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研究生: 陳照臨
Chen, Chao-Lin
論文名稱: 結合脂多醣誘導及原位力學刺激於自體內形成自體移植用血管之動物模式
Combination of inductive effect of lipopolysaccharide and in situ mechanical conditioning for forming an autologous vascular graft in vivo
指導教授: 郭浩然
Guo, How-Ran
胡晉嘉
Hu, Jin-Jia
學位類別: 博士
Doctor
系所名稱: 工學院 - 生物醫學工程學系
Department of BioMedical Engineering
論文出版年: 2019
畢業學年度: 108
語文別: 英文
論文頁數: 91
中文關鍵詞: 體內組織工程脂多醣力學刺激血管移植
外文關鍵詞: In vivo tissue engineering, lipopolysaccharides, mechanical stimulation, vascular graft
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  • 自體血管移植物具有較佳的生物相容性以及臨床預後。先前的研究們曾經將管狀塑膠聚合物植入動物體內,冀望此方法生成的外披管狀組織可作為血管移植物之用,但此方法卻受到外披生成之管狀組織生成率過低以及生成不穩定的影響。為了增強此方法生成外披管狀組織的穩定性,我們利用了一個結合脂多醣(lipopolysaccharide)及自體全血液支架的設計,且進一步於體內培養的過程使用了可週期性搏動矽膠管產生的動態力學刺激,以增強所生成管狀組織的力學性質。此設計的有效性藉由在大鼠的腹腔中置入相關管路組織來驗證,對照組為腹腔中植入同樣設計但無力學刺激之矽膠管。經過24天的體內培養,包括16天動態力學刺激培養後,我們取出植入矽膠管外包覆之管狀組織進行各種分析,並以動物自體主動脈血管插入移植應用。與無週期性體內力學刺激培養生成之管狀組織相比較,有此實驗設計的組別在腹腔內培養期結束時,具有較強的力學性質、較佳的平滑肌分化、較高的膠原蛋白與彈性纖維表現。此管狀組織作為大鼠主動脈移植應用經四個月後仍維持通暢,並有血管內皮與平滑肌細胞分化。這個模式為血管組織工程領域提供了一個新的展望。

    Autologous vascular grafts have the advantages of better biocompatibility and prognosis. However, previous studies that implanted bare polymer tubes in animals to grow autologous tubular tissues were limited by their poor yield rates and instability. To enhance the yield rate of the tubular tissue, we employed a design with the addition of overlaid autologous whole blood scaffold containing lipopolysaccharides (LPS). Furthermore, we applied in vivo dynamic mechanical stimuli through cyclically inflatable silicone tube to improve the mechanical properties of the harvested tissues. The effectiveness of the modification was examined by implanting the tubes in the peritoneal cavity of rats. A group without mechanical stimuli served as the controls. After 24 days of culture including 16 days of cyclic mechanical stimuli, we harvested the tubular tissue forming on the silicone tube for analysis or further autologous interposition vascular grafting. In comparison with those without cyclic dynamic stimuli, tubular tissues with this treatment during in vivo culture had stronger mechanical properties, better smooth muscle differentiation, and more collagen and elastin expression by the end the incubation period in the peritoneal cavity. The grafts remained patent after 4 months of implantation and showed the presence of endothelial and smooth muscle cells. This model shows a new prospect for vascular tissue engineering.

    INTRODUCTION 1 MATERIALS AND METHODS 4 Part I: Without LPS scaffold 4 Part II: With LPS scaffold 12 RESULTS 26 Part I: Without LPS scaffold 26 Part II: With LPS scaffold 31 DISCUSSION 37 Part I: Without LPS scaffold 37 Part II: With LPS scaffold 43 CONCLUSION 53 REFERENCES 54

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