(191ar) Well-Mixed Cancer-on-Chip System for the Simultaneous Evaluation of Toxicity and Efficacy of Anti-Cancer Drugs

Authors: 
Gonzalez Gonzalez, E., EverDo S.A. de C.V., Calle Sexta 816, Col. La herradura, CP. 67140, Guadalupe, Nuevo León, México.
Trujillo-de Santiago, G., Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Alvarez, M. M., Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Gallegos Martínez, S., Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Valverde Rascón, A., Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Anaya Morales, I., Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Cuéllar Monterrubio, A. A., Departamento de Mecatrónica y Eléctrica, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
García Rubio, A., Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Flores García, B., Departamento de Mecatrónica y Eléctrica, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Mendoza Buenrostro, C., Departamento de Mecatrónica y Eléctrica, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Rodríguez-González, C. A., Departamento de Mecatrónica y Eléctrica, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Cancer research relies heavily on static 2D cell culture systems that do not recapitulate the complex physiology of solid tumors. Systems with greater physiological relevance are needed to expedite the testing of the efficacy and safety of novel anti-cancer drugs and to enable personalized medicine applications.

We developed and validated the use of a cancer-on-chip system that is based on the integration of a continuous 3D-printed mini-stirred tank and a portable incubator. This system allows the creation of homogeneous and well-controlled environments for the culture of cancerous 3D microtissues. We fabricated cancerous microtissues by bioprinting recombinant MCF7 cancerous cells (producers of green fluorescent protein) surrounded by human fibroblasts to mimic the coexistence of segregated areas of malignant and healthy cells (sharing surface) in solid tumors. These microtissues were continuously fed with culture medium in the mini-stirred tank and exposed to Docitaxel (as a model drug) for different residence times (ranging from 4 to 36 hours) and doses. Sustained or single injection additions of Docitaxel were tested. We characterized the response of cancerous/healthy microtissues by using fluorescence microscopy combined with immunofluorescence techniques, and RT-PCR to measure changes in cell viability, morphology, and expression of relevant biomarkers.

Our findings suggest that this cancer-on-chip system properly recapitulates the responses of cancerous and normal tissues to insults related to the administration of different concentrations of an anti-cancer drug.