Tae-Hyung Kim^†∥#, Shreyas Shah^†#, Letao Yang^†, Perry T. Yin^‡, Md. Khaled Hossain^⊥, Brian Conley^§, Jeong-Woo Choi ^*∥⊥, and Ki-Bum Lee^*†‡

^† Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, New Jersey 08854, United States
^‡ Department of Biomedical Engineering, Rutgers, The State University of New Jersey, 599 Taylor Road, Piscataway, New Jersey 08854, United States
^§ Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, 604 Allison Road, Piscataway, New Jersey 08854, United States
^∥ Department of Chemical & Biomolecular Engineering, Sogang University 35 Baekbeom-ro, Mapo-gu, Seoul 121-742, Republic of Korea
^⊥ Interdisciplinary Program of Integrated Biotechnology, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 121-742, Republic of Korea

^*Correspondence to Jeong-Woo Choi, Ki-Bum Lee

^# These authors contributed equally to this work

Abstract
Control of stem cell fate by modulating biophysical cues (e.g., micropatterns, nanopatterns, elasticity and porosity of the substrates) has emerged as an attractive approach in stem cell-based research. Here, we report a method for fabricating combinatorial patterns of graphene oxide (GO) to effectively control the differentiation of human adipose-derived mesenchymal stem cells (hADMSCs). In particular, GO line patterns were highly effective for modulating the morphology of hADMSCs, resulting in enhanced differentiation of hADMSCs into osteoblasts. Moreover, by generating GO grid patterns, we demonstrate the highly efficient conversion of mesodermal stem cells to ectodermal neuronal cells (conversion efficiency = 30%), due to the ability of the grid patterns to mimic interconnected/elongated neuronal networks. This work provides an early demonstration of developing combinatorial graphene hybrid-pattern arrays for the control of stem cell differentiation, which can potentially lead to more effective stem cell-based treatment of incurable diseases/disorders.

Keywords:  graphene arrays; combinatorial pattern; cell morphology; adipose-derived stem cells; differentiation