Mediation of the migration of endothelial cells and fibroblasts on polyurethane nanocomposites by the activation of integrin‐focal adhesion kinase signaling

Abstract

Model surfaces of polyurethane-gold nanocomposites (PU-Au) were used to examine cell behavior on nanophase-segregated materials. Previously we showed that endothelial cell (EC) migration on these materials was modulated by the PI3K/Akt/eNOS pathway. The present study, investigated the expressions of alpha5/beta3 (α5β3) integrin, focal adhesion kinase (FAK), and other downstream signal molecules such as the Rho family and matrix metalloproteinases 2 (MMP-2) induced by the materials in two different cells, that is bovine arterial endothelial cells (BAEC) and human skin fibroblasts (HSF). Both cells proliferated better on the more phase-separated PU-Au 43.5 ppm than on the less phase-separated controls (PU and PU-Au 174 ppm). On PU-Au 43.5 ppm, BAEC compared to HSF had denser actin fibers and were more extended. BAEC became rounded with Y-27632 treatment and shrunk with LY294002 treatment. Treatment by inhibitors only caused slight changes in HSF. The migration distance of BAEC on PU-Au 43.5 ppm was greater than that of HSF, and was significantly reduced by LY294002 or Y-27632 but not SU-1498. The expressions of p-FAK, p-RhoA, p-Rac/Cdc42, MMP2, and α5β3 integrin induced by PU-Au 43.5 ppm were more pronounced in BAEC versus HSF. Further enhancement in MMP2 and α5β3 integrin expressions by FAK-GFP transfection was more remarkable for cells on PU-Au 43.5 ppm. Our findings suggested that the integrin α5β3/FAK pathway may be induced by nanophase-separated materials in both ECs and fibroblasts to promote their proliferation/migration, while the crosstalk between the PI3K/Akt/eNOS pathway and FAK/Rho-GTPase activation may account for the greater effect in ECs than in fibroblasts.

In Vitro Study of a Novel Nanogold-Collagen Composite to Enhance the Mesenchymal Stem Cell Behavior for Vascular Regeneration

“…the amount of AuNPs required to change the microstructure may be low. In this situation, a higher concentration of AuNPs often leads to overloading and aggregation of nanoparticles, which adversely interferes with the microstructure and biological performances of the polymer [33], [34], [36]. In this study, the characteristic dimension of collagen in the presence of 43.5 ppm AuNPs was consistent with the favorable dimension in literature (∼100 nm), while the pure collagen revealed the less preferable dimension (∼15 nm).…”

“…Previously we showed that addition of AuNPs into polyurethane, a non-biodegradble polmer, could trigger the αvβ3 integrin/FAK and PI3K/Akt/eNOS signaling pathways and modulate the migration of endothelial cells [33], [34]. In this work, the better stem cell functions on Col-Au nanocomposites were also associated with αvβ3/CXCR4 integrin/FAK/MMP-2 signaling pathway and regulation of Akt/eNOS protein expression.…”

“…AuNPs were demonstrated to have the ability to manipulate the microstructure of a synthetic or natural polymer even in very low concentration [33], [34], [36], [47]. The microstrucutural change of the polymer often led further to improved biological functions.…”

“…The standard procedure of monocyte isolation from human blood sample of volunteer donors and culture method were described previously [34], [39]. Cells were suspended in a medium of RPMI containing 10% FBS and 1% (v/v) antibiotic (10,000 U/ml penicillin G and 10 mg/ml streptomycin) and the cell concentration was adjusted to 1×10 5 cells/ml.…”

Research Status of Tissue Engineering of Endovascular Stent and Spring Ring

“…Endothelial progenitor cells, smooth muscle cells and microporous poly glycolic acid -poly -L -lactic acid) scaffolds in vitro bath, bracket produced capillary like structures. Hung HS [4] and so on, which will be seeded with endothelial progenitor cells, the thin film coated with gelatin coated with a thin layer of polyurethane patch, which is placed in the dog's bilateral internal carotid artery, 1 months and 3 months after implantation, the observation and study of the internal carotid artery intima covered circular stone like monolayer cells, 300 months of new arterial wall thickness of 3 microns, a small amount of smooth muscle cell proliferation, local no thrombosis. In addition to endothelial progenitor cells, vascular endothelial cells, smooth muscle cells, stromal cells can be used as seed cells seeded on the scaffold, which carries the lesion to the lesion site, and can achieve local localization, migration, differentiation and functional expression of cells.…”