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研究生: 徐承瑋
Hsu, Cheng-Wei
論文名稱: 積層製造生醫用鈦金屬表面改質之研究
Surface modification of additive manufactured Titanium alloy in medical application
指導教授: 李澤民
Lee, Tzer-Min
學位類別: 碩士
Master
系所名稱: 醫學院 - 口腔醫學研究所
Institute of Oral Medicine
論文出版年: 2018
畢業學年度: 106
語文別: 中文
論文頁數: 89
中文關鍵詞: 3D列印Ti-6Al-4V微弧氧化TPMS曲面結構彈性模數生物相容性
外文關鍵詞: 3D printing, Ti-6Al-4V, Micro-arc oxidation, Elastic modulus, Biocompatibility
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  • 骨科植入材中使用的材料最常見為金屬材料,其中鈦及其合金擁有良好的抗腐蝕性、延展性、高強度、抗疲勞強度及低密度,因此被廣泛的應用在骨科植入材中。近年來3D列印技術成熟被廣泛應用在研究中,在牙科材料也不例外,3D列印鈦金屬我們可以製造出特定病人的永久植體,以達到較短的手術時間及降低發病率;並利用3D列印列印出不同結構,達到更接近人體骨骼之機械性質,增加植體的生物相容性。由於3D列印的製作方法有別於傳統的熔煉及鑄造的技術,在材料微結構的部分經金相觀察可以發現不同的微結構;且鈦金屬為生物惰性材料,不易與骨細胞產生良好的結合,經過適當表面改質後,能夠使表面的生物活性提高,有助於骨細胞與植入材的結合。本實驗使用微弧氧化(Micro-arc oxidation, MAO)法,利用鈣磷電解液通入高壓電,於材料表面形成微弧火花進而形成氧化層,目的為探討鈦金屬分別利用3D列印經過MAO製程前後是否與醫療級鈦合金之差異,並進行體外試驗觀察。經光學顯微鏡以及XRD分析觀察可以知道不同製程的試片有不同的微結構組成及相組成。本實驗也開發出Ti-6Al-4V之MAO最佳參數,應用在不同試片中無明顯差異,在生物活性分析及體外試驗中可以知道經表面改質後擁有較高之生物活性及細胞活性。為增加植體之臨床生物相容性,解決應力遮蔽效應問題,本實驗也設計低彈性模術之支架結構解決臨床應用之問題。

    Metal is the most common material used in orthopedic implants. Among those materials, titanium and its alloys are widely used in orthopedic implants because of great ductility, high strength, and fatigue strength. Moreover, the most frequently used alloy is Ti-6Al-4V, which has high strength, high wear resistance, good corrosion resistance, etc. In recent years, 3D printing has been widely used in our life, and there is no exception in dental materials, such as dental implants. With 3D printing titanium, people can produce permanent implants for specific patients, and arrange better surgeries for shorter operation time and lower relapse rate. Furthermore, using 3D printer to print a special structure to make the implants have better biocompatibility. Since the 3D printing process differs from traditional smelting and casting, there are some differences in the microstructures of materials that we can observe by OM. Plus, titanium and its alloys cannot bond well with bone cells due to their biological inertness; as a result, with appropriate surface modification, the biological activity of the surface will be increased, which enables the implants to bond better with bond cells. There are various methods for surface modifications, such as alkali treatment, acid treatment, anodizing and calcium phosphate coating. In this experiment, with micro-arc oxidation (MAO) method, high-voltage electricity is steered into the electrolyte of calcium and phosphorus to make micro-arc spark and then form the oxide layer on the surface of the material. The purpose of this experiment is to see whether there is a difference between medical-grade Ti alloys and 3D printing Ti alloys before and after MAO treatment in vitro. It can be seen by optical microscopy and XRD analysis that the test pieces of different processes have different microstructure compositions and phase compositions. This experiment also developed the optimal parameters of MAO for Ti-6Al-4V. There is no significant difference in the application of different test strips. It can be known in biological activity analysis and in vitro tests that it has higher biological activity and cell activity after surface modification. . In order to increase the clinical biocompatibility of implants and solve the problem of stress shielding effect, this experiment also designed the scaffold structure of low elastic molding to solve the clinical application problems.Ti-6Al-4V, 3D printed EBM and 3D printed SLM, and the surface was modified and the biological activity was explored.
    Extended Abstract
    1. Under the observation of the microstructure of the substrate, the phase of the traditional medical grade Ti-6Al-4V is a spherical phase structure, the phase of EBM is a layered phase structure, and the phase of SLM is acicular organization. The difference in the different phase organization is due to the difference in the early effects of the heat effects in the three different processes. And in the microhardness test, it can be found that the hardness is Ti-6Al-4V<3D printing EBM<3D printing SLM.
