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Injury. 2015 Dec;46(12):2351-8. doi: 10.1016/j.injury.2015.09.016. Epub 2015 Sep 28.

The effect of BMP-7 gene activated muscle tissue implants on the repair of large segmental bone defects.

Author information

1
Department of Trauma and Reconstructive Surgery and Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus Dresden, TU Dresden, Dresden, Germany. Electronic address: volker.betz@yahoo.com.
2
Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany.
3
Department of Trauma and Reconstructive Surgery and Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus Dresden, TU Dresden, Dresden, Germany.
4
Sirion Biotech GmbH, Martinsried, Germany.
5
Institute of Biomechanics, Trauma Center Murnau, Murnau, Germany; Paracelsus Medical University, Salzburg, Austria.

Abstract

BACKGROUND:

This study was conducted in order to investigate the effect of Bone Morphogenetic Protein-7 (BMP-7) transduced muscle cells on bone formation and to further develop an innovative abbreviated ex vivo gene therapy for bone repair. As conventional ex vivo gene therapy methods require an elaborative and time-consuming extraction and expansion of cells we evaluated an expedited approach. Fragments of muscle tissue were directly activated by BMP-7 cDNA and implanted into bone defects.

METHODS:

25 male, syngeneic Fischer 344 rats were used in the present study. Muscle tissue was harvested from two donor rats and either transduced with an adenovirus carrying the BMP-7 cDNA or remained unmodified. 5mm osseous defects in the right femora of 23 rats were treated with either unmodified muscle tissue (control group) or BMP-7 activated muscle tissue (treatment group). Six weeks after surgery, rat femora were evaluated by radiographs, micro-computed tomography (μCT) and histology.

RESULTS:

Implantation of BMP-7 activated muscle grafts led to bony bridging in 5 out of 12 defects (41.7%) and to bone formation without bridging in 2 out of 12 defects. In 2 femoral defects of this group radiographs, μCT-imaging and histology did not reveal significant mineralization. Three animals of the BMP-7 treatment group had to be euthanized due to serious wound infection. The bone volume of the treatment group was significantly (p=0.007) higher compared to the control group.

CONCLUSION:

This study shows that BMP-7 gene activated muscle fragments have the potential to regenerate critical-size segmental bone defects in rats. However, further development of this promising expedited treatment modality is required to improve the healing rate and to investigate if the high infection rate is related to treatment with BMP-7 activated muscle grafts.

KEYWORDS:

BMP-7; Bone defect; Bone repair; Gene therapy; Muscle tissue; Tissue engineering

PMID:
26454628
DOI:
10.1016/j.injury.2015.09.016
[Indexed for MEDLINE]

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