臺灣博碩士論文加值系統

生醫材料廣泛應用於製造體內或體外的醫學資材，體內的生醫材料可應用於人工血管、人工骨骼與關節等等。而使用於骨支架之材料，需具備良好生物相容性且需製備成具有適當的機械強度與孔洞大小，以利於骨組織貼附和向內生長之骨支架。因聚酯纖維與鈦棒皆具有良好的機械性質，幾丁聚醣則具有良好的生物相容性及無毒性，故本研究將設計以聚酯纖維與鈦棒製成具有適當的機械強度與孔洞大小之人工複合骨支架，並添加幾丁聚醣藉以增加支架和組織之間的相容性。
本研究將以聚酯長絲為包覆材，鈦棒為芯材，並修正兩種材料後處理的最佳參數值製備成複合人工骨支架。首先將聚酯長絲經併股與加撚加工製備成PET股線，再分別織成多孔性3 D針織物並作層數的變化及鹼處理，再將針織物浸泡於幾丁聚醣溶液中，以冷凍乾燥方式製備成3 D多孔PET/幾丁聚醣圓管針織物。接著將鈦棒作鹼、熱處理，再以電化學法來沉積氫氧基磷灰石後，將樣本浸泡不同天數之模擬體液，增加氫氧基磷灰石之鈣磷比。最後PET/Ti/幾丁聚醣經最佳化參數後處理製程的加工成複合人工骨支架後，分別進行一系列機械性質、實體顯微鏡、SEM、EDS、XRD、FTIR、降解率、重量增加率、pH值測試評估後，最後再進行骨母細胞(MG63)培養及體內測試評估。
研究結果顯示，藉由PET長絲織成3 D圓管針織物，再進行層數的變化及以1wt %的幾丁聚醣溶液處理，使針織物具備3 D多孔與穩定的結構；而鈦棒經由鹼熱處理及電化學沉積60分鐘後，得知在熱處理400 ℃時具有良好的沉積量及鈣磷比；以此兩者最佳參數進行複合，製備成3 D多孔複合PET/Ti/幾丁聚醣人工骨支架，細胞培養結果顯示具有良好的細胞存活率與貼附性。最後以大鼠脛骨鑽孔直徑2 mm，並將本研究研製之複合支架植入六週後，經x光判讀實驗結果顯示脛骨鑽孔的孔洞大小有明顯的縮小情形，發現在第六週組織切片顯示PET/Ti/幾丁聚醣人工複合骨支架已有良好的生物相容性及骨誘導性。

Biomaterials are commonly used as in vitro or in vivo. Synthetic vascular prostheses, artificial bones, and artificial joints are used in vitro. Bone scaffolds demand components with good biocompatibility, mechanical strength, and pore size to help the bone tissue attach to them and allow them to be ingrown. Polyethylene terephthalate (PET) filaments and titanium (Ti) bars both have good mechanical properties while chitosan has good biocompatibility and is non-toxic. Therefore, this study combines these two materials to make the bone scaffolds with appropriate mechanical strength and pore size, after which they are immersed in chitosan solution for a better biocompatibility between the bone scaffolds and tissues.
This study uses PET filaments to wrap the titanium bar, forming the composite artificial bone scaffold with optimum parameters. First, the PET filaments are combined and twisted into plied yarns, and then braided into three-dimensional knitted fabrics. The knitted fabrics, made with various layers, undergo alkali treatment, immersed in chitosan solution, and then freeze-dried, forming the three-dimensional, porous and hollow PET/chitosan knitted fabrics. Second, by electrochemical deposition method, Ti bars that receive alkali treatment and heat treatment can attract phosphate, and are then immersed in the simulated body fluid (SBF) for different days to increase the calcium-phosphorus (Ca/P) ratio of hydroxyapatite. Third, PET knitted fabrics and Ti bars with the optimal parameters are combined and then immersed in chitosan solution, forming the PET/Ti/chitosan bone scaffolds. The resulting bone scaffolds are observed or tested by a stereo microscope, scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and then evaluated for mechanical properties, degradation, weight increase rate, and pH value. Finally, the bone scaffolds are co-cultured with osteosarcoma cells (MG63) and in vivo test.
According to the experimental results, the change in layer number and the immersion in 1 wt% chitosan solution give the PET knitted fabrics a stable structure. Ti bars yield good deposition amount of hydroxyapatite and Ca/P ratio after the alkali treatment, heat treatment, and electrochemical deposition method for 60 minutes, determining the optimal temperature for heat treatment is 400℃.These two materials of optimal parameters are then combined to form the three-dimensional, hollow bone scaffolds. The result of cell culture shows that the resulting bone scaffolds have good cell viability and cell attachment.
Finally, the rats are drilled a hole of a 2-mm diameter in their tibia bones and then implanted with the bone scaffolds. After six weeks, X-ray interpretation shows that the holes in the bones significantly become smaller; at the same time, the tissue slice indicates that PET/Ti/chitosan bone scaffolds have desired biocompatibility and osteoinduction.

