臺灣博碩士論文加值系統

外科手術經常因植入物造成傷口過大或長時間暴露導致組織缺血而手術失敗，此外因周遭醫療環境及設備造成的細菌感染亦為植入物手術失敗的主要原因之一，如果能於植入物表面製備一引導組織生長並能抗菌的塗層，將可大幅降低其醫療風險。
生物活性玻璃為一種矽酸鹽類，具有良好的骨誘導性，過去幾十年裡常被運用於醫療牙科及骨科中; 鍶離子為人體骨頭中微量的元素，先前研究並提出可以促進骨整合以及血管生成; 銀離子可藉由與細胞膜表面鍵結，經由表面電荷不平衡，而造成細菌凋亡達到抗菌，同時含鍶離子及銀離子之生物活性玻璃將可結合其優點達到雙重的效果。
本研究透過旋轉塗佈法製備聚電解質多層膜塗層，於316L不鏽鋼金屬植入物表面進行表面改質修飾，多層膜的主體使用具良好生物相容性的膠原蛋白為正電荷層、生物可降解的γ-聚麩胺酸做為負電荷層及幾丁聚醣作為正電荷層屏障，於負電荷層中摻入以噴霧熱裂解製備含有銀和鍶的生物活性玻璃，藉由體外及體內試驗銀和鍶的釋放，達到抗菌、促進血管生成和骨整合的效果。
實驗結果顯示，摻入含銀和鍶生物玻璃之20層多層膜，膜厚為55.8 ± 1.52μm;利用接觸角測試，得知其接觸角為37.09 o具有良好的親水性; 以奈米壓痕及白光干涉儀測試得知楊氏係數及硬度為5.35 ± 1.55 GPa及0.29 ± 0.09 GPa，粗糙度為374.78 ± 22.27 nm；降解測試顯示膜層能維持長達89天之久；抑菌圈測試顯示本多層膜有長達1個月之久的的抗菌效果；經人工模擬體液浸泡，藉由掃描式電子顯微鏡及X射線衍射分析得知多層膜表面有明顯的磷灰石沉積;MTT 與螢光染色測試顯示多層膜對大鼠骨隨間質幹細胞及人類靜脈內皮細胞有良好的細胞活性，且有高表現的分化和礦化效果。統整以上結果，得知本研究所製備之聚電解質多層膜塗層能有效促進血管生成、骨整合及抗菌效果。

The main causes for failure of implants surgery are long exposure of implants or wounds and tissue ischemia. Besides, the bacterial infection caused by surrounding medical environment and equipment is also one of major risk for failure of surgery. It will greatly reduce the medical risk if we could creat a coating on implants surface for guide tissue growth and antibacteria.
Mesoporous bioactive glasses are mainly silicate and with good osteoinductivity. The mesoporous bioactive glasses have been used in medical dentistry and orthopedics for the past several decades. Strontium ion is a trace element in human bone, and previous studies have proposed it would promote osseointegration and angiogenesis. Silver ions can lead to bacterial apoptosis by bonding to the surface of cell membranes through surface charge imbalance. The bioactive glass containing strontium ions and silver ions will combine their advantages to achieve the multiple functions at the same time.
In this study, the polyelectrolyte multilayers (PEMs) coatings were prepared on 316L stainless steel to functionize the surface by spin-coating. The compostition of the multilayer films was made of biocompatible collagen as positively charged layer and biodegradable γ-poly glutamic acid as negatively charged layer; chitosan with a positively charged layer as the natural barrier; the bioactive glass incorporated with silver and strontium prepared by spray pyrolysis was added into the negatively charged layer. Though in vitro and in vivo tests, the PEMs coating would promote angiogenesis, osseointegration and antibacteria with the release of silver and strontium ions.
Herein, it is comfirmed that bioactive glass was successfully incorporated into the twenty layers polyelectrolyte multilayers. The PEMs coating had good hydrophilicity with a contact angle of 37.09 o; and hardness of 0.29 ± 0.09 GPa, Young’s modulus of 5.35 ± 1.55 GPa and roughness of 374.78±22.27 nm, as observed through nano-indention and white light interferometry. The PEMs coating was not only well antibacterial for one months, as seen in the inhibition zone test, but also biocompatible for rat bone marrow mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs), as studied in the MTT assay. There were more hydroxyapatite depostitions on PEMs surface after being soaked by SBF, as invesgated by scanning electron microscope (SEM) and X-ray diffraction (XRD). Therefore, we believe that this technology will have great potential in surface modification of implants due to its antibacterial, angiogenesis, and osseointegration properties.

