Surface Micro- and Nanoengineering: Applications of Layer-by-Layer Technology as a Versatile Tool to Control Cellular Behavior.

Extracellular matrix (ECM) cues have been widely investigated for their impact on cellular behavior. Among mechanics, physics, chemistry, and topography, different ECM properties have been discovered as important parameters to modulate cell functions, activating mechanotransduction pathways that can influence gene expression, proliferation or even differentiation. Particularly, ECM topography has been gaining more and more interest based on the evidence that these physical cues can tailor cell behavior. Here, an overview of bottom-up and top-down approaches reported to produce materials capable of mimicking the ECM topography and being applied for biomedical purposes is provided. Moreover, the increasing motivation of using the layer-by-layer (LbL) technique to reproduce these topographical cues is highlighted. LbL assembly is a versatile methodology used to coat materials with a nanoscale fidelity to the geometry of the template or to produce multilayer thin films composed of polymers, proteins, colloids, or even cells. Different geometries, sizes, or shapes on surface topography can imply different behaviors: effects on the cell adhesion, proliferation, morphology, alignment, migration, gene expression, and even differentiation are considered. Finally, the importance of LbL assembly to produce defined topographical cues on materials is discussed, highlighting the potential of micro- and nanoengineered materials to modulate cell function and fate.