Injectable Multifunctional Drug Delivery System for Hard Tissue Regeneration under Inflammatory Microenvironments

Detalhes bibliográficos
Autor(a) principal: Bordini, Ester A. F.
Data de Publicação: 2021
Outros Autores: Ferreira, Jessica A., Dubey, Nileshkumar, Ribeiro, Juliana S., De Souza Costa, Carlos A. [UNESP], Soares, Diana G., Bottino, Marco C.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1021/acsabm.1c00620
http://hdl.handle.net/11449/229506
Resumo: Engineering multifunctional hydrogel systems capable of amplifying the regenerative capacity of endogenous progenitor cells via localized presentation of therapeutics under tissue inflammation is central to the translation of effective strategies for hard tissue regeneration. Here, we loaded dexamethasone (DEX), a pleotropic drug with anti-inflammatory and mineralizing abilities, into aluminosilicate clay nanotubes (halloysite clay nanotubes (HNTs)) to engineer an injectable multifunctional drug delivery system based on photo-cross-linkable gelatin methacryloyl (GelMA) hydrogel. In detail, a series of hydrogels based on GelMA formulations containing distinct amounts of DEX-loaded nanotubes was analyzed for physicochemical and mechanical properties and kinetics of DEX release as well as compatibility with mesenchymal stem cells from human exfoliated deciduous teeth (SHEDs). The anti-inflammatory response and mineralization potential of the engineered hydrogels were determined in vitro and in vivo. DEX conjugation with HNTs was confirmed by FTIR analysis. The incorporation of DEX-loaded nanotubes enhanced the mechanical strength of GelMA with no effect on its degradation and swelling ratio. Scanning electron microscopy (SEM) images demonstrated the porous architecture of GelMA, which was not significantly altered by DEX-loaded nanotubes' (HNTs/DEX) incorporation. All GelMA formulations showed cytocompatibility with SHEDs (p < 0.05) regardless of the presence of HNTs or HNTs/DEX. However, the highest osteogenic cell differentiation was noticed with the addition of HNT/DEX 10% in GelMA formulations (p < 0.01). The controlled release of DEX over 7 days restored the expression of alkaline phosphatase and mineralization (p < 0.0001) in lipopolysaccharide (LPS)-stimulated SHEDs in vitro. Importantly, in vivo data revealed that DEX-loaded nanotube-modified GelMA (5.0% HNT/DEX 10%) led to enhanced bone formation after 6 weeks (p < 0.0001) compared to DEX-free formulations with a minimum localized inflammatory response after 7 days. Altogether, our findings show that the engineered DEX-loaded nanotube-modified hydrogel may possess great potential to trigger in situ mineralized tissue regeneration under inflammatory conditions.
id UNSP_8c17a95f11aae735a70437726585537c
oai_identifier_str oai:repositorio.unesp.br:11449/229506
network_acronym_str UNSP
network_name_str Repositório Institucional da UNESP
repository_id_str 2946
spelling Injectable Multifunctional Drug Delivery System for Hard Tissue Regeneration under Inflammatory Microenvironmentsbonedentindexamethasonegelatin methacryloylhydrogelregenerationEngineering multifunctional hydrogel systems capable of amplifying the regenerative capacity of endogenous progenitor cells via localized presentation of therapeutics under tissue inflammation is central to the translation of effective strategies for hard tissue regeneration. Here, we loaded dexamethasone (DEX), a pleotropic drug with anti-inflammatory and mineralizing abilities, into aluminosilicate clay nanotubes (halloysite clay nanotubes (HNTs)) to engineer an injectable multifunctional drug delivery system based on photo-cross-linkable gelatin methacryloyl (GelMA) hydrogel. In detail, a series of hydrogels based on GelMA formulations containing distinct amounts of DEX-loaded nanotubes was analyzed for physicochemical and mechanical properties and kinetics of DEX release as well as compatibility with mesenchymal stem