Injectable Multifunctional Drug Delivery System for Hard Tissue Regeneration under Inflammatory Microenvironments
Autor(a) principal: | |
---|---|
Data de Publicação: | 2021 |
Outros Autores: | , , , , , |
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 |