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首页> 外文期刊>Biomaterials Science >Vasculogenesis and angiogenesis in modular collagen-fibrin microtissues
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Vasculogenesis and angiogenesis in modular collagen-fibrin microtissues

机译：模块化胶原蛋白纤维微组织中的血管生成和血管生成

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The process of new blood vessel formation is critical in tissue development, remodeling and regeneration. Modular tissue engineering approaches have been developed to enable the bottom-up assembly of more complex tissues, including vascular networks. In this study, collagen-fibrin composite microbeads (100-300 μm in diameter) were fabricated using a water-in-oil emulsion technique. Human endothelial cells and human fibroblasts were embedded directly in the microbead matrix at the time of fabrication. Microbead populations were characterized and cultured for 14 days either as free-floating populations or embedded in a surrounding fibrin gel. The collagen-fibrin matrix efficiently entrapped cells and supported their viability and spreading. By 7 days in culture, endothelial cell networks were evident within microbeads, and these structures became more prominent by day 14. Fibroblasts co-localized with endothelial cells, suggesting a pericyte-like function, and laminin deposition indicated maturation of the vessel networks over time. Microbeads embedded in a fibrin gel immediately after fabrication showed the emergence of cells and the coalescence of vessel structures in the surrounding matrix by day 7. By day 14, inosculation of neighboring cords and prominent vessel structures were observed. Microbeads precultured for 7 days prior to embedding in fibrin gave rise to vessel networks that emanated radially from the microbead by day 7, and developed into connected networks by day 14. Lumen formation in endothelial cell networks was confirmed using confocal sectioning. These data show that collagen-fibrin composite microbeads support vascular network formation. Microbeads embedded directly after fabrication emulated the process of vasculogenesis, while the branching and joining of vessels from pre-cultured microbeads resembled angiogenesis. This modular microtissue system has utility in studying the processes involved in new vessel formation, and may be developed into a therapy for the treatment of ischemic conditions.
机译：新血管形成的过程对于组织发育，重塑和再生至关重要。已经开发了模块化组织工程方法，以实现自下而上组装更复杂的组织，包括血管网络。在这项研究中，使用油包水乳液技术制备了胶原蛋白纤维蛋白复合微珠（直径为100-300μm）。在制造时，人内皮细胞和人成纤维细胞直接嵌入微珠基质中。对微珠种群进行特征分析并培养14天，作为自由漂浮种群或嵌入周围的纤维蛋白凝胶中。胶原蛋白纤维蛋白基质有效地捕获了细胞并支持了它们的生存能力和扩散。到培养7天时，微珠内的内皮细胞网络明显可见，到第14天，这些结构变得更加突出。成纤维细胞与内皮细胞共定位，表明具有周细胞样功能，层粘连蛋白沉积表明血管网络随着时间而成熟。制造后立即在纤维蛋白凝胶中包埋的微珠显示，到第7天，细胞的出现和周围基质中血管结构的聚结。到第14天，观察到邻近的脐带和明显的血管结构发生了渗入。在包埋在纤维蛋白中之前预培养7天的微珠形成了从微珠放射状放射的血管网络，并在第14天发展成相连的网络。使用共聚焦切片证实了内皮细胞网络中的管腔形成。这些数据表明胶原蛋白-纤维蛋白复合微珠支持血管网络的形成。制造后直接嵌入的微珠模拟了血管生成的过程，而预培养微珠的血管分支和连接类似于血管生成。这种模块化的微组织系统可用于研究涉及新血管形成的过程，并可发展成为治疗缺血性疾病的疗法。

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