缺血性心臟病（IHD），又稱冠狀動脈心臟病（CHD），係因心臟血管阻塞導致缺 血所致，嚴重者恐引發心肌梗塞或猝死。經皮冠狀動脈介入治療術（PCI）為目前常 見治療方式，透過血管支架撐開血管以恢復血流。近年來，具可降解特性的生物可吸收支架成為研究重點，其中鎂合金因具有適當機械強度與良好生物相容性而備受關注。 然而，鎂合金的快速降解為其臨床應用上的一大限制。此外，內皮癒合與抗血小板貼附等生物相容性因素亦是血管支架臨床成功的關鍵。
本研究以 ZK60 鎂合金為基材，先經氟化與鹼熱處理進行表面改質，再塗覆含有 抗氧化劑α 硫辛酸（α-lipoic acid, ALA）之聚乳酸-羥基乙酸共聚物（PLGA）複合塗層。ALA 具有抗發炎與抗血栓特性。在所有實驗組（包含未處理 ZK60、MgFO、PLGA、 LA0.5 與 LA2）中，LA0.5 組整體表現最佳。該複合塗層能有效提升基材之耐蝕性， 並展現抗氧化能力，同時促進內皮細胞之存活、貼附與遷移。此外，血液相容性試驗 亦顯示其具有抑制血小板貼附的效果。綜合以上結果，ALA/PLGA 複合塗層在生物可降解血管支架的表面改質應用上展現良好潛力。

Ischemic heart disease (IHD), resulting from coronary artery blockage, is a major cause of myocardial infarction and sudden cardiac death. Percutaneous coronary intervention (PCI), which involves the implantation of vascular stents to restore blood flow, is a widely adopted clinical treatment. In recent years, biodegradable stents, particularly those made from magnesium alloys, have received increasing attention due to their favorable mechanical properties and biocompatibility. However, the rapid degradation of magnesium alloys remains a significant limitation. In addition, biocompatibility factors such as endothelial wound healing and anti-platelet adhesion are also crucial for the clinical success of vascular stents.
In this study, ZK60 magnesium alloy was surface-modified through fluorination and alkali-heat treatment, followed by the application of a PLGA composite coating incorporating the antioxidant α-lipoic acid (ALA), which exhibits anti-inflammatory and anti-thrombotic properties. Among all experimental groups, including bare ZK60, MgFO, PLGA, LA0.5, and LA2, the LA0.5 group exhibited the most favorable overall performance. This composite coating effectively enhanced corrosion resistance, provided antioxidant activity, and promoted endothelial cell viability, adhesion, and migration. In addition, hemocompatibility tests demonstrated a reduction in platelet adhesion. These results indicate that the ALA/PLGA composite coating is a promising surface modification strategy for biodegradable vascular stents.

[1] Leys, Didier, "Atherothrombosis: a major health burden," Cerebrovascular diseases, vol. 11, no. Suppl. 2, pp. 1-4, 2001.
[2] Rivera-Caravaca, José Miguel, Camelo-Castillo, Anny, Ramírez-Macías, Inmaculada, Gil-Pérez, Pablo, López-García, Cecilia, Esteve-Pastor, María Asunción et al., "Antithrombotic therapy in patients with peripheral artery disease: A focused review on oral anticoagulation," International Journal of Molecular Sciences, vol. 22, no. 13, p. 7113, 2021.
[3] Brown, Jonathan C, Thomas E, Gerhardt, and Edward, Kwon, "Risk factors for coronary artery disease," 2020.
[4] Khan, Moien AB, Hashim, Muhammad Jawad, Mustafa, Halla, Baniyas, May Yousif, Al Suwaidi, Shaikha Khalid Buti Mohamad, AlKatheeri, Rana et al., "Global epidemiology of ischemic heart disease: results from the global burden of disease study," Cureus, vol. 12, no. 7, 2020.
[5] Simard, Trevor, Hibbert, Benjamin, Ramirez, F Daniel, Froeschl, Michael, Chen, Yong-Xiang, and O'Brien, Edward R, "The evolution of coronary stents: a brief review," Canadian Journal of Cardiology, vol. 30, no. 1, pp. 35-45, 2014.
