Antioxidant and Bone Regeneration Properties of a Hydrogel Loaded with Gallic Acid-Functionalized MgO Nanoparticles to Treat Rheumatoid Arthritis

Abstract Rheumatoid arthritis (RA), an autoimmune disorder, is characterized by prolonged joint inflammation that eventually damages it. The overexpression of matrix metalloproteinases along with an influx of inflammatory cytokines in the joint, hyperplasticity of fibroblast-like synoviocytes, and increased levels of reactive oxygen species (ROS) results in an acidic microenvironment that irreversibly destroys the cartilage and bone. Methotrexate is used to treat RA, but it is associated with side effects, like nephrotoxicity and immunosuppression, and there is a lack of drug-free strategies to target the progression of disease and tissue regeneration. To treat RA and promote the regeneration of bone tissue, we have developed a drug-free, oxidized chondroitin sulfate-dextran hydrogel loaded with gallic acid-functionalized MgO nanoparticles, which demonstrated promising ROS scavenging and anti-inflammatory activities, as assessed using NO scavenging and reverse-transcription polymerase chain reaction analysis. In addition, the hydrogels were found to promote bone tissue regeneration in cell culture, as determined using the alkaline phosphatase assay and Alizarin red staining along with exhibiting apoptotic potential against hyperplastic fibroblast-like synoviocytes. We report, for the first time, gallic acid-grafted MgO nanoparticles that harness intrinsic antioxidant and apoptotic activity for RA therapy. In summary, we have developed a drug-free, multipotent system for alleviating RA by suppressing inflammation and promoting tissue preservation.