Vargas Ronny, Egurbide-Sifre Andrea, Medina Laura
Industrial Pharmacy Department, Faculty of Pharmacy, University of Costa Rica 11501-2060, San José, Costa Rica.
Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII, 27-1, 08028, Barcelona, Spain.
ADMET DMPK. 2021 Mar 22;9(2):111-141. doi: 10.5599/admet.942. eCollection 2021.
Research on alternatives to the use of animal models and cell cultures has led to the creation of organ-on-a-chip systems, in which organs and their physiological reactions to the presence of external stimuli are simulated. These systems could even replace the use of human beings as subjects for the study of drugs in clinical phases and have an impact on personalized therapies. Organ-on-a-chip technology present higher potential than traditional cell cultures for an appropriate prediction of functional impairments, appearance of adverse effects, the pharmacokinetic and toxicological profile and the efficacy of a drug. This potential is given by the possibility of placing different cell lines in a three-dimensional-arranged polymer piece and simulating and controlling specific conditions. Thus, the normal functioning of an organ, tissue, barrier, or physiological phenomenon can be simulated, as well as the interrelation between different systems. Furthermore, this alternative allows the study of physiological and pathophysiological processes. Its design combines different disciplines such as materials engineering, cell cultures, microfluidics and physiology, among others. This work presents the main considerations of OoC systems, the materials, methods and cell lines used for their design, and the conditions required for their proper functioning. Examples of applications and main challenges for the development of more robust systems are shown. This non-systematic review is intended to be a reference framework that facilitates research focused on the development of new OoC systems, as well as their use as alternatives in pharmacological, pharmacokinetic and toxicological studies.
对动物模型和细胞培养替代方法的研究催生了芯片器官系统,该系统可模拟器官及其对外界刺激的生理反应。这些系统甚至可以取代将人类用作临床阶段药物研究对象的做法,并对个性化治疗产生影响。与传统细胞培养相比,芯片器官技术在合理预测功能损伤、不良反应的出现、药代动力学和毒理学特征以及药物疗效方面具有更高的潜力。这种潜力源于将不同细胞系置于三维排列的聚合物片材中并模拟和控制特定条件的可能性。因此,可以模拟器官、组织、屏障或生理现象的正常功能,以及不同系统之间的相互关系。此外,这种替代方法还允许研究生理和病理生理过程。其设计融合了材料工程、细胞培养、微流控和生理学等不同学科。本文介绍了芯片器官系统的主要考量因素、用于其设计的材料、方法和细胞系,以及其正常运行所需的条件。展示了应用实例以及开发更强大系统面临的主要挑战。这篇非系统性综述旨在成为一个参考框架,促进专注于新型芯片器官系统开发的研究,以及其在药理学、药代动力学和毒理学研究中作为替代方法的应用。