Sustained Structural and Functional Deficits in the Porcine Knee Six Months Following Meniscus Destabilization

Osteoarthritis (OA) of the knee is a leading cause of pain and disability. Large animal models that accurately reflect the human OA phenotype are essential for evaluating new therapeutics. This study sought to evaluate a porcine model of knee injury using an enhanced destabilization of the medial meniscus (DMM+) approach in which a 5 mm portion of the medial meniscus anterior (cranial) attachment (cranial medial meniscotibial ligament) was resected. A series of quantitative and semi-quantitative measures of joint-wide structure and function were used to assess joint degeneration at 6 weeks and 6 months postoperatively, including cartilage mechanical testing, subchondral bone analysis, osteochondral and synovial histology and gait analysis. Results showed that early degenerative changes were localized to regions experiencing a change in mechanical loading, with changes including decreased cartilage mechanics and subchondral bone sclerosis. By 6 months, despite resolution of the subchondral bone changes, other features of degeneration became more diffuse, with cartilage softening, synovial inflammation, and altered gait being apparent at this time point, indicating a transition from acute mechanical insult to chronic joint pathology. This large animal model results in OA-like changes to cartilage mechanics and synovium, mimicking some key aspects of human OA, making it a potentially valuable platform in which to test disease-modifying treatments and regenerative strategies.