Osteogenic effects of simvastatin-loaded mesoporous titania thin films

Autores
Lopez Alvarez, Miriam; López Puente, Vanesa; Rodriguez Valencia, Cosme; Angelome, Paula Cecilia; Liz Marzan, Luis M; Serra, Julia; Pastoriza Santos, Isabel; Gonzalez, Pio
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The use of statins in the field of bone regeneration is under current investigation due to the existing demand for non-toxic anabolic agents capable of enhancing bone formation in cases of substantial loss. Simvastatin, a coenzyme currently prescribed in clinics to inhibit cholesterol biosynthesis, has been proven to promote osteogenic differentiation by stimulating bone formation and inhibiting osteoclasts activity. We present the loading of simvastatin in mesoporous TiO2 thin films toward combining the pro-osteogenic properties of this molecule with the demonstrated bioactivity of titania. TiO2 thin films processing and characterization were carried out, as well as evaluation of MC3T3-E1 pre-osteoblasts viability when directly incubated with different concentrations of simvastatin, followed by the analysis of osteogenic activity promoted by simvastatin upon loading in the thin films. The accessible porosity of 36% quantified on the 95 ± 5 nm thick mesoporous thin films, together with pore diameters of 5.5 nm, necks between pores of 2.8 nm and interpore distances of 12 ± 2 nm allow the loading of the simvastatin molecule, as confirmed by FTIR spectroscopy. Simvastatin was found to promote MC3T3-E1 pre-osteoblasts viability at concentrations ≤0.01 g l−1, with a cytotoxicity threshold of 0.05 g l−1. We additionally found that film loadings with 0.001 g l−1 simvastatin promotes statistically higher MC3T3-E1 pre-osteoblast proliferation whereas a higher concentration of 0.01 g l−1 leads to statistically higher osteogenic activity (ALP synthesis), after 21 days of incubation, as compared to unloaded films. These results demonstrate the potential of simvastatin local administration based on bioactive mesoporous thin films to promote pro-osteogenic properties. By focusing this strategy on the coating of metallic prostheses, the supply of simvastatin to the target tissue can be favored and risks of systemic side effects will be reduced while enhancing the osteointegration of the implants.
Fil: Lopez Alvarez, Miriam. Universidad de Vigo; España
Fil: López Puente, Vanesa. Universidad de Vigo; España
Fil: Rodriguez Valencia, Cosme. Universidad de Vigo; España
Fil: Angelome, Paula Cecilia. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Liz Marzan, Luis M. Ikerbasque; España
Fil: Serra, Julia. Universidad de Vigo; España
Fil: Pastoriza Santos, Isabel. Universidad de Vigo; España
Fil: Gonzalez, Pio. Universidad de Vigo; España
Materia
SIMVASTATIN
MESOPOROUS TITANIA
THIN FILMS
DRUG DELIVERY
Nivel de accesibilidad
acceso embargado
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/42364
Acceder
id CONICETDig_83f328fadd6ed6280edc759854f53dc3
oai_identifier_str oai:ri.conicet.gov.ar:11336/42364
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Osteogenic effects of simvastatin-loaded mesoporous titania thin filmsLopez Alvarez, MiriamLópez Puente, VanesaRodriguez Valencia, CosmeAngelome, Paula CeciliaLiz Marzan, Luis MSerra, JuliaPastoriza Santos, IsabelGonzalez, PioSIMVASTATINMESOPOROUS TITANIATHIN FILMSDRUG DELIVERYhttps://purl.org/becyt/ford/2.10https://purl.org/becyt/ford/2The use of statins in the field of bone regeneration is under current investigation due to the existing demand for non-toxic anabolic agents capable of enhancing bone formation in cases of substantial loss. Simvastatin, a coenzyme currently prescribed in clinics to inhibit cholesterol biosynthesis, has been proven to promote osteogenic differentiation by stimulating bone formation and inhibiting osteoclasts activity. We present the loading of simvastatin in mesoporous TiO2 thin films toward combining the pro-osteogenic properties of this molecule with the demonstrated bioactivity of titania. TiO2 thin films processing and characterization were carried out, as well as evaluation of MC3T3-E1 pre-osteoblasts viability when directly incubated with different concentrations of simvastatin, followed by the analysis of osteogenic activity promoted by simvastatin upon loading in the thin films. The accessible porosity of 36% quantified on the 95 ± 5 nm thick mesoporous thin films, together with pore diameters of 5.5 nm, necks between pores of 2.8 nm and interpore distances of 12 ± 2 nm allow the loading of the simvastatin molecule, as confirmed by FTIR spectroscopy. Simvastatin was found to promote MC3T3-E1 pre-osteoblasts viability at concentrations ≤0.01 g l−1, with a cytotoxicity threshold of 0.05 g l−1. We additionally found that film loadings with 0.001 g l−1 simvastatin promotes statistically higher MC3T3-E1 pre-osteoblast proliferation whereas a higher concentration of 0.01 g l−1 leads to statistically higher osteogenic activity (ALP synthesis), after 21 days of incubation, as compared to unloaded films. These results demonstrate the potential of simvastatin local administration based on bioactive mesoporous thin films to promote pro-osteogenic properties. By focusing this strategy on the coating of metallic prostheses, the supply of simvastatin to the target tissue can be favored and risks of systemic side effects will be reduced while enhancing the osteointegration of the implants.Fil: Lopez Alvarez, Miriam. Universidad de Vigo; EspañaFil: López Puente, Vanesa. Universidad de Vigo; EspañaFil: Rodriguez Valencia, Cosme. Universidad de Vigo; EspañaFil: Angelome, Paula Cecilia. