title: A nonelutable low-molecular weight heparin stent coating for improved thromboresistance.
abstract: Low-molecular weight heparin (LMWH) has been widely used as a systemic anticoagulant during percutaneous coronary intervention. In this study, LMWH was covalently immobilized to the surface of a cobalt chromium reservoir-based sirolimus-eluting stent to create a nonelutable nanoscale coating for enhanced thromboresistance. Toludine-blue stained stents revealed uniform heparin coverage on all surfaces of the stent. Scanning electron microscopy of stent strut cross-sections showed identical coating thickness on all sides; while the thickness was determined to be 320 nm by a focus-ion beam system. Secondary ion mass spectrometry showed constant concentrations of O, N, and S atoms throughout the depth of the surface, confirming the uniformity of the heparin coating. The nonelutable nature of the coating was confirmed in a modified Factor Xa inhibition assay which showed the stent had an equivalent of 3-5 heparin units/cm(2), while no elutable heparin was detected in wash solutions. The antithrombin binding capacity of the immobilized heparin was determined to be 60-80 pmol/cm(2) in an antithrombin uptake assay. The enhanced thromboresistance of the heparin coating was demonstrated in an in-vitro bovine blood flow loop which showed minimal visual thrombus accumulation and 95% reduction in platelet deposition compared to uncoated control stents. Drug-eluting stents with such nonelutable LMWH coating would represent a significant advance in the treatment of patients with complex lesions who are at increased risk of developing stent thrombosis.
authors.affiliation: Cordis Corporation, A Johnson & Johnson Company, Warren, New Jersey, USA. jzhong.zhao@gmail.com
authors.forename: Jonathon
authors.initials: J
authors.lastname: Zhao
authors.forename: Robert
authors.initials: R
authors.lastname: Falotico
authors.forename: Thai
authors.initials: T
authors.lastname: Nguyen
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Theodore
authors.initials: T
authors.lastname: Parker
authors.forename: Vipul
authors.initials: V
authors.lastname: Davé
authors.forename: Campbell
authors.initials: C
authors.lastname: Rogers
authors.forename: Johan
authors.initials: J
authors.lastname: Riesenfeld
mesh_terms: D000818:Animals; D001780:Blood Coagulation Tests / Q000379:methods; D001783:Blood Flow Velocity; D002417:Cattle; D002478:Cells, Cultured; D002858:Chromium Alloys; D054855:Drug-Eluting Stents; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D015951:Factor Xa / Q000737:chemistry; D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry*; D006801:Humans; D008422:Materials Testing; D013927:Thrombosis / Q000378:metabolism / Q000517:prevention & control
chemical_list: D002858:Chromium Alloys; D006495:Heparin, Low-Molecular-Weight; D015951:Factor Xa