Variations in in vitro toxicity of silica nanoparticles according to scaffold type in a 3D culture system using a micropillar/microwell chip platform

Abstract

BackgroundAlthough most nanoparticle (NP) toxicity assessments are performed in two-dimensional (2D) cell cultures, such cultures cannot adequately replicate toxicity in the in vivo environment. Micropillar/microwell chips, as 3D cell cultures, provide an environment more similar to in vivo systems. Herein, we compared the cytotoxicity of 20 nm SiO2 NPs using a micropillar/microwell chip platform under (1) serum-containing (SC) or serum-free (SF) medium, (2) 2D and 3D cell culture systems, and (3) Matrigel, alginate, or collagen type I scaffolds. ResultsWhen HepG2 cells were cultured in the 2D culture system, SiO2 NPs induced cytotoxicity in SF medium, but not in SC medium. In contrast, in the 3D culture system using Matrigel, SiO2 NPs were not toxic, regardless of the serum or cell number. SiO2 NPs induced toxicity under SF and low cell numbers in 3D culture systems using alginate or collagen I. Next, to understand the causes of the different cytotoxicity effects of the scaffolds, we analyzed the penetration depth and cellular uptake of SiO2 NPs, and the pore structures of each scaffold. Our results indicate that nanotoxicity can differ according to the scaffold type. ConclusionsScaffold materials should be used based on the characteristics and purposes of the experiment.