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

Abstract

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.

Mechanochemical Patternable ECM‐Mimetic Hydrogels for Programmed Cell Orientation

“…Depending on their 3D biophysical microenvironment, cells can intuitively derive biophysical cues from specific topographies in order to self‐instruct their dynamics and differentiation toward optimizing their biological function. [ 80 ] Thus, engineering surface topographies has been a prolific research topic, achieving promising outcomes with geometrical features such as pillars, pits, and ridge/groove arrays. [ 81–83 ]…”

Polylactic Acid-Based Patterned Matrixes for Site-Specific Delivery of Neuropeptides On-Demand: Functional NGF Effects on Human Neuronal Cells

“…In order to increase the capability of NGF payload, larger microchambers can be used. At the same time, the use of larger (especially taller) microchambers may cause difficulties for cells to freely move, since the surface topography was found to have substantial effects on the cells behavior in different cell types (Norman and Desai, 2006;Bettinger et al, 2009;Ge et al, 2015;Sousa et al, 2019).…”

“…Micro-and nanostructured matrices have prompted new lines of study focusing on cell behavior (adhesion, proliferation, morphology, alignment, migration, gene expression, and even differentiation) and tissue engineering (Sousa et al, 2019). Photolithography and electroplating techniques enable creation of templates with the choice of different geometries.…”

“…MCA could be composed of a variety of hydrophobic polymers, for instance, polylactic acid (PLA) (Zykova et al, 2019), poly(lactic-co-glycolic acid) (Sindeeva et al, 2018a), etc., with various inclusions inserted into the shell of microchambers, such as gold nanoparticles or the aggregates of carbon dots (Sindeeva et al, 2018b;Kurochkin et al, 2020). Having biologically active substances inside microchambers allows spatially and temporally modulated control of cell function, not only due to the periodic structure of the material (Norman and Desai, 2006;Bettinger et al, 2009;Ge et al, 2015;Sousa et al, 2019) but also due to the encapsulated cargo release (Kopach et al, 2019). A wide range of biocompatible polymers for the MCA synthesis enables control of the cargo release rate.…”

Three‐dimensional electrospun nanofibrous scaffolds for bone tissue engineering

“…LbL modification is not limited by the substrate material, which forms a uniform coating on any size and topography of the substrate, and the surface morphology and roughness can be finely adjusted through the assembly cycle (Richardson et al, ). Therefore, it has been widely used to introduce bioactive substances on the surface of tissue engineering scaffolds (Gentile et al, ; Sousa, Arab‐Tehrany, Cleymand, & Mano, ). Gentile et al deposited several polypeptides onto the electrospun mesh by LbL, and found that the osteogenic differentiation of the seeded mesenchymal stem cells was significantly improved.…”