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Liz Marzan, Luis M. Ikerbasque; EspañaFil: Serra, Julia. Universidad de Vigo; EspañaFil: Pastoriza Santos, Isabel. Universidad de Vigo; EspañaFil: Gonzalez, Pio. Universidad de Vigo; EspañaIOP Publishing2018-02info:eu-repo/date/embargoEnd/2018-09-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/42364Lopez Alvarez, Miriam; López Puente, Vanesa; Rodriguez Valencia, Cosme; Angelome, Paula Cecilia; Liz Marzan, Luis M; et al.; Osteogenic effects of simvastatin-loaded mesoporous titania thin films; IOP Publishing; Biomedical Materials; 13; 2; 2-2018; 1-241748-6041CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://iopscience.iop.org/article/10.1088/1748-605X/aa95f1info:eu-repo/semantics/altIdentifier/doi/10.1088/1748-605X/aa95f1info:eu-repo/semantics/embargoedAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:41:40Zoai:ri.conicet.gov.ar:11336/42364instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:41:40.704CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Osteogenic effects of simvastatin-loaded mesoporous titania thin films
title Osteogenic effects of simvastatin-loaded mesoporous titania thin films
spellingShingle Osteogenic effects of simvastatin-loaded mesoporous titania thin films
Lopez Alvarez, Miriam
SIMVASTATIN
MESOPOROUS TITANIA
THIN FILMS
DRUG DELIVERY
title_short Osteogenic effects of simvastatin-loaded mesoporous titania thin films
title_full Osteogenic effects of simvastatin-loaded mesoporous titania thin films
title_fullStr Osteogenic effects of simvastatin-loaded mesoporous titania thin films
title_full_unstemmed Osteogenic effects of simvastatin-loaded mesoporous titania thin films
title_sort Osteogenic effects of simvastatin-loaded mesoporous titania thin films
dc.creator.none.fl_str_mv Lopez Alvarez, Miriam
López Puente, Vanesa
Rodriguez Valencia, Cosme
Angelome, Paula Cecilia
Liz Marzan, Luis M
Serra, Julia
Pastoriza Santos, Isabel
Gonzalez, Pio
author Lopez Alvarez, Miriam
author_facet Lopez Alvarez, Miriam
López Puente, Vanesa
Rodriguez Valencia, Cosme
Angelome, Paula Cecilia
Liz Marzan, Luis M
Serra, Julia
Pastoriza Santos, Isabel
Gonzalez, Pio
author_role author
author2 López Puente, Vanesa
Rodriguez Valencia, Cosme
Angelome, Paula Cecilia
Liz Marzan, Luis M
Serra, Julia
Pastoriza Santos, Isabel
Gonzalez, Pio
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv SIMVASTATIN
MESOPOROUS TITANIA
THIN FILMS
DRUG DELIVERY
topic SIMVASTATIN
MESOPOROUS TITANIA
THIN FILMS
DRUG DELIVERY
purl_subject.fl_str_mv https://purl.org/becyt/ford/2.10
https://purl.org/becyt/ford/2
dc.description.none.fl_txt_mv The use of statins in the field of bone regeneration is under current investigation due to the existing demand for non-toxic anabolic agents capable of enhancing bone formation in cases of substantial loss. Simvastatin, a coenzyme currently prescribed in clinics to inhibit cholesterol biosynthesis, has been proven to promote osteogenic differentiation by stimulating bone formation and inhibiting osteoclasts activity. We present the loading of simvastatin in mesoporous TiO2 thin films toward combining the pro-osteogenic properties of this molecule with the demonstrated bioactivity of titania. TiO2 thin films processing and characterization were carried out, as well as evaluation of MC3T3-E1 pre-osteoblasts viability when directly incubated with different concentrations of simvastatin, followed by the analysis of osteogenic activity promoted by simvastatin upon loading in the thin films. The accessible porosity of 36% quantified on the 95 ± 5 nm thick mesoporous thin films, together with pore diameters of 5.5 nm, necks between pores of 2.8 nm and interpore distances of 12 ± 2 nm allow the loading of the simvastatin molecule, as confirmed by FTIR spectroscopy. Simvastatin was found to promote MC3T3-E1 pre-osteoblasts viability at concentrations ≤0.01 g l−1, with a cytotoxicity threshold of 0.05 g l−1. We additionally found that film loadings with 0.001 g l−1 simvastatin promotes statistically higher MC3T3-E1 pre-osteoblast proliferation whereas a higher concentration of 0.01 g l−1 leads to statistically higher osteogenic activity (ALP synthesis), after 21 days of incubation, as compared to unloaded films. These results demonstrate the potential of simvastatin local administration based on bioactive mesoporous thin films to promote pro-osteogenic properties. By focusing this strategy on the coating of metallic prostheses, the supply of simvastatin to the target tissue can be favored and risks of systemic side effects will be reduced while enhancing the osteointegration of the implants.
