Organ-on-a-chip (OOC) is a very ambitious emerging technology with a high potential to revolutionize many medical and industrial sectors, particularly in preclinical-to-clinical translation in the pharmaceutical arena. In vivo, the function of the organ(s) is orchestrated by a complex cellular structure and physiochemical factors within the extracellular matrix and secreted by various types of cells. The trend in in vitro modeling is to simplify the complex anatomy of the human organ(s) to the minimal essential cellular structure “micro-anatomy” instead of recapitulating the full cellular milieu that enables studying the absorption, metabolism, as well as the mechanistic investigation of drug compounds in a “systemic manner.” However, in order to reflect the human physiology in vitro and hence to be able to bridge the gap between the in vivo and in vitro data, simplification should not compromise the physiological relevance. Engineering principles have long been applied to solve medical challenges, and at this stage of organ-on-a-chip technology development, the work of biomedical engineers, focusing on device engineering, is more important than ever to accelerate the technology transfer from the academic lab bench to specialized product development institutions and to the increasingly demanding market. In this paper, instead of presenting a narrative review of the literature, we systemically present a synthesis of the best available organ-on-a-chip technology from what is found, what has been achieved, and what yet needs to be done. We emphasized mainly on the requirements of a “good in vitro model that meets the industrial need” in terms of the structure (micro-anatomy), functions (micro-physiology), and characteristics of the device that hosts the biological model. Finally, we discuss the biological model–device integration supported by an example and the major challenges that delay the OOC technology transfer to the industry and recommended possible options to realize a functional organ-on-a-chip system.

中文翻译：

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器官芯片工程：弥合实验室和工业之间的差距。

器官芯片（OOC）是一项非常雄心勃勃的新兴技术，具有极大的潜力来彻底改变许多医疗和工业领域，特别是在制药领域的临床前到临床转化方面。在体内，器官的功能由复杂的细胞结构和细胞外基质内的理化因子协调，并由各种类型的细胞分泌。体外建模的趋势是将人体器官的复杂解剖结构简化为最小的基本细胞结构“微观解剖结构”，而不是重现能够研究吸收、代谢以及机制的完整细胞环境。以“系统的方式”研究药物化合物。然而，为了反映体外人体生理学，从而能够弥合体内和体外数据之间的差距，简化不应损害生理相关性。工程原理早已应用于解决医学挑战，在芯片器官技术发展的现阶段，生物医学工程师以器件工程为重点的工作比以往任何时候都更加重要，以加速学术界的技术转移实验室工作台，专门的产品开发机构和日益苛刻的市场。在本文中，我们不是对文献进行叙述性回顾，而是系统地综合了现有的最佳芯片器官技术，包括已发现的内容、已取得的成果以及尚未完成的工作。我们主要强调“满足工业需求的良好体外模型”对生物模型承载设备的结构（微观解剖）、功能（微观生理）和特性的要求。最后，我们讨论了一个示例支持的生物模型-设备集成以及延迟 OOC 技术向行业转移的主要挑战，并推荐了实现功能性器官芯片系统的可能选择。