Anti-Coagulant Surface Modification Of The Nitinol Stents

Shape-memory alloys (Nitinols) possess interesting properties that have stimulated great interest in biomedical devices. But the high nickel content of the material may result in acute nickel toxicity and allergic reaction. In addition, the positive net electrical surface potential and high free surface energy of metals may cause thrombogenicity. Heparinization of Nitinol surface has been shown to be a successful strategy to prevent thrombus formation and improve its hemocompatibility. However, the anticoagulant activity of covalently attached heparin using conventional techniques is often decreased by a chemical activation of heparin or by a too tight attachment of heparin molecules to the surface. Moreover, monomolecular layers may lose their performance faster due to biodegradation in the blood environment. A generally applicable procedure for the bioactive coating of Nitinol implants was developed here on the basis of the layer-by-layer deposition of positively charged photosensitive crosslinker, p-diazonium diphenyl amine polymer (PA), and negatively charged polysaccarides (alginate and heparin)on Nitinol, followed by UV irradiation. The optical intensity of UV/vis spectra increased linearly with the number of layers, indicating the buildup of a multilayer structure and uniform coating. Photoreaction between the sulfate moiety of heparin and diazonium moiety of PA resulted in the covalent connection between them in multilayer coating without compromising its catalytic capacity to promote ATIII-mediated thrombin inactivation. The activated partial thromboplastin time (APTT) and prothrombin time (PT) assays showed that both kinds of multi-component coated Nitinol were less thrombogenic than the uncoated one. Otherwise, Multilayer of Alg/PA/Hep exhibited high hydrophilicity and stability and low surface roughness due to the addition of alginate. This resulted in a strongly reduced platelet adhesion. This way is simple and efficient to cover biomedical devices with a stabilized heparin multilayer of a required and uniform thickness, irrespective of the surface shape. In addition, this effort in improve the stability of heparin coating without compromising its catalytic activity.