Hydrogels in the treatment of rheumatoid arthritis: drug delivery systems and artificial matrices for dynamic in vitro models

Abstract

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disorder that mostly affects the synovial joints and can promote both cartilage and bone tissue destruction. Several conservative treatments are available to relieve pain and control the inflammation; however, traditional drugs administration are not fully effective and present severe undesired side effects. Hydrogels are a very attractive platform as a drug delivery system to guarantee these handicaps are reduced, and the therapeutic effect from the drugs is maximized. Furthermore, hydrogels can mimic the physiological microenvironment and have the mechanical behavior needed for use as cartilage in vitro model. The testing of these advanced delivery systems is still bound to animal disease models that have shown low predictability. Alternatively, hydrogel-based human dynamic in vitro systems can be used to model diseases, bypassing some of the animal testing problems. RA dynamic disease models are still in an embryonary stage since advances regarding healthy and inflamed cartilage models are currently giving the first steps regarding complexity increase. Herein, recent studies using hydrogels in the treatment of RA, featuring different hydrogel formulations are discussed. Besides, their use as artificial extracellular matrices in dynamic in vitro articular cartilage is also reviewed.

Fig. 1

Schematic illustration of the 3D hydrogel models, including hydrogels (encapsulation), porous hydrogels, fibrous hydrogel scaffolds, hydrogel sandwich systems, microwells, hydrogel microparticles, microfluidics, and bioprinted scaffolds. Reprinted from publication [12], Copyright (2019) with permission from John Wiley and Son

Fig. 2

Drug delivery hydrogel in response to several physical and chemical stimuli

Fig. 3

Schematic Illustration of intra-articular injection of NO-Scv Gel in suppressing of RA in a mouse model. Reprinted with permission from [40]. Copyright (2019) American Chemical Society

Fig. 4

(i) Mechanical stimulation bioreactor system. (a) Front view depicting the bioreactor stand (anodized in blue) and the removable polycarbonate culture chamber. (b) Close-up view of PTFE pistons lowered into a standard 24-well plate on the actuator-driven sliding platform. (c) Shear deformation of hydrogel construct fully immersed in culture media. Reprinted with permission from [69]. (ii) (A) CAD design of cartilage-on-a-chip device. (B) Photograph of an actual cartilage-on-a-chip device showing loading of cell-laden hydrogel in the top chamber. (C) Overview picture of three cell culture chambers and right side showing one individual culture chamber featuring CMFDA-stained primary equine chondrocytes cultivated on-chip. (D) Intact cell-laden fibrin hydrogel clot released from the device before downstream analyses and (E) histological section of chondrocytes-on-a-chip. Reprinted from publication [75], Copyright (2021) with permission from Elsevier