Bone forming strategy of low‐intensity pulsed ultrasound and BMP‐2 in distraction osteogenesis

Background Low-intensity pulsed ultrasound (LIPUS) is a special type of acoustic pulsed energy that is increasingly used in orthopedics as a supplementary therapy to promote healing of pathological and traumatic fractures and wounds. Aim/Hypothesis The aim of this study was to evaluate the efficacy of LIPUS and or bone morphogenetic protein (BMP)-2 treatment to determine the optimal strategy for enhancing bone regeneration in distraction osteogenesis (DO). Material and Methods In vitro and in vivo experiments were performed. In in vitro experiments, the effects of LIPUS (frequency, 1.5 MHz+ intensity, 60 mW cm2 + daily for 10 minutes) and BMP-2 (200 ng ml) were evaluated using rat mesenchymal stromal cells (rMSCs). Cell proliferation, alkaline phosphatase activity, gene expression by real-time polymerase chain reaction were performed for analysis. In vivo experiments were performed with LIPUS (frequency, 1.5 MHz+ intensity, 60 mW cm2 + 4 weeks for 20 minutes daily) and BMP-2 (20 μg) using a rabbit mandibular DO model (distraction rate, 1.5 mm day for 5 days). Animals were sacrificed 4 weeks later and micro computed tomography analysis and histological analysis were performed. Results In vitro experiments showed increased level in the rMSCs proliferation, the alkaline phosphatase activity and the osteogenic gene expression when BMP-2 was sequentially used after LIPUS pretreatment. In animal studies, bone formation was significantly increased when LIPUS was applied after distraction and BMP-2 was injected at 2 weeks. Conclusion and Clinical Implications LIPUS and BMP-2 showed various effects on bone regeneration of DO depending on the application strategy. Applying LIPUS prior to BMP-2 administration is the most efficient strategy to promote bone formation in the DO.