Inexpensive and Versatile Paper-Based Platform for 3D Culture of Liver Cells and Related Bioassays

The present study delineates the fabrication of paper-based devices for culturing liver cells and developing related bioassays. The devices were prepared by conventional lab-based LaserJet printing technology and employed for 3D cell culture. Our results demonstrated that the devices efficiently supported the growth of multiple cell types incuding HepG2, HUVEC, fibroblasts, and MSCs. We further showed that the device specifications (grade of paper or design parameters) greatly impacted the functional phenotype of the HepG2 cells. We also explored the application of the developed devices for routine cell culture, drug screening, coculture, and transwell migration assays. The cellular responses observed on the paper under different culture configurations were similar to those obtained in the case of tissue culture plate (TCP). Moreover, we showed that the paper-based devices were compatible with the immunocytochemistry and ELISA procedures (no indication of nonspecific matrix-antibody interaction). Considering the simplicity, experimental flexibility, cost-effectiveness, and multiplexibility of the paper-based liver models, it is deemed to be ideal for developing cell-based bioassays, especially in resource-limited settings.