藻酸為天然的高分子水膠，具有優異的生物相容性與生物降解性，目前廣泛的應用於生物醫學領域上(例如:細胞生物支架、藥物傳遞、仿生器官)，目前利用光化學方法固化藻酸的概念較新穎，可以避免與材料直接接觸，並達到遠端操控預固化的範圍，與過去以擠出式的直接將藻酸材料擠入離子溶液裡做固化反應來比，光化學方法也可以製造較複雜的藻酸結構。但是利用光化學方法固化藻酸需要耗費大量的時間，而結構強度也比較弱。本論文的目的為開發一種全新的反應機制，由藻酸(Alginate)、光敏劑(Photosensitizer)、金屬螯合物、碘鎓鹽類組合而成，能夠快速的釋放出離子，以達到快速光固化藻酸反應。並也搭配PEGDA形成雙網絡結構提升材料的結構韌性。
本研究反應機制為透過丁二酮(BD)或LAP等光敏劑(Photosensitizer)吸收光能後光解使整體反應啟動，提供DPIN (diphenyliodonium nitrate)碘鎓鹽類獲得能量，使Ca-EDTA金屬螯合物快速降解游離出的二價離子與藻酸產生物理性固化交聯。比起以往光反應藻酸固化時間，速度提升了將近40倍。此外，本研究也提供了兩種列印型式的選擇，分別為2.5D的積層製造(layer-by-layer)每層固化的時間可控制在10秒左右，與3D積體式製造(volumetrically)固化時間可以控制在100秒左右。而搭配PEGDA形成的Alginate-PEGDA複合材料抗壓強度為純藻酸酸凝膠的三倍，已達成具有快速光固化製造的高強度機械性能與複雜結構水膠的目標。

Because of their outstanding biocompatibility and biodegradability, hydrogels based on natural polymers have been frequently utilized in a variety of biomedical applications. For example, 3D hydrogels with chemical and physical similarity to the extracellular matrices in tissues are critical for manipulation of living cells. However, the manufacturing of complex hydrogel structures is usually time-consuming, and the mechanical performances of resulting structures are normally poor. The goals of this thesis is to develop rapid additive manufacturing schemes that realize complex hydrogel structures with enhanced mechanical performances. More specifically, DLP (digital light processing) stereolithography is employed to photo-cure composite alginate and PEGDA (poly ethylene glycol diacrylate) hydrogels layer-by-layer or volumetrically.
A high-resolution light projector based on a 1920×1080 micromirror array, is used to dynamically generate the images for photo-gelation of hydrogels. The rapid manufacturing schemes for tough hydrogels are based on (1) formulation of photo-patternable hydrogels, (2) interpenetrating double network composites, (3) dynamically evolving light exposure, and (4) integration and synergy. First of all, photolysis of LAP (lithium phenyl-2,4,6-trimethylbenzoylphosphinate) or diacetyl photosensitizers in the presence of calcium EDTA (ethylenediaminetetraacetic acid) complexes results in releasing of free Ca2+, and therefore selective gelation of an alginate solution. It is also found that the inclusion of DPIN (diphenyliodonium nitrate) in the solution greatly accelerates the gelation process. Furthermore, the inclusion of PEGDA monomers and therefore the resulting interpenetrating network greatly amplifies the toughness of alginate-PEDGA composite. In the prototype demonstration, various 3D hydrogel structures are realized by both layer-by-layer and volumetric exposure processes. The curing time for each layer can be less than 10 seconds, while that for 360˚ volume can be less than 100 seconds. Meanwhile, the compressive strength of alginate-PEDGA composites can be three times higher than that of pure alginate hydrogels. As such, rapid additive manufacturing schemes that realize complex hydrogel structures with enhanced mechanical performances can potentially be accomplished.

摘要 i
致謝 iv
目錄 v
圖目錄 viii
表目錄 xi
第一章、 緒論 1
1.1 前言 1
1.2 水膠 (Hydrogel) 2
1.3 海藻酸(Alginate) 3
1.4 三維列印技術(3D printing) 4
1.4.1 光固化三維列印技術—2.5D manufacturing 5
1.4.2 光固化三維列印技術—3D manufacturing 6
1.5 光聚合反應(photo-polymerization) 7
1.5.1 自由基型聚合反應(Free radical polymerization) 7
1.5.2 陽離子型聚合反應(Cationic polymerization) 8
1.6 研究動機 9
第二章、 文獻回顧 10
2.1 酸對光化學之應用 10
2.1.1 光酸 (Photoacid Generator, PAG)產生 10
2.1.2 酸對碳酸鈣釋放機制 12
2.1.3 螯合物(Chelation) 14
2.1.4 酸對螯合物釋放機制 16
2.2 電子轉移降解機制 18
2.3 三種機制之比較分析 20
2.4 三維列印技術應用於藻酸凝膠化 22
2.4.1 雙網絡結構(Double Network, DN) 22
2.4.2 自由基光固化反應 23
2.4.3 新型的光固化列印(Computed Axial Lithography, CAL) 25
第三章、 工作原理與實驗設計 28
3.1 水膠凝膠原理 28
3.1.1 新型快速光固化藻酸反應過程 28
3.1.2 PEGDA反應過程 30
3.2 材料分析 33
3.2.1 Alginate Gels 33
3.2.2 PEGDA Gels 35
3.2.3 單體(monomer)之分析 35
3.2.4 提高三維列印解析度之分析 36
3.3 DLP三維列印 38
3.3.1 DLP機台介紹 38
3.3.2 DLP製造流程 40
3.4 CAL三維列印 41
3.4.1 CAL機台介紹 41
3.4.2 CAL製造流程 43
第四章、 實驗結果 45
4.1 水膠新型光反應透過DLP光固化技術成型 45
4.1.1 新型藻膠光化學反應之成型時間 45
4.1.2 光固化技術成型之解析度 47
4.2 新型光反應水膠之Z軸高度測試結果 48
4.2.1 透過DLP光固化測試 48
4.2.2 透過CAL光固化測試 50
4.3 水膠固化之應力量測 52
4.4 水膠之特殊性能 54
4.4.1 水膠溶脹情況 54
4.4.2 EDTA降解水膠 55
4.5 細胞相容性之結果 57
第五章、 分析與討論 60
5.1 DLP&CAL分析 60
5.2 光化學固化水膠 61
第六章、 結論與未來工作 63
6.1 結論 63
6.2 未來工作 64
參考資料 65

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