[6] Borhani, Setareh, Hassanajili, Shadi, Ahmadi Tafti, Seyed Hossein, and Rabbani, Shahram, "Cardiovascular stents: overview, evolution, and next generation," Progress in biomaterials, vol. 7, pp. 175-205, 2018.
[7] Drelich, Jaroslaw W and Goldman, Jeremy, "Bioresorbable vascular metallic scaffolds: current status and research trends," Current opinion in biomedical engineering, vol. 24, p. 100411, 2022.
[8] Ho, Ming-Yun, Chen, Chun-Chi, Wang, Chao-Yung, Chang, Shang-Hung, Hsieh, Ming-Jer, Lee, Cheng-Hung et al., "The development of coronary artery stents: from bare-metal to bio-resorbable types," Metals, vol. 6, no. 7, p. 168, 2016.
[9] Buccheri, Dario, Piraino, Davide, Andolina, Giuseppe, and Cortese, Bernardo, "Understanding and managing in-stent restenosis: a review of clinical data, from pathogenesis to treatment," Journal of thoracic disease, vol. 8, no. 10, p. E1150, 2016.
[10] Stefanini, Giulio G, Byrne, Robert A, Windecker, Stephan, and Kastrati, Adnan, "State of the art: coronary artery stents-past, present and future," EuroIntervention, vol. 13, no. 6, pp. 706-716, 2017.
[11] Bowen, Patrick K, Shearier, Emily R, Zhao, Shan, Guillory, Roger J, Zhao, Feng, Goldman, Jeremy et al., "Biodegradable metals for cardiovascular stents: from clinical concerns to recent Zn‐Alloys," Advanced healthcare materials, vol. 5, no. 10, pp. 1121-1140, 2016.
[12] Zhang, Zhao-Qi, Yang, Yong-Xin, Li, Jing-An, Zeng, Rong-Chang, and Guan, Shao- 59Kang, "Advances in coatings on magnesium alloys for cardiovascular stents–a review," Bioactive materials, vol. 6, no. 12, pp. 4729-4757, 2021.
[13] Mueller, Peter P, May, Tobias, Perz, Angela, Hauser, Hansjörg, and Peuster, Matthias, "Control of smooth muscle cell proliferation by ferrous iron," Biomaterials, vol. 27, no. 10, pp. 2193-2200, 2006.
[14] Zhuo, Xiaoru, Wu, Yuna, Ju, Jia, Liu, Huan, Jiang, Jinghua, Hu, Zhichao et al., "Recent progress of novel biodegradable zinc alloys: From the perspective of strengthening and toughening," journal of materials research and technology, vol. 17, pp. 244-269, 2022.
[15] Fu, Jiayin, Su, Yingchao, Qin, Yi-Xian, Zheng, Yufeng, Wang, Yadong, and Zhu, Donghui, "Evolution of metallic cardiovascular stent materials: a comparative study among stainless steel, magnesium and zinc," Biomaterials, vol. 230, p. 119641, 2020.
[16] Teo, Koon K and Yusuf, Salim, "Role of magnesium in reducing mortality in acute myocardial infarction: a review of the evidence," Drugs, vol. 46, no. 3, pp. 347-359, 1993.
[17] Maier, Jeanette AM, "Low magnesium and atherosclerosis: an evidence-based link," Molecular aspects of medicine, vol. 24, no. 1-3, pp. 137-146, 2003.
[18] Gu, Xuenan, Zheng, Yufeng, Cheng, Yan, Zhong, Shengping, and Xi, Tingfei, "In vitro corrosion and biocompatibility of binary magnesium alloys," Biomaterials, vol. 30, no. 4, pp. 484-498, 2009.
[19] Kolte, Dhaval, Vijayaraghavan, Krishnaswami, Khera, Sahil, Sica, Domenic A, and Frishman, William H, "Role of magnesium in cardiovascular diseases," Cardiology in review, vol. 22, no. 4, pp. 182-192, 2014.
[20] Heublein, B, Rohde, R, Kaese, V, Niemeyer, M, Hartung, W, and Haverich, A, "Biocorrosion of magnesium alloys: a new principle in cardiovascular implant technology?," Heart, vol. 89, no. 6, pp. 651-656, 2003.
