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: Jonathon Zhao, Robert Falotico, Thai Nguyen, Yan Cheng, Theodore Parker, Vipul Davé, Campbell Rogers, Johan Riesenfeld
• Journal: Journal of biomedical materials research. Part B, Applied biomaterials (J Biomed Mater Res B Appl Biomater) Vol. 100 Issue 5 Pg. 1274-82 (Jul 2012) ISSN: 1552-4981 [Electronic] United States
• PMID: 22454106 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• Chromium Alloys
• Heparin, Low-Molecular-Weight
• Factor Xa

Topics

• Animals
• Blood Coagulation Tests (methods)
• Blood Flow Velocity
• Cattle
• Cells, Cultured
• Chromium Alloys
• Drug-Eluting Stents
• Endothelial Cells (cytology, metabolism)
• Factor Xa (chemistry)
• Heparin, Low-Molecular-Weight (chemistry)
• Humans
• Materials Testing
• Thrombosis (metabolism, prevention & control)