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標題: 電解沉積肝素複合鍍層於可降解鎂基材應用於心血管支架之研究
Electrolytic Heparin Loaded Composite Coatings on Biodegradable Magnesium for Stents
作者: 林呈叡
Cheng-Ruei Lin
關鍵字: 生物可吸收性支架
absorbable stent
calcium phosphate
pure magnesium
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摘要: Some limitations like the hypersensitivity reaction, the long-term impairment of endothelial response, and the late stent thrombosis for drug-eluting stents using percutaneous transluminal coronary angioplasty (PTCA) are still found. Though the degradable magnesium alloy used to construct an absorbable stent could be another candidate, the poor corrosion resistance is relatively a serious impediment against wider applications of magnesium alloys. In this study, the coatings of zirconia (ZrO2) bottom layer and calcium phosphate (CaP) top layer are carried out on pure magnesium specimens by electrochemical deposition and subsequent annealing, leading to the corrosion current density reduced from 13.3 to 3.86 μA/cm2 derived by potentiodynamic polarization tests in artificial blood plasma at 37 °C. Furthermore, calcium phosphate (CaP), gelatin (Gel) and heparin (Hep) are co-deposited on post CaP/ZrO2 coated specimens in order to fabricate the heparin sustaining release system for promoting the hemocompatibility of magnesium. Heparin loaded composite coatings are analyzed by X-Ray diffractometry (XRD), field emission scanning electron microscope (FESEM), focused ion beam system (FIB), toluidine blue colorimetric assay, UV-visible spectrometer, and indirect endothelial cell viability tests. The drug content increases from 243.56±55.18 μg/cm2 for single layer (CaP-Hep) to 484.19±19.26 μg/cm2 for multilayer (CaP-Gel-Hep/CaP-Hep/CaP/ZrO2) and the sustaining release of the latter lasting for more than 28 days compared with that of the former for 1 day in PBS solution. The cell viability, related to Mg2+ ions in medium extracts which are still toxic to endothelial cells at high concentrations, is 63 % for the uncoated, 97 % for the ZrO2 coated, and 110 % for the CaP/ZrO2 and CaP-Gel-Hep/CaP-Hep/CaP/ZrO2 coated specimens compared with 100 % for the negative control. All results indicate that ZrO2 coated, CaP/ZrO2 coated, and CaP-Gel-Hep/CaP-Hep/CaP/ZrO2 coated magnesium specimens are potential for biodegradable cardiovascular stents.
使用塗藥支架改善的血管成形術仍然存在著術後發炎反應、對血管內皮造成的長期傷害以及支架內再狹窄等風險。雖鎂合金具有較差的耐腐蝕性卻有機會成為生物可降解可吸收性支架的一項選擇。本研究先將氧化鋯(ZrO2)與磷酸鈣鹽(CaP)以電化學方法沉積至純鎂基材上,並進行了熱退火處理。動態極化試驗顯示這樣的表面處理能使鎂基材在37 °C下人工血漿中的腐蝕電流密度13.3下降至3.86 μA/cm2。接著將磷酸鈣鹽(CaP)、明膠(Gel)、肝素(Hep)複合沉積至材料上以建立穩定的肝素釋放系統與提高鎂基材的生物相容性。並以X光繞射儀(XRD)、場發射式電子顯微鏡(FESEM)、多功能聚焦?子束系統(FIB)、甲苯胺藍染色法(Toluidine blue)、分光光度計(UV visible spectrometer)以及間接內皮細胞活性測試(indirect endothelial cell viability tests)檢視含肝素複合鍍層之材料特性以及細胞毒性。結果顯示肝素載量可由單層複材(CaP-Hep)的243.56±55.18 μg/cm2提升至多層複材(CaP-Gel-Hep/CaP-Hep/CaP/ZrO2)的484.19±19.26 μg/cm2。且體外釋放由單層的1天增加為多層的可持續進行至28天以上。細胞活性試驗可發現對未經處理的基材細胞存活率為63 %,而經過ZrO2鍍層沉積可提升至97 %,CaP/ZrO2與CP-Gel-Hep/CaP-Hep/CaP/ZrO2複合鍍層則可再提升至110 %,此結果應與鍍層抗腐蝕效果的提升造成腐蝕電流密度的降低有關,導致基材鎂離子的釋出率下降,也顯示高濃度Mg2+仍對內皮細胞具毒性。由上述結果可說明含肝素複合鍍層之純鎂有機會作為應用於心血管支架的選擇之一。
其他識別: U0005-2811201416175781
文章公開時間: 2017-08-31
Appears in Collections:材料科學與工程學系



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