Intra-articular hydrogel therapeutics exhibit anti-inflammatory effects on cytokine-stimulated equine cartilage and synovial membrane explants.

Hydrogel intra-articular therapeutics exhibit anti-inflammatory biological effects beyond mechanical support in equine joints.

This in vitro study investigated the anti-inflammatory and chondroprotective properties of four intra-articular (IA) therapeutics—triamcinolone acetonide (TA), hyaluronic acid (HA), collagen-elastin hydrogel microparticles (CEHM), and 2.5% polyacrylamide hydrogel (2.5% iPAAG)—on equine articular cartilage (AC) and synovial membrane (SM) explants stimulated with IL-1β or TNF-α. Tissue explants were sourced from horses and treated simultaneously with cytokine stimulation at three dose levels. Inflammatory mediators including nitric oxide (NO), glycosaminoglycans (GAGs), prostaglandin E2 (PGE2), and multiple chemokines (CCL2, CCL3, CCL5, CCL11) were quantified in culture media. All therapeutics reduced cytokine-induced NO production in AC explants, suggesting broad chondroprotective potential. GAG concentrations varied considerably across groups, limiting conclusions about cartilage matrix protection. TA and CEHM demonstrated the most robust anti-inflammatory effects, reducing IL-1β-induced PGE2 in SM and decreasing CCL2 and CCL5 in TNF-α-stimulated SM. iPAAG and HA also showed selective reductions in CCL2. These findings indicate that hydrogel-based IA therapeutics possess biological activity beyond mechanical and viscosupplementary roles. While TA remains the most potent anti-inflammatory agent tested, CEHM showed comparable effects across multiple endpoints, and both iPAAG and HA demonstrated meaningful immunomodulatory activity. These results provide mechanistic support for the clinical use of hydrogel therapeutics in equine joint disease and warrant further in vivo investigation.

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