Treatment of rabbit femoral defect by firearm with BMP-4 gene combined with TGF-beta1.

Background: Firearm bone fractures are difficult to treat compared with general ones as both soft tissue and bone are injured more extensively and severely with contamination in the wound track. The bone morphogenetic protein (BMP) and transforming growth factor (TGF)-beta play an important role in bone fracture healing. Therefore, BMP-4 combined with TGF-beta1 was used to improve and accelerate the repair of rabbit femoral defect resulting from firearm.

Methods: Femoral defect was made with 0.375 g steel ball fired at 350 m/s. At 6 hours after wounding, the debridement and irrigation were performed, followed by trimming the ends of defected bone at day 7. Plasmid-encoded BMP-4 gene identified in vitro and TGF-beta1 were injected into the tissue of upper and lower parts and the epicenter of the defected area at 2 weeks after wounding, again TGF-beta1 was given at 5 weeks. At 3, 7, 11, and 15 weeks after wounding, the expression of mRNA and protein of BMP-4 were detected by reverse transcription-polymerase chain reaction and Western blot. The activity of alkaline phosphatase and calcium content were measured for describing osteogenetic ability. The course and quality of osteogenesis were determined quantitatively by pathohistological and X-ray examinations.

Results: In vivo BMP-4 mRNA and protein could be continually expressed for 8 weeks. The determination of alkaline phosphatase activity and calcium content showed osteogenetic ability was significantly enhanced by BMP-4 gene combined with TGF-beta1. The pathohistological and X-ray examinations revealed that osteogenetic speed was prominently accelerated, and the quality was improved after the treatment.

Conclusion: The repair of rabbit femoral defect resulting from firearm can be significantly improved and accelerated by BMP-4 gene combined with TGF-beta1.