[21] Pan, Changjiang, Zhao, Yongjuan, Yang, Ya, Yang, Minghui, Hong, Qingxiang, Yang, Zhongmei et al., "Immobilization of bioactive complex on the surface of magnesium alloy stent material to simultaneously improve anticorrosion, hemocompatibility and antibacterial activities," Colloids and Surfaces B: Biointerfaces, vol. 199, p. 111541, 2021.
[22] Mao, Lin, Shen, Li, Chen, Jiahui, Zhang, Xiaobo, Kwak, Minsuk, Wu, Yu et al., "A promising biodegradable magnesium alloy suitable for clinical vascular stent application," Scientific reports, vol. 7, no. 1, p. 46343, 2017.
[23] Bai, Lingchuang, Wang, Yahui, Xie, Jia, Zhao, Yuan, and Guan, Shaokang, "Fucoidan-based coating on magnesium alloy improves the hemocompatibility and pro-endothelialization potential for vascular stent application," Materials & Design, vol. 233, p. 112235, 2023.
[24] Liu, Jing, Zheng, Bo, Wang, Pei, Wang, Xingang, Zhang, Bin, Shi, Qiuping et al., "Enhanced in vitro and in vivo performance of Mg–Zn–Y–Nd alloy achieved with APTES pretreatment for drug-eluting vascular stent application," ACS applied materials & interfaces, vol. 8, no. 28, pp. 17842-17858, 2016.
[25] Merson, Dmitry, Vasilev, E, Markushev, M, and Vinogradov, Alexei, "On the corrosion of ZK60 magnesium alloy after severe plastic deformation," Letters on Materials, vol. 7, no. 4, pp. 421-427, 2017.
[26] Li, Zhen, Peng, Zeyin, Qiu, Yubing, Qi, Kai, Chen, Zhenyu, and Guo, Xingpeng, "Study on heat treatment to improve the microstructure and corrosion behavior of ZK60 magnesium alloy," Journal of Materials Research and Technology, vol. 9, no. 5, pp. 11201-11219, 2020.
[27] Choi, HY and Kim, WJ, "Effect of thermal treatment on the bio-corrosion and mechanical properties of ultrafine-grained ZK60 magnesium alloy," Journal of the mechanical behavior of biomedical materials, vol. 51, pp. 291-301, 2015.
[28] Mostaed, Ehsan, Hashempour, Mazdak, Fabrizi, Alberto, Dellasega, David, Bestetti, Massimiliano, Bonollo, Franco et al., "Microstructure, texture evolution, mechanical properties and corrosion behavior of ECAP processed ZK60 magnesium alloy for biodegradable applications," Journal of the Mechanical Behavior of Biomedical Materials, vol. 37, pp. 307-322, 2014.
[29] Fakhar, N and Sabbaghian, M, "A good combination of ductility, strength, and corrosion resistance of fine-grained ZK60 magnesium alloy produced by repeated upsetting process for biodegradable applications," Journal of Alloys and Compounds, vol. 862, p. 158334, 2021.
[30] Zhang, Tiantian, Cui, Hongwei, Cui, Xiaoli, Zhao, Ertuan, Feng, Rui, and Pan, Yaokun, "Investigations on microstructures, mechanical and corrosion properties of Mg-5.5 Zn-0.8 Zr alloys with Sm addition," Materials Research Express, vol. 6, no. 7, p. 076550, 2019.
[31] Fu, Wei, Yang, Hejie, Li, Tianshu, Sun, Jiapeng, Guo, Shengwu, Fang, Daqing et al., "Enhancing corrosion resistance of ZK60 magnesium alloys via Ca microalloying: The impact of nanoscale precipitates," Journal of Magnesium and Alloys, vol. 11, no. 9, pp. 3214-3230, 2023.
[32] Ma, Jun, Zhao, Nan, Betts, Lexxus, and Zhu, Donghui, "Bio-adaption between magnesium alloy stent and the blood vessel: a review," Journal of materials science & technology, vol. 32, no. 9, pp. 815-826, 2016.
[33] Claessen, Bimmer E, Henriques, José PS, Jaffer, Farouc A, Mehran, Roxana, Piek, Jan J, and Dangas, George D, "Stent thrombosis: a clinical perspective," JACC: Cardiovascular interventions, vol. 7, no. 10, pp. 1081-1092, 2014.
