2016-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/653620摘要：傳統3D列印無法完全列印出有實際功能之組織，其最大挑戰為製備出複雜的血管網絡。本計畫擬使用具綠色環保的新穎水性生物可降解聚胺酯作為列印墨水主材料，應用於3D列印仿生組織支架，結合微流體及微機電技術所發展之擬生理微系統，以培養出具微血管結構之仿生組織。本研究擬定三年，第一年為合成不同種類之生物可降解性水性列印材料以及智慧型高分子，透過分子動力模擬建立單體與高分子物化性質資料庫，並將材料應用於控制微組織腔室內的生理環境，同時探討癌細胞在不同材料成分下形成微球的機制。第二年發展創新的多尺度計算方法來模擬高分子墨水材料之特性，進行人工微血管支架雛形列印，引入仿生組織與癌細胞微球的培養技術與擬生理環境的控制技術，設計可控制一毫米級腔室內生理環境的3D組織培養平台。第三年，將生物墨水結合細胞以及生物活性分子，分析列印出支架對於細胞生長、分化與胞外基質分泌之情形，將實驗以及模擬結合建立材料配方與支架材料參數資料庫，嘗試結合擬生理系統以及使用兩種智慧型材料列印並培養出仿正常組織或癌症組織，開發出溫感性含細胞墨水配方。最後建立出3D列印正常微組織與癌症微組織之結構材料配置與結構設計參數模型，未來應用於再生醫學與作為癌症藥物的篩選平台。<br> Abstract: Generating artificial tissues with nature functions has been challenging for the traditional 3D printing technology, especially in the recapitulation of complicated blood vessels network. In this project, a novel material of biodegradable polyurethane (PU) combined with the technologies of microfluidics and microelectromechanics will be employed to print the biomimetic tissue scaffolds containing network of micro vessels through integrated modeling- experimental approaches. This project will be executed for three years. In the first year, various types of biodegradable PU and intelligent polymers will be synthesized, and the database of physicochemical properties between the monomer and polymer will be established by molecular dynamics simulation. In addition, these materials will be applied to control the physiological condition in tissue microenvironment, and the mechanism of tumor spheroid formation on distinct culture materials will be elucidated as well. In the second year, we intend to develop a novel multiscale method to simulate the properties of polymer bio-inks, and to print the prototype of vascularized scaffolds. Furthermore, depending on the culture techniques of biomimetic tissues and tumor spheroids in a simulated physiological condition, we may create a 3D culture platform in which the condition of tiny (1 mm) culture space can be regulated. In the third year, to analyze the effects of materials on cell proliferation and differentiation as well as ECM formation, the bio-ink will be co-printed with cells and some active biomolecules. We will establish the parameter database of material formulae through the combination of experimental and simulated data, and print the normal and tumorigenic tissues using intelligent bio-inks combined with the simulated physiological system. Taken together, this project aim to develop a 3D bio-printing platform that can be used to fabricate complicated microtissues that mimic the physiological and pathological human tissues to be applied in the regenerative medicine and cancer drug screening.