Fabrication of endothelial cell-specific polyurethane surfaces co-immobilized with GRGDS and YIGSR peptides

Abstract

Polyurethane (PU) is widely used as a cardiovascular biomaterial due to its good mechanical properties and hemocompatibility, but it is not adhesive to endothelial cells (ECs). Cell adhesive peptides, GRGDS and YIGSR, were found to promote adhesion and spreading of ECs and showed a synergistic effect when both of them were used. In this study, a surface modification was designed to fabricate an EC-active PU surface capable of promoting endothelialization using the peptides and poly(ethylene glycol) (PEG) spacer, The modified PU surfaces were characterized in vitro. The density of the grafted PEG on the PU surface was measured by acid-base back titration to the terminal-free isocyanate groups. The successful immobilization of peptides was confirmed by amino acid analysis, following hydrolysis, and contact angle measurement. The uniform distribution of peptides on the surface was observed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). To evaluate the EC adhesive property, cell viability test using human umbilical vein EC (HUVEC) was investigated in vitro and enhanced endothelialization was characterized by the introduction of cell adhesive peptides, GRGDS and YIGSR, and PEG spacer. Therefore, GRGDS and YIGSR co-immobilized PU surfaces can be applied to an EC-specific vascular graft with long-term patency by endothelialization.

Multifactorial optimization of endothelial cell growth using modular synthetic extracellular matrices

“…20 Spreading and adhesion of HMVECs was not affected by the presence of YIGSR in addition to RGD, but the adhesion of human vascular smooth muscle cells (HVSMC) was increased. In the other study, HUVEC proliferation was found to be enhanced on a mixture of YIGSR and RGD immobilized to polyurethane, 22 but again, only one roughly equimolar ratio of the two peptides was studied. The fact that only one formulation was investigated in each case most likely points to the technical challenges associated with precisely preparing surfaces with independently controlled amounts of each peptide, and the approach described in the present work offers a route to overcome such issues.…”

“…16, 17 In recent years, YIGSR has been employed as an engineered ligand to modulate the attachment and growth of several cell types on the surface of biomaterials, including endothelial cells. 18–22 The peptide REDV, found in the alternatively spliced type-III connecting segment (IIICS) region of fibronectin, is a ligand to which HUVECs can bind through α4β1 integrin. 23, 24 While all four short peptide ligands, RGDS, YIGSR, IKVAV, and REDV have been shown to modulate endothelial cell behavior, they have not to our knowledge been explored simultaneously.…”

“…18 These materials have been constructed in efforts to control the attachment, spreading, growth, and migration of a variety of cell types on these materials, including endothelial cells. 18–22 Nevertheless, almost all of these previous studies have evaluated surfaces presenting YIGSR by itself, rather than in combination with other peptide ligands. 17–19, 21, 31, 32, 34 RGD, IKVAV, and YIGSR have been investigated in parallel previously, 35 but not in combination.…”

“…This effect appeared to be particularly large in the RGD concentration regimes that most effectively supported endothelial cell growth. Previously, two studies have investigated immobilized YIGSR in combination with RGD, 20, 22 and in each of these previous studies, only one specific combination of peptides has been evaluated, roughly corresponding to equimolar mixtures of RGD and YIGSR. In one study, the behavior of human microvascular endothelial cells (HMVEC) was studied on PEG-acrylate hydrogels derivatized with YIGSR and RGD peptides, and it was found that the YIGSR/RGD combination selectively enhanced the migration of HMVEC over gels functionalized with RGD alone.…”

Surface modification of electrospun poly(L-lactide-co-ɛ-caprolactone) fibrous meshes with a RGD peptide for the control of adhesion, proliferation and differentiation of the preosteoblastic cells

“…collagen, gelatin, and fibronectin), and/or their putative domains (Arg-Gly-Asp (RGD), Tyr-Ile-Gly-Ser-Arg (YIGSR), and Ile-Lys-Val-Ala-Val (IKVAV)), have been employed to control cell function. [18][19][20][21] In particular, the strong affinity of RGD peptide (derived from fibronectin) for integrin receptors has been exploited by many studies. T.G.…”