[34] Sikdar, Soumya, Menezes, Pramod V, Maccione, Raven, Jacob, Timo, and Menezes, Pradeep L, "Plasma electrolytic oxidation (PEO) process—processing, properties, and applications," Nanomaterials, vol. 11, no. 6, p. 1375, 2021.
[35] Tian, Peng and Liu, Xuanyong, "Surface modification of biodegradable magnesium and its alloys for biomedical applications," Regenerative biomaterials, vol. 2, no. 2, pp. 135-151, 2015.
[36] Chiu, K. Y., Wong, M. H., Cheng, F. T., and Man, H. C., "Characterization and corrosion studies of fluoride conversion coating on degradable Mg implants," Surface and Coatings Technology, vol. 202, no. 3, pp. 590-598, 2007 2007.
[37] Li, JN, Cao, Peng, Zhang, XN, Zhang, SX, and He, YH, "In vitro degradation and cell attachment of a PLGA coated biodegradable Mg–6Zn based alloy," Journal of materials science, vol. 45, pp. 6038-6045, 2010.
[38] Da Conceicao, TF, Scharnagl, N, Blawert, C, Dietzel, W, and Kainer, KU, "Surface modification of magnesium alloy AZ31 by hydrofluoric acid treatment and its effect on the corrosion behaviour," Thin Solid Films, vol. 518, no. 18, pp. 5209-5218, 2010.
[39] Zhu, Yanying, Wu, Guangming, Zhao, Qing, Zhang, Yun-Hong, Xing, Guangjian, and Li, Donglin, "Anticorrosive magnesium hydroxide coating on AZ31 magnesium alloy by hydrothermal method," in Journal of Physics: Conference Series, 2009, vol. 188, no. 1: IOP Publishing, p. 012044.
[40] Zhao, Zheng, Zong, Lishuai, Liu, Chengde, Li, Xiangyu, Wang, Chenghao, Liu, Wentao et al., "A novel Mg(OH)2/MgFx(OH)1−x composite coating on biodegradable magnesium alloy for coronary stent application," Corrosion Science, vol. 208, p. 110627, 2022.
[41] Wang, Juan, He, Yonghui, Maitz, Manfred F, Collins, Boyce, Xiong, Kaiqin, Guo, Lisha et al., "A surface-eroding poly (1, 3-trimethylene carbonate) coating for fully biodegradable magnesium-based stent applications: toward better biofunction, biodegradation and biocompatibility," Acta biomaterialia, vol. 9, no. 10, pp. 8678- 8689, 2013.
[42] Jiang, Wensen, Tian, Qiaomu, Vuong, Tiffany, Shashaty, Matthew, Gopez, Chris, Sanders, Tian et al., "Comparison study on four biodegradable polymer coatings for controlling magnesium degradation and human endothelial cell adhesion and spreading," ACS Biomaterials Science & Engineering, vol. 3, no. 6, pp. 936-950, 2017.
[43] Washburn, Newell R, Yamada, Kenneth M, Simon Jr, Carl G, Kennedy, Scott B, and Amis, Eric J, "High-throughput investigation of osteoblast response to polymer crystallinity: influence of nanometer-scale roughness on proliferation," Biomaterials, vol. 25, no. 7-8, pp. 1215-1224, 2004.
[44] Jones, Wright, Li, Xia, Qu, Zhi-chao, Perriott, Laureta, Whitesell, Richard R, and May, James M, "Uptake, recycling, and antioxidant actions of α-lipoic acid in endothelial cells," Free Radical Biology and Medicine, vol. 33, no. 1, pp. 83-93, 2002.
[45] Ying, Zhekang, Xie, Xiaoyun, Chen, Minjie, Yi, Kevin, and Rajagopalan, Sanjay, "Alpha-lipoic acid activates eNOS through activation of PI3-kinase/Akt signaling pathway," Vascular pharmacology, vol. 64, pp. 28-35, 2015.
[46] Heitzer, Thomas, Finckh, Barbara, Albers, Sylvia, Krohn, Karoline, Kohlschütter, Alfried, and Meinertz, Thomas, "Beneficial effects of α-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: relation to parameters of oxidative stress," Free Radical Biology and Medicine, vol. 31, no. 1, pp. 53-61, 2001.
