Biomimetic Heparan Sulfate-Like Coated ePTFE Grafts Reduce In-graft Neointimal Hyperplasia in Ovine Carotids.
BACKGROUND
Thrombogenicity and neointimal hyperplasia are major causes for synthetic vascular graft failure. Bioactive coatings like heparin have improved patency by reducing thrombogenicity, but neointimal hyperplasia still remains an unsolved problem. Surface coatings with heparan sulfate (HS), the major component of the glycocalyx of endothelial cells, have shown reduced platelet and cell adhesion in vitro. The aim of the study was to evaluate the in vivo surface properties of expanded ePTFE vascular grafts with a semisynthetic HS-like coating (SSHS).


METHODS
ePTFE vascular grafts (n = 16, diameter 3.5 mm) covalently coated with SSHS were compared with uncoated grafts (n = 16) of the same diameter in a carotid interposition model in 16 sheep. The grafts were harvested at 20 wk for histological and morphometric analysis.


RESULTS
SSHS-coated grafts showed less neointima formation than uncoated grafts (P < 0.001). There was no evidence for cell or protein adhesion to SSHS-coated grafts, whereas the surface of uncoated ePTFE grafts was covered with a confluent circular layer of neointima. No difference was found concerning reactions at the anastomotic site of the genuine carotid vessel, both groups displayed neointimal hyperplasia.


CONCLUSIONS
ePTFE grafts covalently coated with a semisynthetic SSHS-glycosaminoglycan successfully mimicked the endothelial glycocalyx. They displayed excellent antiadhesive properties preventing neointimal formation on the graft surface. The results indicate that a biomimetic SSHS coating may be a useful component of bioengineered grafts and an alternative to synthetic surfaces and endothelial seeding.
Clinic for Vascular and Endovascular Surgery, University Hospital Münster, Münster, Germany.
Birgit
B
Wulff
Department of Vascular Surgery, St. Franziskus-Hospital GmbH Münster, Münster, Germany.
Stefan
S
Stahlhoff
Institute of Medical Biometry and Statistics and Center for Clinical Trials, Campus Lübeck, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany.
Reinhard
R
Vonthein
Department of Surgery, Agaplesion Diakonieklinikum Hamburg, Hamburg, Germany.
Andreas
A
Schmidt
Department of Pediatric Cardiology and Intensive Care, Georg-August-University Göttingen, Göttingen, Germany.
Matthias
M
Sigler
Clinic for Vascular and Endovascular Surgery, University Hospital Münster, Münster, Germany; Department of Vascular Surgery, St. Franziskus-Hospital GmbH Münster, Münster, Germany.
Giovanni B
GB
Torsello
Clinic for Vascular and Endovascular Surgery, University Hospital Münster, Münster, Germany. Electronic address: Moherten@web.de.
Monika
M
Herten
D000818:Animals; D040761:Biomimetic Materials; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects / Q000295:instrumentation*; D002339:Carotid Arteries / Q000473:pathology / Q000601:surgery*; D002448:Cell Adhesion; D049109:Cell Proliferation; D020099:Coated Materials, Biocompatible; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006497:Heparan Sulfate / Q000008:administration & dosage*; D006965:Hyperplasia; D008422:Materials Testing; D023421:Models, Animal; D058426:Neointima; D011138:Polytetrafluoroethylene; D011474:Prosthesis Design; D034561:Sheep, Domestic; D013997:Time Factors
D020099:Coated Materials, Biocompatible; D006497:Heparan Sulfate; D011138:Polytetrafluoroethylene