Effects of intra-articular 2.5% polyacrylamide hydrogel in an experimental model of equine osteoarthritis

Background: Osteoarthritis (OA) is a leading cause of lameness in horses. Injectable polyacrylamide hydrogels (iPAAGs) have emerged as an intra-articular (IA) treatment option though the mechanism of action is not fully understood. Objectives: To evaluate the symptom- and disease-modifying effects of 2.5% iPAAG in an experimentally-induced model of OA in horses. Study design: In vivo experimental study. Methods: Sixteen horses had an osteochondral fragment created (d0) in one randomly selected middle carpal joint (MCJ); opposite MCJs were sham-operated. OA joints were treated (d14) with 2 mL saline (n=8) or 2.5% iPAAG (n=8). High-speed treadmill exercise commenced on d16 to induce OA. Clinical parameters (lameness, joint effusion, range of motion, flexion response) and synovial fluid were collected weekly to biweekly, respectively. Radiographs were obtained before, d14, and d70 post-surgery. Post-mortem evaluation (d70) included gross, arthroscopic and histopathologic evaluation of the MCJs and measurement of joint capsule stiffness. Results: There were no significant differences in clinical parameters nor endpoint arthroscopic, macroscopic and synovial membrane histopathology scores between treated and control groups. 2.5% iPAAG-treated OA joints had significantly lower (better) overall articular cartilage histology scores and better proteoglycan staining of the intermediate layer of the 3 rd carpal bone articular cartilage. Saline-treated OA joints had significantly increased joint capsule stiffness whereas 2.5% iPAAG-treated joints had stiffness values similar to sham-operated MCJs. Main limitations: Experimentally-induced OA does not fully mimic naturally occurring OA. Horses were followed 56 days post 2.5% iPAAG treatment, which may not have been long enough to fully elucidate treatment effects. Conclusions: Treatment with 2.5% iPAAG showed disease-modifying effects including some ability to mitigate the negative effects of OA on articular cartilage. Treatment also resulted in retention of normal joint capsule elasticity during experimental progression of OA, which likely contributes to the symptom-modifying effects that have been shown in several clinical trials.