6455wileyonlinelibrary.com while graphene oxide (GO) induced differentiation of hMSCs to adipocytes [ 5 ] and myoblasts. [ 7 ] The previous studies indicate that G and GO have distinct properties when utilized as substrates for stem cell culture and differentiation. For example, GO showed higher protein adsorption compared with G. [ 5 ] Although they both enhanced cell adhesion and growth, proteins such as insulin interacted with G and GO in different manners. [ 5 ] GO formed an electrostatic interaction with insulin and preserved the protein structure, while G denatured the native structure. Because the insulin protein structure was preserved on GO, the adipogenic differentiation of hMSCs was signifi cantly enhanced when cultured on GO compared with G. [ 5 ] Although many studies have explored how various properties of G and GO differentiate adult stem cells, [5][6][7][8] there has been no report on the use of G or GO for chondrogenic differentiation. This study reports, for the fi rst time, the use of GO for the chondrogenic differentiation of stem cells.The chondrogenic differentiation of adult stem cells is conventionally achieved through the culture of cells in pellets. [ 9 ] Cell condensation into pellets mimics the chondrogenic progenitor cell derivation during embryogenesis through cell condensation. [ 10 ] However, because the major composition of the pellets is cells and the extracellular matrix (ECM) amount is negligible, the cell-ECM interaction that promotes chondrogenic differentiation [ 11 ] is absent. Addionally, the diffusional limit of approximately 150 -200 µm restricts the mass transportation of many molecules, including oxygen, into the pellets. [ 12 ] Such characteristics thus limit the size of the pellets because pellets larger than the diffusional limit display a necrotic core surrounded by a viable cell layer. To overcome such hurdles, we used GO sheets as both a cell-adhesion substrate and a chondrogenic inducer-delivery carrier for in vitro chondrogenic differentiation of human adipose-derived stem cells (hASCs) in pellets in this study ( Figure 1 ). GO sheets (size = 0.5-1 µm) were utilized to adsorb fi bronectin (FN, a cell-adhesion protein) and transforming growth factor-β3 (TGF-β3) (a chondrogenic inducer) and were then incorporated into hASC pellets. The adsorption of FN and TGF-β3 on GO sheets relies on the surface chemistry of GO. GO features both hydrophobic π domains
Dual Roles of Graphene Oxide in Chondrogenic Differentiation of Adult Stem Cells: Cell-Adhesion Substrate and Growth Factor-Delivery CarrierHee Hun Yoon , Suk Ho Bhang , Taeho Kim , Taekyung Yu , Taeghwan Hyeon , and Byung-Soo Kim * Here, it is shown that graphene oxide (GO) can be utilized as both a celladhesion substrate and a growth factor protein-delivery carrier for the chondrogenic differentiation of adult stem cells. Conventionally, chondrogenic differentiation of stem cells is achieved by culturing cells in pellets and adding the protein transforming growth factor-β3 (TGF-β3), a chondrogenic factor, to ...