cells from human exfoliated deciduous teeth (SHEDs). The anti-inflammatory response and mineralization potential of the engineered hydrogels were determined in vitro and in vivo. DEX conjugation with HNTs was confirmed by FTIR analysis. The incorporation of DEX-loaded nanotubes enhanced the mechanical strength of GelMA with no effect on its degradation and swelling ratio. Scanning electron microscopy (SEM) images demonstrated the porous architecture of GelMA, which was not significantly altered by DEX-loaded nanotubes' (HNTs/DEX) incorporation. All GelMA formulations showed cytocompatibility with SHEDs (p < 0.05) regardless of the presence of HNTs or HNTs/DEX. However, the highest osteogenic cell differentiation was noticed with the addition of HNT/DEX 10% in GelMA formulations (p < 0.01). The controlled release of DEX over 7 days restored the expression of alkaline phosphatase and mineralization (p < 0.0001) in lipopolysaccharide (LPS)-stimulated SHEDs in vitro. Importantly, in vivo data revealed that DEX-loaded nanotube-modified GelMA (5.0% HNT/DEX 10%) led to enhanced bone formation after 6 weeks (p < 0.0001) compared to DEX-free formulations with a minimum localized inflammatory response after 7 days. Altogether, our findings show that the engineered DEX-loaded nanotube-modified hydrogel may possess great potential to trigger in situ mineralized tissue regeneration under inflammatory conditions.Department of Cariology Restorative Sciences University of Michigan, 1011 N. University AveDepartment of Physiology and Pathology Araraquara School of Dentistry Universidade Estadual Paulista (UNESP), 1680 Humaitá StreetDepartment of Operative Dentistry Endodontics and Dental Materials Bauru School of Dentistry Sao Paulo University (USP), Al. Dr. Octavio Pinheiro Brizola, 9-75Department of Biomedical Engineering College of Engineering University of Michigan, 2200 Bonisteel Blvd.Department of Physiology and Pathology Araraquara School of Dentistry Universidade Estadual Paulista (UNESP), 1680 Humaitá StreetUniversity of MichiganUniversidade Estadual Paulista (UNESP)Universidade de São Paulo (USP)Bordini, Ester A. F.Ferreira, Jessica A.Dubey, NileshkumarRibeiro, Juliana S.De Souza Costa, Carlos A. [UNESP]Soares, Diana G.Bottino, Marco C.2022-04-29T08:33:01Z2022-04-29T08:33:01Z2021-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1021/acsabm.1c00620ACS Applied Bio Materials.2576-6422http://hdl.handle.net/11449/22950610.1021/acsabm.1c006202-s2.0-85114732155Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengACS Applied Bio Materialsinfo:eu-repo/semantics/openAccess2024-09-27T14:04:20Zoai:repositorio.unesp.br:11449/229506Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-27T14:04:20Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Injectable Multifunctional Drug Delivery System for Hard Tissue Regeneration under Inflammatory Microenvironments
title Injectable Multifunctional Drug Delivery System for Hard Tissue Regeneration under Inflammatory Microenvironments
spellingShingle Injectable Multifunctional Drug Delivery System for Hard Tissue Regeneration under Inflammatory Microenvironments
Bordini, Ester A. F.
bone
dentin
dexamethasone
gelatin methacryloyl
hydrogel
regeneration
title_short Injectable Multifunctional Drug Delivery System for Hard Tissue Regeneration under Inflammatory Microenvironments
title_full Injectable Multifunctional Drug Delivery System for Hard Tissue Regeneration under Inflammatory Microenvironments
title_fullStr Injectable Multifunctional Drug Delivery System for Hard Tissue Regeneration under Inflammatory Microenvironments
title_full_unstemmed Injectable Multifunctional Drug Delivery System for Hard Tissue Regeneration under Inflammatory Microenvironments
title_sort Injectable Multifunctional Drug Delivery System for Hard Tissue Regeneration under Inflammatory Microenvironments
author Bordini, Ester A. F.
author_facet Bordini, Ester A. F.
