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低强度脉冲超声联合重组人骨形态发生蛋白-9 促进颅骨骨缺损骨形成:大鼠初步实验研究。

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.

机构信息

Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.

出版信息

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

DOI:10.1007/s00784-021-03897-6
PMID:33755786
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 mm vs. 1.76 ± 0.44 mm, 1.25 ± 0.31 mm vs. 0.88 ± 0.22 mm, 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.

摘要

目的

本研究旨在评估负载于可吸收胶原海绵(ACS)上的重组人骨形态发生蛋白-9(rhBMP-9)与低强度脉冲超声(LIPUS)联合应用对大鼠颅骨缺损骨形成的影响。

材料与方法

在 18 只 Wistar 大鼠颅骨上制作圆形颅骨缺损,将其分为 LIPUS 应用(+)和 LIPUS 非应用(-)组。每组 36 个缺损分别接受 ACS 植入(ACS 组)、rhBMP-9/ACS(rhBMP-9/ACS 组)或手术对照(对照组),得到以下 6 个组:ACS(+/ -)、rhBMP-9/ACS(+/ -)和对照组(+/ -)。LIPUS 应用组在术后立即开始每天接受 LIPUS 照射。4 周后,处死动物并进行组织学和微计算机断层扫描检查。

结果

所有部位的术后临床愈合均顺利。与 LIPUS 非应用组相比,LIPUS 应用组观察到更多的新骨。ACS(+)组新骨形成面积(NBA)/总缺损面积(TA)(46.49 ± 7.56%)明显大于 ACS(-)组(34.31 ± 5.68%)和对照组(-)组(31.13 ± 6.74%)(p < 0.05)。rhBMP-9/ACS(+)组的骨体积、NBA 和 NBA/TA 明显大于 rhBMP-9/ACS(-)组(2.46 ± 0.65 mm 比 1.76 ± 0.44 mm,1.25 ± 0.31 mm 比 0.88 ± 0.22 mm,62.80 ± 11.87% 比 42.66 ± 7.03%)(p < 0.05)。此外,rhBMP-9/ACS(+)组在所有组中表现出最高水平的骨形成。

结论

在其限度内,可以得出结论,LIPUS 具有成骨促进潜力,并增强了大鼠颅骨缺损中 rhBMP-9 诱导的骨形成。

临床相关性

rhBMP-9 联合 LIPUS 刺激的应用可能是一种用于颅面/种植体周围骨缺损的潜在骨再生治疗方法。

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