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

• Published in: Clinical oral investigations Vol. 25; no. 10; pp. 5917 - 5927
• Main Authors: Imafuji, Takatomo, Shirakata, Yoshinori, Shinohara, Yukiya, Nakamura, Toshiaki, Noguchi, Kazuyuki
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-10-2021; Springer Nature B.V
• Subjects: Animals; Bone growth; Bone healing; Bone Morphogenetic Protein 2; Bone morphogenetic protein 9; Collagen; Computed tomography; Dentistry; Growth Differentiation Factor 2; Humans; Medicine; Original Article; Osteogenesis; Rats; Rats, Wistar; Recombinant Proteins; Ultrasonic imaging; Ultrasonic Waves; Ultrasound; X-Ray Microtomography; Animal experiment; Bone formation; Bone morphogenetic protein; Wound healing; Low-intensity pulsed ultrasound
• ISSN: 1432-6981; 1436-3771
• DOI: 10.1007/s00784-021-03897-6

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 mm
3
vs. 1.76 ± 0.44 mm
3
, 1.25 ± 0.31 mm
2
vs. 0.88 ± 0.22 mm
2
, 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.