Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Campus Monterrey, CP 64849 Monterrey, Nuevo León, Mexico.
Departamento de Mecatrónica e Ingeniería Eléctrica, Escuela de Ingeniería y Ciencias, Tecnológico de Monterrey, Monterrey, Nuevo León, CP 64849, Mexico.
Biofabrication. 2024 Jul 23;16(4). doi: 10.1088/1758-5090/ad5765.
Tumor-on-chips (ToCs) are useful platforms for studying the physiology of tumors and evaluating the efficacy and toxicity of anti-cancer drugs. However, the design and fabrication of a ToC system is not a trivial venture. We introduce a user-friendly, flexible, 3D-printed microfluidic device that can be used to culture cancer cells or cancer-derived spheroids embedded in hydrogels under well-controlled environments. The system consists of two lateral flow compartments (left and right sides), each with two inlets and two outlets to deliver cell culture media as continuous liquid streams. The central compartment was designed to host a hydrogel in which cells and microtissues can be confined and cultured. We performed tracer experiments with colored inks and 40 kDa fluorescein isothiocyanate dextran to characterize the transport/mixing performances of the system. We also cultured homotypic (MCF7) and heterotypic (MCF7-BJ) spheroids embedded in gelatin methacryloyl hydrogels to illustrate the use of this microfluidic device in sustaining long-term micro-tissue culture experiments. We further demonstrated the use of this platform in anticancer drug testing by continuous perfusion of doxorubicin, a commonly used anti-cancer drug for breast cancer. In these experiments, we evaluated drug transport, viability, glucose consumption, cell death (apoptosis), and cytotoxicity. In summary, we introduce a robust and friendly ToC system capable of recapitulating relevant aspects of the tumor microenvironment for the study of cancer physiology, anti-cancer drug transport, efficacy, and safety. We anticipate that this flexible 3D-printed microfluidic device may facilitate cancer research and the development and screening of strategies for personalized medicine.
肿瘤芯片（Tumor-on-chips，ToCs）是研究肿瘤生理学和评估抗癌药物疗效和毒性的有用平台。然而，ToC 系统的设计和制造并非易事。我们引入了一种用户友好、灵活的 3D 打印微流控装置，可用于在受控环境下培养癌细胞或嵌入水凝胶中的癌细胞球体。该系统由两个侧向流动隔室（左侧和右侧）组成，每个隔室有两个入口和两个出口，以连续的液体流输送细胞培养基。中央隔室设计用于容纳水凝胶，其中可以限制和培养细胞和微组织。我们使用有色墨水和 40 kDa 荧光素异硫氰酸酯葡聚糖进行示踪实验，以表征系统的传输/混合性能。我们还培养了嵌入明胶甲基丙烯酰基水凝胶中的同质（MCF7）和异质（MCF7-BJ）球体，以说明该微流控装置在维持长期微组织培养实验中的用途。我们进一步通过连续灌注多柔比星（一种常用于乳腺癌的抗癌药物）展示了该平台在抗癌药物测试中的用途。在这些实验中，我们评估了药物传输、细胞活力、葡萄糖消耗、细胞死亡（凋亡）和细胞毒性。总之，我们引入了一种强大而友好的 ToC 系统，能够再现肿瘤微环境的相关方面，用于研究癌症生理学、抗癌药物传输、疗效和安全性。我们预计这种灵活的 3D 打印微流控装置将促进癌症研究以及个性化医疗策略的开发和筛选。
