Enhanced osteogenic differentiation of human mesenchymal stem cells using size-controlled graphene oxide flakes

Recently, it has been revealed that the physical microenvironment can be translated into cellular mechanosensing to direct human mesenchymal stem cell (hMSC) differentiation. Graphene oxide (GO), a major derivative of graphene, has been regarded as a promising material for stem cell lineage specification due to its biocompatibility and unique physical properties to interact with stem cells. Especially, the lateral size of GO flakes is regarded as the key factor regulating cellular response caused by GO. In this work, GO that had been mechanically created and had an average diameter of 0.9, 1.1, and 1.7 m was produced using a ball-mill process. When size-controlled GO flakes were applied to hMSCs, osteogenic differentiation was enhanced by GO with a specific average diameter of 1.7 μm. It was confirmed that osteogenic differentiation was increased due to the enhanced expression of focal adhesion and the development of focal adhesion subordinate signals via extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase (MEK) pathway. These results suggest that size-controlled GO flakes could be efficient materials for promoting osteogenesis of hMSCs. Results of this study could also improve our understanding of the correlation between hMSCs and cellular responses to GO.