{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T03:44:14Z","timestamp":1775187854619,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T00:00:00Z","timestamp":1591920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lateral ligament tears, also known as high\u2010grade ankle sprains, are common, debilitating, and usually heal slowly. Ten to thirty percent of patients continue to suffer from chronic pain and ankle instability even after 3 to 9 months. Previously, we showed that the recombinant human amelogenin (rHAM<jats:sup>+<\/jats:sup>) induced regeneration of fully transected rat medial collateral ligament, a common proof\u2010of\u2010concept model. Our aim was to evaluate whether rHAM<jats:sup>+<\/jats:sup> can regenerate torn ankle calcaneofibular ligament (CFL), an important component of the lateral ankle stabilizers. Right CFLs of Sabra rats were transected and treated with 0, 0.5, or 1\u2009\u00b5g\/\u00b5L rHAM<jats:sup>+<\/jats:sup> dissolved in propylene glycol alginate (PGA). Results were compared with the normal group, without surgery. Healing was evaluated 12 weeks after treatment by mechanical testing (ratio between the right and left, untransected ligaments of the same rat), and histology including immunohistochemical staining of collagen I and S100. The mechanical properties, structure, and composition of transected ligaments treated with 0.5\u2009\u03bcg\/\u03bcL rHAM<jats:sup>+<\/jats:sup> (experimental) were similar to untransected ligaments. PGA (control) treated ligaments were much weaker, lax, and unorganized compared with untransected ligaments. Treatment with 1\u2009\u03bcg\/\u03bcL rHAM<jats:sup>+<\/jats:sup> was not as efficient as 0.5\u2009\u03bcg\/\u03bcL rHAM<jats:sup>+<\/jats:sup>. Normal arrangement of collagen I fibers and of proprioceptive nerve endings, parallel to the direction of the force, was detected in ligaments treated with 0.5\u2009\u03bcg\/\u03bcL rHAM<jats:sup>+<\/jats:sup>, and scattered arrangement, resembling scar tissue, in control ligaments. In conclusion, we showed that rHAM<jats:sup>+<\/jats:sup> induced significant mechanical and structural regeneration of torn rat CFLs, which might be translated into treatment for grades 2 and 3 ankle sprain injuries.<\/jats:p>","DOI":"10.1002\/jor.24718","type":"journal-article","created":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T08:14:02Z","timestamp":1589530442000},"page":"1540-1547","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Regeneration of grade 3 ankle sprain, using the recombinant human amelogenin protein (rHAM<sup>+<\/sup>) in a rat model"],"prefix":"10.1002","volume":"39","author":[{"given":"Salem","family":"Hanhan","sequence":"first","affiliation":[{"name":"Faculty of Dental Medicine Institute of Dental Sciences, The Hebrew University\u2010Hadassah School of Dental Medicine  Jerusalem 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