Organ-on-a-chip technologies for biomedical research and drug development: A focus on the vasculature.

Smart medicine Pub Date : 2023-02-26 Epub Date: 2023-02-24 DOI:10.1002/SMMD.20220030
Diosangeles Soto Veliz, Kai-Lan Lin, Cecilia Sahlgren
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Abstract

Current biomedical models fail to replicate the complexity of human biology. Consequently, almost 90% of drug candidates fail during clinical trials after decades of research and billions of investments in drug development. Despite their physiological similarities, animal models often misrepresent human responses, and instead, trigger ethical and societal debates regarding their use. The overall aim across regulatory entities worldwide is to replace, reduce, and refine the use of animal experimentation, a concept known as the Three Rs principle. In response, researchers develop experimental alternatives to improve the biological relevance of in vitro models through interdisciplinary approaches. This article highlights the emerging organ-on-a-chip technologies, also known as microphysiological systems, with a focus on models of the vasculature. The cardiovascular system transports all necessary substances, including drugs, throughout the body while in charge of thermal regulation and communication between other organ systems. In addition, we discuss the benefits, limitations, and challenges in the widespread use of new biomedical models. Coupled with patient-derived induced pluripotent stem cells, organ-on-a-chip technologies are the future of drug discovery, development, and personalized medicine.

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用于生物医学研究和药物开发的芯片上器官技术:聚焦血管。
目前的生物医学模型无法复制人类生物学的复杂性。因此,经过数十年的研究和数十亿美元的药物开发投资后,近 90% 的候选药物在临床试验中失败。尽管动物模型在生理上具有相似性,但它们往往错误地反映了人类的反应,反而引发了有关使用动物模型的伦理和社会争论。全球监管机构的总体目标是取代、减少和完善动物实验的使用,这一理念被称为 "三R原则"。为此,研究人员开发了实验替代品,通过跨学科方法提高体外模型的生物学相关性。本文重点介绍了新兴的芯片上器官技术(也称为微生理系统),重点是血管模型。心血管系统将包括药物在内的所有必要物质输送到全身,同时负责热调节和其他器官系统之间的交流。此外,我们还讨论了广泛使用新型生物医学模型的好处、局限性和挑战。器官芯片技术与源自患者的诱导多能干细胞相结合,将成为药物发现、开发和个性化医疗的未来。
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