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論文中文名稱:以快速原型沉積法製作3D多孔纖維材質皮膚敷料 [以論文名稱查詢館藏系統]
論文英文名稱:Preparation of 3D Fibrous Wound Dressings With Rapid Prototyping Technique [以論文名稱查詢館藏系統]
院校名稱:臺北科技大學
學院名稱:工程學院
系所名稱:生物科技研究所
畢業學年度:98
出版年度:99
中文姓名:王馨薇
英文姓名:Hsin-Wei Wang
研究生學號:97688003
學位類別:碩士
語文別:中文
口試日期:2010-07-16
論文頁數:132
指導教授中文名:林忻怡
指導教授英文名:Hsin-Yi Lin
口試委員中文名:謝學真;黃聲東
口試委員英文名:Hsyue-Jen Hsieh;SHENG-TUNG HUANG
中文關鍵詞:快速原型褐藻酸鈉皮膚傷口敷料多孔性纖維材質支架
英文關鍵詞:rapid prototypingalginateskin wound dressingfibrous porous scaffolds
論文中文摘要:理想情況下,皮膚傷口敷料可排除傷口滲出物使傷口保持乾燥,提供濕潤的環境避免傷口脫水,讓氧氣流通,以幫助組織再生。傳統的水凝膠敷料,由於表面缺乏孔洞,氣體流通和清除滲出物能力欠佳。本研究以快速原型技術及濕紡技術,製造出褐藻酸鈉多孔性纖維材質皮膚敷料,並探討其物理化學性質與無孔洞薄膜作比較,評估是否適合作為皮膚傷口敷材。快速原型(RP)製作可控制纖維和孔洞大小的三維(3D)結構。我們也調查操作參數與敷材特性間的相關變化。這些參數包括出膠壓力、針頭孔徑、針頭移動速度、藻酸濃度和鈣離子濃度,以及針頭提高高度。褐藻酸水凝膠因其高生物相容性及生物降解性常被利用於組織工程和創傷敷料之應用。褐藻酸容易與鈣離子產生交聯(cross-link),形成膠體。
以快速原型技術,在不同參數下製造出多孔性纖維材質皮膚敷料的物理化學性質結果顯示出增加出膠壓力、加大針頭孔徑和針頭提高高度,以及減少藻酸濃度、鈣離子濃度和針頭移動速度,均能使樣品纖維變粗且孔隙變小,此改變能有效降低樣品釋放鹽酸四環素效率、膨潤率、降解率,且增加樣品拉伸強度。透濕性測試結果顯示以快速原型技術製造之敷材透濕值略高於正常皮膚並低於無蓋容器(open cup)的透濕值,可有效保持傷口濕潤排除受傷後傷口滲出之水分。抗菌試驗結果顯示敷材緩慢釋放能抑制大腸桿菌的生長。與快速原型同樣參數下製出的濕紡樣品,孔隙相對較大且結構較為鬆散,導致濕紡樣品膨潤率、藥物釋放速率比快速原型樣品快,此外,濕紡樣品的拉伸強度較低。多孔纖維狀敷材與藻酸薄膜比較結果,薄膜具有較高的釋放率、膨潤率,進而提升楊氏係數。薄膜透濕性測試結果顯示會隨著褐藻酸濃度提高而下降,透濕性不佳。本實驗結果顯示快速原型沉積系統相較於薄膜與濕紡系統有較緩慢的藥物釋放效果能抑制大腸桿菌的生長以及較高的機械性質。
論文英文摘要:Ideally, skin wound dressings should keep the wound dry by allowing the evaporation of wound exudates and provide adequate moisture while avoiding the dehydration of the wound. They should also allow oxygen exchange to aid tissue regenerations. Traditional hydrogel slabs have the disadvantage of poor air circulation and little exudate removal capability due to the lack of pores in their structure. In this study, rapid prototyping and wet spinning technology to produce sodium alginate porous fibrous wound dressings, and to explore the physical and chemical properties compared with the non-porous film to assess the suitability of a skin wound dressings. The parameters included the pneumatic pressure, needle aperture, needle speed, alginate and calcium concentrations, and the distance between the needle tip and the top layer. Alginate is a biodegradable biocompatible natural polymer that has been used in tissue engineering applications. Alginate forms hydrogel when calcium ions are added in its polymer network.
