Cardiovascular diseases are a leading cause of death worldwide,and effective treatment for cardiac disease has been a research focal point.Although the development of new drugs and strategies has never ceased,the exis...Cardiovascular diseases are a leading cause of death worldwide,and effective treatment for cardiac disease has been a research focal point.Although the development of new drugs and strategies has never ceased,the existing drug development process relies primarily on rodent models such as mice,which have significant shortcomings in predicting human responses.Therefore,human-based in vitro cardiac tissue models are considered to simulate physiological and functional characteristics more effectively,advancing disease treatment and drug development.The microfluidic device simulates the physiological functions and pathological states of the human heart by culture,thereby reducing the need for animal experimentation and enhancing the efficiency and accuracy of the research.The basic framework of cardiac chips typically includes multiple functional units,effectively simulating different parts of the heart and allowing the observation of cardiac cell growth and responses under various drug treatments and disease conditions.To date,cardiac chips have demonstrated significant application value in drug development,toxicology testing,and the construction of cardiac disease models;they not only accelerate drug screening but also provide a new research platform for understanding cardiac diseases.In the future,with advancements in functionality,integration,and personalised medicine,cardiac chips will further simulate multiorgan systems,becoming vital tools for disease modelling and precision medicine.Here,we emphasised the development history of cardiac organ chips,highlighted the material selection and construction strategy of cardiac organ chip electrodes and hydrogels,introduced the current application scenarios of cardiac organ chips,and discussed the development opportunities and prospects for their of biomedical applications.展开更多
Nowadays the pharmaceutical industry is facing long and expensive drug discovery processes. Current preclinical drug evaluation strategies that utilize oversimplified cell cultures and animal models cannot satisfy the...Nowadays the pharmaceutical industry is facing long and expensive drug discovery processes. Current preclinical drug evaluation strategies that utilize oversimplified cell cultures and animal models cannot satisfy the growing demand for new and effective drugs. The microengineered biomimetic system, namely organ-on-chip (OOC), simulating both the biology and physiology of human organs, has shown greater advantages than traditional models in drug efficacy and safety evaluation. The microengineered co-culture models recapitulate the complex interactions between different types of cells in vivo. Organ-on-chip system has also avoided the substantial interspecies differences in key disease pathways and disease-induced changes in gene expression profiles between human and other animal models. Biomimetic microsystems representing different organs have been integrated into a single microdevice and linked by a microfluidic circulatory system in a physiologically relevant manner. In this review, I outline the current development of organ-on-chip, and their applications in drug discovery. This human-on-chip system can model the complex, dynamic process of drug absorption, distribution, metabolism and excretion, and more reliably evaluate drug efficacy and toxicity. I also discuss, for the next generation of organ-on-chip, more research is required to identify suitable materials that can be used to mass produce organs-on-chips at low cost, and to scale up the system to be suitable for high-throughput analysis and commercial applications. There are more aspects that need to be further studied, thereby bring a much better tool to patients, drug developers, and clinicians.展开更多
