Toxicological evaluation of ionic liquid in a biological functional tissue construct model based on nano-hydroxyapatite/chitosan/gelatin hybrid scaffolds

Jingjing Zhu; Qian Kong; Shuangshuang Zheng; Yiwei Wang; Zeren Jiao; Yi Nie; Tianqing Liu; Kedong Song

doi:10.1016/j.ijbiomac.2020.04.267

Toxicological evaluation of ionic liquid in a biological functional tissue construct model based on nano-hydroxyapatite/chitosan/gelatin hybrid scaffolds

Int J Biol Macromol. 2020 May 5:158:800-810. doi: 10.1016/j.ijbiomac.2020.04.267. Online ahead of print.

Authors

Jingjing Zhu¹, Qian Kong¹, Shuangshuang Zheng², Yiwei Wang³, Zeren Jiao⁴, Yi Nie⁵, Tianqing Liu⁶, Kedong Song⁷

Affiliations

¹ State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China.
² Zhengzhou Institute of Emerging Industrial Technology, Zhengzhou 450000, China.
³ Burns Research Group, ANZAC Research Institute, University of Sydney, Concord, NSW 2139, Australia.
⁴ Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3122, USA.
⁵ Zhengzhou Institute of Emerging Industrial Technology, Zhengzhou 450000, China; Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: ynie@ipe.ac.cn.
⁶ State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China. Electronic address: liutq@dlut.edu.cn.
⁷ State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China. Electronic address: Kedongsong@dlut.edu.cn.

PMID: 32387353
DOI: 10.1016/j.ijbiomac.2020.04.267

Abstract

The application of ionic liquid is attracting more attentions as green replacement for volatile organic solvents. However, the toxic effects and risks of ionic liquid in different biological systems for human health and environment are poorly evaluated. Among all ionic liquids, 1-ethyl-3-methylimidazolium diethylphosphate ([Emim]DEP-type) ionic liquid is still at the early phase of development, and its toxicity remains unclear. In this study, we fabricated a 3D biological functional tissue construct model based on nano-hydroxyapatite, chitosan and gelatin hybrid scaffold and evaluated its toxic effects of [Emim]DEP-type ionic liquid. As a control group, the examination of ionic liquid's toxic effects on the pre-osteoblast cell line (MC3T3-E1) was detected in 2D cultures. The MTT assay showed that [Emim]DEP-type ionic liquid inhibited the proliferation of cells on both 2D cultures and 3D tissue constructs. This effect was correlated with culturing time and concentration, while the IC50 on 3D scaffolds (12,566, 9015, 7896 μg/mL, at 24 h, 48 h and 72 h, respectively) was found significantly higher compared to 2D cultures (3959, 2226, 1884 μg/mL). Flow cytometry analysis and scanning electron microscope demonstrated that when [Emim]DEP-type ionic liquid acted on MC3T3-E1 cells for 48 h, the shape of 2D cells shrank, together with decreased surface adhesion.

Keywords: Cytotoxicity; Ionic liquid; Three-dimensional tissue constructs.