Dynamic Adhesion of Endothelial Progenitor Cells On Peptide-Coupled Hydrogels Under Flow

Endothelial progenitor cells (EPCs) have the potential to become a reliable source of autologous cells for endothelialization of intravascular devices and vascularization of tissue engineered constructs. We have characterized the rolling velocity and transient adhesion of EPCs on different peptide-coupled hydrogels using a parallel plate flow chamber. These results will be applied in the design of future biomaterial surfaces to enhance endothelialization and improve EPC strength of adhesion under shear. EPCs are blood-derived cells and little is currently known about their response to shear stress.  For these studies, umbilical cord blood outgrowth endothelial colony forming cells (ECFCs), one type of EPCs, were used. To assess the specific interactions required for EFCFs to interact with material coatings under shear, copolymers poly(ethylene glycol) diacrylate (PEG-DA) and acryl-PEG-peptides were formed.  Peptides included Arg-Gly-Asp-Ser (RGDS), Arg-Glu-Asp-Val (REDV), Tyr-Ile-Gly-Ser-Arg (YIGSR), and Arg-Gly-Glu-Ser (RGES). Shear experiments were performed to examine EFCF rolling and adhesion on the hydrogel surfaces. First, ECFCs were dissociated and suspended in flow media. Using a Glycotech parallel plate flow chamber, the ECFC cell suspension was then sheared over hydrogels containing peptides at shear rates of 20s^-1, 40s^-1, 80s^-1, and 120s^-1. Rolling velocity of ECFCs was shown to relate to shear rates and adhesion material surface. Future studies will investigate the role of specific integrin binding sites in ECFC rolling and capture under shear stress.  Capture of rolling ECFCs could be maximized by engineering biomaterials to incorporate the appropriate binding ligands. Our results provide a better understanding of ECFCs-material interactions under physiological shear stress and will aid in the design of materials for stent coating and vascular grafts as well as for other intravascular applications.