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研究生： 林立涵
Lin, Li-Han
論文名稱： 多酚負載PLGA塗布之鎂支架於抗腐蝕性及促進內皮化應用
Anti-corrosion and Enhanced Endothelization of Polyphenol-loaded PLGA Coating for Magnesium Alloy Cardiovascular Stents
指導教授： 葉明龍
Yeh, Ming-Long
學位類別： 碩士
Master
系所名稱： 工學院 - 生物醫學工程學系
Department of BioMedical Engineering
論文出版年： 2020
畢業學年度： 108
語文別： 英文
論文頁數： 54
中文關鍵詞： 鎂合金 、心血管支架 、沒食子酸 、內皮化 、抗腐蝕
外文關鍵詞： Magnesium alloy, Cardiovascular stents, Gallic acid, Endothelization, Anticorrosion
相關次數： 點閱：104  下載：7 
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    • 比起生物可吸收的高分子支架，可吸收的鎂支架由於具有更好的機械性能而成為治療心肌灌注的解決方案。然而，未經改質處理的鎂合金無法提供適當的降解速率以適應血管重建的速度。而適當的內皮化，去覆蓋置放支架區域是預防性介入性治療手術後關鍵的血管內皮重塑過程。沒食子酸(Gallic acids, GA)是一種酚酸，其具有抗發炎，改善內皮細胞粘附力和抑制平滑肌細胞增殖的細胞生理的調節功能。然而，由於其高抗氧化活性和酸性環境，直接暴露於高濃度的GA容易導致細胞凋亡。因此，小分子洗脫塗層(PLGA(GA))採用三明治結構設計，GA層包裹在兩個聚D，L-丙交酯-乙交酯(PLGA)層之間，從而提高了耐腐蝕性鎂合金也可以防止GA突然釋放。在電化學分析中，PLGA(GA)夾層塗層可增強ZK60 Mg合金的2000倍的耐腐蝕性(以電流密度(µA / cm2)計)。從PLGA(GA)塗層釋放的GA分子通過捕獲自由基抑制氧化及發炎，並選擇性地促進內皮細胞的增殖並抑制平滑肌細胞的生長。在細胞遷移試驗中，PLGA(GA)延遲了平滑肌細胞的遷移，並展現內皮細胞的潛在遷移能力。 PLGA(GA)三明治塗層不僅提高了鎂合金的耐蝕性，而且有利於內皮化，這對於開發功能性血管支架具有預防晚期支架再狹窄化的巨大潛力。

    Absorbable magnesium stents have become an alternative to treat restenosis owing to better mechanical properties than bioabsorbable polymer. However, without modification, Mg alloys cannot provide the proper degradation rate required to match the vascular reform speed. A proper endothelialization covers the scaffolding region and induces regeneration. Gallic acids (GA) is a phenolic acid with attractive biological functions including anti-inflammation and the ability to promote endothelial cell proliferation and inhibit smooth muscle cell (SMC) growth. However, direct exposure to high concentrations of GA can cause cell apoptosis. Thus, a small-molecule eluting coating (PLGA(GA)) is designed using a sandwich-like configuration with a GA layer enclosed between PLGA layers, which increases the anticorrosion of magnesium alloys and prevents burst release of GA. In the electrochemical analysis, it was found that the PLGA(GA) sandwich coating enhanced corrosion resistance 2000 times (at a current density of (µA/cm 2 )) more than ZK60. The released GA molecules from PLGA(GA) inhibit oxidation by capturing free radicals and selectively promote the proliferation of endothelial cells and inhibit SMCs growth. In the cell migration assay, PLGA(GA) delayed wound closure in smooth muscle cells while showing potential migration ability in endothelial cells. The PLGA(GA) sandwich coating not only improved the corrosion resistance but also benefited endothelization, and thus has great potential to develop functional vascular stents that prevent late-stent restenosis.

    中文摘要 I Abstract II 誌謝 III Table of contents IV Lists of figures VII Lists of tables IX Chapter 1 INTRODUCTION 1 1.1 Biodegradable cardiovascular stents 1 1.2 Magnesium alloys 3 1.3 The comparison of surface modification 5 1.4 Polymetric coating 7 1.4.1 Strategies to find the ideal biodegradable polymer 7 1.4.2 Strategies to control the degradation rate 8 1.4.3 Strategies to increase biocompatibility 9 1.5 Phenolic molecules 10 1.6 Motivation 10 Chapter 2 MATERIALS AND METHODS 13 2.1 Experimental equipment and materials 13 2.1.1 Magnesium alloy 13 2.1.2 Experimental materials 13 2.1.3 Experimental equipment 14 2.2 Experimental methods 15 2.2.1 Alkaline heat treatment 15 2.2.2 Poly(lactic-co-glycolic acids) dip coating 15 2.2.3 Phenolic loaded coating 16 2.3 Experimental setup 16 2.4 Materials characterization 17 2.4.1 Surface morphology and chemical composition analysis 17 2.4.2 Functional group measurement & X-ray diffraction 17 2.5 Corrosion resistance analysis 17 2.5.1 Revised simulated body fluid solution 17 2.5.2 Hydrogen release 18 2.5.3 Electrochemical test 18 2.6 In vitro test 18 2.6.1 Cell culture 18 2.6.2 Cytotoxicity test/Cell viability 19 2.6.3 Cell adhesion 20 2.6.4 Cell migration 20 2.6.5 Hemolysis tests 20 2.6.6 Free radical activity tests 21 2.7 Statistic analysis 21 Chapter 3 RESULTS 23 3.1 XRD analysis 23 3.2 SEM images 23 3.2.1 Gallic acids content analysis 23 3.2.2 PLGA(GA) results 25 3.3 EDS analysis 26 3.4 FT-IR analysis 28 3.5 Hydrogen release compared with Bare ZK60, PLGA, and the optimized PLGA(GA) 29 3.6 Potential dynamic test 30 3.6.1 AHT analysis 30 3.6.2 Gallic acids content analysis 31 3.6.3 The optimized PLGA(GA) results 32 3.7 Cell viability 33 3.7.1 Polymetric concentration analysis 33 3.7.2 Gallic acids content analysis 34 3.7.3 The optimized PLGA(GA) results 35 3.8 Cell adhesion 37 3.8.1 AHT analysis 37 3.8.2 Polymetric coating 37 3.8.3 PLGA(GA) film 38 3.9 Cell migration of EC and SMC on PLGA(GA) film 39 3.10 Hemolysis 42 3.11 Free radical activity test 42 3.12 ZK60-stent prototype 43 Chapter 4 DISCUSSION 45 Chapter 5 CONCLUSION 48 References 49

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