Surface Roughness and Substrate Stiffness Synergize To Drive Cellular Mechanoresponse

) and different substrate stiffnesses. We observed that MSCs responded to surface roughness in a stiffness-dependent manner by reorganizing the surface hierarchical structure. Surprisingly, the cellular mechanoresponse and osteogenesis were obviously enhanced on very soft hydrogels (3.8 kPa) with high surface roughness, which was comparable to or even better than that on smooth stiff substrates. These findings extend our understanding of the interactions between cells and biomaterials, highlighting an effective noninvasive approach to regulate stem cell fate via synergetic physical cues.