目錄

摘要 i
ABSTRACT iii
致謝 v
目錄 vi
表目錄 xi
圖目錄 xiii
第一章 序論 1
1.1 前言 1
1.2 研究動機與目的 2
第二章 文獻回顧 3
2.1骨骼 3
2.1.1骨組織工程 4
2.1.2骨骼組織修復 6
2.2骨科醫療植入物 7
2.2.1金屬植入物 8
2.2.2非金屬植入物 10
2.3骨整合與感染防治之重要性 11
2.3.1血管生成 12
2.3.2鍶(Strontium) 13
2.4抗菌塗層 14
2.5聚電解質多層膜 16
2.6本研究之製膜材料簡介 18
2.6.1膠原蛋白 20
2.6.2 γ-聚麩胺酸 21
2.6.3幾丁聚醣 22
2.6.4生物活性玻璃 23
第三章 實驗設備材料與方法 25
3.1 實驗材料 25
3.1.1 細胞株及動物來源 25
3.1.2 實驗基材 25
3.1.3 實驗藥品 25
3.1.4生物活性玻璃製備 27
3.1.5聚電解質多層膜溶液配置 28
3.1.6 抗菌實驗溶液配置 30
3.1.7 體外試驗溶液配置 31
3.1.8 細胞分化與礦化反應溶液配置 33
3.2實驗設備 36
3.2.1儀器設備 36
3.2.2 實驗耗材 37
3.3實驗方法 39
3.3.1實驗設計 39
3.3.2實驗代號 39
3.3.3試片製備 40
3.4 材料與性質分析 41
3.4.1 X光繞射儀 41
3.4.2 高解析熱場發射掃描式電子顯微鏡 42
3.4.3 接觸角分析儀 43
3.4.4 奈米壓痕量測儀 44
3.4.5 白光干涉儀 46
3.4.6 全波長吸收光暨螢光複合分析系統 47
3.4.7 降解測試 48
3.4.8 離子釋放 49
3.4.9 抑菌圈 50
3.5體外測試 52
3.5.1 人工模擬體液測試 52
3.5.2 細胞毒性測試 53
3.5.3 鹼性磷酸酶含量檢測 54
3.5.4 鈣含量測試 56
3.5.5 螢光染色 58
3.6體內測試(頭蓋骨植入) 59
3.7統計分析 60
第四章 結果與討論 61
4.1 生物活性玻璃體外與抗菌分析 61
4.1.1 生物活性玻璃添加比例分析 61
4.1.2 生物活性玻璃細胞毒性測試 62
4.1.3 生物活性玻璃抗菌測試 63
4.2 生物活性玻璃體內測試(頭蓋骨植入) 64
4.3 聚電解質多層膜材料與性質分析 65
4.3.1 含鍶生物活性玻璃濃度條件最佳化 65
4.3.2 含銀和鍶生物活性玻璃濃度條件最佳化 66
4.3.3聚電解質多層膜接觸角分析 67
4.3.4聚電解質多層膜表面與厚度分析 68
4.3.5聚電解質多層膜硬度與楊式係數分析 69
4.3.6聚電解質多層膜表面粗糙度分析 71
4.3.7聚電解質多層膜降解測試 73
4.4 聚電解質多層膜抗菌測試 75
4.4.1抑菌圈 75
4.5聚電解質多層膜體外測試 77
4.5.1 人工模擬體液測試 77
4.5.2細胞毒性測試 79
4.5.3鹼性磷酸酶含量測試 81
4.5.4鈣含量測試 82
4.5.5離子釋放 83
4.5.6螢光染色 85
4.6聚電解質多層膜體內測試(頭蓋骨植入) 90
第五章 結論 92
附錄 94
參考文獻 95

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