博碩士論文 93323059 詳細資訊




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姓名 陳志維(Chih-Wei Chen)  查詢紙本館藏   畢業系所 機械工程學系
論文名稱 模擬注流式生物反應器之流場及細胞生長
(Modeling of Media Flow And Engineered Cartilage Growth in a Perfusion Bioreactor)
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摘要(中) 注流式生物反應器系統的發展是為了改善體外培養時質量傳輸到三維組織工程支架的問題。除了促進養分和代謝產物的交換外,此系統同時提供了種植在支架內的細胞流體剪應力的作用。本文建立注流式系統的數學模型來說明並預測軟骨細胞在多孔性聚合物支架的增生和移動,以及養分消耗和新陳代謝產物生成的行為。包含了改良的Contois細胞生長模型,其中養分的飽和、代謝產物抑制描述了細胞在支架上的增生。並利用靜態培養時支架四周養分充足的極端例子,來瞭解養分和代謝產物的質量傳輸對系統的影響。結果顯示靜態培養模擬和實驗比較可以證實養分和代謝產物僅依靠擴散作用來傳輸的話,細胞必然會集中增生於支架外圍處。而在有注流影響下所得到的細胞平均總量會比靜態培養來的多,在空間的分布也較為均勻,且隨著對流速度的增加而更明顯,但最後會趨向一漸進值。在流量0.0024 cm^3/s的條件下,支架處的平均流體剪應力約為0.06 mPa (6e-4 dyne/cm^2),和文獻的結果相比是類似的。細胞具有的隨機漫步行為會影響細胞在培養時的數量上的多寡,且隨著隨機漫步速度增加則細胞分布的更加均勻,而其他物理參數的定性分析,以及細胞初始不均勻種植和改變管徑大小對於注流系統的影響也會在文中加以討論。
摘要(英) Perfusion bioreactor systems have been developed to improve mass transport throughout three-dimensional tissue-engineered scaffolds cultured in vitro. In addition to enhancing the exchange of nutrients depletion and product accumulation, these systems simultaneously deliver flow-mediated shear stresses to cells seeded within the constructs. In this work, a computational model explaining, as well as predicting, cell proliferation and random walk within the porous scaffold, nutrients consumption and product accumulation, is developed. It incorporates a modified Contois cell-growth model that includes the effects of nutrient saturation, competitive product inhibition to describe the scaffold–cell system. To assess the extent to which mass transfer can be influenced theoretically, extreme cases were distinguished in which the culture medium was assumed fully sufficient in static culture. A comparison between predictions and experimental evidence found in the literature shows that cell-scaffold constructs that rely solely on diffusion for supply of nutrients will inevitably produce proliferation-dominated regions near the outer edge of the scaffold. When the cells are cultured in a scaffold subjected to a perfused velocity field, they penetrate to a greater extent into the scaffold core and give uniform spatial distribution. The amount of cells in the perfusion culture is more than in static culture, and increases with the velocity of perfusion, and it will tend to a constant as the perfusion is intensified. Relating the simulation results to perfusion experiments, an average surface shear stress of 0.06 mPa (6e-4 dyne/cm^2) was found at a flow rate of 0.0024 cm^3/s, and which is similar with other studies. We find the properties of random walks will influence the growth of cells, and it may let cell distribute uniformly when the random walk velocity increases. A parametric analysis is performed and the result is compared qualitatively with previous findings in the literature. Additional cases, where cell nonuniform-seeding and the change of tube diameter can be influential for a perfusion bioreactor system, are also studied.
關鍵字(中) ★ 生物反應器
★ 軟骨細胞
★ 支架
關鍵字(英) ★ modeling
★ chondrocytes
★ perfusion
★ scaffold
★ fluid shear stress
論文目次 中文摘要 Ⅰ
英文摘要 Ⅱ
目錄 Ⅳ
表目錄 Ⅵ
圖目錄 Ⅶ
符號說明 Ⅹ
第一章 緒論 1
1.1 前言 1
1.2 研究背景 1
1.3 研究動機 3
第二章 數學模型 5
2.1 基本假設與多孔介質概念 5
2.2 描述注流式流場之連續方程式及動量方程式 7
2.3 描述養分和代謝產物之濃度守恆方程式 9
2.4 描述細胞之質量守恆方程式 13
2.5 方程式簡化 16
2.6 無因次方程式與無因次參數定義 17
2.7 無因次化邊界條件 20
2.7.1 無注流情況 20
2.7.2 有注流影響 21
第三章 數值方法 25
3.1 COMSOL簡介 25
3.2 通式 25
3.3 弱解式 26
3.4 網格設計 27
3.4.1 無注流情況 27
3.4.2 有注流影響 27
3.5 誤差與精確度 28
第四章 模擬結果與分析 29
4.1 靜態培養的比較 29
4.2 單層和三層模型的差異 30
4.3 注流的影響 31
4.4 系統參數對注流培養的影響 34
4.4.1 Φ,c0的影響 34
4.4.2 K’pr的影響 35
4.4.3 C的影響 35
4.4.4 Λ的影響 35
4.5 細胞不均勻種植對培養的影響 36
4.5.1 靜態培養 36
4.5.2 注流式培養 36
4.6 改變管徑對培養的影響 37
第五章 結論與未來展望 38
參考文獻 41
附錄 48
附表 53
附圖 58
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指導教授 鍾志昂(Chih-Ang Chung) 審核日期 2006-7-12
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