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人体器官芯片构建的研究进展

Advances in the construction of human organs-on-chips
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摘要 人体器官芯片通过在微流体芯片上构建微缩组织或器官来模拟人体组织或器官的结构、功能及微环境.人体器官芯片研究的提出,为药物临床前试验中动物模型的低通量、高花费、跨物种差异、重现性差等问题提供了解决方案,或将成为下一代通用体外评价模型.本文综述了人体器官芯片的类型与特征,总结了人体器官芯片构建的普遍设计思路,并从细胞、芯片材料与加工、微环境构建与器官芯片测量几方面对器官芯片的构建进行技术拆解,最后讨论了目前器官芯片研究所面临的挑战与机遇. Drug development is expensive,time-consuming and high-risk.Although great progress has been made in the understanding of human physiology and pathology,the average cost of a new drug has been growing during the past halfcentury.About 80%drug candidates failed in the clinical trials attributing to their low efficacy and toxicity.These issues indicate that the pre-clinical models could not accurately predict the behaviors of the investigational drugs in human bodies.To date,animal studies remain the gold standard in preclinical testing of new drugs.However,the discordance between animal models and human bodies frequently causes poor reproducibility of new drug behaviors in clinical trials,in addition to the limitations of animal studies such as low throughput,long cycle,high cost,and ethical issues.Therefore,alternative tools to animal models are highly demanded in drug development to bridge the gap between animal models and human bodies.Human organs-on-a-chips(OOCs),also known as human microphysiological systems,are engineered devices aimed at mimicking the structures,functions and microenvironments of human tissues/organs by constructing miniature tissues/organs in microfluidic chips with specific designs.The concept of OOC was proposed in the late 1990s and representatively demonstrated by the research of lung-on-a-chip,where the breath motion of lung was recapitulated through the construction of the alveolar-capillary interface in a microfluidic chip.Distinct from tissue engineering and organoids,currently OOCs focus on mimicking specific structures and functions of human tissues/organs rather than reproducing the entire tissues/organs,enabling OOCs with advantages in cost,time,and throughput.Meanwhile,with the help of engineering technologies,OOCs could not only precisely reconstruct the tissue/organ-level architectures but also manipulate the inner physical,chemical and mechanical cues in a spatiotemporal manner,providing bio-mimicking microenvironments for the reconstructed tissues/organs.Owing to these advantages,OOCs have obtained extensive attention in the past decade and have been widely applied in life science research,disease studies,drug screening,and precision medicine.Different types of OOC devices,such as heart-on-a-chip,skin-on-a-chip,liver-on-a-chip,kidney-on-achip,brain-on-a-chip,have been proposed by numerous researchers,and series of commercial approachable OOC devices have been launched by spin-off companies such as Emulate,Mimetas,Avatarget,Daxiang,showing the great potentials of OOCs as alternatives to animal models in preclinical studies of new drugs.In this review,we comprehensively overview the recent advances in the construction of human OOCs.The concepts,types,and features of the current human OOCs are first summarized and discussed.The general design strategies and working principles in the construction of human OOCs are then concluded.The key points in generating human OOCs are summarized into four aspects:Cell culture,chip materials and manufacturing,microenvironment construction,and measurement of OOCs,and progress in each aspect is described in detail with corresponding examples.In the end,the current challenges and future opportunities covering laboratory research,government policies,and commercial products are revealed.
作者 曾易 顾忠泽 Yi Zeng;Zhongze Gu(State Key Laboratory of Digital Medical Engineering,School of Biological Science and Medical Engineering,Southeast University,Nanjing 210096,China)
出处 《科学通报》 EI CAS CSCD 北大核心 2023年第36期4954-4967,共14页 Chinese Science Bulletin
基金 江苏省自然科学基金(BK20202013) 国家自然科学基金(22202040) 中国科学技术协会青年人才托举工程(2022QNRC001) 中国博士后科学基金(2022TQ0064,2022M710688)资助。
关键词 器官芯片 微流体芯片 微环境构建 生物医学传感 organs-on-chips microfluidic chips microenvironments biomedical sensing
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