Results show that the increase in pneumatic pressure, needle aperture, needle  distance and reduction in alginate, calcium ion concentrations and needle speed were able to increase the fiber diameters and reduce the porosities of the samples. Larger fibers and lower porosities reduced the samples’ release efficacies of tetracycline HCl (TCH), swelling ratios, degradation rates, and increase their tensile strengths. The results from the water vapor transmission test showed that all samples had higher water vapor transmission rates (WVTR) than the normal skin and much lower WVTR than an open cup. They were expected to better keep the skin wound moisturized. The antibacterial test showed the samples slowly release TCH could inhibit localized E. coli. growth. When the wet spinning sample is made under the same parameter as the rapid prototype, its pores are contrarily lager and its structure is much looser. This makes its swelling rate and the speed of drug release rate faster than rapid prototyping. In addition, the tensile strength of the wet spinning sample is lower. The results from the porous fibrous wound dressings are also compared to those of alginate film. Film has a high release rate, swelling rate, and thus enhance the Young's modulus. Film water vapor permeability test results show that the increase in alginate concentrations, moisture permeability is not good. The experimental results show that the rapid prototyping tooling system has slower drug release effects to be able to inhibit the growth of E. coli and higher mechanical properties than the wet-spinning system.
論文目次:中文摘要………………………………………………………………i
英文摘要……………………………………………………………iii
誌謝……………………………………………………………………v
目錄………………………………………………………………… vi
表目錄……………………………………………………………… x
圖目錄……………………………………………………………… xi
第一章 緒論…………………………………………………………1
1.1 前言 …………………………………………………………… 1
1.2 文獻回顧…………………………………………………………2
1.2.1敷材在組織工程上之應用…………………………………… 2
1.2.2褐藻酸鈉……………………………………………………… 3
1.2.3快速原型沉積系統(Rapid Prototyping, RP)………………5
1.2.4 抗生素(四環黴素)之抗菌機制………………………………6
1.3 以RP製作水凝膠敷材在組織工程上之應用……………………8
第二章 實驗材料與方法……………………………………………9
2.1 實驗材料…………………………………………………………9
2.1.1 菌種來源.…………………………………………………… 9
2.1.2 實驗藥品………………………………………………………9
2.1.3儀器設備………………………………………………………11
2.2 實驗方法……………………………………………………… 12
2.2.1 快速原型沉積系統儀器架設……………………………… 12
2.2.1.1 製做長方形樣品之程式範本…………………………… 13
2.2.2 褐藻酸經氯化鈣交聯物薄膜、敷材的製備……………… 14
