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
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
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DOI：
10.1007/s00784-021-03897-6
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发表时间：
2021-03
影响因子：
3.4
通讯作者：
T. Imafuji;Y. Shirakata;Yukiya Shinohara;Toshiaki Nakamura;K. Noguchi
中科院分区：
文献类型：
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作者：
T. Imafuji;Y. Shirakata;Yukiya Shinohara;Toshiaki Nakamura;K. Noguchi
本研究的目的是评价重组人骨形态发生蛋白-9（rhBMP-9）负载于可吸收胶原海绵（ACS）和低强度脉冲超声（LIPUS）对大鼠颅骨缺损骨形成的联合作用。分为应用LIPUS（+）和未应用LIPUS（-）组。每组36个缺损接受ACS植入（ACS组）、ACS + rhBMP-9（rhBMP-9/ACS组）或手术对照（对照组），产生以下6组：ACS（+/−）、rhBMP-9/ACS（+/−）和对照（+/−）。LIPUS应用组在手术后立即开始接受每日LIPUS暴露。在第4周，动物被处死，他们的缺陷进行了组织学和microcomputedtomography.ResultsPostoperative临床愈合是平安无事的，在所有网站。与未应用LIPUS组相比，在应用LIPUS组中观察到更多的新骨。ACS（+）组中的新形成骨面积（NBA）/总缺损面积（TA）（46.49 ± 7.56%）显著大于ACS（-）组（34.31 ± 5.68%）和对照（-）组（31.13 ± 6.74%）（p< 0.05）。rhBMP-9/ACS（+）组的骨体积、NBA和NBA/TA显著大于rhBMP-9/ACS（-）组（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 2，62.80 ± 11.87% vs42.66 ± 7.03%）（p< 0.05）。结论在一定范围内，LIPUS对大鼠颅骨缺损具有促骨形成作用，并能促进rhBMP-9诱导的骨形成。临床意义应用rhBMP-9与LIPUS联合应用可作为一种潜在的骨再生治疗方法，用于治疗颅面/种植体周围骨缺损。
ObjectivesThe 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 methodsCircular 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.ResultsPostoperative 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 mm3vs. 1.76 ± 0.44 mm3, 1.25 ± 0.31 mm2vs. 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.ConclusionWithin their limits, it can be concluded that LIPUS had osteopromotive potential and enhanced rhBMP-9-induced bone formation in calvarial defects of rats.Clinical relevanceThe use of rhBMP-9 with LIPUS stimulation can be a potential bone regenerative therapy for craniofacial/peri-implant bone defects.