Utilization of a genetically modified muscle flap for local BMP-2 production and its effects on bone healing: a histomorphometric and radiological study in a rat model.
OBJECTIVE
We developed an experimental rat model to explore the possibility of enhancing the healing of critical-size bone defects. The aim of this study was to demonstrate the feasibility of this concept by achieving high local BMP-2 expression via a transduced muscle flap that would facilitate bony union while minimizing systemic sequelae.


METHODS
The transduction potential of the adenoviral vector encoding for BMP-2 was tested in different cell lines in vitro. In vivo experiments consisted of harvesting a pedicled quadriceps femoris muscle flap with subsequent creation of a critical-size defect in the left femur in Sprague-Dawley rats. Next, the pedicled muscle flap was perfused with high titers of Ad.BMP-2 and Ad.GFP virus, respectively. Twelve animals were divided into three groups comparing the effects of Ad.BMP-2 transduction to Ad.GFP and placebo. Bone healing was monitored radiologically with subsequent histological analysis post-mortem.


RESULTS
The feasibility of this concept was demonstrated by successful transduction in vitro and in vivo as evidenced by a marked increase of BMP-2 expression. The three examined groups only showed minor difference regarding bone regeneration; however, one complete bridging of the defect was observed in the Ad.BMP-2 group. No evidence of systemic viral contamination was noted.


CONCLUSIONS
A marked increase of local BMP-2 expression (without untoward systemic sequelae) was detected. However, bone healing was not found to be significantly enhanced, possibly due to the small sample size of the study.
Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Hugstetterstr. 55, D-79106, Freiburg, Germany. florian.lampert@uniklinik-freiburg.de.
Florian M
FM
Lampert
Division of Plastic and Reconstructive Surgery, Stanford University Medical Center, 770 Welch Road, Suite 400, Palo Alto, CA, 94304-5715, USA. amomeni@stanford.edu.
Arash
A
Momeni
Department of Ophthalmology, University MedicalCenter Hamburg-Eppendorf, Haus West 40 (W40), Martinistr. 52, D-20246, Hamburg, Germany. f.filev@uke.de.
Filip
F
Filev
Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Hugstetterstr. 55, D-79106, Freiburg, Germany. torio@acredis.com.
Nestor
N
Torio-Padron
Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Hugstetterstr. 55, D-79106, Freiburg, Germany. guenter.finkenzeller@uniklinik-freiburg.de.
Günter
G
Finkenzeller
Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Hugstetterstr. 55, D-79106, Freiburg, Germany. bjoern.stark@uniklinik-freiburg.de.
G Björn
GB
Stark
Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Krankenhausstrasse 12, 91054, Erlangen, Germany. Dominik.Steiner@uk-erlangen.de.
Dominik
D
Steiner
Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Hugstetterstr. 55, D-79106, Freiburg, Germany. georgios.koulaxouzidis@uniklinik-freiburg.de.
Georgios
G
Koulaxouzidis
D000256:Adenoviridae; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D001861:Bone Regeneration; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000628:therapy; D005599:Fractures, Ununited / Q000000981:diagnostic imaging / Q000628:therapy*; D015316:Genetic Therapy; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D052097:Quadriceps Muscle / Q000378:metabolism; D011859:Radiography; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic
D055396:Bone Morphogenetic Protein 2