2.3 實驗設計與架構 ….....21
2.3.1褐藻酸經氯化鈣其交聯物薄膜、敷材分組表………………21
2.3.2褐藻酸經氯化鈣交聯物薄膜、敷材物理化學性質測試架構23
2.3.2.1掃描式電子顯微鏡(SEM)…………………………………24
2.3.2.2孔隙度測試 ( Porosity test )…………………………24
2.3.2.3 張力測試 ( Tensile Properties )……………………24
2.3.2.4 降解測試 (Degradation analysis) ………………… 24
2.3.2.5 膨潤率 ( Swell ratio)…………………………………25
2.3.2.6 藥物釋放率 (Drug release efficiency)…………… 25
2.3.2.7 抗生素藥物釋放率 (Antibiotic drug release efficiency) ……………………………………………………… 26
2.3.2.8 透濕性測試 (Water Vapor Transmission rate)…… 26
2.3.2.9 抑菌圈 (Inhibition zone) 抗菌測試 ……………… 27
2.3.3 統計分析…………………………………………………… 29
第三章 結果與討論 ……………………………………………… 30
3.1 薄膜與多孔性3D敷材外觀…………………………………… 30
3.1.1無孔洞交聯薄膜………………………………………………30
3.1.2濕紡 Wet spinning製出3D多孔敷材……………………… 33
3.1.3 快速原型沉積法(RP)製出3D多孔敷材…………………… 37
3.2 以 SEM 觀察薄膜與多孔性 3D 敷材…………………………41
3.2.1無孔洞交聯薄膜………………………………………………41
3.2.2濕紡 Wet spinning製出3D多孔敷材……………………… 43
3.2.3 快速原型沉積法(RP)製出3D多孔敷材…………………… 46
3.3 敷材孔隙度測試 ( Porosity test ) ………………………54
3.3.1 快速原型沉積法(RP)製出3D多孔敷材…………………… 54
3.4 張力測試 (Tensile Properties) ………………………… 55
3.4.1無孔洞交聯薄膜………………………………………………55
3.4.2 濕紡 Wet spinning製出3D多孔敷材………………………56
3.4.3 快速原型沉積法(RP)製出3D多孔敷材…………………… 58
3.4.4 交聯薄膜、濕紡與快速原型沉積法之敷材……………… 60
3.5降解測試(Degradation analysis) ………………………… 61
3.5.1無孔洞交聯薄膜………………………………………………61
3.5.2 濕紡 Wet spinning製出3D多孔敷材………………………63
3.5.3 快速原型沉積法(RP)製出3D多孔敷材…………………… 65
3.5.4交聯薄膜、濕紡與快速原型沉積法之敷材…………………67
3.6 膨潤率 ( Swell ratio) …………………………………… 68
3.6.1無孔洞交聯薄膜………………………………………………68
3.6.2 濕紡 Wet spinning製出3D多孔敷材………………………69
3.6.3 快速原型沉積法(RP)製出3D多孔敷材…………………… 72
3.6.4 交聯薄膜、濕紡與快速原型沉積法之敷材……………… 76
3.7 釋放率(Release efficeiency) …………………………… 77
3.7.1無孔洞交聯薄膜………………………………………………77
3.7.1.1 薄膜之血清蛋白藥物釋放率……………………………77
3.7.1.2 薄膜之鹽酸四環素藥物釋放率…………………………78
3.7.2 濕紡 Wet spinning製出3D多孔敷材………………………79
3.7.2.1 濕紡敷材之血清蛋白藥物釋放率………………………79
3.7.2.2 濕紡敷材之鹽酸四環素藥物釋放率……………………82
3.7.3 快速原型沉積法(RP)製出3D多孔敷材…………………… 85
3.7.3.1 RP敷材之血清蛋白藥物釋放率………………………… 85
3.7.3.2 RP敷材之鹽酸四環素藥物釋放率………………………90
3.7.4 交聯薄膜、濕紡與快速原型沉積法之敷材……………… 94
3.7.4.1 褐藻酸交聯薄膜與3D多孔性敷材對於血清蛋白的釋放果
……………………………………………………………………… 94
3.7.4.2 褐藻酸交聯薄膜與3D多孔性敷材對於鹽酸四環素的釋放效果…………………………………………………………………… 95
3.8 透濕性測試 (Water Vapor Transmission rate) …………96
3.8.1無孔洞交聯薄膜………………………………………………96
3.8.2濕紡 Wet spinning製出3D多孔敷材……………………… 97
3.8.3 快速原型沉積法(RP)製出3D多孔敷材…………………… 99
3.8.4 褐藻酸交聯薄膜與3D多孔性敷材對於透濕性效果………101
3.9 抑菌圈 (Inhibition zone) 抗菌測試 ……………………102
3.9.1 無孔洞交聯薄膜……………………………………………102
3.9.2 濕紡 Wet spinning製出3D多孔敷材…………………… 106
