The effect of cyclic fluid perfusion on the proinflammatory tissue environment in osteoarthritis using equine joint-on-a-chip models.

Abstract

Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage degradation, chronic inflammation, and progressive joint dysfunction. Despite rising incidences driven by ageing and increasing obesity, potent treatments remain elusive, exacerbating the socioeconomic burden. OA pathogenesis involves an imbalance in extracellular matrix (ECM) turnover, mediated by inflammatory cytokines and matrix-degrading enzymes, leading to oxidative stress, chondrocyte apoptosis, and ECM degradation. Additionally, synovial inflammation (synovitis) plays a critical role in disease progression through molecular crosstalk with cartilage and other joint tissues. Existing in vitro and in vivo OA models face significant limitations in replicating human pathophysiology, particularly the complex interplay between joint tissues. Equine models, due to their anatomical and cellular similarities to humans, offer translational relevance but remain underutilized. This study aims to develop an advanced 3D coculture system using equine chondrocytes and synoviocytes to simulate tissue-level interactions and fluid mechanical forces involved in OA. By incorporating inflammatory stimuli and gravity-driven cyclic fluid actuation, this model enables the study of OA-related molecular interactions in both healthy and diseased conditions under dynamic fluid conditions. Findings from this research provide important insights into pathological tissue crosstalk. In turn, this can help to better understand underlying inflammatory pathways and the potential contribution of fluid flow as an influential factor on the tissue microenvironment.