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

Area of Science:

• Biomaterials Science
• Rheumatology
• Drug Delivery Systems

Background:

• Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by persistent synovitis, leading to cartilage degradation, bone erosion, and functional impairment.
• Current management of RA relies on conventional synthetic, biologic, and targeted synthetic disease-modifying antirheumatic drugs (DMARDs).
• Hydrogel-based local therapy presents a potential adjunct for managing RA in specific joints, complementing systemic treatments.

Purpose of the Study:

• To evaluate local hydrogel therapies for rheumatoid arthritis (RA) using a pathological axis and a materials-science framework.
• To assess the evidence for hydrogels in modulating the inflamed joint microenvironment and protecting against RA-related tissue damage.
• To identify gaps in current research and propose future directions for hydrogel-based RA treatment.

Main Methods:

• A narrative, evidence-graded review of local hydrogel therapies for RA.
• Classification of evidence based on direct RA data, transferable data from related models, or mechanistic studies.
• Evaluation of therapeutic outcomes including immunomodulation, structural protection, tissue repair, and functional disease modification.

Main Results:

• Preclinical evidence supports hydrogels for sustained local drug delivery and synovial immunomodulation in RA models.
• Selected hydrogel systems demonstrate potential for cartilage protection and anti-erosive effects.
• Durable restoration of multiple joint tissues and significant functional recovery remain insufficiently demonstrated.

Conclusions:

• Hydrogels offer a versatile platform for local therapy in RA, with demonstrated potential for immunomodulation and some structural protection.
• Further research is crucial, focusing on RA-relevant long-term models, in vivo pharmacokinetics, standardized endpoints, safety, and combination therapy with systemic DMARDs.
• Optimizing hydrogel properties and delivery strategies is essential to achieve comprehensive joint restoration and functional recovery in RA management.