Rezaei Kolahchi Ahmad, Khadem Mohtaram Nima, Pezeshgi Modarres Hassan, Mohammadi Mohammad Hossein, Geraili Armin, Jafari Parya, Akbari Mohsen, Sanati-Nezhad Amir
BioMEMS and Bioinspired Microfluidic Laboratory, Department of Mechanical and Manufacturing Engineering, University of Calgary, 2500 University Drive NW, Calgary, AB T2N 1N4, Canada.
Laboratory for Innovations in MicroEngineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, Canada.
Micromachines (Basel). 2016 Sep 8;7(9):162. doi: 10.3390/mi7090162.
Development of predictive multi-organ models before implementing costly clinical trials is central for screening the toxicity, efficacy, and side effects of new therapeutic agents. Despite significant efforts that have been recently made to develop biomimetic in vitro tissue models, the clinical application of such platforms is still far from reality. Recent advances in physiologically-based pharmacokinetic and pharmacodynamic (PBPK-PD) modeling, micro- and nanotechnology, and in silico modeling have enabled single- and multi-organ platforms for investigation of new chemical agents and tissue-tissue interactions. This review provides an overview of the principles of designing microfluidic-based organ-on-chip models for drug testing and highlights current state-of-the-art in developing predictive multi-organ models for studying the cross-talk of interconnected organs. We further discuss the challenges associated with establishing a predictive body-on-chip (BOC) model such as the scaling, cell types, the common medium, and principles of the study design for characterizing the interaction of drugs with multiple targets.
在开展成本高昂的临床试验之前,开发预测性多器官模型对于筛选新型治疗药物的毒性、疗效和副作用至关重要。尽管最近在开发仿生体外组织模型方面付出了巨大努力,但此类平台的临床应用仍远未实现。基于生理的药代动力学和药效学(PBPK-PD)建模、微纳技术以及计算机模拟建模方面的最新进展,已促成了用于研究新型化学药物和组织-组织相互作用的单器官和多器官平台。本综述概述了用于药物测试的基于微流控的芯片器官模型的设计原则,并突出了在开发用于研究相互连接器官之间串扰的预测性多器官模型方面的当前技术水平。我们还讨论了建立预测性芯片人体(BOC)模型所面临的挑战,例如缩放、细胞类型、通用培养基以及用于表征药物与多个靶点相互作用的研究设计原则。