The blood and vascular cell compatibility of heparin-modified ePTFE vascular grafts.
Prosthetic vascular grafts do not mimic the antithrombogenic properties of native blood vessels and therefore have higher rates of complications that involve thrombosis and restenosis. We developed an approach for grafting bioactive heparin, a potent anticoagulant glycosaminoglycan, to the lumen of ePTFE vascular grafts to improve their interactions with blood and vascular cells. Heparin was bound to aminated poly(1,8-octanediol-co-citrate) (POC) via its carboxyl functional groups onto POC-modified ePTFE grafts. The bioactivity and stability of the POC-immobilized heparin (POC-Heparin) were characterized via platelet adhesion and clotting assays. The effects of POC-Heparin on the adhesion, viability and phenotype of primary endothelial cells (EC), blood outgrowth endothelial cells (BOECs) obtained from endothelial progenitor cells (EPCs) isolated from human peripheral blood, and smooth muscle cells were also investigated. POC-Heparin grafts maintained bioactivity under physiologically relevant conditions in vitro for at least one month. Specifically, POC-Heparin-coated ePTFE grafts significantly reduced platelet adhesion and inhibited whole blood clotting kinetics. POC-Heparin supported EC and BOEC adhesion, viability, proliferation, NO production, and expression of endothelial cell-specific markers von Willebrand factor (vWF) and vascular endothelial-cadherin (VE-cadherin). Smooth muscle cells cultured on POC-Heparin showed increased expression of α-actin and decreased cell proliferation. This approach can be easily adapted to modify other blood contacting devices such as stents where antithrombogenicity and improved endothelialization are desirable properties.
Biomedical Engineering Department, Northwestern University, Evanston, IL 60208, USA.
Ryan A
RA
Hoshi
Robert
R
Van Lith
Michele C
MC
Jen
Josephine B
JB
Allen
Karen A
KA
Lapidos
Guillermo
G
Ameer
D000328:Adult; D001672:Biocompatible Materials / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000648:ultrastructure; D001807:Blood Vessel Prosthesis; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002951:Citrates; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D008422:Materials Testing; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D010641:Phenotype; D056951:Photoelectron Spectroscopy; D010973:Platelet Adhesiveness / Q000187:drug effects; D011108:Polymers; D011138:Polytetrafluoroethylene / Q000494:pharmacology*; D013927:Thrombosis / Q000473:pathology
D001672:Biocompatible Materials; D002951:Citrates; D020099:Coated Materials, Biocompatible; D011108:Polymers; C513817:poly(1,8-octanediol citrate); D009569:Nitric Oxide; D011138:Polytetrafluoroethylene; D006493:Heparin