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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\u2009mm portion of the medial meniscus anterior (cranial) attachment (cranial medial meniscotibial ligament) was resected. A series of quantitative and semi\u2010quantitative measures of joint\u2010wide 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\u2010like changes to cartilage mechanics and synovium, mimicking some key aspects of human OA, making it a potentially valuable platform in which to test disease\u2010modifying treatments and regenerative strategies.<\/jats:p>","DOI":"10.1002\/jor.70124","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T10:16:32Z","timestamp":1768385792000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sustained Structural and Functional Deficits in the Porcine Knee Six Months Following Meniscus Destabilization"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1799-2312","authenticated-orcid":false,"given":"Brendan D.","family":"Stoeckl","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Department of Bioengineering University 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