BACKGROUND Restoration of massive bone defects remains a huge challenge for orthopedic surgeons. Insufficient vascularization and slow bone regeneration limited the application of tissue engineering in bone defect. The effect of electromagnetic field (EMF) on bone defect has been reported for many years. However, sinusoidal EMF (SEMF) combined with tissue engineering in bone regeneration remains poorly investigated. METHODS In the present study, we investigated the effect of SEMF and vascular endothelial growth factor (VEGF) on osteogenic and vasculogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs). Furthermore, pretreated rBMSC- laden polycaprolactone-hydroxyapatite (PCL/HA) scaffold was constructed and implanted into the subcritical cranial defect of rats. The bone formation and vascularization were evaluated 4 and 12 weeks after implantation. RESULTS It was shown that SEMF and VEGF could enhance the protein and mRNA expression levels of osteoblast- and endothelial cell-related markers, respectively. The combinatory effect of SEMF and VEGF slightly promoted the angiogenic differentiation of rBMSCs. The proteins of Wnt1, low-density lipoprotein receptor-related protein 6 (LRP-6), and β-catenin increased in all inducted groups, especially in SEMF + VEGF group. The results indicated that Wnt/β-catenin pathway might participate in the osteogenic and angiogenic differentiation of rBMSCs. Histological evaluation and reconstructed 3D graphs revealed that tissue-engineered constructs significantly promoted the new bone formation and angiogenesis compared to other groups. CONCLUSION The combinatory effect of SEMF and VEGF raised an efficient approach to enhance the osteogenesis and vascularization of tissue-engineered constructs, which provided a useful guide for regeneration of bone defects.

中文翻译：

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正弦波电磁场和VEGF的组合作用促进了大鼠亚临界颅骨缺损中间充质干细胞的PCL / HA植入物的成骨和血管生成。

背景技术对于整形外科医生而言，修复大量骨缺损仍然是巨大的挑战。血管生成不足和骨再生缓慢限制了组织工程在骨缺损中的应用。电磁场（EMF）对骨缺损的影响已有多年报道。然而，正弦电动势（SEMF）结合组织工程在骨再生中的研究仍很少。方法在本研究中，我们研究了SEMF和血管内皮生长因子（VEGF）对大鼠骨髓间充质干细胞（rBMSCs）成骨和血管生成分化的影响。此外，构建了经过预处理的载有rBMSC的聚己内酯-羟基磷灰石（PCL / HA）支架，并将其植入大鼠的亚临界颅骨缺损中。植入后4和12周评估骨形成和血管形成。结果表明，SEMF和VEGF可以分别提高成骨细胞和内皮细胞相关标志物的蛋白质和mRNA表达水平。SEMF和VEGF的联合作用略微促进了rBMSCs的血管生成分化。Wnt1，低密度脂蛋白受体相关蛋白6（LRP-6）和β-catenin的蛋白在所有诱导组中均增加，特别是在SEMF + VEGF组中。结果表明，Wnt /β-catenin途径可能参与了rBMSCs的成骨和血管生成分化。组织学评估和重建的3D图显示，与其他组相比，组织工程构造明显促进了新的骨形成和血管生成。