Hydrogels as Local Structural-Protective Platforms in Rheumatoid Arthritis: An Evidence-Graded Review Across the...

Rheumatoid arthritis (RA) is a systemic autoimmune disease in which persistent synovitis drives interconnected cartilage degradation, bone erosion, and functional decline. Conventional synthetic, biologic, and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) remain the foundation of RA management. Hydrogel-based local therapy should therefore be positioned as an adjunct for selected joints rather than as a substitute for systemic disease control. Hydrogels provide a versatile local materials platform because their injectability, tunable crosslinking, tissue retention, stimulus-responsive release, interfacial adhesion, lubrication, and extracellular matrix-mimetic properties can be tailored to the inflamed joint microenvironment. This narrative, evidence-graded review evaluates local hydrogel therapies using two complementary frameworks: the synovium-cartilage-bone pathological axis and a materials-science chain linking composition and crosslinking to structure and properties, release and degradation, and tissue-level outcomes. Evidence is classified as direct RA evidence, transferable evidence from related disease or tissue-engineering models, or conceptual evidence from mechanistic and materials-science studies. Therapeutic outcomes are separately graded as local immunomodulation, structural protection, tissue repair, or functionally validated structural disease modification. Current preclinical evidence supports the use of hydrogels for sustained local delivery and synovial immunomodulation, while selected systems demonstrate cartilage-protective or anti-erosive effects. However, durable multitissue restoration accompanied by functional recovery remains insufficiently demonstrated. Future studies should prioritize RA-relevant long-term models, in vivo intra-articular pharmacokinetics and biodistribution, standardized structural and functional endpoints, repeat-dose safety, and evaluation as add-on therapy to systemic DMARDs.