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姓名 吳思穎(Szu-ying Wu)  查詢紙本館藏   畢業系所 機械工程學系
論文名稱 體外培養內皮細胞形成毛細血管結構前期之穩定性分析及模擬
(Simulation and stability analysis for the early stage in vitro endothelial vasculogensis.)
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摘要(中) 人體內的各個器官以及組織都佈滿著許多的毛細血管,其為血液與周圍組織進行物質交換的場所,主要由一層內皮細胞所組成。人體必須透過毛細血管才有辦法對器官及組織供給氧氣以及營養物質,同時代謝對人體有害的產物,以維持器官及組織的功能。因此,為防止人造組織及器官壞死,必須培養出分佈完整的毛細血管網路。
本文透過建立包含細胞密度、基質密度以及基質位移量的數學模型,模擬培養內皮細胞在纖維基質上形成毛細血管結構前期之分佈形態變化,描述細胞的遷徙特性以及基質受到細胞遷徙之牽引力而產生的位移。藉由線性穩定性分析的方式,本文討論系統參數的改變能夠促進或抑制細胞產生不均勻分佈的形態,據此將參數歸納為不穩定參數以及穩定參數,以作為執行非線性數值模擬前的初步分析。非線性計算結果顯示由於細胞與基質力交互作用的關係使細胞與基質分佈產生網狀結構,細胞分佈呈現數量較低的空隙,隨著時間的變化其空隙部分將擴大並與相鄰空隙進行合併。透過改變細胞種植的密度以及定義網狀結構指標,模擬結果顯示必須在適當的細胞數量下,細胞才能帶動基質產生網狀結構,符合文獻的實驗結果。
摘要(英) Various organs and tissues of the human body are covered with capillaries, mainly composed of a layer of endothelial cells. The capillaries are where blood and surrounding tissues exchange materials. The human body relies on the capillaries to provide the organs and tissues with oxygen and nutrients; at the same time capillaries help remove the metabolic waste to maintain the tissue function. In order to prevent necrosis of tissues and organs, the whole network of the capillaries is essential to engineered tissues.
By developing a mathematical model that includes cell density, gel density, and gel displacement, this study simulates the early stage behavior of vasculogenesis generated by the endothelial cells cultured on the fibrin gel. The model describes the cell migration characteristics and the gel displacement by the traction of the cells. A linear analysis is performed to check whether the system parameters will enhance or inhibit the cells to form a non-uniform distribution. By classifying the parameter as being stabiling and destabilizing, nonlinear stimulations are also carried out.
Results from simulation show that due to the cell-gel interaction, the lacunae will appear over the cell population. As time goes by, the lacunae will expand and combine with other lacunaes in the surrounding. By testing the cell number density and defining the structure of network index, simulations show the gel’s network structure forms only for a adequate amount of cells.
關鍵字(中) ★ 穩定性分析
★ 細胞牽引力
★ 纖維基質
★ 毛細血管
★ 內皮細胞
關鍵字(英) ★ capillary
★ endothelial cell
★ fibrin gel
★ cell traction
★ stability analysis
論文目次 中文摘要 I
Abstract II
誌謝 III
目錄 IV
表目錄 VII
圖目錄 VIII
符號說明 XI
第一章 緒論 1
1.1. 前言 1
1.2. 文獻回顧 2
1.3. 研究動機 5
第二章 數學模型 7
2.1. 物理系統 7
2.2. 統御方程式 7
2.2.1 細胞密度方程式 7
2.2.2 基質密度方程式 10
2.2.3 基質應力方程式 10
2.3. 初始與邊界條件 13
2.3.1 初始條件 13
2.3.2 邊界條件 13
2.4. 無因次化 15
第三章 線性穩定性分析 20
3.1. 線性擾動方程式 20
3.2. 正規模態展開 21
3.3. 線性系統之參數分析 25
3.3.1 細胞趨觸性與細胞擴散性之比值h 25
3.3.2 無因次化之細胞極限牽引力因子N2 26
3.3.3 基質底部剪應力修正係數A 27
3.3.4 基質蒲松比 27
3.3.5 無因次化之基質遠距彈性應力因子 、 28
3.3.6 基質黏滯性與基質彈性之比值 、 29
3.3.7 無因次化之初始基質厚度κ 30
第四章 非線性分析 43
4.1. 數值方法 43
4.1.1 COMSOL Multiphysics簡介 43
4.1.2 方程式之設置 43
4.1.3 網格設置 47
4.1.4 誤差與精確度 48
4.2. 實驗比較 49
4.2.1 細胞網狀結構的形成 49
4.2.2 細胞數量的影響 50
4.3. 非線性穩定性分析 52
第五章 細胞網狀形態分佈特性 62
5.1. 細胞初始種植方式之影響 62
5.2. 細胞網狀分佈之力學機制 64
5.3. 參數分析 66
第六章 結論與未來展望 94
參考文獻 96
附錄A. 基質底部黏附力 101
附錄B. 基質厚度表示式 104
附錄C. 拉普拉斯運算子之物理意義 106
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指導教授 鍾志昂(Chih-Ang Chung) 審核日期 2012-7-30
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