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微工程器官芯片平台迈向个性化医疗。

Microengineered Organ-on-a-chip Platforms towards Personalized Medicine.

机构信息

Institute of Biomaterials and Tissue Engineering, Huaqiao University, Xiamen 361021, China.

College of Chemical Engineering, Huaqiao University, Xiamen 361021, China.

出版信息

Curr Pharm Des. 2018;24(45):5354-5366. doi: 10.2174/1381612825666190222143542.

Abstract

Current preclinical drug evaluation strategies that are explored to predict the pharmacological parameters, as well as toxicological issues, utilize traditional oversimplified cell cultures and animal models. However, these traditional approaches are time-consuming, and cannot reproduce the functions of the complex biological tissue architectures. On the other hand, the obtained data from animal models cannot be precisely extrapolated to humans because it sometimes results in the distinct safe starting doses for clinical trials due to vast differences in their genomes. To address these limitations, the microengineered, biomimetic organ-on-a-chip platforms fabricated using advanced materials that are interconnected using the microfluidic circuits, can stanchly reiterate or mimic the complex tissue-organ level structures including the cellular architecture and physiology, compartmentalization and interconnectivity of human organ platforms. These innovative and cost-effective systems potentially enable the prediction of the responses toward pharmaceutical compounds and remarkable advances in materials and microfluidics technology, which can rapidly progress the drug development process. In this review, we emphasize the integration of microfluidic models with the 3D simulations from tissue engineering to fabricate organ-on-a-chip platforms, which explicitly fulfill the demand of creating the robust models for preclinical testing of drugs. At first, we give a brief overview of the limitations associated with the current drug development pipeline that includes drug screening methods, in vitro molecular assays, cell culture platforms and in vivo models. Further, we discuss various organ-on-a-chip platforms, highlighting their benefits and performance in the preclinical stages. Next, we aim to emphasize their current applications toward pharmaceutical benefits including the drug screening as well as toxicity testing, and advances in personalized precision medicine as well as potential challenges for their commercialization. We finally recapitulate with the lessons learned and the outlook highlighting the future directions for accelerating the clinical translation of delivery systems.

摘要

当前探索的用于预测药理学参数和毒理学问题的临床前药物评估策略,利用了传统的过于简化的细胞培养和动物模型。然而,这些传统方法既耗时又无法复制复杂的生物组织架构的功能。另一方面,从动物模型获得的数据不能精确地外推到人类,因为由于它们的基因组存在巨大差异,有时会导致临床试验的起始安全剂量明显不同。为了解决这些限制,使用先进材料制造的微工程、仿生器官芯片平台,通过微流控电路相互连接,可以稳定地重复或模拟包括细胞结构和生理学、人体器官平台的分隔和连通性在内的复杂组织-器官水平结构。这些创新且具有成本效益的系统有可能预测药物化合物的反应,并在材料和微流控技术方面取得显著进展,从而快速推进药物开发过程。在这篇综述中,我们强调了微流控模型与组织工程的 3D 模拟的集成,以制造器官芯片平台,这明确满足了为临床前药物测试创建稳健模型的需求。首先,我们简要概述了当前药物开发管道所面临的局限性,包括药物筛选方法、体外分子测定、细胞培养平台和体内模型。此外,我们讨论了各种器官芯片平台,强调了它们在临床前阶段的优势和性能。接下来,我们旨在强调它们在药物筛选和毒性测试、个性化精准医学的进展以及其商业化的潜在挑战方面的当前应用。最后,我们总结了经验教训和展望,强调了加速输送系统临床转化的未来方向。

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