Synergistic Effect of Surface Chemistry and Surface Topography Gradient on Osteogenic/Adipogenic Differentiation of hMSCs.

Much attention has been paid to understanding the individual effects of surface chemistry or topography on cell behavior. However, the synergistic influence of both surface chemistry and surface topography on differentiation of human mesenchymal stem cells (hMSCs) should also be addressed. Here, gold nanoparticles were immobilized in an increasing number density manner to achieve a surface topography gradient; a thin film rich in amine (-NH2) or methyl (-CH3) chemical groups was plasma-polymerized to adjust the surface chemistry of the outermost layer (ppAA and ppOD, respectively). hMSCs were cultured on these model substrates with defined surface chemistry and surface topography gradient. The morphology and focal adhesion (FA) formation of hMSCs were first examined. hMSC differentiation was then co-induced in osteogenic and adipogenic medium, as well as in the presence of extracellular-signal-regulated kinase1/2 (ERK1/2) and RhoA/Rho-associated protein kinase (ROCK) inhibitors. The results show that the introduction of nanotopography could enhance FA formation and osteogenesis but inhibited adipogenesis on both ppAA and ppOD surfaces, indicating that the surface chemistry could regulate hMSC differentiation, in a surface topography-dependent manner. RhoA/ROCK and ERK1/2 signaling pathways may participate in this process. This study demonstrated that surface chemistry and surface topography can jointly affect cell morphology, FA formation, and thus osteogenic/adipogenic differentiation of hMSCs. These findings highlight the importance of the synergistic effect of different material properties on regulation of cell response, which has important implications in designing functional biomaterials.