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In vivo systemic toxicity assessment of an oxidized dextrin‐based hydrogel and its effectiveness as a carrier and stabilizer of granular synthetic bone substitutes

dc.contributor.authorPereira, Isabel
dc.contributor.authorFraga, Sónia
dc.contributor.authorMaltez, Luís
dc.contributor.authorRequicha, João
dc.contributor.authorGuardão, Luísa
dc.contributor.authorOliveira, Joana
dc.contributor.authorPrada, Justina
dc.contributor.authorAlves, Helena
dc.contributor.authorSantos, José Domingos
dc.contributor.authorTeixeira, João Paulo
dc.contributor.authorPereira, José Eduardo
dc.contributor.authorSoares, Raquel
dc.contributor.authorGama, Francisco Miguel
dc.date.accessioned2020-04-27T07:27:57Z
dc.date.available2020-04-27T07:27:57Z
dc.date.issued2019-04-12
dc.description.abstractThe worldwide incidence of bone disorders is raising, mainly due to aging population. The lack of effective treatments is pushing the development of synthetic bone substitutes (SBSs). Most ceramic-based SBSs commercially available display limited handling properties. Attempting to solve these issues and achieve wider acceptance by the clinicians, granular ceramics have been associated with hydrogels (HGs) to produce injectable/moldable SBSs. Dextrin, a low-molecular-weight carbohydrate, was used to develop a fully resorbable and injectable HG. It was first oxidized with sodium periodate and then cross-linked with adipic acid dihydrazide. The in vivo biocompatibility and safety of the dextrin-based HG was assessed by subacute systemic toxicity and skin sensitization tests, using rodent models. The results showed that the HG did not induce any systemic toxic effect, skin reaction, or genotoxicity, neither impaired the bone repair/regeneration process. Then, the HG was successfully combined with granular bone substitute, registered as Bonelike (250-500 μm) to obtain a moldable/injectable SBS, which was implanted in tibial fractures in goats for 3 and 6 weeks. The obtained results showed that HG allowed the stabilization of the granules into the defect, ensuring effective handling, and molding properties of the formulation, as well as an efficient cohesion of the granules.pt_PT
dc.description.sponsorshipIsabel Pereira was supported by the grant SFRH/BD/90066/2012 from FCT, Portugal. This work was funded by the project “DEXGELERATION – Advanced solutions for bone regeneration based on dextrin hydrogels” (Norte-07-0202-FEDER-038853) and the project “iBone Therapies – innovative therapies for bone regeneration” (NORTE-01-0247-FEDER-003262). The authors acknowledge the funding from FCT under the scope of the strategic funding of UID/BIO/04469/2013 and UID/BIM/04293/2013 units and COMPETE 2020 (POCI-01- 0145-FEDER-006684), BioTecNorte operation (NORTE-01- 0145-FEDER-000004) and NORTE-01-0145-FEDER-000012 funded by FEDER under the scope of Norte2020—Programa Operacional Regional do Norte.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Biomed Mater Res A. 2019 Aug;107(8):1678-1689. doi: 10.1002/jbm.a.36683. Epub 2019 Apr 12pt_PT
dc.identifier.doi10.1002/jbm.a.36683pt_PT
dc.identifier.issn1549-3296
dc.identifier.urihttp://hdl.handle.net/10400.18/6526
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWiley Periodicalspt_PT
dc.relationDEXTRIN INJECTABLE HYDROGEL FOR TISSUE HEALING AND REGENERATION
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/doi/full/10.1002/jbm.a.36683pt_PT
dc.subjectIn vivo Biocompatibilitypt_PT
dc.subjectBone Regenerationpt_PT
dc.subjectDextrinpt_PT
dc.subjectInjectable Hydrogelpt_PT
dc.subjectSynthetic Bone Substitutespt_PT
dc.subjectGenotoxicidade Ambientalpt_PT
dc.titleIn vivo systemic toxicity assessment of an oxidized dextrin‐based hydrogel and its effectiveness as a carrier and stabilizer of granular synthetic bone substitutespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDEXTRIN INJECTABLE HYDROGEL FOR TISSUE HEALING AND REGENERATION
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F90066%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIO%2F04469%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F04293%2F2013/PT
oaire.citation.endPage1689pt_PT
oaire.citation.issue8pt_PT
oaire.citation.startPage1678pt_PT
oaire.citation.titleJournal of Biomedical Materials Research Part Apt_PT
oaire.citation.volume107pt_PT
oaire.fundingStream5876
oaire.fundingStream5876
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctDe acordo com política editorial da revista.pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationdabf6315-4fcd-4c1a-9766-751328fca4c3
relation.isProjectOfPublicatione0cdb9ba-e86f-40f5-85aa-2dd8b6f272fb
relation.isProjectOfPublicationfa9009ed-65e1-4108-bd20-1304211124ea
relation.isProjectOfPublication.latestForDiscoverye0cdb9ba-e86f-40f5-85aa-2dd8b6f272fb

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