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通过在大鼠牵张成骨模型中激活 HIF-1α/VEGF 实现的手风琴技术增强骨再生。

Enhancement of bone regeneration with the accordion technique via HIF-1α/VEGF activation in a rat distraction osteogenesis model.

机构信息

Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Department of Orthopaedics & Traumatology, Stem Cells and Regeneration Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.

出版信息

J Tissue Eng Regen Med. 2018 Feb;12(2):e1268-e1276. doi: 10.1002/term.2534. Epub 2017 Nov 17.

DOI:10.1002/term.2534
PMID:28763580
Abstract

Axial micromotion of bone fragments promotes callus formation and bone healing during the process of distraction osteogenesis (DO). This study investigated the effects of the combined axial compression and distraction (accordion) technique on bone regeneration in rat DO model. Male Sprague-Dawley rats (n = 62) underwent right tibial transverse osteotomy and were randomly divided into four groups after lengthening: control (no manipulation) and three experimental groups assigned on the basis of the period of accordion manoeuvres in the consolidation phase (Groups 1, 2, and 3 with accordion technique applied at Weeks 1, 3, and 5, respectively). Animals were terminated at 1 week after each accordion phase (i.e., Weeks 2, 4, and 6). Callus formation was monitored by X-ray radiography; new bone quality was evaluated by microcomputed tomography, histological analysis, and mechanical testing. Serum levels of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were measured. Callus formation after accordion manoeuvre at Week 3 (Group 2) increased significantly over time of consolidation. The microcomputed tomography and mechanical analysis revealed Group 2 had more newly formed bone and superior mechanical properties in contrast to the other groups at termination. Histomorphological and immunohistochemical analyses confirmed a greater degree of osteogenesis and angiogenesis corresponding to increased serum levels of HIF-1α and VEGF in Group 2. The accordion technique was effective in promoting bone consolidation via activation of HIF-1α/VEGF during DO. The accordion technique may be used in the middle phase of bone consolidation to promote bone formation in patients undergoing DO treatment.

摘要

在骨延长成骨术(DO)过程中,骨碎片的轴向微动促进了骨痂的形成和骨愈合。本研究探讨了轴向压缩与牵拉(手风琴)技术联合应用对大鼠 DO 模型骨再生的影响。雄性 Sprague-Dawley 大鼠(n=62)行右侧胫骨横断截骨术,延长后根据巩固期手风琴操作的时间段随机分为四组:对照组(无操作)和三个实验组(根据手风琴技术在第 1、3 和 5 周应用的时间段分配)。在每次手风琴阶段结束后 1 周(即第 2、4 和 6 周)处死动物。通过 X 射线放射照相监测骨痂形成;通过微计算机断层扫描、组织学分析和机械测试评估新骨质量。测量缺氧诱导因子(HIF)-1α和血管内皮生长因子(VEGF)的血清水平。第 3 周(第 2 组)手风琴操作后的骨痂形成随巩固时间的推移显著增加。与其他组相比,微计算机断层扫描和机械分析显示第 2 组在终止时具有更多的新形成骨和更好的机械性能。组织形态学和免疫组织化学分析证实,与其他组相比,第 2 组具有更高的成骨和血管生成程度,相应地,HIF-1α 和 VEGF 的血清水平也更高。在手风琴技术的作用下,在 DO 期间通过激活 HIF-1α/VEGF 可有效促进骨整合。在手风琴技术可能在骨整合的中期用于促进接受 DO 治疗的患者的骨形成。

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