    2. Ti metal is a biologically inert material. In this experiment, the micro-arc oxidation (MAO) surface treatment method was successfully used, and the positive voltage, negative voltage frequency and duty ratio were adjusted to the optimal parameters, respectively, the positive voltage was 350 V, and the negative voltage was -150 V, frequency is 100 Hz, duty cycle 90% is the best parameter of traditional medical grade Ti-6Al-4V, and it is found that there is no significant difference between the three on the 3D printed test piece, indicating that the process is very Good applicability.
    3. The micro-arc oxidation process developed in this experiment will not be different due to the difference in substrate process and shape. In the future, the treatment effect will be changed regardless of the difference in the label, shape, microstructure and trace elements of the implant.
    4. Sr has been found to have good biological activity in the literature [40], and at the same time, in addition to the MAO reaction, elements such as Ca, P and Sr have been added, and the surface-modified group has been proved in the biological activity experiment. Biological activity was significantly higher than the untreated group.
    5. In in vitro cell experiments, the cells are more evenly attached to the MAO-treated surface, meaning that the cells are compared to the unmodified group. In the cell proliferation experiment, it is further explained that the number of cell proliferation after surface modification is larger than that of the untreated test piece, and has statistical significance.
    Keywords: 3D printing, Ti-6Al-4V, Micro-arc oxidation, Elastic modulus, Biocompatibility

    目錄 摘要 I Abstract II Extended Abstract IV 致謝 VI 目錄 VII 第一章 緒論 1 前言 1 生醫材料介紹 1 生醫用金屬材料的介紹 2 積層製造(Additive manufacturing technologies) 3 1. 研究動機與目的 4 第二章 文獻回顧 6 1. 基材分析 6 2. 鈦金屬表面改質 7 2.1 表面生物活性陶瓷製備 7 2.2 水熱處理法 8 2.3 溶膠-凝膠法 9 2.4 氣溶膠沉積法 9 2.5 脈衝雷射沉積法 9 2.6 陽極氧化法 10 3. 人工模擬體液(SBF) 12 4. 多孔性鈦塗層 12 4.1 真空燒結法(Vacuum Sintering) 12 4.2 擴散接合法(Diffusion Bonding) 13 4.3 電槳熔射法(Plasma Spraying) 13 第三章 實驗方法與流程 16 1. 實驗用品 16 2. 實驗架構 19 3. 支架結構設計 19 4. 表面改質 19 4.1 Ti-6Al-4V表面微弧氧化處理 20 5. 材料分析 20 5.1 基材機械性質 20 5.2 基材微結構 20 5.3 表面型態 21 5.4 相組成分析 21 5.5 表面粗糙度 21 5.6 鈣磷化合物塗層厚度量測 21 5.7 生物陶瓷塗層製備與生物活性評估 21 5.8 親疏水性測試 22 6. 生物親和性測試 22 6.1 細胞親和性評估 22 6.2 細胞附著形態分析 23 6.3 細胞增生活性分析 23 6.4 細胞分生活性分析 23 第四章 結果 25 1. 基材分析 25 1.1 金相 25 1.2 微硬度 26 5. 