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

Detalhes bibliográficos
Autor(a) principal: Pereira, Isabel
Data de Publicação: 2019
Outros Autores: Fraga, Sónia, Maltez, Luís, Requicha, João, Guardão, Luísa, Oliveira, Joana, Prada, Justina, Alves, Helena, Santos, José Domingos, Teixeira, João Paulo, Pereira, José Eduardo, Soares, Raquel, Gama, Francisco Miguel
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/6526
Resumo: The 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.
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spelling In vivo systemic toxicity assessment of an oxidized dextrin‐based hydrogel and its effectiveness as a carrier and stabilizer of granular synthetic bone substitutesIn vivo BiocompatibilityBone RegenerationDextrinInjectable HydrogelSynthetic Bone SubstitutesGenotoxicidade AmbientalThe 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.Isabel 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.Wiley PeriodicalsRepositório Científico do Instituto Nacional de SaúdePereira, IsabelFraga, SóniaMaltez, LuísRequicha, JoãoGuardão, LuísaOliveira, JoanaPrada, JustinaAlves, HelenaSantos, José DomingosTeixeira, João PauloPereira, José EduardoSoares, RaquelGama, Francisco Miguel2020-04-27T07:27:57Z2019-04-122019-04-12T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/6526engJ Biomed Mater Res A. 2019 Aug;107(8):1678-1689. doi: 10.1002/jbm.a.36683. Epub 2019 Apr 121549-329610.1002/jbm.a.36683info:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:41:35Zoai:repositorio.insa.pt:10400.18/6526Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:41:21.568443Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv In vivo systemic toxicity assessment of an oxidized dextrin‐based hydrogel and its effectiveness as a carrier and stabilizer of granular synthetic bone substitutes
title In vivo systemic toxicity assessment of an oxidized dextrin‐based hydrogel and its effectiveness as a carrier and stabilizer of granular synthetic bone substitutes
spellingShingle In vivo systemic toxicity assessment of an oxidized dextrin‐based hydrogel and its effectiveness as a carrier and stabilizer of granular synthetic bone substitutes
Pereira, Isabel
In vivo Biocompatibility
Bone Regeneration
Dextrin
Injectable Hydrogel
Synthetic Bone Substitutes
Genotoxicidade Ambiental
title_short In vivo systemic toxicity assessment of an oxidized dextrin‐based hydrogel and its effectiveness as a carrier and stabilizer of granular synthetic bone substitutes
title_full In vivo systemic toxicity assessment of an oxidized dextrin‐based hydrogel and its effectiveness as a carrier and stabilizer of granular synthetic bone substitutes
title_fullStr In vivo systemic toxicity assessment of an oxidized dextrin‐based hydrogel and its effectiveness as a carrier and stabilizer of granular synthetic bone substitutes
title_full_unstemmed In vivo systemic toxicity assessment of an oxidized dextrin‐based hydrogel and its effectiveness as a carrier and stabilizer of granular synthetic bone substitutes
title_sort In vivo systemic toxicity assessment of an oxidized dextrin‐based hydrogel and its effectiveness as a carrier and stabilizer of granular synthetic bone substitutes
author Pereira, Isabel
author_facet Pereira, Isabel
Fraga, Sónia
Maltez, Luís
Requicha, João
Guardão, Luísa
Oliveira, Joana
Prada, Justina
Alves, Helena
Santos, José Domingos
Teixeira, João Paulo
Pereira, José Eduardo
Soares, Raquel
Gama, Francisco Miguel
author_role author
author2 Fraga, Sónia
Maltez, Luís
Requicha, João
Guardão, Luísa
Oliveira, Joana
Prada, Justina
Alves, Helena
Santos, José Domingos
Teixeira, João Paulo
Pereira, José Eduardo
Soares, Raquel
Gama, Francisco Miguel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Pereira, Isabel
Fraga, Sónia
Maltez, Luís
Requicha, João
Guardão, Luísa
Oliveira, Joana
Prada, Justina
Alves, Helena
Santos, José Domingos
Teixeira, João Paulo
Pereira, José Eduardo
Soares, Raquel
Gama, Francisco Miguel
dc.subject.por.fl_str_mv In vivo Biocompatibility
Bone Regeneration
Dextrin
Injectable Hydrogel
Synthetic Bone Substitutes
Genotoxicidade Ambiental
topic In vivo Biocompatibility
Bone Regeneration
Dextrin
Injectable Hydrogel
Synthetic Bone Substitutes
Genotoxicidade Ambiental
description The 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.
publishDate 2019
dc.date.none.fl_str_mv 2019-04-12
2019-04-12T00:00:00Z
2020-04-27T07:27:57Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/6526
url http://hdl.handle.net/10400.18/6526
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv J Biomed Mater Res A. 2019 Aug;107(8):1678-1689. doi: 10.1002/jbm.a.36683. Epub 2019 Apr 12
1549-3296
10.1002/jbm.a.36683
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dc.publisher.none.fl_str_mv Wiley Periodicals
publisher.none.fl_str_mv Wiley Periodicals
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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