Department of Life Science , University of Seoul , Seoul 02504 , Republic of Korea.
Department of Mechanical Engineering , Hanbat National University , Daejeon 34158 , Republic of Korea.
ACS Appl Mater Interfaces. 2020 Feb 12;12(6):6924-6932. doi: 10.1021/acsami.9b21471. Epub 2020 Jan 29.
Three-dimensional (3D) cell culture platforms have recently received a great deal of attention, as these systems are able to recapitulate the in vivo microenvironment of tissues or tumors. Herein, we describe adjustable and versatile elastomeric well structures for spheroid formation and their use for in situ analyses as a tunable 3D cell culture platform. Elastomeric spherical wells are fabricated using a one-step interfacial reaction between aqueous droplets on immiscible liquid polydimethylsiloxane (PDMS) without any template or expensive equipment. Because of their differing surface tensions, spherical wells are spontaneously formed on liquid PDMS with various sizes and curvatures that are easily controlled. Using arrays of these optimized wells, single tumor spheroids within each well were successfully formed at high efficiency (up to 97%) by coculturing tumor cells and fibroblasts to reflect the complex microenvironment of cancer tissue. Moreover, the tumor spheroids formed within the interfacial wells were directly applied for observing drug responses and monitoring reactive oxygen species (ROS) to investigate tumor cell responses to drugs or their 3D microenvironment. We believe that our proposed platform provides a significant contribution to the multimodal analyses of anticancer therapeutics and the tumor microenvironment.
三维（3D）细胞培养平台最近受到了广泛关注，因为这些系统能够重现组织或肿瘤的体内微环境。在这里，我们描述了用于球体形成的可调节和通用的弹性井结构及其作为可调 3D 细胞培养平台的原位分析用途。弹性球形井是使用在不使用任何模板或昂贵设备的情况下在不混溶的液体聚二甲基硅氧烷（PDMS）上的水相液滴之间的一步界面反应来制造的。由于它们的表面张力不同，因此球形井可以在具有各种尺寸和曲率的液体 PDMS 上自发形成，并且很容易控制。使用这些优化井的阵列，可以通过共培养肿瘤细胞和成纤维细胞来高效地（高达 97％）在每个井中形成单个肿瘤球体，以反映癌症组织的复杂微环境。此外，直接将在界面井中形成的肿瘤球体应用于观察药物反应和监测活性氧（ROS），以研究肿瘤细胞对药物或其 3D 微环境的反应。我们相信，我们提出的平台为抗癌治疗和肿瘤微环境的多模式分析提供了重要贡献。