試片表面分析 26 2.1 表面形貌 26 2.2 表面元素分析 27 2.3 鍶(Sr)的添加 28 2.3.1. 含鍶(Sr)表面形貌 29 2.3.2. 含鍶(Sr)表面元素分析 29 2.4 相組成分析 29 2.5 親水性 30 2.6 粗糙度 30 2.7 橫截面分析 30 6. 生物活性分析 31 7. 細胞活性分析 32 4.1 細胞形貌 32 4.2 細胞增生試驗 33 4.3 細胞分化試驗 33 8. 3D 結構分析 34 第五章 討論 36 第六章 結論 39 參考文獻 40 表1. 實驗組別命名 50 表2. IOS23317之SBF溶液含量規範 51 表3. Ti基材之機械性質整理 52 表4. 積層製造Ti基材之研究整理 53 表1. 實驗組別命名 50 表2. IOS23317之SBF溶液含量規範 51 表3. Ti基材之機械性質整理 52 表4. 積層製造Ti基材之研究整理 53 圖1. 骨整合為人工關節與組織良好鍵結[5] 57 圖2. (a) 陽極氧化表面之電子顯微鏡圖(b) 陽極氧化表面浸泡模擬體液後具有鈣磷化合物之電顯微鏡圖[26] 57 圖3. MAO處理不同階段的微弧放電示意圖。 (a)階段I,(b)階段II,(c)階段III和(d)階段IV[30] 58 圖4. 增材製造工藝的示意圖[37] 59 圖 5. 積層製造 Electron Beam Melting(左圖),Selective Laser Melting (右圖)[37] 59 圖6. 實驗流程圖 60 圖7實驗方法流程圖 61 圖8實驗參數 62 圖9. 傳統Ti-6Al-4V之金相照片 63 圖10. 3D列印EBM之金相照片 64 圖11. 3D列印SLM之金相照片 65 圖12. 傳統Ti-6Al-4V,3D列印EBM及3D列印SLM之維氏硬度分析 66 圖13. 微弧氧化(MAO)利用直流電調控正電壓參數,正電壓分別250、300、350、400及450V之SEM照片 67 圖14. 微弧氧化(MAO利用正電壓350 V,負電壓分別-50、-100、-150及-200V調控負電壓參數之SEM照片 68 圖15. 微弧氧化(MAO)利用正電壓350 V,負電壓-150 V,頻率及占空比分別-50、-100、-150及-200V 69 圖16. 微弧氧化(MAO)正電壓350V,負電壓-150V,頻率500及100 Hz,占控比90%調控表面元素含量 70 圖17. 微弧氧化(MAO)正電壓350V,負電壓-150V,頻率100 Hz,占控比90%進行傳統Ti-6Al-4V, 71 圖18. 微弧氧化(MAO)正電壓350V,負電壓-150V,頻率100 Hz,占控比90%並添加Sr元素進行傳統Ti-6Al-4V,3D 列印EBM及3D 列印SLM SrMAO處理之SEM/EDS分析 72 圖19. 傳統Ti-6Al-4V,3D 列印EBM及3D 列印SLM基材之XRD 73 圖20. 傳統Ti-6Al-4V,3D 列印EBM及3D 列印SLM MAO處理之TF-XRD分析 74 圖21. 傳統Ti-6Al-4V,3D 列印EBM及3D 列印SLM SrMAO處理之TF-XRD分析 75 圖22左圖為沒有經過表面處理的組別之親水性,右圖為MAO表面處理之親水性 76 圖23傳統Ti-6Al-4V,3D 列印EBM及3D 列印SLM之MAO處理後表面親水性比較 76 圖24. 傳統Ti-6Al-4V,3D 列印EBM及3D 列印SLM之SrMAO處理後表面親水性比較 76 圖25. 傳統Ti-6Al-4V,3D 列印EBM及3D 列印SLM之SrMAO處理後表面粗糙度比較 77 圖26. 傳統Ti-6Al-4V之SrMAO處理後橫截面SEM/EDS分析 78 圖27. 3D 列印EBM之SrMAO處理後橫截面SEM/EDS分析 79 圖28. 3D列印SLM之SrMAO處理後橫截面SEM/EDS分析 80 圖29. 傳統Ti-6Al-4V之SrMAO處理後浸泡SBF之生物活性分析,分別浸泡1、3及7天之SEM/EDS分析 81 圖30. 3D列印EBM之SrMAO處理後浸泡SBF之生物活性分析,分別浸泡1、3及7天之SEM/EDS分析 82 圖31. 3D列印EBM之SrMAO處理後浸泡SBF之生物活性分析,分別浸泡1、3及7天之SEM/EDS分析 83 圖32. 傳統Ti-6Al-4V,3D 列印EBM及3D 列印SLM SrMAO處理前後培養細胞3小時之細胞型態 84 圖33. 傳統Ti-6Al-4V,3D 列印EBM及3D 列印SLM SrMAO處理前後培養細胞24小時之細胞型態 85 圖34. 傳統Ti-6Al-4V,3D 列印EBM及3D 列印SLM SrMAO處理前後培養細胞1, 3及7天之細胞增生分析 86 圖35. 傳統Ti-6Al-4V,3D 列印EBM及3D 列印SLM SrMAO處理前後培養細胞1, 3及7天之細胞增生統計分析 86 圖36. 傳統Ti-6Al-4V,3D 列印EBM及3D 列印SLM SrMAO處理前後培養細胞1, 3及7天之細胞分化分析 87 圖37. 傳統Ti-6Al-4V,3D 列印EBM及3D 列印SLM SrMAO處理前後培養細胞1, 3及7天之細胞分化統計分析 87 圖38. 左圖為本實驗設計之3D設計圖,右圖為Micro-CT拍攝之照片 88 圖39. 3D structure之SEM照片 89 圖40. 3D structure經MAO處理後之SEM照片 89

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