Peptide-grafted poly(ethylene glycol) hydrogels support dynamic adhesion of endothelial progenitor cells

Abstract

This study investigated the dynamic adhesion of endothelial progenitor cells (EPCs) to peptide-grafted poly(ethylene glycol) diacrylate (PEGDA) hydrogels and determined the relative ability of RGDS, REDV and YIGSRG peptides to reduce the velocity of EPC rolling. Circulating EPCs are key mediators of endothelium repair and have been shown to accelerate re-endothelialization, which is important in reducing the incidence of restenosis following stent placement and occlusion of small diameter vascular grafts. However, to exploit these capabilities for tissue engineering applications, more knowledge is needed about EPC binding to the vascular wall under shear and, in particular, whether the incorporation of peptide ligands into biomaterials can support the process of EPC rolling or maintain EPC adhesion. This study specifically examined one type of EPCs endothelial colony forming cells (ECFCs), based on their ability to be expanded in culture and differentiate into mature endothelial cells. The amount of grafted PEG-peptide was shown to be dependent on the concentration of PEG-peptide grafting solution photopolymerized onto the hydrogel surface. The ECFC strength of adhesion on PEG-RDGS grafted hydrogels exceeded 350 dyn cm(-2) for 85% of adherent cells. PEG-RGDS grafted hydrogels supported ECFC rolling, whereas ECFC velocity on the negative control PEG-RGES grafted hydrogels and on the "blank slate" PEGDA hydrogels was substantially higher than the cutoff velocity for cell rolling. The ECFC rolling velocity on PEG-RDGS grafted hydrogels depended on the shear rate; as shear rate was increased from 20 s(-1) to 120 s(-1), ECFC rolling velocity increased from 103±3 μm s(-1) to 741±28 μm s(-1). REDV and YIGSRG, which are known to preferentially support endothelial cell adhesion, also supported ECFC rolling. Interestingly, the rolling velocity of ECFCs on PEG-REDV grafted hydrogels was significantly lower than on PEG-YIGSRG or on PEG-RGDS grafted hydrogels. Understanding the dynamic adhesion of ECFCs to peptide-grafted hydrogels is the first step towards understanding the similarities and differences of EPCs from mature endothelial cells and improving the ability to sequester EPCs to biomaterial surfaces in order to promote intravascular re-endothelialization.

Keywords: Endothelial colony forming cell; Endothelialization; Hydrogel; Peptide; Shear stress.