Electrolytic deposition of hydroxyapatite/calcium phosphate-heparin/ gelatin-heparin tri-layer composites on NiTi alloy to enhance drug loading and prolong releasing for biomedical applications

摘要

Although the initial success of bare metal stents has significantly reduced the restenosis rate for percutaneous transluminal coronary angioplasty from 35% to 25%, the biological mechanism such as vascular smooth muscle cells (VSMCs) proliferation and neo-intimal hyperplasia still may 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), without any additive or solvent, is co-deposited on hydroxyapatite (HA) coated NiTi alloy in order to enhance the drug load and the sustaining release for promoting the hemo-compatibility of NiTi substrate. Polarization tests were carried out in several solutions to investigate deposition mechanisms. Heparin contained composite coatings were characterized by X-ray diffractometry, Field emission scanning electron microscope, Fourier transform infrared spectroscopy, toluidine blue colorimetric assay, UV-visible spectrometer and kinetic clotting tests. The consequences indicate that heparin accompanied respectively with CaP, and Gel through ionic bonds can be loaded on the NiTi alloy. The porous post-HA coating can dramatically enhance the heparin content from 148 for the single layer coating (CaP-Hep) to 325 mu g/cm(2) for the tri-layer coating (HA/CaP-Hep/Gel-Hep), also resulting in the heparin release duration from 1 to 35 days, supposed to meet the requirement to prevent the proliferation of VSMCs. Both the drug content and releasing time are remarkable. As the result of clotting tests in vitro, 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.