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

Abstract

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.

Decellularized Human Chorion Membrane as a Novel Biomaterial for Tissue Regeneration

“…Sulfated glycosaminoglycans (GAGs) content of HCM, dHCM and TL was quantified as previously described [ 29 ]. Samples were digested with 0.5 mg/mL papain (#P4762, Sigma-Aldrich, St. Louis, MO, USA) and the supernatant was stained with 1,9-dimethylmethylene blue (DMB).…”

Biomaterials for Sequestration of Growth Factors and Modulation of Cell Behavior

“…Several of these studies have focused on the functionalization of electrospun PCL nanofiber meshes for tissue engineering applications. [136][137][138] A first proof-of-concept was developed using antibodies against TGF-β1, FGF-2, and VEGF, either individually, with FGF-2 and VEGF antibodies being randomly mixed, or used side by side. [136] All types of functionalization were shown to be successful in capturing their respective GF from a complex biological fluid, i.e., platelet lysate.…”

“…[136] This concept has been further explored in the development of bioactive scaffolds to promote chondrogenic differentiation [137] and to modulate the action of proinflammatory cytokines. [138] In the first case, anti-TGF-β3 and anti-insulin-like growth factor-I (IGF-I) antibodies were tethered to the fiber scaffolds, and tested for the effects on human bone marrow-derived MSCs cultured under basal culture medium over 28 days. Observation of spherical morphology typical of chondrocytes and deposition of collagen type II suggested the formation of a cartilage-like ECM (Figure 4a).…”

“…Antibody‐grafted scaffolds could capture and retain TNF‐α produced by macrophages, while primary human articular chondrocytes could be cultured on the meshes for 28 days with retention of their typical phenotype. [ 138 ] However, it remains to be assessed if the ability to capture the cytokine can provide benefits to the cultured chondrocytes.…”

Sustained Local Delivery of Diclofenac from Three-Dimensional Ultrafine Fibrous Protein Scaffolds with Ultrahigh Drug Loading Capacity

“…As a result, the functional components with poor stability in plasma or low in solubility in the aqueous phase can be readily delivered to the target area. The total dosage and infusion frequency required for effective treatments can be substantially reduced [14,17,18,19]. Therefore, the ultrafine fibers loaded with functional components are favored once applied as tissue engineering scaffolds.…”