title: In vivo evaluation of biomimetic fluorosurfactant polymer-coated expanded polytetrafluoroethylene vascular grafts in a porcine carotid artery bypass model.
abstract: OBJECTIVE
  The objective of this study was to evaluate the potential for biomimetic self-assembling fluorosurfactant polymer (FSP) coatings incorporating heptamaltose (M7-FSP) to block nonspecific protein adsorption, the cell adhesive RGD peptide (RGD-FSP), or the endothelial cell-selective CRRETAWAC peptide (cRRE-FSP) to improve patency and endothelialization in small-diameter expanded polytetrafluoroethylene (ePTFE) vascular graft implants.
  
  
  METHODS
  ePTFE vascular grafts (4 mm in diameter, 5 cm in length) were coated with M7-FSP, RGD-FSP, or cRRE-FSP by dissolving FSPs in distilled water and flowing solution through the graft lumen for 24 hours. Coatings were confirmed by receding water contact angle measurements on the lumen surface. RGD-FSP and cRRE-FSP grafts were presodded in vitro with porcine pulmonary artery endothelial cells (PPAECs) using a custom-designed flow system. PPAEC coverage on the lumen surface was visualized with epifluorescent microscopy and quantified. Grafts were implanted as carotid artery interposition bypass grafts in seven pigs for 33 ± 2 days (ePTFE, n = 3; M7-FSP, n = 4; RGD-FSP, n = 3; cRRE-FSP, n = 4). Patency was confirmed immediately after implantation with duplex color flow ultrasound and at explantation with contrast-enhanced angiography. Grafts were sectioned for histology and stained: Movat pentachrome stain to outline vascular layers, immunofluorescent staining to identify endothelial cells (anti-von Willebrand factor antibody), and immunohistochemical staining to identify smooth muscle cells (anti-smooth muscle α-actin antibody). Neointima to lumen area ratio was determined to evaluate neointimal hyperplasia.
  
  
  RESULTS
  Receding water contact angle measurements on graft luminal surfaces were significantly lower (P < .05) on FSP-coated ePTFE surfaces (M7-FSP, 40 ± 16 degrees; RGD-FSP, 25 ± 10 degrees; cRRE-FSP, 33 ± 16 degrees) compared with uncoated ePTFE (126 ± 2 degrees), confirming presence of the FSP layer. In vitro sodding of PPAECs on RGD-FSP and cRRE-FSP grafts resulted in a confluent monolayer of PPAECs on the luminal surface, with a similar cell population on RGD-FSP (1200 ± 187 cells/mm(2)) and cRRE-FSP (1134 ± 153 cells/mm(2)) grafts. All grafts were patent immediately after implantation, and one of three uncoated, two of three RGD-FSP, two of four M7-FSP, and two of four cRRE-FSP grafts remained patent after 1 month. PPAEC coverage of the lumen surface was seen in all patent grafts. RGD-FSP grafts had a slightly higher neointima to lumen area ratio (0.53 ± 0.06) compared with uncoated (0.29 ± 0.15), M7-FSP (0.20 ± 0.15), or cRRE-FSP (0.17 ± 0.09) grafts.
  
