- 學位論文
製備明膠及膠原蛋白為基材之水膠以應用於控制藥物釋放
Fabrication of Gelatin- and Collagen-Based Hydrogels for Controlled Drug Release
摘要
明膠(gelatin)和膠原蛋白(collagen)擁有極佳的生物相容性、生物可降解性及生物活性。然而，當他們被用作生醫材料時，它們具有機械性質不佳及降解速度過快的問題，需要被克服。在本研究中，我們製備了以明膠及膠原蛋白為基材之水膠(hydrogel)以應用於控制藥物釋放。為了增強它們的物理性質，我們試著將一些小分子─羧基甜菜鹼甲基丙烯酸酯(carboxybetaine mathacrylate, CBMA)及聚乙二醇雙丙烯酸酯(poly(ethylene glycol) diacrylate, PEGDA)─分別加入明膠及膠原蛋白水膠中。 在第一部分研究中，我們合成了明膠甲基丙烯酸酯(gelatin methacrylate, GelMA)，並將其與羧基甜菜鹼甲基丙烯酸酯混合、形成水膠，以調控以明膠為基材之水膠的性質。當羧基甜菜鹼甲基丙烯酸酯加入時，所形成的水膠具有較佳的機械性質、較慢的降解速度及減緩的藥物釋放速率。此外，此水膠亦具有良好的細胞存活率。而在動物實驗中，裝載著血管內皮生長因子(vascular endothelial growth factor, VEGF)的水膠亦展現出良好的血管新生情形。 在第二部分研究中，我們合成了以順丁烯二酸酐(maleic anhydride)修飾之膠原蛋白分子(maleilated collagen, ColMA)，並將其與聚乙二醇雙丙烯酸酯混合、形成水膠。差式掃描熱量分析(DSC analysis)的結果顯示以順丁烯二酸酐修飾之膠原蛋白分子仍然保有三股螺旋(triple helix)結構。雖然此水膠的機械性質並無明顯改善，但是聚乙二醇雙丙烯酸酯的加入依然提升了水膠的交聯速度，並控制了高分子量的異硫氰酸螢光素葡聚醣(fluorescein isothiocyanate-dextran, FITC-dextran)之釋放速率。
並列摘要
Gelatin and collagen possess excellent biocompatibility, biodegradability and bioactivity. However, their poor mechanical properties and fast degradation rates need to be overcome while they are used for biomedical applications. In this study, we fabricated gelatin- and collagen-based hydrogels for controlled drug release. To improve their physical properties, we tried to incorporate small molecules, carboxybetaine methacrylate (CBMA) and poly(ethylene glycol) diacrylate (PEGDA), into gelatin and collagen hydrogels, respectively. In the first part of study, gelatin methacrylate (GelMA) was firstly synthesized and then formed hydrogels together with CBMA to modulate the properties of gelatin-based hydrogels. With the incorporation of CBMA, better mechanical property, slower degradation rate and retarded drug release rate were observed. GelMA/CBMA hydrogels also showed good cell viability. As to the in vivo test, vascular endothelial growth factor (VEGF)-loaded GelMA/CBMA hydrogels displayed a certain degree of angiogenesis. In the second part of study, maleilated collagen (ColMA) was synthesized and incorporated with PEGDA to form ColMA/PEGDA hydrogels. DSC analysis indicated that ColMA still retained the triple helical structure. Although there was no significant improvement in mechanical properties of ColMA/PEGDA hydrogels, however, the introduction of PEGDA resulted in an enhanced crosslinking rate and a controlled release of fluorescein isothiocyanate-dextran (FITC-dextran) with higher molecular weight.