title: Evaluation of Ad-BMP-2 for enhancing fracture healing in an infected defect fracture rabbit model.
abstract: The objective of this study was to evaluate the use of adenoviral transfer of the BMP-2 gene (Ad-BMP-2) for enhancing healing in an infected defect fracture model. A femoral defect stabilized with plates and screws was surgically created in sixty-four skeletally mature New Zealand white rabbits. Experimental groups were: (1) non-infected Ad-luciferase (Ad-LUC, NONLUC), (2) non-infected Ad-BMP-2 (NONBMP), (3) infected Ad-LUC (INFLUC), and (4) infected Ad-BMP-2 (INFBMP). A sclerosing agent was applied to the ends of the bone at surgery to facilitate the development of osteomyelitis. Fracture healing was evaluated radiographically and histologically. Data were analyzed using an ANOVA, with statistical significance set as p<0.05. Rabbits in the non-infected and infected groups that were treated with Ad-BMP-2 had earlier initial- and bridging-callus formation, and a higher overall external callus grade compared to rabbits in the Ad-LUC groups. Rabbits in the Ad-LUC groups had more defect ossification compared to rabbits in the Ad-BMP-2 groups. There was a trend for rabbits in the Ad-BMP-2 group that were euthanized at 2 and 4 weeks after surgery to have more bone and cartilage compared to rabbits in the Ad-LUC group. The results of this study suggest that Ad-BMP-2 enhances the early stages of healing in an infected defect fracture. The results of our study were not as favorable as those reported in previous studies because animals healed by a large bridging callus and not by defect ossification. This could have been a result of the sclerosing agent, which may have damaged the cells in the defect.
authors.affiliation: Orthopaedic Research Laboratory, Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA. southwoo@vet.upenn.edu
authors.forename: Louise L
authors.initials: LL
authors.lastname: Southwood
authors.forename: David D
authors.initials: DD
authors.lastname: Frisbie
authors.forename: Chris E
authors.initials: CE
authors.lastname: Kawcak
authors.forename: Steven C
authors.initials: SC
authors.lastname: Ghivizzani
authors.forename: Chris H
authors.initials: CH
authors.lastname: Evans
authors.forename: C Wayne
authors.initials: CW
authors.lastname: McIlwraith
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D017102:Fracture Healing / Q000502:physiology*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D010019:Osteomyelitis / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D011817:Rabbits; D013203:Staphylococcal Infections / Q000150:complications; D016212:Transforming Growth Factor beta
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta