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. 2021 Oct;25(10):5917-5927.
doi: 10.1007/s00784-021-03897-6. Epub 2021 Mar 23.

Enhanced bone formation of calvarial bone defects by low-intensity pulsed ultrasound and recombinant human bone morphogenetic protein-9: a preliminary experimental study in rats

Takatomo Imafuji  1 , Yoshinori Shirakata  2 , Yukiya Shinohara  1 , Toshiaki Nakamura  1 , Kazuyuki Noguchi  1
Affiliations

Enhanced bone formation of calvarial bone defects by low-intensity pulsed ultrasound and recombinant human bone morphogenetic protein-9: a preliminary experimental study in rats

Takatomo Imafuji et al. Clin Oral Investig. 2021 Oct.

Abstract

Objectives: The aim of this study was to evaluate the combined effects of recombinant human bone morphogenetic protein - 9 (rhBMP-9) loaded onto absorbable collagen sponges (ACS) and low-intensity pulsed ultrasound (LIPUS) on bone formation in rat calvarial defects.

Materials and methods: Circular calvarial defects were surgically created in 18 Wistar rats, which were divided into LIPUS-applied (+) and LIPUS-non-applied (-) groups. The 36 defects in each group received ACS implantation (ACS group), ACS with rhBMP-9 (rhBMP-9/ACS group), or surgical control (control group), yielding the following six groups: ACS (+/-), rhBMP-9/ACS (+/-), and control (+/-). The LIPUS-applied groups received daily LIPUS exposure starting immediately after surgery. At 4 weeks, animals were sacrificed and their defects were investigated histologically and by microcomputed tomography.

Results: Postoperative clinical healing was uneventful at all sites. More new bone was observed in the LIPUS-applied groups compared with the LIPUS-non-applied groups. Newly formed bone area (NBA)/total defect area (TA) in the ACS (+) group (46.49 ± 7.56%) was significantly greater than that observed in the ACS (-) (34.31 ± 5.68%) and control (-) (31.13 ± 6.74%) groups (p < 0.05). The rhBMP-9/ACS (+) group exhibited significantly greater bone volume, NBA, and NBA/TA than the rhBMP-9/ACS (-) group (2.46 ± 0.65 mm3 vs. 1.76 ± 0.44 mm3, 1.25 ± 0.31 mm2 vs. 0.88 ± 0.22 mm2, and 62.80 ± 11.87% vs. 42.66 ± 7.03%, respectively) (p < 0.05). Furthermore, the rhBMP-9/ ACS (+) group showed the highest level of bone formation among all groups.

Conclusion: Within their limits, it can be concluded that LIPUS had osteopromotive potential and enhanced rhBMP-9-induced bone formation in calvarial defects of rats.

Clinical relevance: The use of rhBMP-9 with LIPUS stimulation can be a potential bone regenerative therapy for craniofacial/peri-implant bone defects.

Keywords: Animal experiment; Bone formation; Bone morphogenetic protein; Low-intensity pulsed ultrasound; Wound healing.

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