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Stiffness of the aligned fibers affects structural and functional integrity of the oriented endothelial cells.
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2020-03-21 , DOI: 10.1016/j.actbio.2020.03.022 Bingcheng Yi 1 , Yanbing Shen 1 , Han Tang 1 , Xianliu Wang 1 , Yanzhong Zhang 2
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2020-03-21 , DOI: 10.1016/j.actbio.2020.03.022 Bingcheng Yi 1 , Yanbing Shen 1 , Han Tang 1 , Xianliu Wang 1 , Yanzhong Zhang 2
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Promoting healthy endothelialization of the tissue-engineered vascular grafts is of great importance in preventing the occurrence of undesired post-implantation complications including neointimal hyperplasia, late thrombosis, and neoatherosclerosis. Previous researches have demonstrated the crucial role of scaffold topography or stiffness in modulating the behavior of the monolayer endothelial cells (ECs). However, effects of the stiffness of scaffolds with anisotropic topography on ECs within vivo like oriented morphology has received little attention. In this study, aligned fibrous substrates (AFSs) with tunable stiffness (14.68-2141.72 MPa), similar to the range of stiffness of the healthy and diseased subendothelial matrix, were used to investigate the effects of fiber stiffness on ECs' attachment, orientation, proliferation, function, remodeling and dysfunction. The results demonstrate that stiffness of the AFSs, capable of providing topographical cues, is a crucial endothelium-protective microenvironmental factor by maintaining stable and quiescent endothelium with in vivo like orientation and strong cell-cell junctions. Stiffer AFSs exacerbated the disruption of endothelium integrity, the occurrence of endothelial-to-mesenchymal transition (EndMT), and the inflammation-induced activation in the endothelial monolayer. This study provides new insights into the understanding on how the stiffness of biomimicking anisotropic substrate regulates the structural and functional integrity of the in vivo like endothelial monolayer, and offers essential designing parameters in engineering biomimicking small-diameter vascular grafts for the regeneration of viable blood vessels. STATEMENT OF SIGNIFICANCE: In vascular tissue engineering, promoting endothelialization on scaffold surface has been considered as a paramount strategy to reduce post-implantation complications. Electrospun aligned fibers have been known to provide contact guidance effect in directing endothelial cells' oriented growth, however, whether the formed EC monolayer in 'correct' orientation shape is of 'correct' function hasn't been explored yet. Given the recognized important role of substrate stiffness in endothelial function, AFSs across physiologically relevant range of moduli (14.68-2141.72 MPa) while maintaining consistent surface chemistry and topographical features were employed to investigate the fiber stiffness effects on ECs function in anisotropic morphology. This study will provide more insightful perspectives in the physiologically remodeling progression of vascular endothelium and design of vascular scaffolds.
中文翻译：
排列的纤维的刚度影响定向的内皮细胞的结构和功能完整性。
促进组织工程化的血管移植物的健康内皮化对于防止发生不良的植入后并发症（包括新内膜增生，晚期血栓形成和新动脉粥样硬化）至关重要。以前的研究表明，支架的拓扑结构或刚度在调节单层内皮细胞（EC）行为中起着至关重要的作用。然而，具有各向异性形貌的支架的刚度对体内ECs样定向形态学的影响很少受到关注。在这项研究中，使用具有可调刚度（14.68-2141.72 MPa）的对齐纤维基质（AFS），与健康和患病的内皮下基质的刚度范围相似，来研究纤维刚度对EC附着，方向，扩散，功能，重塑和功能障碍。结果表明，能够提供地形提示的AFS的硬度是至关重要的内皮保护微环境因子，其通过维持具有体内样取向和牢固的细胞-细胞连接的稳定且静止的内皮。僵硬的AFS加剧了内皮完整性的破坏，内皮向间充质转化（EndMT）的发生以及炎症诱导的内皮单层激活。这项研究提供了新的见解，以了解仿生各向异性底物的硬度如何像单层内皮细胞一样调节体内结构和功能的完整性，并为工程仿生小直径血管移植物以再生可行血管提供了重要的设计参数。 。意义声明：在血管组织工程中，促进支架表面内皮化已被认为是减少植入后并发症的最重要策略。已知电纺取向纤维在引导内皮细胞的定向生长中提供接触引导作用，但是，尚未探讨形成的“正确”取向形状的EC单层是否具有“正确”功能。考虑到底物硬度在内皮功能中的重要作用，在生理相关模量范围（14.68-2141.72 MPa）且保持一致的表面化学和形貌特征的AFS被用于研究纤维硬度对各向异性形态中ECs功能的影响。
更新日期：2020-03-21
中文翻译：
排列的纤维的刚度影响定向的内皮细胞的结构和功能完整性。
促进组织工程化的血管移植物的健康内皮化对于防止发生不良的植入后并发症（包括新内膜增生，晚期血栓形成和新动脉粥样硬化）至关重要。以前的研究表明，支架的拓扑结构或刚度在调节单层内皮细胞（EC）行为中起着至关重要的作用。然而，具有各向异性形貌的支架的刚度对体内ECs样定向形态学的影响很少受到关注。在这项研究中，使用具有可调刚度（14.68-2141.72 MPa）的对齐纤维基质（AFS），与健康和患病的内皮下基质的刚度范围相似，来研究纤维刚度对EC附着，方向，扩散，功能，重塑和功能障碍。结果表明，能够提供地形提示的AFS的硬度是至关重要的内皮保护微环境因子，其通过维持具有体内样取向和牢固的细胞-细胞连接的稳定且静止的内皮。僵硬的AFS加剧了内皮完整性的破坏，内皮向间充质转化（EndMT）的发生以及炎症诱导的内皮单层激活。这项研究提供了新的见解，以了解仿生各向异性底物的硬度如何像单层内皮细胞一样调节体内结构和功能的完整性，并为工程仿生小直径血管移植物以再生可行血管提供了重要的设计参数。 。意义声明：在血管组织工程中，促进支架表面内皮化已被认为是减少植入后并发症的最重要策略。已知电纺取向纤维在引导内皮细胞的定向生长中提供接触引导作用，但是，尚未探讨形成的“正确”取向形状的EC单层是否具有“正确”功能。考虑到底物硬度在内皮功能中的重要作用，在生理相关模量范围（14.68-2141.72 MPa）且保持一致的表面化学和形貌特征的AFS被用于研究纤维硬度对各向异性形态中ECs功能的影响。
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