Bone regeneration is a multi-step, overlapping process, in which angiogenesis and osteogenesis are the key players. Several attempts have been made to promote angiogenesis-coupled osteogenesis using scaffolding technology. However, the recreation of functional vasculature during bone regeneration is an unparalleled challenge. In this study, a dual drug-delivering polycaprolactone-collagen fibrous scaffold is reported to promote early osteogenesis and angiogenesis. Simvastatin as a pro-angiogenic and dexamethasone as an osteoinductive drug were encapsulated to functionalize the electrospun fibers. The optically transparent fibrous mat represented the sustained and sequential release of drugs for 28 days. The fibrous mesh increased cell proliferation and enhanced the osteogenic differentiation up to 21 days. The alkaline phosphatase activity and mineral deposition were comparatively higher on dual drug-releasing fibers when compared to control fibers. The dual drug-releasing osteoconductive fibers demonstrated osteogenesis as early as 7 days with a 3.7 and 1.5 fold increase in the expression of osteogenic differentiation markers (RUNX2 and osteocalcin), respectively. In vitro angiogenesis using primary human umbilical vein endothelial cells (pHUVECs) showed no significant difference in cell proliferation among control fibers and dual drug-releasing fibers. However, the angioinductive nature of simvastatin released from the fibers demonstrated tube formation and 2 fold higher angiogenic score. The mRNA and protein expression study of angiogenic markers (VEGFR2 and eNOS) by polymerase chain reaction and western blotting depicted the angioinducing potential of dual drug-releasing fibers. VEGFR2 and eNOS mRNA expressions increased by 1.1 and 1.6 fold, respectively, whereas their protein expression increased by 3.2 and 1.7 fold, respectively. The overall results demonstrate the synergistic effect of osteoconductive substrate and osteoinductive dual drugs to promote early osteogenesis, and release of the pro-angiogenic drug promotes angiogenesis.

中文翻译：

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双重药物递送聚己内酯-胶原支架诱导早期成骨分化和耦合血管生成。

骨再生是一个多步骤、重叠的过程，其中血管生成和骨生成是关键参与者。已经进行了几次尝试以使用支架技术促进血管生成耦合的骨生成。然而，在骨再生过程中恢复功能性脉管系统是一项无与伦比的挑战。在这项研究中，据报道，一种双重药物递送聚己内酯 - 胶原纤维支架可促进早期成骨和血管生成。将辛伐他汀作为促血管生成剂和地塞米松作为骨诱导药物进行封装以功能化电纺纤维。光学透明的纤维垫代表药物持续和连续释放 28 天。纤维网增加了细胞增殖并增强了成骨分化长达 21 天。与对照纤维相比，双释药纤维的碱性磷酸酶活性和矿物质沉积相对较高。早在 7 天时，双重释放药物的骨传导纤维就证明了成骨，成骨分化标志物（RUNX2 和骨钙素）的表达分别增加了 3.7 和 1.5 倍。使用原代人脐静脉内皮细胞 (pHUVEC) 进行的体外血管生成显示，对照纤维和双重药物释放纤维之间的细胞增殖没有显着差异。然而，从纤维中释放的辛伐他汀的血管诱导性质证明了管形成和 2 倍高的血管生成评分。通过聚合酶链反应和蛋白质印迹法对血管生成标志物（VEGFR2 和 eNOS）的 mRNA 和蛋白质表达研究描述了双重药物释放纤维的血管诱导潜力。VEGFR2 和 eNOS mRNA 表达分别增加了 1.1 和 1.6 倍，而它们的蛋白质表达分别增加了 3.2 和 1.7 倍。总体结果表明骨传导底物和骨诱导双重药物的协同作用促进早期成骨，促血管生成药物的释放促进血管生成。