{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T21:19:16Z","timestamp":1779311956492,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T00:00:00Z","timestamp":1604620800000},"content-version":"am","delay-in-days":361,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T00:00:00Z","timestamp":1573430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH\u201014\u20101\u20100327"],"award-info":[{"award-number":["W81XWH\u201014\u20101\u20100327"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Joint stiffness due to fibrosis\/capsule contracture is a seriously disabling complication of articular injury that surgical interventions often fail to completely resolve. Fibrosis\/contracture is associated with the abnormal persistence of myofibroblasts, which over\u2010produce and contract collagen matrices. We hypothesized that intra\u2010articular therapy with drugs targeting myofibroblast survival (sulfasalazine), or collagen production (\u03b2\u2010aminopropionitrile and <jats:italic>cis<\/jats:italic>\u2010hydroxyproline), would reduce joint stiffness in a rabbit model of fibrosis\/contracture. Drugs were encapsulated in poly[lactic\u2010co\u2010glycolic] acid pellets and implanted in joints after fibrosis\/contracture induction. Capsule \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) expression and intimal thickness were evaluated by immunohistochemistry and histomorphometry, respectively. Joint stiffness was quantified by flexion\u2010extension testing. Drawer tests were employed to determine if the drugs induced cruciate ligament laxity. Joint capsule fibroblasts were tested in vitro for contractile activity and \u03b1\u2010SMA expression. Stiffness in immobilized joints treated with blank pellets (control) was significantly higher than in non\u2010immobilized, untreated joints (normal) (<jats:italic>p<\/jats:italic>\u2009=\u20090.0008), and higher than in immobilized joints treated with sulfasalazine (<jats:italic>p<\/jats:italic>\u2009=\u20090.0065). None of the drugs caused significant cruciate ligament laxity. Intimal thickness was significantly lower than control in the normal and sulfasalazine\u2010treated groups (<jats:italic>p<\/jats:italic>\u2009=\u20090.010 and 0.025, respectively). Contractile activity in the cells from controls was significantly increased versus normal (<jats:italic>p<\/jats:italic>\u2009=\u20090.001). Sulfasalazine and \u03b2\u2010aminopropionitrile significantly inhibited this effect (<jats:italic>p<\/jats:italic>\u2009=\u20090.005 and 0.0006, respectively). \u03b1\u2010SMA expression was significantly higher in control versus normal (<jats:italic>p<\/jats:italic>\u2009=\u20090.0021) and versus sulfasalazine (<jats:italic>p<\/jats:italic>\u2009=\u20090.0007). These findings support the conclusion that sulfasalazine reduced stiffness by clearing myofibroblasts from fibrotic joints. Statement of clinical significance: The results provide proof\u2010of\u2010concept that established joint stiffness can be resolved non\u2010surgically. \u00a9 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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