Institute of Biomaterials and Tissue Engineering, Huaqiao University, Xiamen 361021, China.
Fujian Provincial Key Laboratory of Biochemical Technology (Huaqiao University), Xiamen 361021, China.
Molecules. 2019 Feb 14;24(4):675. doi: 10.3390/molecules24040675.
With advantageous features such as minimizing the cost, time, and sample size requirements, organ-on-a-chip (OOC) systems have garnered enormous interest from researchers for their ability for real-time monitoring of physical parameters by mimicking the in vivo microenvironment and the precise responses of xenobiotics, i.e., drug efficacy and toxicity over conventional two-dimensional (2D) and three-dimensional (3D) cell cultures, as well as animal models. Recent advancements of OOC systems have evidenced the fabrication of 'multi-organ-on-chip' (MOC) models, which connect separated organ chambers together to resemble an ideal pharmacokinetic and pharmacodynamic (PK-PD) model for monitoring the complex interactions between multiple organs and the resultant dynamic responses of multiple organs to pharmaceutical compounds. Numerous varieties of MOC systems have been proposed, mainly focusing on the construction of these multi-organ models, while there are only few studies on how to realize continual, automated, and stable testing, which still remains a significant challenge in the development process of MOCs. Herein, this review emphasizes the recent advancements in realizing long-term testing of MOCs to promote their capability for real-time monitoring of multi-organ interactions and chronic cellular reactions more accurately and steadily over the available chip models. Efforts in this field are still ongoing for better performance in the assessment of preclinical attributes for a new chemical entity. Further, we give a brief overview on the various biomedical applications of long-term testing in MOCs, including several proposed applications and their potential utilization in the future. Finally, we summarize with perspectives.
由于具有降低成本、时间和样本量需求等优势，器官芯片 (OOC) 系统因其能够实时监测物理参数而受到研究人员的极大关注，通过模拟体内微环境和外源性物质（如药物功效和毒性）的精确反应，超越了传统的二维 (2D) 和三维 (3D) 细胞培养以及动物模型。OOC 系统的最新进展证明了“多器官芯片”(MOC) 模型的制造，该模型将分离的器官腔室连接在一起，以模拟用于监测多个器官之间复杂相互作用以及多个器官对药物化合物的动态反应的理想药代动力学和药效学 (PK-PD) 模型。已经提出了许多种类的 MOC 系统，主要集中在这些多器官模型的构建上，而如何实现连续、自动化和稳定的测试仅有少数研究，这仍然是 MOC 发展过程中的一个重大挑战。本文强调了实现 MOC 长期测试的最新进展，以提高其实时监测多器官相互作用和慢性细胞反应的能力，使其更准确、更稳定地应用于现有的芯片模型。在评估新化学实体的临床前属性方面，该领域仍在不断努力以实现更好的性能。此外，我们简要概述了 MOC 中长期测试的各种生物医学应用，包括几个已提出的应用及其未来的潜在应用。最后，我们进行了总结。
