小腸絨毛之仿生三維微結構製作

Biomimetic 3D micro-structure process of small intestinal villi

黃裕勝(Yu-Sheng Huang)

指導教授 ： 傅建中

國立清華大學/工學院/奈米工程與微系統研究所/碩士(2010年)

摘要

人體的器官或組織大部分都缺乏再生能力，當器官或組織功能受到損傷時，希望能藉由移植手術去修復人體的組織進而使功能恢復，但移植手術需面臨器官捐贈來源不足和免疫系統排斥的問題，因而近年來正逐漸發展組織工程。在現今消化道疾病中，短腸症(short bowel syndrome, SBS)的病患因小腸被切除，使得養份吸收受到影響，而危害人們的生命。腸的組織工程則是希望藉由從體外去生長新的小腸組織，再移植進入人體體內解決有短腸症疾病的病患。在組織工程中，若能提供一個外型、尺寸與待修補組織一樣的支架，則能利用此支架培養新的組織進而修補缺陷。因此，本論文的研究重點著重於製作仿小腸絨毛結構的支架（scaffold），並提供一個適合小腸細胞生長的環境，增加結構的表面積，改善原先支架吸收表面積不足的問題。
為了製作仿小腸絨毛結構的支架，本論文採用由實驗室所發展出的背面曝光技術(backside exposure)。在微影製程中，光的繞射與吸收效應對微結構的形狀占有重大的影響，因此本文將以Matlab軟體模擬光學繞射，並對光的繞射、吸收效應與光阻鍵結強度做探討。
本論文利用SU-8光阻、翻模技術與PLA材料製作出微結構，再將PLA結構浸入稀釋的丙酮溶液之中，去改變結構頂端的幾何形狀，使結構更趨近小腸絨毛的形狀。經由實驗得到一組最佳之參數，製作出仿生小腸絨毛微結構支架，並於結構支架上培養小腸細胞形成組織，使組織成功貼附於3D結構上生長，利用掃瞄式電子顯微鏡(Scanning Electron Microscope)與共軛焦顯微鏡(Confocal microscope)拍攝細胞生長的結果。

關鍵字

小腸組織工程 ； 絨毛結構支架

並列摘要

Almost all organs or tissues are not able to regenerate by themselves again; hence, the only way we can repair our tissues or organs is to utilize transplant techniques. However, today we face some serious problem derived from transplantation, such as, the insufficient source from organ donation and immune system rejection. Recent years, there is a great development of tissue engineering. In today's digestive tract disease, because of removing their small intestine, patients who endowed with short bowel syndrome are suffered from absorption of nutrients, thus threatening people's lives. By adding new small intestine in vitro as well as transplanting it into the human body, intestinal tissue engineering attempts to save patients who suffered by short bowel syndrome. In tissue engineering, if we can provide a scaffold that is with the same shape as well as size of tissues, we can take advantage of this scaffold to regenerate new tissues and thereby repair human small intestine. Taken together, this study not only aims to produce a biomimetic structure scaffold of intestinal villi, but also to provide a better atmosphere for the growth of intestinal cells as well. Aforementioned technique can increase surface area of the structure as well as improve the original problem of scaffold.
In order to produce biomimetic scaffold structure of intestinal villi, our laboratory developed backside exposure technology. In the photolithography process, optical diffraction and material absorption effect exerts a significant influence on the microstructure shape. Hence, this thesis attempts to explore the diffraction, absorption and photoresist threshold of dose on the basis of Matlab simulation of optical diffraction.
This thesis utilize SU-8 photoresist, molding technology and PLA materials to produce micro-structure, sequentially immersing the the PLA structure into acetone diluted among the top and thereby shifting the geometry of the structure that enables the structure more close to the shape of the small intestine villi. Through our experiment, we acquire a set of best parameters to produce the biomimetic scaffold structure of intestinal villi and cultured in the scaffold structure of intestinal cells into tissues. As a consequence, we successfully attached on the 3D structure to the tissues, by observing the growth of cell growth on the basis of SEM and Confocal.

並列關鍵字

small intestinal tissue engineered ； villi scaffold

參考文獻

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