Heparin Contained Multilayer Composite Coatings on NiTi Alloy By Electrochemical Methods for Reducing in-Stent Restenosis

Abstract

Although the initial success of bare metal stents (BMS) has significantly reduced the restenosis rate from 35% for Percutaneous transluminal coronary angioplasty (PTCA) to 25%, the biological mechanism such as smooth muscle cell proliferation and neointimal hyperplasia may still induce in-stent restenosis (ISR). Therefore, some drug eluting stents have been introduced to reduce ISR. In this study, heparin (Hep) combined with calcium phosphate (CaP) and gelatin (Gel) was co-deposited on NiTi alloy by electrochemical methods in order to fabricate the sustained heparin releasing system for promoting the hemo-compatibility of NiTi substrate. Polarization tests were carried out in several solutions to investigate deposition mechanisms. Heparin contained composite coatings are characterized by X-ray diffractometry (XRD), Field emission scanning electron microscope (FESEM), Fourier transform infrared spectroscopy (FTIR), toluidine blue colorimetric assay, UV-visible spectrometer and kinetic clotting tests. The consequences indicate that heparin accompanied with CaP, and Gel through ionic bonds can be loaded on the NiTi alloy, respectively. The post porous HA coating can enhance the drug content from 147.06±68.66 of the single layer coating (CaP-Hep) to 191.58±11.87 of the bilayer coating (HA/CaP-Hep) and further to 324.87±4.94 μg/cm2 of the trilayer coating (HA/CaP-Hep/Gel-Hep) by adding the third layer which also results in the in vitro heparin release prolonging from 1 day burst to more than 35 days sustaining release. As the result of clotting tests, drug loaded composite coatings reveal good anticoagulant property which is proportional to the cumulative content of drug release in an hour, indicating no denaturalization of heparin found during the electrochemical process. Keywords: Ni-Ti alloy; in-stent restenosis (ISR); heparin; calcium phosphate; gelatin