  
  CONCLUSIONS
  Biomimetic FSP-coated ePTFE grafts can be used successfully in vivo and have potential to support endothelialization. Grafts modified with the M7-FSP and cRRE-FSP showed lower intimal hyperplasia compared with RGD-FSP grafts.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio. Electronic address: jbastijanic@case.edu.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Bastijanic
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Roger E
authors.initials: RE
authors.lastname: Marchant
authors.affiliation: Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Faina
authors.initials: F
authors.lastname: Kligman
authors.affiliation: Division of Vascular Surgery and Endovascular Therapy, University Hospitals, Cleveland, Ohio.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Allemang
authors.affiliation: Division of Vascular Surgery and Endovascular Therapy, University Hospitals, Cleveland, Ohio.
authors.forename: Ryan O
authors.initials: RO
authors.lastname: Lakin
authors.affiliation: Division of Vascular Surgery and Endovascular Therapy, University Hospitals, Cleveland, Ohio.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kendrick
authors.affiliation: Division of Vascular Surgery and Endovascular Therapy, University Hospitals, Cleveland, Ohio.
authors.forename: Vikram S
authors.initials: VS
authors.lastname: Kashyap
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio; Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Kandice
authors.initials: K
authors.lastname: Kottke-Marchant
mesh_terms: D000818:Animals; D040761:Biomimetic Materials; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation / Q000379:methods*; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D002448:Cell Adhesion; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D005260:Female; D006965:Hyperplasia; D008422:Materials Testing; D023421:Models, Animal; D058426:Neointima; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry*; D011138:Polytetrafluoroethylene / Q000737:chemistry*; D011474:Prosthesis Design; D062326:Re-Epithelialization; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry*; D034421:Sus scrofa; D013997:Time Factors; D054457:Tissue Scaffolds; D014654:Vascular Patency
chemical_list: D020099:Coated Materials, Biocompatible; D009842:Oligopeptides; D010456:Peptides, Cyclic; D011108:Polymers; D013501:Surface-Active Agents; C047981:arginyl-glycyl-aspartic acid; D011138:Polytetrafluoroethylene
references.citation: Biomaterials. 2009 Oct;30(28):4898-906
references.pmid: 19540587
references.citation: Tissue Eng. 2005 May-Jun;11(5-6):887-95
references.pmid: 15998228
references.citation: Circulation. 2005 Jul 5;112(1):12-8
references.pmid: 15983250
references.citation: J Vasc Surg. 2010 Jul;52(1):232-6
references.pmid: 20471778
references.citation: J Surg Res. 2008 Aug;148(2):230-7
references.pmid: 18028957
references.citation: Cardiovasc Res. 2001 Dec;52(3):372-86
references.pmid: 11738054
references.citation: J Biomed Mater Res A. 2014 Aug;102(8):2857-63
references.pmid: 24123752
references.citation: J Biomater Sci Polym Ed. 2005;16(7):875-91
references.pmid: 16128294
references.citation: ACS Appl Mater Interfaces. 2013 Aug 14;5(15):7360-9
references.pmid: 23859593
references.citation: J Biomed Mater Res A. 2012 Aug;100(8):2204-10
references.pmid: 22623267
references.citation: Eur J Vasc Endovasc Surg. 1996 Oct;12 (3):321-30
references.pmid: 8896475
references.citation: Eur J Vasc Surg. 1991 Feb;5(1):93-103
references.pmid: 1826274
references.citation: J Biomed Mater Res A. 2009 Feb;88(2):348-58
references.pmid: 18286624
references.citation: J Biol Chem. 1998 Oct 2;273(40):25664-72
references.pmid: 9748233
references.citation: Clin Hemorheol Microcirc. 2005;33(3):227-34
references.pmid: 16215288
references.citation: Circulation. 2014 Jan 21;129(3):e28-e292
references.pmid: 24352519
references.citation: Biomaterials. 2013 Apr;34(11):2588-99
references.pmid: 23352039
references.citation: Perfusion. 2013 Sep;28(5):440-8
references.pmid: 23703290
references.citation: PLoS One. 2009 Nov 05;4(11):e7718
references.pmid: 19890388
references.citation: Surg Today. 2004;34(12):1025-30
references.pmid: 15580386
references.citation: Tissue Eng. 2005 Sep-Oct;11(9-10):1379-91
references.pmid: 16259593
references.citation: J Cell Biol. 1994 Feb;124(3):373-80
references.pmid: 7507494
references.citation: Ann Vasc Surg. 2009 Nov-Dec;23 (6):764-9
references.pmid: 19540713
references.citation: Biomaterials. 2006 Oct;27(28):4846-55
references.pmid: 16762410
references.citation: Biomaterials. 2013 Jan;34(1):30-41
references.pmid: 23069711
references.citation: J Thorac Cardiovasc Surg. 2007 May;133(5):1163-70
references.pmid: 17467424
references.citation: Vasc Endovascular Surg. 2011 Oct;45(7):598-603
references.pmid: 21757494
references.citation: Biomaterials. 2007 Feb;28(6):1191-7
references.pmid: 17087991
references.citation: Biomaterials. 2012 Apr;33(10 ):2880-91
references.pmid: 22244694
references.citation: J Vasc Surg. 2010 Jul;52(1):176-95
references.pmid: 20299181
references.citation: Endothelium. 2006 Nov-Dec;13(6):385-401
references.pmid: 17169771
references.citation: Vasc Endovascular Surg. 2012 Apr;46(3):212-22
references.pmid: 22308212
references.citation: Biomaterials. 2007 Aug;28(24):3537-48
references.pmid: 17507089
references.citation: J Biomed Mater Res A. 2011 Oct;99(1):67-73
references.pmid: 21800416