[47] Lai, Yuan-Shu, Shih, Ching-Yu, Huang, Yu-Feng, and Chou, Tz-Chong, "Antiplatelet activity of α-lipoic acid," Journal of agricultural and food chemistry, vol. 58, no. 15, pp. 8596-8603, 2010.
[48] Lee, Kyeong-Min, Park, Keun-Gyu, Kim, Yong-Deuk, Lee, Hyo-Jung, Kim, Hyoung Tae, Cho, Won-Hyun et al., "Alpha-lipoic acid inhibits fractalkine expression and prevents neointimal hyperplasia after balloon injury in rat carotid artery," Atherosclerosis, vol. 189, no. 1, pp. 106-114, 2006.
[49] Rochette, Luc and Ghibu, Steliana, "Mechanics insights of alpha-lipoic acid against cardiovascular diseases during COVID-19 infection," International Journal of Molecular Sciences, vol. 22, no. 15, p. 7979, 2021.
[50] Khan, Ahsan Riaz, Grewal, Navdeep Singh, Zhou, Chao, Yuan, Kunshan, Zhang, Hai-Jun, and Jun, Zhang, "Recent advances in biodegradable metals for implant applications: Exploring in vivo and in vitro responses," Results in Engineering, vol. 20, p. 101526, 2023.
[51] 林立涵, "多酚負載 PLGA 塗布之鎂支架於抗腐蝕性及促進內皮化應用," 碩士, 生物醫學工程學系, 國立成功大學, 台南市, 2020. [Online]. Available: https://hdl.handle.net/11296/76gh39
[52] Saberi, Abbas, Bakhsheshi-Rad, Hamid Reza, Abazari, Somayeh, Ismail, Ahmad Fauzi, Sharif, Safian, Ramakrishna, Seeram et al., "A comprehensive review on surface modifications of biodegradable magnesium-based implant alloy: Polymer coatings opportunities and challenges," Coatings, vol. 11, no. 7, p. 747, 2021.
[53]"Lipoic (Thioctic) Acid, in Cell Culture." https://www.sigmaaldrich.com/TW/zh/technical-documents/technical-article/cell-culture-and-cell-culture-analysis/mammalian-cell-culture/lipoic-acid (accessed 2025).
[54] Sheng, Yu-Jane, Jiang, Shaoyi, and Tsao, Heng-Kwong, "Effects of geometrical characteristics of surface roughness on droplet wetting," The Journal of chemical physics, vol. 127, no. 23, 2007.
[55] Al-Azzam, Nosayba and Alazzam, Anas, "Micropatterning of cells via adjusting surface wettability using plasma treatment and graphene oxide deposition," Plos one, vol. 17, no. 6, p. e0269914, 2022.
[56] Zhao, Zheng, Zong, Lishuai, Liu, Chengde, Wang, Chenghao, Qi, Chunwei, Wang, Ning et al., "Dual strengthened corrosion control of biodegradable coating on magnesium alloy for vascular stent application," Progress in Organic Coatings, vol. 174, p. 107297, 2023.
[57] Biewenga, Gerreke Ph, Haenen, Guido RMM, and Bast, Aalt, "The pharmacology of the antioxidant lipoic acid," General Pharmacology: The Vascular System, vol. 29, no. 3, pp. 315-331, 1997.
[58] Yang, Yu, Xiao, Yong, Jiang, Yue, Luo, Jiajun, Yuan, Jingwen, Yan, Junfeng et al., "Alpha‐Lipoic Acid Promotes Intestinal Epithelial Injury Repair by Regulating MAPK Signaling Pathways," Mediators of Inflammation, vol. 2022, no. 1, p. 1894379, 2022.
[59] Höhn, Sarah, Virtanen, Sannakaisa, and Boccaccini, Aldo R, "Protein adsorption on magnesium and its alloys: A review," Applied Surface Science, vol. 464, pp. 212-219, 2019.
[60] Williams, Olivia and Sergent, Shane R, "Histology, platelets," 2020.
[61] Koh, Li Buay, Rodriguez, Isabel, and Zhou, Jijie, "Platelet adhesion studies on nanostructured poly (lactic‐co‐glycolic‐acid)–carbon nanotube composite," Journal of Biomedical Materials Research Part A: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials, vol. 86, no. 2, pp. 394-401, 2008.