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基于环烯烃聚合物的无溶剂大规模生产微生理系统。

Cyclo olefin polymer-based solvent-free mass-productive microphysiological systems.

机构信息

Incubation Center Organs On Chip Project, Ushio INC, 1-6-5 Marunouchi, Chiyoda-ku, Tokyo 100-8150, Japan.

Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan.

出版信息

Biomed Mater. 2021 Mar 1;16(3). doi: 10.1088/1748-605X/abe660.

DOI:10.1088/1748-605X/abe660
PMID:33588402
Abstract

A microphysiological system (MPS) holds great promise for drug screening and toxicological testing as an alternative to animal models. However, this platform faces several challenges in terms of the materials used (e.g. polydimethylsiloxane; PDMS). For instance, absorption of drug candidates and fluorescent dyes into PDMS, as well as the effect elicited by materials on cultured cells, can cause inaccurate or misleading results in cell assays. The use of PDMS also poses challenges for mass production and long-term storage of fabricated MPSs. Hence, to circumvent these issues, herein we describe the development of a cyclo olefin polymer (COP)-based MPS using photobonding processes and vacuum ultraviolet (VUV), designated as COP-VUV-MPS. COP is an amorphous polymer with chemical/physical stability, high purity and optical clarity. Due to the thermostability and high modulus of COP, the metal molding processes was applied for mass production of MPSs without deformation of microstructures and with quick fabrication cycle time (approx. 10 min/cycle). Moreover, VUV photobonding process with an excimer light at a 172nm wavelength allowed assembling COP materials without the use of additional solvents and tapes, which might cause cell damages. In comparison with the conventional MPS made of PDMS (PDMS-MPS), COP-VUV-MPS showed improved chemical resistance without causing molecule absorption. Moreover, COP-VUV-MPS maintained the stemness of environmentally sensitive human-induced pluripotent stem cells without causing undesired cellular phenotypes or gene expression. These results suggest that COP-VUV-MPS may be broadly applicable for the advancement of MPS and applications in drug development, as well astoxicological testing.

摘要

微生理系统 (MPS) 作为动物模型的替代方法,在药物筛选和毒理学测试方面具有广阔的前景。然而,该平台在所用材料(例如聚二甲基硅氧烷;PDMS)方面面临着一些挑战。例如,药物候选物和荧光染料被 PDMS 吸收,以及材料对培养细胞的影响,可能会导致细胞测定中出现不准确或误导性的结果。PDMS 的使用也给制造的 MPS 的大规模生产和长期储存带来了挑战。因此,为了解决这些问题,本文描述了使用光键合工艺和真空紫外线 (VUV) 开发基于环烯烃聚合物 (COP) 的 MPS,称为 COP-VUV-MPS。COP 是一种具有化学/物理稳定性、高纯度和光学透明度的无定形聚合物。由于 COP 的热稳定性和高模量,金属成型工艺被应用于 MPS 的大规模生产,而不会使微结构变形,并且制造周期时间很快(约 10 分钟/循环)。此外,使用波长为 172nm 的准分子光的 VUV 光键合工艺允许组装 COP 材料,而无需使用可能导致细胞损伤的额外溶剂和胶带。与由 PDMS 制成的传统 MPS(PDMS-MPS)相比,COP-VUV-MPS 表现出更好的耐化学性,而不会导致分子吸收。此外,COP-VUV-MPS 保持了对环境敏感的人类诱导多能干细胞的干性,而不会引起不期望的细胞表型或基因表达。这些结果表明,COP-VUV-MPS 可能广泛适用于 MPS 的发展以及药物开发和毒理学测试中的应用。

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