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近年来用于体外药物筛选和细胞治疗的细胞培养平台的进展:从传统策略到微流控策略。

Recent Advances on Cell Culture Platforms for In Vitro Drug Screening and Cell Therapies: From Conventional to Microfluidic Strategies.

机构信息

Physics Centre of Minho and Porto Universities (CF-UM-UP), Campus de Gualtar, University of Minho, Braga, 4710-057, Portugal.

LaPMET-Laboratory of Physics for Materials and Emergent Technologies, University of Minho, 4710-057, Braga, Portugal.

出版信息

Adv Healthc Mater. 2023 Jul;12(18):e2202936. doi: 10.1002/adhm.202202936. Epub 2023 Mar 20.

Abstract

The clinical translations of drugs and nanomedicines depend on coherent pharmaceutical research based on biologically accurate screening approaches. Since establishing the 2D in vitro cell culture method, the scientific community has improved cell-based drug screening assays and models. Those advances result in more informative biochemical assays and the development of 3D multicellular models to describe the biological complexity better and enhance the simulation of the in vivo microenvironment. Despite the overall dominance of conventional 2D and 3D cell macroscopic culture methods, they present physicochemical and operational challenges that impair the scale-up of drug screening by not allowing a high parallelization, multidrug combination, and high-throughput screening. Their combination and complementarity with microfluidic platforms enable the development of microfluidics-based cell culture platforms with unequivocal advantages in drug screening and cell therapies. Thus, this review presents an updated and consolidated view of cell culture miniaturization's physical, chemical, and operational considerations in the pharmaceutical research scenario. It clarifies advances in the field using gradient-based microfluidics, droplet-based microfluidics, printed-based microfluidics, digital-based microfluidics, SlipChip, and paper-based microfluidics. Finally, it presents a comparative analysis of the performance of cell-based methods in life research and development to achieve increased precision in the drug screening process.

摘要

药物和纳米医学的临床转化取决于基于生物学准确筛选方法的连贯药物研究。自从建立 2D 体外细胞培养方法以来,科学界已经改进了基于细胞的药物筛选测定和模型。这些进展导致更具信息量的生化测定和 3D 多细胞模型的发展,以更好地描述生物学复杂性并增强对体内微环境的模拟。尽管传统的 2D 和 3D 细胞宏观培养方法总体上占主导地位,但它们存在物理化学和操作方面的挑战,由于不允许高并行化、多药物组合和高通量筛选,因此阻碍了药物筛选的扩大化。它们与微流控平台的结合和互补性使基于微流控的细胞培养平台得以发展,在药物筛选和细胞治疗方面具有明确的优势。因此,本综述介绍了细胞培养微型化在药物研究场景中的物理、化学和操作考虑因素的最新和综合观点。它使用基于梯度的微流体、基于液滴的微流体、基于印刷的微流体、基于数字的微流体、SlipChip 和基于纸张的微流体阐明了该领域的进展。最后,它对基于细胞的方法在生命研究和开发中的性能进行了比较分析,以实现药物筛选过程的更高精度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e17d/11468737/cfa6a7ae0446/ADHM-12-2202936-g007.jpg

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