The blood and vascular cell compatibility of heparin-modified ePTFE vascular grafts

Ryan A. Hoshi, Robert Van Lith, Michele C. Jen, Josephine B. Allen, Karen A. Lapidos, Guillermo Ameer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

180 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)30-41
Number of pages12
JournalBiomaterials
Volume34
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • Aminated poly(1,8-octanediol-co-citrate) (POC)
  • Elastomer
  • Endothelial cell
  • Hemocompatibility
  • Heparin
  • Progenitor cell
  • Smooth muscle cell
  • Vascular graft

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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