Neuronal differentiation of human mesenchymal stem cells in response to the domain size of graphene substrates

Graphene is a non-cytotoxic monolayer platform with unique physical, chemical, and biological properties. It has been demonstrated that graphene substrate may provide a promising biocompatible scaffold for stem cell therapy. Since chemical vapor deposited graphene has a two dimensional poly-crystalline structure, it is important to control the individual domain size to obtain desirable properties for nano-material. However, the biological effects mediated by differences in domain size of graphene have not yet been reported. Based on the control of graphene domain achieved by one-step growth (1step-G, small domain) and two-step growth (2step-G, large domain) process, we found that the neuronal differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs) highly depended on the graphene domain size. The defects at the domain boundaries in 1step-G graphene was higher (x 8.5) and had a relatively low (13% lower) contact angle of water droplet than 2step-G graphene, leading to enhanced cell-substrate adhesion and up-regulated neuronal differentiation of hMSCs. We confirmed that the strong interactions between cells and defects at the domain boundaries in 1step-G graphene can be obtained due to their relatively high surface energy, which is stronger than interactions between cells and graphene surfaces. Our results may provide valuable information on the development of graphene-based scaffold by understanding which properties of graphene domain influence cell adhesion efficacy and stem cell differentiation. This article is protected by copyright. All rights reserved.