Injectable alginate hydrogel for enhanced spatiotemporal control of lentivector delivery in murine skeletal muscle

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dc.contributor.authorStilhano, Roberta Sessa [UNIFESP]
dc.contributor.authorMadrigal, Justin L.
dc.contributor.authorWong, Kevin
dc.contributor.authorWilliams, Priscilla A.
dc.contributor.authorMartin, Priscila Keiko Matsumoto [UNIFESP]
dc.contributor.authorYamaguchi, Fabio Seiji Mazzi
dc.contributor.authorSamoto, Vivian Yochiko [UNIFESP]
dc.contributor.authorHan, Sang Won [UNIFESP]
dc.contributor.authorSilva, Eduardo Alexandre
dc.date.accessioned2019-07-22T15:46:34Z
dc.date.available2019-07-22T15:46:34Z
dc.date.issued2016
dc.description.abstractHydrogels are an especially appealing class of biomaterials for gene delivery vehicles as they can be introduced into the body with minimally invasive procedures and are often applied in tissue engineering and regenerative medicine strategies. In this study, we show for the first time the use of an injectable alginate hydrogel for controlled delivery of lentivectors in the skeletal muscle of murine hindlimb. We propose to alter the release rates of lentivectors through manipulation of the molecular weight distribution of alginate hydrogels. The release of lentivector was tested using two different ratios of low and high molecular weight (MW) alginate polymers (75/25 and 25/75 low/high MW). The interdependency of lentivector release rate and alginate degradation rate was assessed in vitro. Lentivector-loaded hydrogels maintained transduction potential for up to one week in vitro as demonstrated by the continual transduction of HEK-293T cells. Injection of lentivector-loaded hydrogel in vivo led to a sustained level of transgene expression for more than two months while minimizing the copies of lentivirus genome inserted into the genome of murine skeletal muscle cells. This strategy of spatiotemporal control of lentivector delivery from alginate hydrogels may provide a versatile tool to combine gene therapy and biomaterials for applications in regenerative medicine. (C) 2016 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniv Fed Sao Paulo, Dept Biophys, Sao Paulo, Brazil
dc.description.affiliationUniv Calif Davis, Dept Biomed Engn, 1 Shields Ave, Davis, CA 95616 USA
dc.description.affiliationIrmandade Santa Casa Misericordia Sao Paulo, Dept Internal Med, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biophys, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipUniversity of California, Davis
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.description.sponsorshipAmerican Heart Association
dc.description.sponsorshipHellman Family
dc.description.sponsorshipFAPESP scholarship
dc.description.sponsorshipHHMI Integrating Medicine into Basic Science fellowship
dc.description.sponsorshipIDFAPESP: 2015/20206-8pt
dc.description.sponsorshipIDAHA: 15BGIA25730057
dc.description.sponsorshipIDFAPESP scholarship: 2012/00,753-6pt
dc.format.extent42-49
dc.identifierhttps://dx.doi.org/10.1016/j.jconrel.2016.06.047
dc.identifier.citationJournal Of Controlled Release. Amsterdam, v. 237, p. 42-49, 2016.
dc.identifier.doi10.1016/j.jconrel.2016.06.047
dc.identifier.issn0168-3659
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/50971
dc.identifier.wosWOS:000381368300005
dc.language.isoeng
dc.publisherElsevier Science Bv
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectGene therapyen
dc.subjectSustained gene deliveryen
dc.subjectBiodegradable gelsen
dc.subjectTissue engineeringen
dc.subjectRegenerative medicineen
dc.titleInjectable alginate hydrogel for enhanced spatiotemporal control of lentivector delivery in murine skeletal muscleen
dc.typeinfo:eu-repo/semantics/article
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