3.9.3 快速原型沉積法(RP)製出3D多孔敷材……………………112
3.9.4 褐藻酸交聯薄膜與3D多孔性敷材之抗菌效果……………120
第四章 結論………………………………………………………121
參考文獻……………………………………………………………123
附錄
1. 牛血清蛋白標準曲線………………………………………… 130
2. 鹽酸四環素標準曲線………………………………………… 131
3. 快速原型沉積法(RP)製出3D多孔敷材在水中之降解率…… 132


表目錄

表 2.1 配置Agar plate所需藥品……………………………… 9
表 2.2 配置食鹽緩衝溶液(PBS)所需藥品…………………… 10
表 2.3 配置樣品所需藥品………………………………………10
表 2.4 實驗所需藥品……………………………………………10
表 2.5 儀器設備…………………………………………………11
表 2.6 褐藻酸經氯化鈣其交聯物薄膜組別……………………21
表 2.7 褐藻酸經氯化鈣其交聯物濕紡敷材組別………………21
表 2.8 褐藻酸經氯化鈣其交聯物RP敷材組別…………………22
表 3.1 以濕紡在不同的參數設計下製出不同型態的敷材,其改變參數後之纖維大小………………………………………………… 43
表 3.2 RP在不同的參數設計下製出不同型態的3D多孔敷材,其改變參數後之纖維大小……………………………………………… 47
表 3.3 不同交聯條件下褐藻酸薄膜之膨潤率( In 90min) …68



圖目錄

圖 1.1 褐藻酸鈉之結構………………………………………… 3
圖 1.2 褐藻酸鈉與氯化鈣交聯形成egg-box模式………………4
圖 1.3 四環黴素(Tetracycline)之結構……………………… 7
圖 2.1 快速原型沉積系統裝置圖………………………………12
圖 2.2 交聯薄膜與敷材製備流程圖……………………………14
圖 2.3 張力測試所需狗骨頭形狀薄膜…………………………15
圖 2.4 濕紡注入24孔盤中………………………………………17
圖 2.5 快速原型沉積系統………………………………………19
圖 2.6 交聯薄膜與敷材測試架構………………………………23
圖 3.1 褐藻酸鈉經氯化鈣其交聯複合物薄膜外觀……………31
圖 3.2 褐藻酸鈉經氯化鈣在不同交聯條件下其交聯複合物薄膜外觀…………………………………………………………………… 32
圖 3.3 以濕紡製作3D多孔性敷材外觀…………………………34
圖 3.4 以濕紡製作3D多孔性敷材乾燥後樣品結構圖…………35
圖 3.5 以濕紡製作3D多孔性敷材乾燥後樣品結構圖…………36
圖 3.6 利用快速原型沉積系統製模技術 ( RP )所做出的3D多孔敷材外觀…………………………………………………………… 38
圖 3.7 利用快速原型沉積系統製模技術 ( RP ) 製作出3D多孔敷材乾燥後樣品結構圖……………………………………………… 39
圖 3.8 利用快速原型沉積系統 ( RP ) 製作出3D多孔敷材乾燥後樣品結構圖 ……………………………………………………… 40
圖 3.9 不同交聯條件下的褐藻酸交聯薄膜結構圖(700X) … 42
圖 3.10 濕紡在不同參數下的敷材結構SEM圖………………… 44
圖 3.11 RP在不同出膠壓力下的3D多孔敷材結構SEM圖……… 48
圖 3.12 RP在不同針頭孔徑下的3D多孔敷材結構SEM圖……… 49
圖 3.13 RP在不同Calcium濃度下的3D多孔敷材結構SEM圖……50
圖 3.14 RP在不同Alginate濃度下的3D多孔敷材結構SEM圖… 51
圖 3.15 RP在不同針頭提高層面高度下的3D多孔敷材結構SEM圖
……………………………………………………………………… 52
圖 3.16 RP在不同針頭移動速度下的3D多孔敷材結構SEM圖… 53
圖 3.17 快速原型沉積系統,在不同的參數設計下所製出3D多孔敷材之孔隙度變化…………………………………………………… 54
圖 3.18 交聯薄膜楊氏係數………………………………………55
圖 3.19 濕紡 Wet spinning 在不同參數條件下之張力測試圖(楊氏係數) …………………………………………………………… 57
圖 3.20 快速原型沉積法(RP)在不同參數條件下之張力測試圖(楊氏係數)………………………………………………………………59
圖3.21 褐藻酸交聯薄膜(Film)與3D多孔性敷材[以濕紡(Wet spinning)與快速原型系統(RP)參製成]之張力測試圖(楊氏係數)
……………………………………………………………………… 61
圖 3.22 交聯薄膜在不同參數下之降解率………………………62
圖 3.23 濕紡 (Wet spinning) 在不同參數下之敷材降解率…64
圖 3.24 快速原型沉積法(RP)在不同參數下之敷材降解率……66
圖 3.25 交聯薄膜、濕紡與快速原型沉積法之敷材在相同參數下
之敷材降解率……………………………………………………… 67
圖 3.26 交聯薄膜在不同交聯條件下之膨潤曲線………………68
圖 3.27 濕紡敷材在不同出膠空氣壓力下之膨潤曲線…………69
圖 3.28 濕紡敷材在不同針頭孔徑下之膨潤曲線………………70
圖 3.29 濕紡敷材在不同交聯鈣離子濃度下之膨潤曲線………70
