Various factors, including the phylogenetic distance between laboratory animals and humans, the discrepancy between current in vitro systems and the human body, and the restrictions of in silico modelling, have generated the need for new solutions to the ever-increasing worldwide dilemma of substance testing. This review provides a historical sketch on the accentuation of this dilemma, and highlights fundamental limitations to the countermeasures taken so far. It describes the potential of recently-introduced microsystems to emulate human organs in 'organ-on-a-chip' devices. Finally, it focuses on an in-depth analysis of the first devices that aimed to mimic human systemic organ interactions in 'human-on-a-chip' systems. Their potential to replace acute systemic toxicity testing in animals, and their inability to provide alternatives to repeated dose long-term testing, are discussed. Inspired by the latest discoveries in human biology, tissue engineering and micro-systems technology, this review proposes a paradigm shift to overcome the apparent challenges. A roadmap is outlined to create a new homeostatic level of biology in 'human-on-a-chip' systems in order to, in the long run, replace systemic repeated dose safety evaluation and disease modelling in animals.

译文

各种因素,包括实验动物与人类之间的系统发育距离,当前的体外系统与人体之间的差异以及计算机模拟的限制,都需要新的解决方案来解决全球范围内不断增长的难题。物质测试。这篇评论提供了关于这一困境加剧的历史草图,并强调了迄今为止采取的对策的根本局限性。它描述了最近引入的微系统在 “芯片上的器官” 设备中模拟人体器官的潜力。最后,它着重于对旨在模仿 “芯片上的人” 系统中人体全身器官相互作用的第一批设备的深入分析。讨论了它们替代动物急性全身毒性测试的潜力,以及它们无法提供重复剂量长期测试的替代方法。受人类生物学,组织工程和微系统技术的最新发现的启发,这篇综述提出了克服明显挑战的范式转变。概述了在 “芯片上的人” 系统中创建新的生物稳态水平的路线图,以便从长远来看取代动物的系统重复剂量安全性评估和疾病建模。

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