{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T10:06:08Z","timestamp":1776765968646,"version":"3.51.2"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,7,16]],"date-time":"2008-07-16T00:00:00Z","timestamp":1216166400000},"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":[[2009,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fracture healing requires coordinated coupling between osteogenesis and angiogenesis in which vascular endothelial growth factor (VEGF) plays a key role. We hypothesized that targeted over\u2010expression of angiogenic and osteogenic factors within the fracture would promote bone healing by inducing development of new blood vessels and stimulating\/affecting proliferation, survival, and activity of skeletal cells. Using a cell\u2010based method of gene transfer, without viral vector, 5.0\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> fibroblasts transfected with VEGF were delivered to a 10\u2010mm bone defect in rabbit tibiae (Group 1) (<jats:italic>n<\/jats:italic>\u2009=\u20099); control groups were treated with fibroblasts (Group 2) (<jats:italic>n<\/jats:italic>\u2009=\u20097), or saline (Group 3) (<jats:italic>n<\/jats:italic>\u2009=\u20097) only. After 12 weeks, eight tibial fractures healed in Group 1, compared to four each in Groups 2 and 3. In Group 1, ossification was seen across the entire defect; in Groups 2 and 3, the defects were fibrous and sparsely ossified. Group 1 had more positively stained (CD31) vessels than Groups 2 and 3. MicroCT 3\u2010D showed complete bridging of the new bone for Group 1, but incomplete healing for Groups 2 and 3. MicroCT bone structural parameters showed significant differences between VEGF treatment and control groups (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). These results indicate that the cell\u2010based VEGF gene therapy has significant angiogenic and osteogenic effects to enhance healing of a segmental defect in the long bone of rabbits. \u00a9 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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