Biofunctional nanofibrous substrate for local TNF-capturing as a strategy to control inflammation in arthritic joints
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/1822/60119 |
Resumo: | Rheumatoid arthritis (RA) is an autoimmune disease that affects the synovial cavity of joints, and its pathogenesis is associated with an increased expression of pro-inflammatory cytokines, namely tumour necrosis factor-alpha (TNF-α). It has been clinically shown to have an adequate response to systemic administration of TNF-α inhibitors, although with many shortcomings. To overcome such limitations, the immobilization of a TNF-α antibody on a nanofibrous substrate to promote a localized action is herein proposed. By using this approach, the antibody has its maximum therapeutic efficacy and a prolonged therapeutic benefit, avoiding the systemic side-effects associated with conventional biological agents’ therapies. To technically achieve such a purpose, the surface of electrospun nanofibers is initially activated and functionalized, allowing TNF-α antibody immobilization at a maximum concentration of 6 µg/mL. Experimental results evidence that the biofunctionalized nanofibrous substrate is effective in achieving a sustained capture of soluble TNF-α over time. Moreover, cell biology assays demonstrate that this system has no deleterious effect over human articular chondrocytes metabolism and activity. Therefore, the developed TNF-capturing system may represent a potential therapeutic approach for the local management of severely affected joints. |
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Biofunctional nanofibrous substrate for local TNF-capturing as a strategy to control inflammation in arthritic jointsantibody immobilizationelectrospun nanofibersTNF- capturehuman articular chondrocytesrheumatoid arthritisTNF-α captureScience & TechnologyRheumatoid arthritis (RA) is an autoimmune disease that affects the synovial cavity of joints, and its pathogenesis is associated with an increased expression of pro-inflammatory cytokines, namely tumour necrosis factor-alpha (TNF-α). It has been clinically shown to have an adequate response to systemic administration of TNF-α inhibitors, although with many shortcomings. To overcome such limitations, the immobilization of a TNF-α antibody on a nanofibrous substrate to promote a localized action is herein proposed. By using this approach, the antibody has its maximum therapeutic efficacy and a prolonged therapeutic benefit, avoiding the systemic side-effects associated with conventional biological agents’ therapies. To technically achieve such a purpose, the surface of electrospun nanofibers is initially activated and functionalized, allowing TNF-α antibody immobilization at a maximum concentration of 6 µg/mL. Experimental results evidence that the biofunctionalized nanofibrous substrate is effective in achieving a sustained capture of soluble TNF-α over time. Moreover, cell biology assays demonstrate that this system has no deleterious effect over human articular chondrocytes metabolism and activity. Therefore, the developed TNF-capturing system may represent a potential therapeutic approach for the local management of severely affected joints.This research was funded by the Portuguese Foundation for Science and Technology (FCT), namely the Post-doc fellowships of Marta Alves da Silva and Cristina Cunha (SFRH/BPD/73322/2010 and SFRH/BPD/96176/2013, respectively) and the Starting Investigator Grant of Agostinho Carvalho and Albino Martins (IF/00735/2014 and IF/00376/2014, respectively). It was also acknowledged the funded projects SPARTAN (PTDC/CTM-BIO/4388/2014) and FROnTHERA (NORTE-01-0145-FEDER-000023).info:eu-repo/semantics/publishedVersionMultidisciplinary Digital Publishing InstituteUniversidade do MinhoBacelo, ElisaAlves da Silva, MartaCunha, CristinaFaria, SusanaCarvalho, AgostinhoReis, R. L.Martins, AlbinoNeves, Nuno M.2019-04-082019-04-08T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/60119eng2079-499110.3390/nano9040567info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:08:13Zoai:repositorium.sdum.uminho.pt:1822/60119Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:59:25.776989Repositório 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 |
Biofunctional nanofibrous substrate for local TNF-capturing as a strategy to control inflammation in arthritic joints |
title |
Biofunctional nanofibrous substrate for local TNF-capturing as a strategy to control inflammation in arthritic joints |
spellingShingle |
Biofunctional nanofibrous substrate for local TNF-capturing as a strategy to control inflammation in arthritic joints Bacelo, Elisa antibody immobilization electrospun nanofibers TNF- capture human articular chondrocytes rheumatoid arthritis TNF-α capture Science & Technology |
title_short |
Biofunctional nanofibrous substrate for local TNF-capturing as a strategy to control inflammation in arthritic joints |
title_full |
Biofunctional nanofibrous substrate for local TNF-capturing as a strategy to control inflammation in arthritic joints |
title_fullStr |
Biofunctional nanofibrous substrate for local TNF-capturing as a strategy to control inflammation in arthritic joints |
title_full_unstemmed |
Biofunctional nanofibrous substrate for local TNF-capturing as a strategy to control inflammation in arthritic joints |
title_sort |
Biofunctional nanofibrous substrate for local TNF-capturing as a strategy to control inflammation in arthritic joints |
author |
Bacelo, Elisa |
author_facet |
Bacelo, Elisa Alves da Silva, Marta Cunha, Cristina Faria, Susana Carvalho, Agostinho Reis, R. L. Martins, Albino Neves, Nuno M. |
author_role |
author |
author2 |
Alves da Silva, Marta Cunha, Cristina Faria, Susana Carvalho, Agostinho Reis, R. L. Martins, Albino Neves, Nuno M. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Bacelo, Elisa Alves da Silva, Marta Cunha, Cristina Faria, Susana Carvalho, Agostinho Reis, R. L. Martins, Albino Neves, Nuno M. |
dc.subject.por.fl_str_mv |
antibody immobilization electrospun nanofibers TNF- capture human articular chondrocytes rheumatoid arthritis TNF-α capture Science & Technology |
topic |
antibody immobilization electrospun nanofibers TNF- capture human articular chondrocytes rheumatoid arthritis TNF-α capture Science & Technology |
description |
Rheumatoid arthritis (RA) is an autoimmune disease that affects the synovial cavity of joints, and its pathogenesis is associated with an increased expression of pro-inflammatory cytokines, namely tumour necrosis factor-alpha (TNF-α). It has been clinically shown to have an adequate response to systemic administration of TNF-α inhibitors, although with many shortcomings. To overcome such limitations, the immobilization of a TNF-α antibody on a nanofibrous substrate to promote a localized action is herein proposed. By using this approach, the antibody has its maximum therapeutic efficacy and a prolonged therapeutic benefit, avoiding the systemic side-effects associated with conventional biological agents’ therapies. To technically achieve such a purpose, the surface of electrospun nanofibers is initially activated and functionalized, allowing TNF-α antibody immobilization at a maximum concentration of 6 µg/mL. Experimental results evidence that the biofunctionalized nanofibrous substrate is effective in achieving a sustained capture of soluble TNF-α over time. Moreover, cell biology assays demonstrate that this system has no deleterious effect over human articular chondrocytes metabolism and activity. Therefore, the developed TNF-capturing system may represent a potential therapeutic approach for the local management of severely affected joints. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-04-08 2019-04-08T00:00:00Z |
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/1822/60119 |
url |
http://hdl.handle.net/1822/60119 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2079-4991 10.3390/nano9040567 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute |
publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799132386178367488 |