Electrically controlled mRNA delivery using a polypyrrole-graphene oxide hybrid film to promote osteogenic differentiation of human mesenchymal stem cells

Huijung Kim; Kübra Solak; Yoojoong Han; Yeon-Woo Cho; Kyeong-Mo Koo; Chang-Dae Kim; Zhengtang Luo; Hyungbin Son; Hyung-Ryong Kim; Ahmet Mavi; Tae-Hyung Kim

doi:10.1007/s12274-022-4613-y

Electrically controlled mRNA delivery using a polypyrrole-graphene oxide hybrid film to promote osteogenic differentiation of human mesenchymal stem cells

Nano Res. 2022;15(10):9253-9263. doi: 10.1007/s12274-022-4613-y. Epub 2022 Jul 23.

Authors

Huijung Kim^#¹, Kübra Solak^#², Yoojoong Han¹, Yeon-Woo Cho¹, Kyeong-Mo Koo¹, Chang-Dae Kim¹, Zhengtang Luo³, Hyungbin Son¹, Hyung-Ryong Kim⁴, Ahmet Mavi^{5

6}, Tae-Hyung Kim¹

Affiliations

¹ School of Integrative Engineering, Chung-Ang University, 84 Heukseuk-ro, Dongjak-gu, Seoul, 06974 Republic of Korea.
² Department of Nanoscience and Nanoengineering, Graduate School of Natural and Applied Sciences, Atatürk University, Erzurum, 25240 Turkey.
³ Department of Chemical and Biological Engineering, Hong Kong University of Science and Technology, Kowloon, Hong Kong, 999077 China.
⁴ Department of Pharmacology, College of Dentistry, Jeonbuk National University, Jeonju, 54896 Republic of Korea.
⁵ Department of Nanoscience and Nanoengineering, Institute of Science, Atatürk University, Erzurum, 25240 Turkey.
⁶ Department of Mathematics and Science Education, Education Faculty of Kazim Karabekir, Atatürk University, Erzurum, 25240 Turkey.

^# Contributed equally.

Abstract

Direct messenger ribonucleic acid (mRNA) delivery to target cells or tissues has revolutionized the field of biotechnology. However, the applicability of regenerative medicine is limited by the technical difficulties of various mRNA-loaded nanocarriers. Herein, we report a new conductive hybrid film that could guide osteogenic differentiation of human adipose-derived mesenchymal stem cells (hADMSCs) via electrically controlled mRNA delivery. To find optimal electrical conductivity and mRNA-loading capacity, the polypyrrole-graphene oxide (PPy-GO) hybrid film was electropolymerized on indium tin oxide substrates. We found that the fluorescein sodium salt, a molecule partially mimicking the physical and chemical properties of mRNAs, can be effectively absorbed and released by electrical stimulation (ES). The hADMSCs cultivated on the PPy-GO hybrid film loaded with pre-osteogenic mRNAs showed the highest osteogenic differentiation under electrical stimulation. This platform can load various types of RNAs thus highly promising as a new nucleic acid delivery tool for the development of stem cell-based therapeutics.

Electronic supplementary material: Supplementary material (electrochemical and FT-IR analysis on the film, additional SEM, AFM and C-AFM images of the film, optical and fluorescence images of cells, and the primers used for RT-qPCR analysis) is available in the online version of this article at 10.1007/s12274-022-4613-y.

Keywords: electrical release; graphene oxide; mesenchymal stem cells; messenger ribonucleic acid (mRNA) delivery; polypyrrole.