Poly(ethylene glycol)-based Hydrogel to Support Endothelialization and Vascularization by Endothelial Progenitor Cells

Abstract

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. Endothelial colony forming cells (ECFCs) are one type of EPCs; ECFCs are highly proliferative and are capable of forming mature and functional endothelial cells for vessel repair and postnatal angiogenesis. However, currently little is known about the homing of these circulating ECFCs. This research investigated the rolling of ECFCs on peptide-grafted hydrogels using a parallel plate flow chamber in order to mimic the dynamic adhesion of ECFCs under conditions simulating physiological arterial flow. Poly(ethylene glycol) diacrylate (PEGDA) was chosen to be the hydrogel backbone. Due to the ability of PEGDA to inhibit protein adsorption, it can be used as a "blank slate" to examine the specific interactions of cells with the covalently incorporated peptides. To assess the specific interactions required for ECFCs to interact with material coatings under shear, peptides including RGDS, REDV, YIGSR, and RGES were coupled to acryloyl-PEG and grafted onto the surface of PEG hydrogels. To study the effect of shear on cell rolling, the ECFC cell suspension was sheared over the hydrogels at rates of 20 s-1, 40 s-1, 80 s-1, and 120 s-1. ECFC rolling was significantly slower on REDV-grafted hydrogels. Further investigation of integrin-specific novel peptides has shown that ECFC capture under shear can be enhanced by the combination of REDV and CRRETAWAC. These results can be applied in the future for modification of biomaterial surfaces to enhance endothelialization. Isolation of ECFCs from horse and encapsulation of equine ECFCs using fibrinogen modified PEG hydrogels have also been pursued to illustrate the potential application of ECFCs in veterinary medicine.