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Reconfigurable Microphysiological Systems for Modeling Innervation and Multitissue Interactions

机译:可重构Microphysiological系统神经支配和Multitissue交互建模

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摘要

Tissue-engineered models continue to experience challenges in delivering structural specificity, nutrient delivery, and heterogenous cellular components, espedaily for organ-systems that require functional inputs/outputs and have high metabolic requirements, such as the heart. While soft lithography has provided a means to recapitulate complex architectures in the dish, it is plagued with a number of prohibitive shortcomings. Here, concepts from microfluidics, tissue engineering, and layer-by-layer fabrication are applied to develop reconfigurable, inexpensive microphysiological systems that facilitate discrete, 3D cell compartmentalization, and improved nutrient transport. This fabrication technique includes the use of the meniscus pinning effect, photocrosslinkable hydrogels, and a commercially available laser engraver to cut flow paths. The approach is low cost and robust in capabilities to design complex, multilayered systems with the inclusion of instrumentation for real-time manipulation or measures of cell function. In a demonstration of the technology, the hierarchal 3D micro-environment of the cardiac sympathetic nervous system is replicated. Beat rate and neurite ingrowth are assessed on-chip and quantification demonstrates that sympathetic-cardiac coculture increases spontaneous beat rate, while drug-induced increases in beating lead to greater sympathetic innervation. Importantly, these methods may be applied to other organ-systems and have promise for future applications in drug screening, discovery, and personal medicine.
机译:组织工程模型继续体验挑战提供结构特异性,营养输送,异质的细胞组件,espedaily器官系统需要功能的输入/输出和高代谢需求,如心脏。软光刻技术提供了一种手段概括复杂的架构在盘子里,与一些禁止性的困扰的缺点。组织工程和分层技术制造应用于发展可重构、廉价microphysiological系统,促进离散,3 d细胞划分,改善营养交通工具。半月板的使用固定效应,photocrosslinkable水凝胶和商业化可用激光雕刻切割流路径。方法是低成本和强大的功能设计复杂,多层系统的包含实时的仪器操纵或细胞功能的措施。演示的技术等级三维心脏交感神经的微环境神经系统复制。芯片上的神经突长在肉内评估量化表明sympathetic-cardiac coculture增加自发的击败,而药物引起增加跳动导致更大的同情神经支配。应用于其他器官系统和承诺未来在药物筛选中的应用发现,和个人药品。

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