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The Scientific World Journal
Volume 2012 (2012), Article ID 560142, 9 pages
http://dx.doi.org/10.1100/2012/560142
Research Article

Effect of a Novel Nonviral Gene Delivery of BMP-2 on Bone Healing

1Center for Musculoskeletal Surgery and Julius Wolff Institute, Charité-University Medicine Berlin, Campus Virchow, Augustenburger Platz 1, 13353 Berlin, Germany
2Institute for Experimental Oncology and Therapy, Technical University Munich, 81675 Munich, Germany
3Department for Trauma and Reconstructive Surgery, University of Heidelberg, 69118 Heidelberg, Germany
4Berlin-Brandenburg Center for Regenerative Therapies, Charité-University Medicine Berlin, 13353 Berlin, Germany

Received 2 August 2012; Accepted 30 September 2012

Academic Editors: A. Bandyopadhyay and M. Deng

Copyright © 2012 P. Schwabe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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. Conclusion. 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.