Evaluation of late outgrowth endothelial progenitor cell and umbilical vein endothelial cell responses to thromboresistant collagen‐mimetic hydrogels

Abstract Bioactive coatings which support the adhesion of late‐outgrowth peripheral blood endothelial progenitor cells (EOCs) are actively being investigated as a means to promote rapid endothelialization of “off‐the‐shelf,” small‐caliber arterial graft prostheses following implantation. In the present work, we evaluated the behavior of EOCs on thromboresistant graft coatings based on the collagen‐mimetic protein Scl2‐2 and poly(ethylene glycol) (PEG) diacrylate. Specifically, the attachment, proliferation, migration, and phenotype of EOCs on PEG‐Scl2‐2 hydrogels were evaluated as a function of Scl2‐2 concentration (4, 8, and 12 mg/mL) relative to human umbilical vein endothelial cells (HUVECs). Results demonstrate the ability of each PEG‐Scl2‐2 hydrogel formulation to support EOC and HUVEC adhesion, proliferation, and spreading. However, only the 8 and 12 mg/mL PEG‐Scl2‐2 hydrogels were able to support stable EOC and HUVEC confluence. These PEG‐Scl2‐2 formulations were, therefore, selected for evaluation of their impact on EOC and HUVEC phenotype relative to PEG‐collagen hydrogels. Cumulatively, both gene and protein level data indicated that 8 mg/mL PEG‐Scl2‐2 hydrogels supported similar or improved levels of EOC maturation relative to PEG‐collagen controls based on evaluation of CD34, VEGFR2, PECAM‐1, and VE‐Cadherin. The 8 mg/mL PEG‐Scl2‐2 hydrogels also appeared to support similar or improved levels of EOC homeostatic marker expression relative to PEG‐collagen hydrogels based on von Willebrand factor, collagen IV, NOS3, thrombomodulin, and E‐selectin assessment. Combined, the present results indicate that PEG‐Scl2‐2 hydrogels warrant further investigation as “off‐the‐shelf” graft coatings. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1712–1724, 2017.