中文摘要 I
Abstract III
目錄 V
圖目錄 IX
表目錄 XII
第一章 緒論 1
1.1前言 1
1.2研究背景 2
1.2.1骨骼的形成 2
1.2.2骨骼的組成物 5
1.2.3骨的礦物質生成 6
1.2.4骨骼重建機制 7
1.2.5自然性骨科材料 8
1.2.6人工骨科材料之分類 9
1.2.6.1金屬材料 9
1.2.6.2高分子材料 11
1.2.6.3陶瓷材料 15
1.2.6.4複合材料 16
1.3文獻回顧 19
1.4骨科材料專利 22
1.5研究動機與目的 26
第二章原理 28
2.1轉筒式撚線機加撚原理 28
2.3電化學原理 32
2.3.1鹼熱處理對鈦金屬離子交換反應之原理 32
2.4 冷凍乾燥原理 34
2.5 專有名詞解釋 35
第三章實驗材料與方法 37
3.1 實驗流程與說明 37
3.2模擬體液的製備 44
3.3實驗參數設計 45
3.4分析測試方法 46
3.4.1紗線拉伸強力、強度測試 46
3.4.2針織物拉伸強度測試 46
3.4.3幾丁聚醣降解率測試 46
3.4.4重量增加率 47
3.4.5 結晶型態分析 47
3.4.6傅立葉紅外線光譜儀(FTIR) 測試分析 47
3.4.7掃描式電子顯微鏡 (Scanning Electron Microscope, SEM) 48
3.4.8能量散佈光譜儀 (Energy Dispersive Spectrometer, EDS) 48
3.4.9 pH值測試 48
3.5體外測試-細胞培養 49
3.5.1細胞解凍與分盤 49
3.5.2細胞相容性分析 49
3.5.3細胞貼附性分析 50
3.5.4細胞毒性分析(MTT Assay) 50
3.6體內測試-動物實驗 51
3.6.1動物實驗步驟 51
3.6.2 X光影像判讀 53
3.6.3組織切片分析 53
3.7實驗材料及藥品 54
3.8實驗器材與設備 55
第四章 結果與討論 56
4.1不同股數與撚係數對PET紗線最大斷裂強度 57
4.2 不同股數與撚係數對PET圓管針織物機械性質之影響 59
4.3 PET單、雙層圓管針織物之機械性質 61
4.4 PET單、雙層圓管針織物之實體顯微鏡觀察 62
4.5 PET圓管針織物經NaOH處理後之最大斷裂拉伸強力 64
4.6 PET/幾丁聚醣圓管針織物之實體顯微鏡分析 66
4.7 PET/幾丁聚醣圓管針織物之SEM觀察 67
4.8 PET/幾丁聚醣圓管針織物之最大斷裂拉伸強力 71
4.9 幾丁聚醣在針織物中之含量 73
4.10 幾丁聚醣薄膜經由NaOH處理後之FTIR分析 75
4.11幾丁聚醣經NaOH處理後之降解率 77
4.12鈦棒電化學處理之SEM觀察 80
4.13鈦棒電化學處理後之FTIR分析 88
4.14鈦棒經由不同高溫處理電化學之重量增加率 90
4.15鈦棒經由電化學處理後浸泡模擬體液之重量增加率 92
4.16鈦棒不同溫度處理以電化學處理後浸泡模擬體液之表面觀察 97
4.17鈦棒浸泡21天模擬體液之結晶分析 116
4.18鈦棒浸泡模擬體液之鈣磷比 120
4.19 PET/Ti/幾丁聚醣複合人工骨支架之pH值分析 122
4.20細胞共培養與細胞存活率 124
4.21細胞貼附性 129
4.22 動物實驗 133
4.23 X光影像判讀 135
4.24 組織學分析 137
第五章結論 148
第六章建議 151
參考文獻 152

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