.1002/BTM2.10043en_US
dc.rightsCreative Commons Attribution 4.0 International Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceWileyen_US
dc.titleSynthetic nanoscale electrostatic particles as growth factor carriers for cartilage repairen_US
dc.typeArticleen_US
dc.identifier.citationShah, Nisarg J. et al. “Synthetic Nanoscale Electrostatic Particles as Growth Factor Carriers for Cartilage Repair.” Bioengineering & Translational Medicine 1, 3 (September 2016): 347–356 © 2016 The Authorsen_US
dc.contributor.departmentMassachusetts Institute of Technology. Institute for Soldier Nanotechnologiesen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Electrical Engineering and Computer Scienceen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Mechanical Engineeringen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorShah, Nisarg
dc.contributor.mitauthorGeiger, Brett Charles
dc.contributor.mitauthorQuadir, Mohiuddin Abdul
dc.contributor.mitauthorHyder, MD Nasim
dc.contributor.mitauthorKrishnan, Yamini
dc.contributor.mitauthorGrodzinsky, Alan J
dc.contributor.mitauthorHammond, Paula T
dc.relation.journalBioengineering & Translational Medicineen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2018-09-06T16:26:54Z
dspace.orderedauthorsShah, Nisarg J.; Geiger, Brett C.; Quadir, Mohiuddin A.; Hyder, Nasim; Krishnan, Yamini; Grodzinsky, Alan J.; Hammond, Paula T.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0003-1727-5732
dc.identifier.orcidhttps://orcid.org/0000-0003-2649-8655
dc.identifier.orcidhttps://orcid.org/0000-0002-5568-6455
dc.identifier.orcidhttps://orcid.org/0000-0001-7880-1391
dc.identifier.orcidhttps://orcid.org/0000-0002-4942-3456
mit.licensePUBLISHER_CCen_US


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