{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:42:48Z","timestamp":1789717368387,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,2,18]],"date-time":"2005-02-18T00:00:00Z","timestamp":1108684800000},"content-version":"vor","delay-in-days":1815,"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":[[2000,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A study was performed in dogs to evaluate the dose\u2010response characteristics and effectiveness of recombinant human bone morphogenetic protein\u20102 with a collagen sponge carrier in a segmental defect model. Twenty\u2010seven dogs underwent bilateral radial osteotomies with creation of a 2.5\u2010cm diaphyseal defect. All received autogenous cancellous bone graft in one defect and a collagen implant in the other. These implants contained recombinant human bone morphogenetic protein\u20102 at the following doses: group 1 at 0 \u03bcg (three dogs, 0 \u03bcg\/ml total implant volume), group 2 at 150 \u03bcg (three dogs, 50 \u03bcg\/ml), group 3 at 600 \u03bcg (three dogs, 200 \u03bcg\/ml), group 4 at 2,400 \u03bcg (three dogs, 800 \u03bcg\/ml), group 5 at 0 \u03bcg (five dogs, 0 \u03bcg\/ml), group 6 at 150 \u03bcg (five dogs, 200 \u03bcg\/ml), and group 7 at 600 \u03bcg (five dogs, 50 \u03bcg\/ml). The defects were stabilized with external fixators. The dogs in group 1\u20134 were killed at 12 weeks postoperatively, and those in groups 5\u20137 were killed at 24 weeks postoperatively except for one dog in group 7, which was killed at 48 weeks. Evaluation included monthly radiographs, biomechanical testing, and nondemineralized histology. All 27 radii with autogenous cancellous bone graft and all 19 implants treated with recombinant human bone morphogenetic protein\u20102 achieved radiographic and histologic union and gross stability. The eight radii treated with collagen carrier alone went on to radiographic and histologic nonunion and were grossly unstable at death. A dose\u2010dependent occurrence of cyst\u2010like bone voids was noted radiographically and histologically. Biomechanical performance tended to be better at the lowest dose studied at 12 weeks, and all three doses performed better than the placebo (p &lt; 0.05) at 12 and 24 weeks. By 24 weeks, radiolucent areas corresponding to histologic bone voids persisted radiographically, although there was evidence of early bone remodeling. This remodeling progressed to 48 weeks in the single animal followed to this time point, although bone voids remained. These radiologic findings were confirmed histologically. Recombinant human bone morphogenetic protein\u20102 in a collagen sponge carrier has significant osteoinductive activity in this canine segmental defect model. A dose\u2010response relationship is evident, with heterotopic bone and cyst\u2010like void formation at higher doses and a minimum effective dose of 0\u2010150 \u03bcg. At 12 and 24 weeks postoperatively, biomechanical parameters achieved by defects treated with recombinant human bone morphogenetic protein\u20102 were comparable with those of autograft controls and were significantly stronger than those of the placebo (p &lt; 0.05).<\/jats:p>","DOI":"10.1002\/jor.1100180218","type":"journal-article","created":{"date-parts":[[2005,2,24]],"date-time":"2005-02-24T05:37:28Z","timestamp":1109223448000},"page":"289-302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":133,"title":["Evaluation of recombinant human bone morphogenetic protein\u20102 as a bone\u2010graft substitute in a canine segmental defect model"],"prefix":"10.1002","volume":"18","author":[{"given":"Marcus F.","family":"Sciadini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth 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