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高纯度镁钉通过激活 VHL/HIF-1α/VEGF 信号通路增强牵张成骨模型中的骨整合。

High-purity magnesium pin enhances bone consolidation in distraction osteogenesis model through activation of the VHL/HIF-1α/VEGF signaling.

机构信息

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

Suzhou Origin Medical Technology Co. Ltd, Suzhou, China.

出版信息

J Biomater Appl. 2020 Aug;35(2):224-236. doi: 10.1177/0885328220928550. Epub 2020 May 28.

DOI:10.1177/0885328220928550
PMID:32460592
Abstract

Distraction osteogenesis has widespread clinical use in the treatment of large bone defects. Nonetheless, the prolonged consolidation period carries the risk of complications. Magnesium-based materials have been shown to promote bone regeneration in fracture healing both in vitro and in vivo. Here, we investigated whether high-purity magnesium could enhance bone formation in distraction osteogenesis. High-purity magnesium pins were placed into the medullary cavity in the rat distraction osteogenesis model. Results showed that the bone volume/total tissue volume, bone mineral density, and mechanical properties of new callus were significantly higher in the high-purity magnesium group compared to stainless steel and control group (p < 0.01). Histological analyses confirmed improved bone consolidation and vascularization in high-purity magnesium group. Further, polymerase chain reaction-array investigation, Western blot, and immunohistochemical results found that vascular endothelial growth factor and hypoxia inducible factor-1α were highly expressed in the high-purity magnesium group, while Von Hippel-Lindau protein was the opposite (p < 0.01). In conclusion, high-purity magnesium implants have the potential to enhance angiogenesis and bone consolidation in the distraction osteogenesis application, and this process might be via the regulation of Von Hippel-Lindau/hypoxia inducible factor-1α/vascular endothelial growth factor signaling.

摘要

牵引成骨术在治疗大骨缺损方面具有广泛的临床应用。然而,延长的愈合期会带来并发症的风险。研究表明,镁基材料在体外和体内都能促进骨折愈合中的骨再生。在这里,我们研究了高纯镁是否能增强牵引成骨中的骨形成。在大鼠牵引成骨模型中,将高纯镁钉置于髓腔内。结果表明,与不锈钢和对照组相比,高纯镁组的骨体积/组织总体积、骨密度和新生骨痂的力学性能显著提高(p<0.01)。组织学分析证实,高纯镁组骨整合和血管化得到改善。此外,聚合酶链反应-阵列研究、Western blot 和免疫组织化学结果发现,高纯镁组血管内皮生长因子和缺氧诱导因子-1α高度表达,而 Von Hippel-Lindau 蛋白则相反(p<0.01)。总之,高纯镁植入物有可能增强牵引成骨应用中的血管生成和骨整合,这一过程可能是通过 Von Hippel-Lindau/缺氧诱导因子-1α/血管内皮生长因子信号的调节。

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