Hydrogels in Autoimmune Disease: A Comprehensive Review of Current Research and Clinical Potentials.

Research Objective: Autoimmune diseases are chronic conditions in which the immune system abnormally attacks the body's own tissues. Their incidence is on the rise, and the pathogenesis remains incompletely understood. The clinical manifestations are complex and diverse. Despite active treatment, some patients still have poor therapeutic outcomes and rely on immunosuppressants for a long time. Although these drugs can control symptoms, they are associated with increased infection risks and serious side effects such as organ toxicity. Hydrogels are three-dimensional network structures with excellent water absorption properties, good biocompatibility, injectability, and physical and chemical properties. By loading adjuvants, drugs, cells, and other substances, they are applied in the establishment of disease models, drug delivery, bioimaging and biosensors, tissue engineering, and other fields, providing new strategies for studying disease pathogenesis, drug screening, local targeted delivery, and immune regulation. This article aims to systematically review the mechanism of action and research progress of hydrogels in the treatment of autoimmune diseases and assess their potential for clinical translation. Research Methods: Relevant literature on the medical applications of hydrogels published from January 1, 2004 to October 31, 2025 was retrieved, and the scope was narrowed down to studies on their application in autoimmune diseases for summary and analysis. Main Results: The main findings are as follows: (1) Through bibliometric analysis, it was found that research on hydrogels in the medical field is increasingly prominent, with studies in autoimmune diseases mainly focusing on drug delivery; (2) By constructing injectable bioadhesive hydrogels, the adhesion of hydrogels to joint tissues is enhanced, prolonging drug retention time and improving treatment efficiency; (3) Specific hydrogel designs can actively regulate immune cell functions - for example, inhibiting inflammation-related signaling pathways to reverse M1 polarization of macrophages and ferritin autophagy/ferroptosis in chondrocytes, maintaining the integrity of cartilage structure, and inducing mitochondrial dysfunction to promote apoptosis of FLS and macrophages and regulate the inflammatory microenvironment; (4) Hydrogel microneedle systems, as transdermal drug delivery platforms, have shown good compliance and efficacy in rheumatoid arthritis. Summary: Hydrogel technology, through localized, controllable, and intelligent drug delivery, is expected to break through the bottlenecks of traditional autoimmune disease treatment. Current research is gradually evolving from passive carriers to active participants in immune regulation as "intelligent platforms", and their potential to reshape the inflammatory microenvironment has been verified in animal models. However, issues such as material degradability, long-term biological safety, and consistency in large-scale production still need to be further addressed in preclinical and clinical studies. Future interdisciplinary collaboration and translational medical research are key to promoting the development of this field.