Wang Ying I, Oleaga Carlota, Long Christopher J, Esch Mandy B, McAleer Christopher W, Miller Paula G, Hickman James J, Shuler Michael L
1 Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
2 NanoScience Technology Center, University of Central Florida, Orlando, FL 32826, USA.
Exp Biol Med (Maywood). 2017 Nov;242(17):1701-1713. doi: 10.1177/1535370217694101. Epub 2017 Feb 17.
Integrated multi-organ microphysiological systems are an evolving tool for preclinical evaluation of the potential toxicity and efficacy of drug candidates. Such systems, also known as Body-on-a-Chip devices, have a great potential to increase the successful conversion of drug candidates entering clinical trials into approved drugs. Systems, to be attractive for commercial adoption, need to be inexpensive, easy to operate, and give reproducible results. Further, the ability to measure functional responses, such as electrical activity, force generation, and barrier integrity of organ surrogates, enhances the ability to monitor response to drugs. The ability to operate a system for significant periods of time (up to 28 d) will provide potential to estimate chronic as well as acute responses of the human body. Here we review progress towards a self-contained low-cost microphysiological system with functional measurements of physiological responses. Impact statement Multi-organ microphysiological systems are promising devices to improve the drug development process. The development of a pumpless system represents the ability to build multi-organ systems that are of low cost, high reliability, and self-contained. These features, coupled with the ability to measure electrical and mechanical response in addition to chemical or metabolic changes, provides an attractive system for incorporation into the drug development process. This will be the most complete review of the pumpless platform with recirculation yet written.
集成多器官微生理系统是一种不断发展的工具,用于对候选药物的潜在毒性和疗效进行临床前评估。这类系统,也被称为芯片上的人体装置,在提高进入临床试验的候选药物成功转化为获批药物方面具有巨大潜力。要吸引商业应用,系统需要价格低廉、易于操作且能给出可重复的结果。此外,测量功能反应的能力,如器官替代物的电活动、力的产生和屏障完整性,增强了监测对药物反应的能力。能够长时间(长达28天)运行一个系统将提供估计人体慢性和急性反应的潜力。在此,我们综述了一种具有生理反应功能测量的独立低成本微生理系统的进展。影响声明 多器官微生理系统是有望改善药物研发过程的装置。无泵系统的开发代表了构建低成本、高可靠性且独立的多器官系统的能力。这些特性,再加上除了化学或代谢变化之外测量电和机械反应的能力,为纳入药物研发过程提供了一个有吸引力的系统。这将是迄今对具有再循环功能的无泵平台最全面的综述。