title: 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.
authors.affiliation: Department of Engineering Science, Trinity University, San Antonio, Texas.
authors.forename: Dany J
authors.initials: DJ
authors.lastname: Munoz-Pinto
authors.affiliation: Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York.
authors.forename: Josh D
authors.initials: JD
authors.lastname: Erndt-Marino
authors.affiliation: Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York.
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Becerra-Bayona
authors.affiliation: Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York.
authors.forename: Viviana R
authors.initials: VR
authors.lastname: Guiza-Arguello
authors.affiliation: Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York.
authors.forename: Satyavrata
authors.initials: S
authors.lastname: Samavedi
authors.affiliation: Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York.
authors.forename: Sarah
authors.initials: S
authors.lastname: Malmut
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina.
authors.forename: William M
authors.initials: WM
authors.lastname: Reichert
authors.affiliation: Center for Infectious and Inflammatory Diseases, TAM Health Science Center, Houston, Texas.
authors.forename: Brooke
authors.initials: B
authors.lastname: Russell
authors.affiliation: Center for Infectious and Inflammatory Diseases, TAM Health Science Center, Houston, Texas.
authors.forename: Magnus
authors.initials: M
authors.lastname: Höök
authors.affiliation: Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York.
authors.forename: Mariah S
authors.initials: MS
authors.lastname: Hahn
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen / Q000737:chemistry*; D042783:Endothelial Cells / Q000166:cytology*; D066026:Endothelial Progenitor Cells / Q000166:cytology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D016023:Integrins / Q000032:analysis; D008422:Materials Testing; D011092:Polyethylene Glycols / Q000737:chemistry*; D014471:Umbilical Veins / Q000166:cytology*
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D016023:Integrins; C437167:poly(ethylene glycol)diacrylate; D011092:Polyethylene Glycols; D003094:Collagen
keywords: Scl2-2 coatings; cell adhesion; endothelial progenitor cells; endothelialization; migration; phenotype; vascular grafts