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Biofunctional Nanofibrous Substrate for Local TNF-Capturing as a Strategy to Control Inflammation in Arthritic Joints

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 syst...

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Autores principales: Bacelo, Elisa, Alves da Silva, Marta, Cunha, Cristina, Faria, Susana, Carvalho, Agostinho, Reis, Rui L., Martins, Albino, Neves, Nuno M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523323/
https://www.ncbi.nlm.nih.gov/pubmed/30965588
http://dx.doi.org/10.3390/nano9040567
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author Bacelo, Elisa
Alves da Silva, Marta
Cunha, Cristina
Faria, Susana
Carvalho, Agostinho
Reis, Rui L.
Martins, Albino
Neves, Nuno M.
author_facet Bacelo, Elisa
Alves da Silva, Marta
Cunha, Cristina
Faria, Susana
Carvalho, Agostinho
Reis, Rui L.
Martins, Albino
Neves, Nuno M.
author_sort Bacelo, Elisa
collection PubMed
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.
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spelling pubmed-65233232019-06-03 Biofunctional Nanofibrous Substrate for Local TNF-Capturing as a Strategy to Control Inflammation in Arthritic Joints Bacelo, Elisa Alves da Silva, Marta Cunha, Cristina Faria, Susana Carvalho, Agostinho Reis, Rui L. Martins, Albino Neves, Nuno M. Nanomaterials (Basel) Article 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. MDPI 2019-04-08 /pmc/articles/PMC6523323/ /pubmed/30965588 http://dx.doi.org/10.3390/nano9040567 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bacelo, Elisa
Alves da Silva, Marta
Cunha, Cristina
Faria, Susana
Carvalho, Agostinho
Reis, Rui L.
Martins, Albino
Neves, Nuno M.
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
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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523323/
https://www.ncbi.nlm.nih.gov/pubmed/30965588
http://dx.doi.org/10.3390/nano9040567
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