圖 3.30 濕紡敷材在不同褐藻酸濃度下之膨潤曲線……………71
圖 3.31 RP在不同出膠壓力下之膨潤率圖………………………73
圖3.32 RP在不同針頭孔徑下之膨潤率圖……………………… 73
圖3.33 RP在不同Calcium 濃度下之膨潤率圖………………… 74
圖3.34 RP在不同Alginate濃度下之膨潤率圖………………… 74
圖3.35 RP在不同針頭提高層面高度下之膨潤率圖…………… 75
圖3.36 RP在不同針頭移動速度下之膨潤率圖………………… 75
圖 3.37 褐藻酸交聯薄膜(Film)與3D多孔性敷材[以濕紡(Wet spinning)、快速原型系統 (RP)]之膨潤率………………………76
圖3.38 交聯薄膜在不同交聯條件下之血清蛋白釋放曲線…… 77
圖3.39 交聯薄膜在不同交聯條件下之鹽酸四環素釋放曲線… 78
圖3.40 濕紡在不同出膠壓力下之血清蛋白藥物釋放圖……… 79
圖3.41 濕紡在不同針頭孔徑下之血清蛋白藥物釋放圖……… 80
圖3.42 濕紡在不同交聯鈣離子濃度下之血清蛋白藥物釋放圖 80
圖3.43 濕紡在不同藻酸濃度下之血清蛋白藥物釋放圖……… 81
圖 3.44 濕紡在不同出膠壓力下之鹽酸四環素藥物釋放圖……82
圖3.45 濕紡在不同針頭孔徑下之鹽酸四環素藥物釋放圖…… 83
圖3.46 濕紡在不同交聯鈣離子濃度下之鹽酸四環素藥物釋放圖
……………………………………………………………………… 83
圖3.47 濕紡在不同藻酸濃度下之鹽酸四環素藥物釋放圖…… 84
圖3.48 RP在不同出膠壓力下之血清蛋白藥物釋放圖………… 86
圖3.49 RP在不同針頭孔徑下之血清蛋白藥物釋放圖………… 86
圖 3.50 RP在不同Calcium 濃度下之血清蛋白藥物釋放圖……87
圖 3.51 RP在不同Alginate濃度下之血清蛋白藥物釋放圖……88
圖3.52 RP在不同針頭提高層面高度下之血清蛋白藥物釋放能力
……………………………………………………………………… 88
圖3.53 RP在不同針頭移動速度下(V-30mm/s 、50mm/s)之血清蛋白藥物釋放圖………………………………………………………… 89
圖3.54 RP在不同針頭移動速度下(V-50mm/s 、70mm/s) 之血清蛋白藥物釋放圖………………………………………………………… 89
圖 3.55 RP在不同出膠壓力下之鹽酸四環素藥物釋放圖………91
圖3.56 RP在不同針頭孔徑下之鹽酸四環素藥物釋放圖……… 91
圖3.57 RP在不同Calcium 濃度下之鹽酸四環素藥物釋放圖… 92
圖3.58 RP在不同Alginate濃度下之鹽酸四環素藥物釋放圖… 92
圖3.59 RP在不同針頭提高層面高度下之鹽酸四環素藥物釋放能力…………………………………………………………………… 93
圖3.60 RP在不同針頭移動速度下之鹽酸四環素藥物釋放圖… 93
圖 3.61 褐藻酸交聯薄膜(Film)與3D多孔性敷材[以濕紡(Wet spinning)、快速原型系統 (RP)]之血清蛋白藥物釋放率………94
圖 3.62 褐藻酸交聯薄膜(Film)與3D多孔性敷材[以濕紡(Wet spinning)、快速原型系統 (RP)]之鹽酸四環素釋放率…………95
圖 3.63 交聯薄膜在不同交聯條件下之透濕圖…………………96
圖 3.64 濕紡 Wet spinning 在不同參數條件下之透濕圖……98
圖 3.65 快速原型在不同參數條件下之透濕圖……………… 100
圖 3.66 褐藻酸交聯薄膜與3D多孔性敷材在相同參數條件下之透濕圖…………………………………………………………………… 101
圖 3.67 交聯薄膜在不同參數下抑菌圈(直徑)圖………………103
圖 3.68 交聯薄膜在不同交聯鈣離子濃度下的抑菌圈試驗圖…104
圖 3.69 交聯薄膜在不同藻酸濃度下的抑菌圈試驗圖…………105
圖 3.70 濕紡在不同參數下的3D多孔敷材抑菌圈(直徑)圖……107
圖 3.71 濕紡在不同出膠壓力下的3D多孔敷材抑菌圈試驗圖…108
圖 3.72 濕紡在不同針頭孔徑下的3D多孔敷材抑菌圈試驗圖…109
圖 3.73 濕紡在不同交聯Calcium濃度下的3D多孔敷材抑菌圈試驗圖…………………………………………………………………… 110
圖 3.74 濕紡在不同藻酸濃度下的3D多孔敷材抑菌圈試驗圖…111
圖 3.75 快速原型3D多孔敷材在不同參數條件下的抑菌圈(直徑)圖…………………………………………………………………… 113
圖 3.76 RP在不同出膠壓力下的3D多孔敷材抑菌圈試驗圖……114
圖 3.77 RP在不同針頭孔徑下的3D多孔敷材抑菌圈試驗圖……115
圖 3.78 RP在不同交聯鈣離子濃度下的3D多孔敷材抑菌圈試驗圖
……………………………………………………………………… 116
圖 3.79 RP在不同藻酸濃度下的3D多孔敷材抑菌圈試驗圖……117
圖 3.80 RP在不同針頭提高層面高度下的3D多孔敷材抑菌圈試驗圖…………………………………………………………………… 118
圖 3.81 RP在不同針頭移動速度下的3D多孔敷材抑菌圈試驗圖119
圖 3.82 交聯薄膜與3D多孔性敷材在相同參數條件下的抑菌圈(直徑)圖…………………………………………………………………120
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