Abstract

We developed a multi-channel cell chip containing a three-dimensional (3D) scaffold for horizontal co-culture and drug toxicity screening in multi-organ culture (human glioblastoma, cervical cancer, normal liver cells, and normal lung cells). The polydimethylsiloxane (PDMS) multi-channel cell chip (PMCCC) was based on fused deposition modeling (FDM) technology. The architecture of the PMCCC was an open-type cell chip and did not require a pump or syringe. We investigated cell proliferation and cytotoxicity by conducting 3-(4,5-dimethylthiazol-2-yl)-2,5-dphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays and analysis of oleanolic acid (OA)-treated multi-channel cell chips. The results of the MTT and LDH assays showed that OA treatment in the multi-channel cell chip of four cell lines enhanced chemoresistance of cells compared with that in the 2D culture. Furthermore, we demonstrated the feasibility of the application of our multi-channel cell chip in various analysis methods through Annexin V-fluorescein isothiocyanate/propidium iodide staining, which is not used for conventional cell chips. Taken together, the results demonstrated that the PMCCC may be used as a new 3D platform because it enables simultaneous drug screening in multiple cells by single point injection and allows analysis of various biological processes.

Highlights

  • We demonstrated that the cytotoxic effect of oleanolic acid (OA)

  • Increased drug resistance in BNL-CL2, L132, U87, and HeLa cell lines cultured on the PDMS multi-channel cell chip (PMCCC)

  • lactate dehydrogenase (LDH) assay results showed that BNL-CL2 (66%), L-132 (34.32%), U87 (70.76%), and HeLa cells (39.68%) cultured on the PMCCC had a lower cytotoxicity compared with the 2D plate at 300 μg/mL OA

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Techniques for three-dimensional (3D) scaffold fabrication include solvent casting, gas forming, salt leaching, fiber binding, and membrane lamination [1]. It is difficult to control the shape and pore size of interconnected porous structures and scaffolds [2,3,4]. A 3D organ printing system can overcome the limitations of existing methods by distributing the filaments of the material in a layer-by-layer manner to produce scaffolds with various sizes, shapes, and internal architectures [5]. The porosity of a 3D printed scaffold allows the transport of nutrients and metabolic waste, making these scaffolds suitable surfaces ideal for cell adhesion and proliferation [6,7]

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