The effect of BMP-7 gene activated muscle tissue implants on the repair of large segmental bone defects. Issue 12 (December 2015)

• Record Type: Journal Article
• Authors: Betz, Volker M.; Betz, Oliver B.; Rosin, Tom; Keller, Alexander; Thirion, Christian; Salomon, Michael; Manthey, Suzanne; Augat, Peter; Jansson, Volkmar; Müller, Peter E.; Rammelt, Stefan; Zwipp, Hans
• Is Part Of: Injury. Volume 46:Issue 12(2015)
• Page Start: 2351
• Page End: 2358
• Publication Date: 2015-12
• Subjects: Bone repair -- Bone defect -- Tissue engineering -- Muscle tissue -- Gene therapy -- BMP-7; Wounds and injuries -- Surgery -- Periodicals; Accidents -- Periodicals; Wounds and Injuries -- surgery -- Periodicals; Lésions et blessures -- Chirurgie -- Périodiques; Electronic journals; Electronic journals; 617.1
• DOI: 10.1016/j.injury.2015.09.016
• Languages: English
• ISSNs: 0020-1383

Abstract

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. 5 mm 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.