Biofunctional nanofibrous substrate for local TNF-capturing as a strategy to control inflammation in arthritic joints

Detalhes bibliográficos
Autor(a) principal: Bacelo, Elisa
Data de Publicação: 2019
Outros Autores: Alves da Silva, Marta, Cunha, Cristina, Faria, Susana, Carvalho, Agostinho, Reis, R. L., Martins, Albino, Neves, Nuno M.
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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spelling 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
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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
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instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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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
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