Many recent advances in biomedical research are related to the combination of biology and microengineering. Microfluidic devices, such as organ-on-a-chip systems, integrate with living cells to allow for the detailed ...Many recent advances in biomedical research are related to the combination of biology and microengineering. Microfluidic devices, such as organ-on-a-chip systems, integrate with living cells to allow for the detailed in vitro study of human physiology and pathophysiology. With the poor translation from animal models to human models, the organ-on-a-chip technology has become a promising substitute for animal testing, and their small scale enables precise control of culture conditions and high-throughput experiments, which would not be an economically sound model on a macroscopic level. These devices are becoming more and more common in research centers, clinics, and hospitals, and are contributing to more accurate studies and therapies, making them a staple technology for future drug design.展开更多
背景:近年来,许多研究证实类装配体可弥补类器官无法完全重现细胞与细胞、细胞与基质间的互作关系的缺点,但处于发展初期的类装配体构建方式种类繁多,更无统一标准。目的:综述目前类装配体的构建方法、应用和优缺点,为促进体外细胞模型...背景:近年来,许多研究证实类装配体可弥补类器官无法完全重现细胞与细胞、细胞与基质间的互作关系的缺点,但处于发展初期的类装配体构建方式种类繁多,更无统一标准。目的:综述目前类装配体的构建方法、应用和优缺点,为促进体外细胞模型的发展和完善提供指导。方法:以“assembloids,organoids,tumor microenvironment,organoids AND assemble,organoids AND microenvironment”为英文检索词,以“类装配体、类器官、类组装体、肿瘤微环境、类器官重组、多细胞模型”为中文检索词,检索PubMed、中国知网及万方数据库,在排除无关文章及去重后筛选出94篇文章进行综述。结果与结论:①根据细胞来源的不同,可将类装配体的构建方法分为自体组装、直接组装及混合组装3种;根据细胞培养方式的差异,又可分为悬浮培养法、“基质”培养法、器官芯片培养法和3D生物打印法。②自体组装过程涵盖细胞和组织的发育等早期过程,因此,在器官发育和发育障碍等领域有广阔的前景,而分化成熟细胞的功能相对较完善,由它们直接组装成的类装配体在功能障碍及细胞损伤性疾病的研究中更具潜力;自体组装或在器官移植方面更胜一筹,直接组装将更适用于组织损伤的修复,混合组装综合了前两者的优势,多用于探索微环境中细胞的生理和病理机制以及药物筛选等领域。③虽然不同的类装配体各具优势,但都面临脉管系统不完善的难题;每种类装配体构建方法也存在各自的局限性,如自体组装形成的类装配体中细胞分化程度与体内的差异,直接组装模型的细胞种类固定、无法完全反映复杂的体内微环境等均是亟待解决的难题。④将来随着类装配体培养技术的不断完善,研究者们可以在体外组装出具有更复杂组织结构的仿生类器官,为研究人类组织和器官生理及病理过程提供无限趋近真实的模型。展开更多
基金supported by the National Natural Science Foundation of China(Nos.32430057,U21A20173,32201083 and 32071355)the Guangdong Basic and Applied Basic Research Foundation(No.2023B1515120055).
文摘Cardiovascular diseases are a leading cause of death worldwide,and effective treatment for cardiac disease has been a research focal point.Although the development of new drugs and strategies has never ceased,the existing drug development process relies primarily on rodent models such as mice,which have significant shortcomings in predicting human responses.Therefore,human-based in vitro cardiac tissue models are considered to simulate physiological and functional characteristics more effectively,advancing disease treatment and drug development.The microfluidic device simulates the physiological functions and pathological states of the human heart by culture,thereby reducing the need for animal experimentation and enhancing the efficiency and accuracy of the research.The basic framework of cardiac chips typically includes multiple functional units,effectively simulating different parts of the heart and allowing the observation of cardiac cell growth and responses under various drug treatments and disease conditions.To date,cardiac chips have demonstrated significant application value in drug development,toxicology testing,and the construction of cardiac disease models;they not only accelerate drug screening but also provide a new research platform for understanding cardiac diseases.In the future,with advancements in functionality,integration,and personalised medicine,cardiac chips will further simulate multiorgan systems,becoming vital tools for disease modelling and precision medicine.Here,we emphasised the development history of cardiac organ chips,highlighted the material selection and construction strategy of cardiac organ chip electrodes and hydrogels,introduced the current application scenarios of cardiac organ chips,and discussed the development opportunities and prospects for their of biomedical applications.
