A “Cell‐Friendly” Window for the Interaction of Cells with Hyaluronic Acid/Poly‐l‐Lysine Multilayers

Abstract

Polyelectrolyte multilayers assembled from hyaluronic acid (HA) and poly-l-lysine (PLL) are most widely studied showing excellent reservoir characteristics to host molecules of diverse nature; however, thick (HA/PLL) films are often found cell repellent. By a systematic study of the adhesion and proliferation of various cells as a function of bilayer number "n" a correlation with the mechanical and chemical properties of films is developed. The following cell lines have been studied: mouse 3T3 and L929 fibroblasts, human foreskin primary fibroblasts VH-Fib, human embryonic kidney HEK-293, human bone cell line U-2-OS, Chinese hamster ovary CHO-K and mouse embryonic stem cells. All cells adhere and spread well in a narrow "cell-friendly" window identify in the range of n = 12-15. At n < 12, the film is inhomogeneous and at n > 15, the film is cell repellent for all cell lines. Cellular adhesion correlates with the mechanical properties of the films showing that softer films at higher "n" number exhibiting a significant decrease of the Young's modulus below 100 kPa are weakly adherent to cells. This trend cannot be reversed even by coating a strong cell-adhesive protein fibronectin onto the film. This indicates that mechanical cues plays a major role for cell behavior, also in respect to biochemical ones.

Layer-By-Layer Assemblies of Biopolymers: Build-Up, Mechanical Stability and Molecular Dynamics

“…Cross-linking can have profound effects on the stability of PEMs. Thus, it is known that cellular adhesion correlates with the mechanical properties of the films showing that softer films are weakly adherent to cells [ 171 ]. Cross-linking improves cell adhesion and proliferation, typically due to the change in PEM mechanical properties [ 172 ].…”

Hyaluronan‐based hydrogels as versatile tumor‐like models: Tunable ECM and stiffness with genipin‐crosslinking

“…For example, (HA/PLL) LbL films were designed for the culture of endothelial cells and showed a better proliferation when the films were mechanically favorable (Chang et al, ). Recently, Madaboosi et al () illustrated that the thicker a HA/PLL multilayer film, the more cell repellent it is, regarding various type of cells from various tissues (fibroblasts, stem cells, from kidney, bone, and ovary).…”

“…Recently, Madaboosi et al (2018) illustrated that the thicker a HA/PLL multilayer film, the more cell repellent it is, regarding various type of cells from various tissues (fibroblasts, stem cells, from kidney, bone, and ovary).…”

Polyelectrolyte Multilayer Capsule (PEMC)-Based Scaffolds for Tissue Engineering

“…There are five main types of LbL deposition: the immersive [ 122 ], spin [ 123 ], spray [ 124 ], electromagnetic [ 125 ], and fluidic [ 126 ] techniques. In many cases, the main driving force responsible for the formation of multilayers is an electrostatic attraction.…”

“…Scaffolds formed with smaller or larger PEMCs have been shown to be cell repellent, and this may be caused by both topological or mechanical issues due to scaffold internal structure. One would expect that such scaffolds assembled from biopolymers such as the hyaluronic acid/PLL pair may also possess good cell adhesion if their mechanical properties are suitable [ 122 ].…”