title: Combined effect of BMP-2 gene transfer and bioactive glass microspheres on enhancement of new bone formation.
abstract: Adenovirus-mediated recombinant human BMP-2 (RAdBMP-2) gene transfer has been found to have significant osteoinductive properties. The hypothesis of the current study was that bioactive glass surface could provide favorable osteoconductive conditions for cellular action of osteoinductive RAdBMP-2 gene transfer. In the rat proximal tibia, a portion of the medullary cavity was evacuated and filled with bioactive glass microspheres and injected with adenovirus carrying the human BMP-2 gene (BG/RAdBMP-2). Control defects filled with BG microspheres were injected with adenovirus carrying the LacZ reporter gene (BG/RAdLacZ) or saline (BG). Empty control defects were also used. Bone healing response was analyzed at 4 days, and at 2 and 8 weeks by radiography, peripheral quantitative computed tomography (pQCT), histomorphometry, and backscattered electron imaging of scanning electron microscopy (BEI-SEM) equipped with energy dispersive X-ray analysis (EDXA). In empty controls, the amount of intramedullary new bone peaked at 2 weeks, whereas defects filled with bioactive glass with and without RAdBMP-2 gene transfer showed a constant time-related increase of intramedullary new bone. At 8 weeks, there was significantly more new bone in defects treated with BG and RAdBMP-2 than in defects left to heal without filling (p < 0.001). Compared with the other controls (BG only or BG/RAdLacZ), the difference was not significant. In the current model, the osteopromotive effect of bioactive glass microspheres appears synergistic with the osteoinductive action of BMP-2 gene transfer, or one overshadows the other, as no additive effect was observed.
authors.affiliation: Department of Orthopaedic Surgery and Traumatology, University of Turku, Kiinamyllynkatu 4-8, FIN-20520 Turku, Finland.
authors.forename: V-V
authors.initials: VV
authors.lastname: Välimäki
authors.forename: J J
authors.initials: JJ
authors.lastname: Yrjans
authors.forename: E
authors.initials: E
authors.lastname: Vuorio
authors.forename: H T
authors.initials: HT
authors.lastname: Aro
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D016723:Bone Remodeling; D005260:Female; D018014:Gene Transfer Techniques; D007763:Lac Operon; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D051381:Rats; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: C525718:BMP2 protein, human; D001672:Biocompatible Materials; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta