In vivo systemic toxicity assessment of an oxidized dextrin‐based hydrogel and its effectiveness as a carrier and stabilizer of granular synthetic bone substitutes
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , , |
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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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 |
format |
article |
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 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/embargoedAccess |
eu_rights_str_mv |
embargoedAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Wiley Periodicals |
publisher.none.fl_str_mv |
Wiley Periodicals |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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