Biomimetic Heparan Sulfate-Like Coated ePTFE Grafts Reduce In-graft Neointimal Hyperplasia in Ovine Carotids

Abstract

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 invitro. The aim of the study was to evaluate the invivo surface properties of expanded ePTFE vascular grafts with a semisynthetic HS-like coating (SSHS). ePTFE vascular grafts (n=16, diameter 3.5mm) 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 20wk for histological and morphometric analysis. 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. 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.