文摘Nowadays the pharmaceutical industry is facing long and expensive drug discovery processes. Current preclinical drug evaluation strategies that utilize oversimplified cell cultures and animal models cannot satisfy the growing demand for new and effective drugs. The microengineered biomimetic system, namely organ-on-chip (OOC), simulating both the biology and physiology of human organs, has shown greater advantages than traditional models in drug efficacy and safety evaluation. The microengineered co-culture models recapitulate the complex interactions between different types of cells in vivo. Organ-on-chip system has also avoided the substantial interspecies differences in key disease pathways and disease-induced changes in gene expression profiles between human and other animal models. Biomimetic microsystems representing different organs have been integrated into a single microdevice and linked by a microfluidic circulatory system in a physiologically relevant manner. In this review, I outline the current development of organ-on-chip, and their applications in drug discovery. This human-on-chip system can model the complex, dynamic process of drug absorption, distribution, metabolism and excretion, and more reliably evaluate drug efficacy and toxicity. I also discuss, for the next generation of organ-on-chip, more research is required to identify suitable materials that can be used to mass produce organs-on-chips at low cost, and to scale up the system to be suitable for high-throughput analysis and commercial applications. There are more aspects that need to be further studied, thereby bring a much better tool to patients, drug developers, and clinicians.
文摘Many recent advances in biomedical research are related to the combination of biology and microengineering. Microfluidic devices, such as organ-on-a-chip systems, integrate with living cells to allow for the detailed in vitro study of human physiology and pathophysiology. With the poor translation from animal models to human models, the organ-on-a-chip technology has become a promising substitute for animal testing, and their small scale enables precise control of culture conditions and high-throughput experiments, which would not be an economically sound model on a macroscopic level. These devices are becoming more and more common in research centers, clinics, and hospitals, and are contributing to more accurate studies and therapies, making them a staple technology for future drug design.
文摘背景:近年来,许多研究证实类装配体可弥补类器官无法完全重现细胞与细胞、细胞与基质间的互作关系的缺点,但处于发展初期的类装配体构建方式种类繁多,更无统一标准。目的:综述目前类装配体的构建方法、应用和优缺点,为促进体外细胞模型的发展和完善提供指导。方法:以“assembloids,organoids,tumor microenvironment,organoids AND assemble,organoids AND microenvironment”为英文检索词,以“类装配体、类器官、类组装体、肿瘤微环境、类器官重组、多细胞模型”为中文检索词,检索PubMed、中国知网及万方数据库,在排除无关文章及去重后筛选出94篇文章进行综述。结果与结论:①根据细胞来源的不同,可将类装配体的构建方法分为自体组装、直接组装及混合组装3种;根据细胞培养方式的差异,又可分为悬浮培养法、“基质”培养法、器官芯片培养法和3D生物打印法。②自体组装过程涵盖细胞和组织的发育等早期过程,因此,在器官发育和发育障碍等领域有广阔的前景,而分化成熟细胞的功能相对较完善,由它们直接组装成的类装配体在功能障碍及细胞损伤性疾病的研究中更具潜力;自体组装或在器官移植方面更胜一筹,直接组装将更适用于组织损伤的修复,混合组装综合了前两者的优势,多用于探索微环境中细胞的生理和病理机制以及药物筛选等领域。③虽然不同的类装配体各具优势,但都面临脉管系统不完善的难题;每种类装配体构建方法也存在各自的局限性,如自体组装形成的类装配体中细胞分化程度与体内的差异,直接组装模型的细胞种类固定、无法完全反映复杂的体内微环境等均是亟待解决的难题。④将来随着类装配体培养技术的不断完善,研究者们可以在体外组装出具有更复杂组织结构的仿生类器官,为研究人类组织和器官生理及病理过程提供无限趋近真实的模型。
基金Key Program of Natural Science Foundation of Shenzhen(JCYJ20220818102218039)Shenzhen Science and Technology Program(KCXFZ20230731093559005)+2 种基金Natural Science Foundation of Shenzhen(JCYJ20210324133412033)Guangdong Province Innovation Team Project for Universities(2023KCXTD049)Shenzhen Key Medical Discipline Construction Fund(SZXK045)。
