Endothelial cells form the interior layer of blood vessels and, as such, are constantly exposed to shear stress and mechanical strain. While the impact of shear stress on angiogenesis is widely studied, the role of mechanical strain is less understood. To this end, endothelial cells and fibroblasts are cocultured under oscillatory strain to create a vessel network. The two cell types show distinctly different sensitivities to the mechanical stimulation. The fibroblasts, sense the stress directly, and respond by increased alignment, proliferation, differentiation, and migration, facilitated by YAP translocation into the nucleus. In contrast, the endothelial cells form aligned vessels by tracking fibroblast alignment. YAP inhibition in constructs under mechanical strain results in vessel destruction whereas less damage is observed in the YAP‐inhibited static control. Moreover, the mechanical stimulation enhances vessel development and stabilization. Additionally, vessel orientation is preserved upon implantation into a mouse dorsal window chamber and promotes the invading host vessels to orient in the same manner. This study sheds light on the mechanisms by which mechanical strain affects the development of blood vessels within engineered tissues. This can be further utilized to engineer a more organized and stable vasculature suitable for transplantation of engineered grafts.

中文翻译：

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振荡应变通过成纤维细胞 YAP 介导的机械敏感性促进血管稳定和对准

内皮细胞形成血管的内层，因此不断暴露于剪切应力和机械应变。虽然剪切应力对血管生成的影响得到了广泛研究，但机械应变的作用却知之甚少。为此，内皮细胞和成纤维细胞在振荡应变下共培养以创建血管网络。这两种细胞类型对机械刺激表现出明显不同的敏感性。成纤维细胞直接感知压力，并通过 YAP 易位进入细胞核促进排列、增殖、分化和迁移的增加来做出反应。相反，内皮细胞通过跟踪成纤维细胞排列来形成排列的血管。机械应变下结构中的 YAP 抑制会导致血管破坏，而在 YAP 抑制的静态对照中观察到的损伤较小。此外，机械刺激增强了血管的发育和稳定性。此外，血管定向在植入小鼠背窗室后得以保留，并促进入侵的宿主血管以相同的方式定向。这项研究揭示了机械应变影响工程组织内血管发育的机制。这可以进一步用于设计适合工程移植物移植的更有组织且稳定的脉管系统。