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In Vivo bone tissue induction by freeze-dried collagen-nanohydroxyapatite matrix loaded with BMP2/NS1 mRNAs lipopolyplexes

2021-04-23Journal article Open access
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dc.contributor.authorWang, Pinpin
dc.contributor.authorPerche, Federico
dc.contributor.authorMidoux, Patrick
dc.contributor.authorCabral, Cátia S. D.
dc.contributor.authorMalard, Virginie
dc.contributor.authorCorreia, I.J.
dc.contributor.authorEI-Hafci, Hanane
dc.contributor.authorPetite, Hervé
dc.contributor.authorLogeart-Avramoglou, Delphine
dc.contributor.authorPichon, Chantal
dc.date.accessioned2021-07-30T10:30:37Z
dc.date.available2023-07-30T00:30:21Z
dc.date.issued2021-04-23
dc.description.abstractMessenger RNA (mRNA) activated matrices (RAMs) are interesting to orchestrate tissue and organ regeneration due to the in-situ and sustained production of functional proteins. However, the immunogenicity of in vitro transcribed mRNA and the paucity of proper in vivo mRNA delivery vector need to be overcome to exert the therapeutic potential of RAM. We developed a dual mRNAs system for in vitro osteogenesis by co-delivering NS1 mRNA with BMP2 mRNA to inhibit RNA sensors and enhance BMP-2 expression. Next, we evaluated a lipopolyplex (LPR) formulation platform for in vivo mRNA delivery and adapted the LPRs for RAM preparation. The LPR formulated BMP2/NS1 mRNAs were incorporated into an optimized collagen-nanohydroxyapatite scaffold and freeze-dried to prepare ready-to-use RAMs. The loaded BMP2/NS1 mRNAs lipopolyplexes maintained their spherical morphology in the RAM, thanks to the core-shell structure of LPR. The mRNAs release from RAMs lasted for 16 days resulting in an enhanced prolonged transgene expression period compared to direct cell transfection. Once subcutaneously implanted in mice, the BMP2/NS1 mRNAs LPRs containing RAMs (RAM-BMP2/NS1) induced significant new bone tissue than those without NS1 mRNA, eight weeks post implantation. Overall, our results demonstrate that the BMP2/NS1 dual mRNAs system is suitable for osteogenic engagement, and the freeze-dried RAM-BMP2/NS1 could be promising off-the-shelf products for clinical orthopedic practice.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.jconrel.2021.04.021pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/11197
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.subjectAnimalspt_PT
dc.subjectBone Regenerationpt_PT
dc.subjectCollagenpt_PT
dc.subjectDurapatitept_PT
dc.subjectMicept_PT
dc.subjectNanoparticlespt_PT
dc.subjectRNA, Messengerpt_PT
dc.subjectBone Morphogenetic Protein 2pt_PT
dc.subjectBone and Bonespt_PT
dc.subjectOsteogenesispt_PT
dc.subjectTissue Scaffoldspt_PT
dc.titleIn Vivo bone tissue induction by freeze-dried collagen-nanohydroxyapatite matrix loaded with BMP2/NS1 mRNAs lipopolyplexespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage200pt_PT
oaire.citation.startPage188pt_PT
oaire.citation.titleJournal of Controlled Releasept_PT
oaire.citation.volume334pt_PT
person.familyNameCabral
person.familyNameJoaquim Sobreira Correia
person.givenNameCátia Solange Duarte
person.givenNameIlídio
person.identifierUMbJ1KMAAAAJ
person.identifier.ciencia-id8D18-367B-2572
person.identifier.ciencia-idF610-7373-DC81
person.identifier.orcid0000-0002-4247-4816
person.identifier.orcid0000-0003-1613-9675
person.identifier.scopus-author-id57207108629
person.identifier.scopus-author-id7003557499
rcaap.embargofctO copyright do artigo foi cedido à editorapt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication59ebcf02-e077-44f7-89c6-d601a9c96529
relation.isAuthorOfPublicationf2c3e779-34a2-4309-950a-80687664c6ad
relation.isAuthorOfPublication.latestForDiscovery59ebcf02-e077-44f7-89c6-d601a9c96529

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