Ferreira, Jessica A.
Dubey, Nileshkumar
Ribeiro, Juliana S.
De Souza Costa, Carlos A. [UNESP]
Soares, Diana G.
Bottino, Marco C.
author_role author
author2 Ferreira, Jessica A.
Dubey, Nileshkumar
Ribeiro, Juliana S.
De Souza Costa, Carlos A. [UNESP]
Soares, Diana G.
Bottino, Marco C.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv University of Michigan
Universidade Estadual Paulista (UNESP)
Universidade de São Paulo (USP)
dc.contributor.author.fl_str_mv Bordini, Ester A. F.
Ferreira, Jessica A.
Dubey, Nileshkumar
Ribeiro, Juliana S.
De Souza Costa, Carlos A. [UNESP]
Soares, Diana G.
Bottino, Marco C.
dc.subject.por.fl_str_mv bone
dentin
dexamethasone
gelatin methacryloyl
hydrogel
regeneration
topic bone
dentin
dexamethasone
gelatin methacryloyl
hydrogel
regeneration
description Engineering multifunctional hydrogel systems capable of amplifying the regenerative capacity of endogenous progenitor cells via localized presentation of therapeutics under tissue inflammation is central to the translation of effective strategies for hard tissue regeneration. Here, we loaded dexamethasone (DEX), a pleotropic drug with anti-inflammatory and mineralizing abilities, into aluminosilicate clay nanotubes (halloysite clay nanotubes (HNTs)) to engineer an injectable multifunctional drug delivery system based on photo-cross-linkable gelatin methacryloyl (GelMA) hydrogel. In detail, a series of hydrogels based on GelMA formulations containing distinct amounts of DEX-loaded nanotubes was analyzed for physicochemical and mechanical properties and kinetics of DEX release as well as compatibility with mesenchymal stem cells from human exfoliated deciduous teeth (SHEDs). The anti-inflammatory response and mineralization potential of the engineered hydrogels were determined in vitro and in vivo. DEX conjugation with HNTs was confirmed by FTIR analysis. The incorporation of DEX-loaded nanotubes enhanced the mechanical strength of GelMA with no effect on its degradation and swelling ratio. Scanning electron microscopy (SEM) images demonstrated the porous architecture of GelMA, which was not significantly altered by DEX-loaded nanotubes' (HNTs/DEX) incorporation. All GelMA formulations showed cytocompatibility with SHEDs (p < 0.05) regardless of the presence of HNTs or HNTs/DEX. However, the highest osteogenic cell differentiation was noticed with the addition of HNT/DEX 10% in GelMA formulations (p < 0.01). The controlled release of DEX over 7 days restored the expression of alkaline phosphatase and mineralization (p < 0.0001) in lipopolysaccharide (LPS)-stimulated SHEDs in vitro. Importantly, in vivo data revealed that DEX-loaded nanotube-modified GelMA (5.0% HNT/DEX 10%) led to enhanced bone formation after 6 weeks (p < 0.0001) compared to DEX-free formulations with a minimum localized inflammatory response after 7 days. Altogether, our findings show that the engineered DEX-loaded nanotube-modified hydrogel may possess great potential to trigger in situ mineralized tissue regeneration under inflammatory conditions.
publishDate 2021
dc.date.none.fl_str_mv 2021-01-01
2022-04-29T08:33:01Z
2022-04-29T08:33:01Z
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://dx.doi.org/10.1021/acsabm.1c00620
ACS Applied Bio Materials.
2576-6422
http://hdl.handle.net/11449/229506
10.1021/acsabm.1c00620
2-s2.0-85114732155
url http://dx.doi.org/10.1021/acsabm.1c00620
http://hdl.handle.net/11449/229506
identifier_str_mv ACS Applied Bio Materials.
2576-6422
10.1021/acsabm.1c00620
2-s2.0-85114732155
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv ACS Applied Bio Materials
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv repositoriounesp@unesp.br
_version_ 1813546373914558464