Enhanced Effect of Polyethyleneimine-Modified Graphene Oxide and Simvastatin on Osteogenic Differentiation of Murine Bone Marrow-Derived Mesenchymal Stem Cells

Abstract

Statin derivatives traditionally have been used for the treatment of hyperlipidemia, but recent studies have shown their ability to regulate bone metabolism and promote bone growth. In this study, simvastatin (Sim), a new therapeutic candidate for bone regeneration, was combined with graphene oxide (GO), which has recently attracted much interest as a drug delivery method, to produce a compound substance effective for bone regeneration. To create a stable and homogenous complex with Sim, GO was modified with polyethylenimine, and the effect of modification was analyzed using Fourier transform infrared spectroscopy, zeta potential, and cytotoxicity testing. More specifically, the osteogenic differentiation potential expected by the combination of the two effective materials for osteogenic differentiation, GO and Sim, was evaluated in mesenchymal stem cells. Compared with control groups with GO and Sim used separately, the GO/Sim complex showed excellent osteogenic differentiation properties, with especially enhanced effects in the complex containing < 1 μM Sim.

Keywords

• simvastatin
• graphene oxide
• polyethylenimine
• mesenchymal stem cells
• osteogenic differentiation