組織工程要能夠運用到再生醫學上最主要關鍵就是三維的血管網絡生成，由於產生這些血管網絡才能充分確保組織含有足夠的氧氣、養份和清除廢物的能力，為了血管網絡的形成，開發在臨床上使用的生物材料必須 確保能夠及時快速的與宿主血管互相聯結，才能使血液流通，避免組織內的細胞失去生存能力。
　　膠原蛋白水凝膠成功的誘導使內皮前驅細胞(Endothelial colony forming cells,ECFCs)轉換成血管的形態，不幸的是膠原蛋白水凝膠會很快速的收縮退化，而且它的機械性能非常差，未來用於修復的不同組織時被受限制，因此，利用化學改質的方法來改善膠原蛋白的這些特性，是我們這篇研究最主要的目的。
　　為了改善膠原蛋白的這些缺點，我們利用酪胺(tyramine)結合小鼠膠原蛋白改質，成功開發出利用辣根過氧化物酶(horseradish peroxidase/HRP)和過氧化氫(hydrogen peroxide/H2O2)這兩種化學酶進行膠聯反應的小鼠膠原蛋白水凝膠，利用這種水凝膠做為植入式生物材料，我們探討了材料本身的特性以及利用內皮前驅細胞(Endothelial colony forming cells,ECFCs)和間葉系幹細胞(mesenchymal stem cells，MSCs)進行了體內和體外的血管網絡新生研究。
　　在我們的結果中發現，我們調整小鼠膠原蛋白水凝膠的成膠時間從70秒至550秒，小鼠膠原蛋白水凝膠的確具有可調控式的成膠時間，此外，我們的研究中也成功的利用改變辣根過氧化物酶(horseradish peroxidase/HRP)和過氧化氫(hydrogen peroxide/H2O2)或調整蛋白質濃度使得小鼠膠原蛋白水凝膠的機械強度可以從22 Pa達到2005 Pa，證實了小鼠膠原蛋白水凝膠在調控成膠時間、機械強度上都有不錯的表現。
　　另外一方面，我們從細胞實驗的結果發現小鼠膠原蛋白水凝膠提供良好的生長環境，不論是在2D還是3D培養下，細胞都有不錯的存活率，還能夠有效的使細胞增殖。從上面這些結果我們認定小鼠膠原蛋白水凝膠是可調控成膠時間、可調控機械性質、並且提供良好細胞生長環境的一種生物相容性材料。

The success of tissue engineering as a feasible approach in regenerative medicine relies largely on the ability to generate 3D vascular networks that guarantee adequate oxygenation, nutrient delivery and removal of waste products. These vascular networks would need to be developed within clinically suitable biomaterials and in a timely manner to ensure rapid reconnection with the host vasculature and to avoid loss of cellular viability. Collagen hydrogels first appeared promising for endothelial colony-forming cells (ECFC)-mediated vascular morphogenesis. Unfortunately, their extensive contraction, rapid degradation and poor mechanical properties constituted major disadvantages toward their utilization as appropriate substrates for growth and cell delivery on wound location. The present study has investigated the enzyme-mediated method to solve these drawbacks by incorporating phenol moiety into collagen hydrogels with tunable stiffness in controlled conditions. We report a collagen hydrogel, synthesized by conjugating tyramine to mice autologous collagen. We evaluated gelation profiles during the peroxidase-catalyzed enzyme reaction, the mechanical properties and proteolytic degradability of the hydrogels. We also studied the growth of endothelial colony forming cells (ECFCs)and mesenchymal stem cells(MSCs) on the hydrogels. In our reaserch, we developed a collagen hydrogel can regulate gelatione time and mechanical properties, the gelation time can be regulated from 70 s to 550 s. And the storage modulus can be regulated from 22 Pa to 2005 Pa. The effect of enzymatic cross-linking of type I collagen gels as the embedding scaffold of umbilical cord blood-derived ECFCs and human white adipose tissue derived mesenchymal stem cells (MSCs) on generating extensive capillary-like networks in vitro and in vivo was investigated. In the result, we improved this collagen hydrogel providing a biocompatible environment for cells in 2D culture or 3D culture.

中文摘要 2
英文摘要 3
第一章 前言 4
1.血管新生與再生對於組織工程的重要性 4
2.膠原蛋白之介紹 6
3.開發膠原蛋白水凝膠動機 9
第二章 實驗步驟 11
第三章 實驗結果 20
1.小鼠膠原蛋白萃取與特性分析 20
2.水凝膠合成與分析 25
3.體外細胞模式評估小鼠膠原蛋白水凝膠的生物相容性 42
4.小鼠膠原蛋白水凝膠在動物體內骨修復之評估 66
第四章 討論 75
第五章 參考文獻 83

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