Analysis of Thickness and Roughness Effects of Artificial Basement Membranes on Endothelial Cell Functions

Abstract

Various cells and tissues are highly organized in vivo by basement membranes (BMs) and thus promising artificial BMs (A-BMs) constructed by electrospinning and layer-by-layer (LbL) assembly have recently attracted much attention in tissue engineering field. However, control of cell adhesion, morphology, and migration of the attached cells on the A-BMs was not reported yet. In this study, we investigated both thickness and roughness-dependent effects of A-BMs on the functions of endothelial cells (ECs), which resulted from different assembly concentrations. The results indicated that the roughness of A-BMs increased gradually with the increase of nanofilm thickness. ECs adhesion, spreading and proliferation were inhibited on thicker A-BMs surface with larger roughness, while interendothelial junctions and barrier effect of confluent ECs monolayer on thicker A-BMs surface were compensated by increasing seeding cell number and expanding culture time. Our study highlights the influence of LbL assembly conditions on endothelial functions, which offers a new criterion for the design of A-BMs in well-organized 3D tissues.

Structuring Nanofibers of SMEC Sheets: A New Approach to Control Self‐Folded Shape by Uniaxial Stretching

“…Indeed, the rough side of the self-folded sheet facing always the outside and the smooth side thus the inside, these smart sheets would perfectly fit the antagonistic requirements for intravascular implants, i.e., to present i) a strong adhesion to the vessels epithelium promoted by the rough surface and ii) a flat surface toward the vessels lumen to avoid fluids flow perturbation and cells adhesion and so prevent late thrombosis and restenosis. [28,[38][39][40][41][42] Optimization of the self-folding and roughness of the sheets can be envisioned by notably reducing the size of the honeycomb structure. A model predicting the self-folded geometry in function of strain and initial size of the composite sheet could be developed as a tool for surgeons in line with the personalized medicine philosophy.…”

Biofabrication of engineered blood vessels for biomedical applications

“…The change of pH from 7.4 to 5 can decrease crosslinking degree by degradation of Schiff base crosslinking, causing the compression modulus to decrease from 15.77 ± 3.96 kPa to 4.8 ± 1.35 kPa [ 46 ]. Nevertheless, precaution should be taken to avoid the loss of the endothelial phenotype through endothelial-to-mesenchymal transition in the presence of material with a high stiffness, which is correlated to elastic modulus [ 121 ]. It was demonstrated by Zhang et al that ECs could not attached on poly(L-lysine)/hyaluronate acid polyelectrolyte film with lower stiffness of 196 ± 41 kPa but can maintain ECs phenotype at elastic modulus of 317 ± 30 to 431 ± 39 kPa.…”

“…Other than stiffness, the BM can also influence the formation of endothelium through its topography [ 118 ]. ECs can sense topographical features in micro and nanoscale including basement membrane roughness, thickness, pore architecture, and fiber alignment then change their cellular behavior through mechanosignaling [ 121 ]. Thus, different behaviors such as cell elongation, cell alignment, chemokine secretion, ECM production, and tissue remodeling capacity can be regulated through adjustments of scaffold topography [ 6 ].…”

“…In biomimetic blood vessel engineering, scaffolds with designed fibrous and porous structures can control cytoskeletal reorganization of ECs by regulating integrin binding and focal adhesion complex formation [ 124 ]. For example, layer-by-layer assembled electrospun nanofilms with greater roughness present inhibiting effects on adhesion of human umbilical vessel endothelial cells (HUVECs) [ 121 ]. In the case of porous structures, the pore size of vascular support scaffolds can be adjusted to control vessel invasion to adjacent tissue constructs [ 86 ].…”

“…After fabrication of scaffolds to support blood vessel engineering, surface modification by physical modification, surface adsorption, plasma treatment, and chemical modification can be performed to further improve the surface characteristics of biomaterials such as hydrophilicity/hydrophobicity and hemocompatibility [ 99 , 113 , 148 ]. The surface of a scaffold material should be smooth and possess hydrophilicity to avoid adhesion and accumulation of platelets, while be able to interact with vascular cells [ 121 , 149 , 150 ]. Cell adhesion on the scaffold surface is also greatly influenced by hydrophilicity where very highly hydrophilic surfaces have no affinity to protein and resulting in poor cell adhesion [ 103 ].…”