Stimulation of Microvascular Networks on Sulfonated Polyrotaxane Surfaces with Immobilized Vascular Endothelial Growth Factor

Abstract

Modulation of material properties and growth factor application are critical in constructing suitable cell culture environments to induce desired cellular functions. Sulfonated polyrotaxane (PRX) surfaces with immobilized vascular endothelial growth factors (VEGFs) are prepared to improve network formation in vascular endothelial cells. Sulfonated PRXs, whereby sulfonated α‐cyclodextrins (α‐CDs) are threaded onto a linear poly(ethylene glycol) chain capped with bulky groups at both terminals, are coated onto surfaces. The molecular mobility of sulfonated PRX surfaces is modulated by tuning the number of threading α‐CDs. VEGF is immobilized onto surfaces with varying mobility. Low mobility and VEGF‐immobilization reinforce cell proliferation, yes‐associated protein activity, and rhoA, pdgf, ang‐1, and pecam‐1 gene expression. Highly mobile surfaces and soluble VEGF weakly affect these cell responses. Network formation is strongly stimulated in vascular endothelial cells only on low‐mobility VEGF‐immobilized surfaces, suggesting that molecular mobility and VEGF immobilization synergistically control cell function.

Delayed Senescence of Human Vascular Endothelial Cells by Molecular Mobility of Supramolecular Biointerfaces

“…This suggests that the cells can distinguish differences in the molecular mobility of polyrotaxane surfaces, which is consistent with our previous studies. [35,37] Reportedly, subcellular YAP localization depends on the elastic modulus and surface nanostructure of cell-adhesive substrates. [14,39] As the polystyrene surface coated with a thin layer of SPE-PRX 5 or SPE-PRX 86 was rigid and extremely smooth (Figure S1, Supporting Information), these material parameters are expected to minimally impact cellular YAP localization in the present study.…”

“…[29][30][31][32][33][34] We fabricated cell-adhesive surfaces coated with molecularly mobile polyrotaxanes and explored the potential effects of molecular mobility on cellular responses. [29][30][31][32][33][34][35][36][37][38] On culturing various types of cells, such as human umbilical vein endothelial cells (HUVECs), [35] human bone marrow-derived mesenchymal stem cells (HBmMSCs), [36] human hepatomaderived cell line, [37] and mouse Kupffer cell line, [38] polyrotaxane surfaces with high mobility tended to promote cytoplasmic YAP localization in adherent cells, whereas those with low mobility tended to promote nuclear YAP localization. The molecular mobility of polyrotaxane surfaces affects cellular functions, such as stemness, [36] protein secretion, [37] and immune responses.…”

“…The molecular mobility of polyrotaxane surfaces affects cellular functions, such as stemness, [36] protein secretion, [37] and immune responses. [38] Notably, polyrotaxane surfaces with low mobility promoted the proliferation of HUVECs and contributed to vascular network formation over a short cultivation period of 5 d. [35] Given these cellular responses, the molecular mobility of polyrotaxane may be a material parameter for regulating cellular functions through the Hippo-YAP signaling pathway.…”

Polyrotaxanes as emerging biomaterials for tissue engineering applications: a brief review

“…Formation of microvascular networks in implanted biomaterials is one of the key events for a successful tissue regeneration, as these microvessels are necessary for the efficient transport of cells, nutrients, and removal of the wastes [59]. It was observed that the molecular mobility of PRXs could be used to modulate the formation of microvascular networks [60]. Human umbilical vein endothelial cells (HUVECs) were cultured on VEGFimmobilized S-PRX surfaces, and they respond to different molecular mobility was studied.…”

Biological Effects of Polyrotaxane Surfaces on Cellular Responses of Fibroblast, Preosteoblast and Preadipocyte Cell Lines

“…For instance, it has been observed that a variation in matrix stiffness from soft to rigid can direct mesenchymal stem cell (MSC) fate [5]. Apart from this, we have developed cell culture surfaces using supramolecular polymers, polyrotaxanes (PRXs), and succeeded in regulating cellular functions such as adhesion [6], proliferation [7], and differentiation [8]. PRX is a supermolecule consisting of cyclic molecules threaded onto the axis polymer.…”