In biotechnology, SAMs and NC hydrogels of functional nanomaterials are of high interest as 2D and 3D cell culture systems, respectively, to mimic natural ECM and to control cell behaviors. Advanced biotechnological approaches often use nanoscale topography together with suitable surface functionalization, as a model of ECM, to control cell behaviors and tissue formation. SAMs of NMs are effective ECM models as 2D surfaces due to their larger nanostructured surface areas which provide higher molecular density by functionalization on a planar substrate than molecular SAMs. Additionally, NC hydrogels, produced by cross-linking of organic polymers with NMs, are excellent candidates as 3D cell culture systems owing to their optical, cell-compatibility and the extraordinary mechanical properties.