title: Effect of a novel nonviral gene delivery of BMP-2 on bone healing.
abstract: BACKGROUND
  Gene therapeutic drug delivery approaches have been introduced to improve the efficiency of growth factors at the site of interest. This study investigated the efficacy and safety of a new nonviral copolymer-protected gene vector (COPROG) for the stimulation of bone healing.
  
  
  METHODS
  In vitro, rat osteoblasts were transfected with COPROG + luciferase plasmid or COPROG + hBMP-2 plasmid. In vivo, rat tibial fractures were intramedullary stabilized with uncoated versus COPROG+hBMP-2-plasmid-coated titanium K-wires. The tibiae were prepared for biomechanical and histological analyses at days 28 and 42 and for transfection/safety study at days 2, 4, 7, 28, and 42.
  
  
  RESULTS
  In vitro results showed luciferase expression until day 21, and hBMP-2-protein was measured from day 2 - day 10. In vivo, the local application of hBMP-2-plasmid showed a significantly higher maximum load after 42 days compared to that in the control. The histomorphometric analysis revealed a significantly less mineralized periosteal callus area in the BMP-2 group compared to the control at day 28. The rt-PCR showed no systemic biodistribution of luciferase RNA.
  
  
  CONCLUSIONS
  A positive effect on fracture healing by nonviral BMP-2 plasmid application from COPROG-coated implants could be shown in this study; however, the effect of the vector may be improved with higher plasmid concentrations. Transfection showed no biodistribution to distant organs and was considered to be safe.
authors.affiliation: Center for Musculoskeletal Surgery and Julius Wolff Institute, Charité-University Medicine Berlin, Campus Virchow, Augustenburger Platz 1, 13353 Berlin, Germany. philipp.schwabe@charite.de
authors.forename: P
authors.initials: P
authors.lastname: Schwabe
authors.forename: S
authors.initials: S
authors.lastname: Greiner
authors.forename: R
authors.initials: R
authors.lastname: Ganzert
authors.forename: J
authors.initials: J
authors.lastname: Eberhart
authors.forename: K
authors.initials: K
authors.lastname: Dähn
authors.forename: A
authors.initials: A
authors.lastname: Stemberger
authors.forename: C
authors.initials: C
authors.lastname: Plank
authors.forename: G
authors.initials: G
authors.lastname: Schmidmaier
authors.forename: B
authors.initials: B
authors.lastname: Wildemann
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000627:therapeutic use*; D002214:Capsules / Q000008:administration & dosage / Q000138:chemical synthesis*; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D005260:Female; D017102:Fracture Healing / Q000187:drug effects*; D015316:Genetic Therapy / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013978:Tibial Fractures / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D014162:Transfection / Q000379:methods; D016896:Treatment Outcome; D018406:Virus Physiological Phenomena
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D002214:Capsules; D004247:DNA