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

Journal of Orthopaedic Surgery and Research

Georgios Koulaxouzidis⁴  Dominik Steiner¹  G Björn Stark⁴  Günter Finkenzeller⁴  Nestor Torio-Padron⁴  Filip Filev²  Arash Momeni³  Florian M Lampert⁴ 

[1] Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Krankenhausstrasse 12, Erlangen, 91054, Germany;Department of Ophthalmology, University MedicalCenter Hamburg-Eppendorf, Haus West 40 (W40), Martinistr. 52, Hamburg, D-20246, Germany;Division of Plastic and Reconstructive Surgery, Stanford University Medical Center, 770 Welch Road, Suite 400, Palo Alto 94304-5715, CA, USA;Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Hugstetterstr. 55, Freiburg, D-79106, Germany

关键词: Tissue engineering;    Translational medicine;    Regenerative medicine;    BMP-2;    Bone morphogenetic protein;    Reconstructive microsurgery;    Gene therapy;    Bone regeneration;   

Others  :  1227842
DOI  :  10.1186/s13018-015-0196-6

 received in 2014-12-04, accepted in 2015-03-10,  发布年份 2015

【 摘 要 】

Aim of the study

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.

【 授权许可】

   
2015 Momeni et al.; licensee BioMed Central.

【 图 表 】

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