Fil: Lopez Alvarez, Miriam. Universidad de Vigo; España
Fil: López Puente, Vanesa. Universidad de Vigo; España
Fil: Rodriguez Valencia, Cosme. Universidad de Vigo; España
Fil: Angelome, Paula Cecilia. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Liz Marzan, Luis M. Ikerbasque; España
Fil: Serra, Julia. Universidad de Vigo; España
Fil: Pastoriza Santos, Isabel. Universidad de Vigo; España
Fil: Gonzalez, Pio. Universidad de Vigo; España
description The use of statins in the field of bone regeneration is under current investigation due to the existing demand for non-toxic anabolic agents capable of enhancing bone formation in cases of substantial loss. Simvastatin, a coenzyme currently prescribed in clinics to inhibit cholesterol biosynthesis, has been proven to promote osteogenic differentiation by stimulating bone formation and inhibiting osteoclasts activity. We present the loading of simvastatin in mesoporous TiO2 thin films toward combining the pro-osteogenic properties of this molecule with the demonstrated bioactivity of titania. TiO2 thin films processing and characterization were carried out, as well as evaluation of MC3T3-E1 pre-osteoblasts viability when directly incubated with different concentrations of simvastatin, followed by the analysis of osteogenic activity promoted by simvastatin upon loading in the thin films. The accessible porosity of 36% quantified on the 95 ± 5 nm thick mesoporous thin films, together with pore diameters of 5.5 nm, necks between pores of 2.8 nm and interpore distances of 12 ± 2 nm allow the loading of the simvastatin molecule, as confirmed by FTIR spectroscopy. Simvastatin was found to promote MC3T3-E1 pre-osteoblasts viability at concentrations ≤0.01 g l−1, with a cytotoxicity threshold of 0.05 g l−1. We additionally found that film loadings with 0.001 g l−1 simvastatin promotes statistically higher MC3T3-E1 pre-osteoblast proliferation whereas a higher concentration of 0.01 g l−1 leads to statistically higher osteogenic activity (ALP synthesis), after 21 days of incubation, as compared to unloaded films. These results demonstrate the potential of simvastatin local administration based on bioactive mesoporous thin films to promote pro-osteogenic properties. By focusing this strategy on the coating of metallic prostheses, the supply of simvastatin to the target tissue can be favored and risks of systemic side effects will be reduced while enhancing the osteointegration of the implants.
publishDate 2018
dc.date.none.fl_str_mv 2018-02
info:eu-repo/date/embargoEnd/2018-09-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/42364
Lopez Alvarez, Miriam; López Puente, Vanesa; Rodriguez Valencia, Cosme; Angelome, Paula Cecilia; Liz Marzan, Luis M; et al.; Osteogenic effects of simvastatin-loaded mesoporous titania thin films; IOP Publishing; Biomedical Materials; 13; 2; 2-2018; 1-24
1748-6041
CONICET Digital
CONICET
url http://hdl.handle.net/11336/42364
identifier_str_mv Lopez Alvarez, Miriam; López Puente, Vanesa; Rodriguez Valencia, Cosme; Angelome, Paula Cecilia; Liz Marzan, Luis M; et al.; Osteogenic effects of simvastatin-loaded mesoporous titania thin films; IOP Publishing; Biomedical Materials; 13; 2; 2-2018; 1-24
1748-6041
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://iopscience.iop.org/article/10.1088/1748-605X/aa95f1
info:eu-repo/semantics/altIdentifier/doi/10.1088/1748-605X/aa95f1
dc.rights.none.fl_str_mv info:eu-repo/semantics/embargoedAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv embargoedAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv IOP Publishing
publisher.none.fl_str_mv IOP Publishing
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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