Operationalizing the Use of Biofabricated Tissue Models as Preclinical Screening Platforms for Drug Discovery and Development.
Operationalizing the Use of Biofabricated Tissue Models as Preclinical Screening Platforms for Drug Discovery and Development.
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DOI：
10.1177/24725552211030903
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发表时间：
2021-10
期刊：
影响因子：
3.1
通讯作者：
Ferrer, Marc
中科院分区：
文献类型：
--
作者：
Jung, Olive;Song, Min Jae;Ferrer, Marc
关键词：
正在开发各种复杂的体外模型（CIVM），用于科学研究和临床前药物疗效和安全性测试。希望这些CIVM将模拟人类生理学和病理学，并比目前使用的细胞测定法更准确地预测临床反应。将这些CIVM整合到药物发现和开发管道中需要严格的科学验证，包括细胞，形态和功能表征;临床生物标志物的基准测试;以及作为稳健和可重复的筛选平台的可操作性。确定每个CIVM所需的生理复杂程度以准确再现天然样稳态和疾病表型以及临床药理学反应将是至关重要的。选择在药物发现和开发管道的每个阶段使用哪种CIVM将由适合每个目的的方法驱动，基于特定的疾病病理机制来建模和筛选所需的通量。在不同的CIVM中，生物制造的组织等同物正在成为稳健和通用的细胞测定平台。生物制造技术，包括使用水凝胶和生物材料的生物打印方法，使得能够在多孔板平台中生产具有一系列生理复杂性和受控空间布置的组织，这使得它们适合于中等通量筛选。然而，使用现有的自动化筛选平台操作这种3D生物制造模型带来了一系列独特的挑战。这些挑战将从这个角度进行讨论，包括来自一个致力于设计和开发自动化筛查检测方法的实验室的例子和想法。
A wide range of complex in vitro models (CIVM) are being developed for scientific research and preclinical drug efficacy and safety testing. The hope is that these CIVMs will mimic human physiology and pathology and predict clinical responses more accurately than the cellular assays currently used. The integration of these CIVMs into the drug discovery and development pipeline requires rigorous scientific validation, including cellular, morphological, and functional characterization; benchmarking of clinical biomarkers; and operationalization as robust and reproducible screening platforms. It will be critical to establish the degree of physiological complexity that is needed in each CIVM to accurately reproduce native-like homeostasis and disease phenotypes, as well as clinical pharmacological responses. Choosing which CIVM to use at each stage of the drug discovery and development pipeline will be driven by a fit-per-purpose approach, based on the specific disease pathomechanism to model and screening throughput needed. Among the different CIVMs, biofabricated tissue equivalents are emerging as robust and versatile cellular assay platforms. Biofabrication technologies, including bioprinting approaches with hydrogels and biomaterials, have enables the production of tissues with a range of physiological complexity and controlled spatial arrangements in multi-well plate platforms, which make them amenable for medium throughput screening. However, operationalization of such 3D biofabricated models using existing automation screening platforms comes with a unique set of challenges. These challenges will be discussed in this perspective, including examples and thoughts coming from a laboratory dedicated to designing and developing assays for automated screening.
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DOI：
10.1038/s41578-021-00279-y
发表时间：
2021
期刊：
Nature reviews. Materials
影响因子：
--
作者：
Hofer M;Lutolf MP
通讯作者：
Lutolf MP
影响因子：
3.7
作者：
Anguiano M;Castilla C;Maška M;Ederra C;Peláez R;Morales X;Muñoz-Arrieta G;Mujika M;Kozubek M;Muñoz-Barrutia A;Rouzaut A;Arana S;Garcia-Aznar JM;Ortiz-de-Solorzano C
通讯作者：
Ortiz-de-Solorzano C
DOI：
10.1177/2472555220942764
发表时间：
2020-10
期刊：
SLAS discovery : advancing life sciences R & D
影响因子：
--
作者：
Bar H;Zweifach A
通讯作者：
Zweifach A
影响因子：
5.8
作者：
Dingle, Yu-Ting L.;Liaudanskaya, Volha;Kaplan, David L.
通讯作者：
Kaplan, David L.
影响因子：
4.6
作者：
Boussaad I;Cruciani G;Bolognin S;Antony P;Dording CM;Kwon YJ;Heutink P;Fava E;Schwamborn JC;Krüger R
通讯作者：
Krüger R