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

OBJECTIVE: To investigate whether IA hydrogel therapeutics alter the inflammatory and/or degradative responses of articular cartilage (AC) and synovial membrane (SM) to cytokine stimulation.

METHODS: AC and SM tissue explants were stimulated with interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α) and simultaneously treated with triamcinolone acetonide, hyaluronic acid, collagen-elastin hydrogel microparticles (CEHM), or 2.5% polyacrylamide hydrogel (2.5% iPAAG) at 3 doses. Synovial membrane (n = 9 explants, 3 horses) was stimulated/treated for 18 hours, whereas AC (12 explants, 6 horses) was stimulated/treated for 2 days, followed by replacement with basal media every 2 days for 8 days. Nitric oxide and glycosaminoglycan concentrations were measured in AC media by Greiss reaction and dimethylmethylene blue assays, respectively. Prostaglandin E2 was measured by ELISA along with C-C motif chemokine ligand (CCL)-2, CCL3, CCL5, CCL11, TNF-α, and IL-1β by fluorescent bead-based multiplex immunoassay on SM media.

RESULTS: Cytokine-induced nitric oxide production by AC was reduced by all therapeutics. Glycosaminoglycan concentrations in AC explant media varied substantially in all groups. Triamcinolone acetonide and CEHM reduced IL-1β-induced prostaglandin E2 production by SM explants. Triamcinolone acetonide, CEHM, and 2.5% iPAAG decreased CCL2 concentrations in TNF-α-stimulated SM explants. Triamcinolone acetonide and CEHM also decreased CCL5 concentrations in TNF-α-stimulated SM explants.

CONCLUSIONS: All therapeutics reduced some proinflammatory effects of IL-1β or TNF-α stimulation on AC and SM explants, with the most profound suppression by triamcinolone acetonide and CEHM.

CLINICAL RELEVANCE: This study suggests that CEHM, 2.5% iPAAG, and hyaluronic acid may have additional biological mechanisms of action beyond mechanical support and viscosupplementation.