Author(s):
Bacelo, Elisa ; Alves da Silva, Marta ; Cunha, Cristina ; Faria, Susana ; Carvalho, Agostinho ; Reis, R. L. ; Martins, Albino ; Neves, Nuno M.
Date: 2019
Persistent ID: https://hdl.handle.net/1822/60119
Origin: RepositóriUM - Universidade do Minho
Subject(s): antibody immobilization; electrospun nanofibers; TNF- capture; human articular chondrocytes; rheumatoid arthritis; TNF-α capture
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.