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系統識別號 U0026-0708201823572600
論文名稱(中文) 製備線性與星狀聚賴胺酸/肝素水膠攜帶生長因子應用於傷口癒合
論文名稱(英文) Synthesis of Linear and Star Poly(L-lysine)/Heparin Hydrogel Carrying Growth Factor for Wound Healing Applications
校院名稱 成功大學
系所名稱(中) 化學工程學系
系所名稱(英) Department of Chemical Engineering
學年度 106
學期 2
出版年 107
研究生(中文) 許芳鳴
研究生(英文) Fang-Ming Hsu
學號 N36054453
學位類別 碩士
語文別 中文
論文頁數 76頁
口試委員 指導教授-詹正雄
口試委員-林睿哲
口試委員-吳文中
口試委員-胡晉嘉
口試委員-林宏殷
中文關鍵字 聚賴氨酸  水膠  生長因子  傷口癒合 
英文關鍵字 poly(L-lysine)  hydrogels  growth factor  wound healing 
學科別分類
中文摘要 如何促進傷口癒合一直以來都是生醫領域的重要課題,特別是對於糖尿病患者,或是處於化學治療中的癌症患者等傷口不易復原的人而言,更顯得尤為重要。而生長因子是一種具有調控細胞的更新、分化、增殖的功能的有力蛋白質,因此在傷口癒合相關研究中備受關注。而肝素是一種已知對生長因子具有高度親和力的糖胺聚醣,本研究中透過開發陽離子聚胺酸水膠,與肝素複合,希望能達到充分攜帶生長因子的效果。在研究過程中透過天然、無生物毒性的京尼平把聚賴胺酸交聯,以形成具高度生物相容性的陽離子聚胺酸水膠。所製備出之水膠能與肝素形成穩定的複合結構,並能夠完全地攜帶生長因子。此外,這些水膠的澎潤特性與機械性質,可以藉由聚賴胺酸構形或聚合度的變化進而加以調節。在溶血性試驗以及細胞毒性實驗中都有良好的表現,在小鼠傷口癒合模型的試驗中,也達成促進傷口癒合的效果。
英文摘要 How to promote the healing of wounds is an important topic in the biomedicine field for a long period especially for diabetic patients or cancer patients undergoing chemotherapy with chronic wounds. Growth factors are a potent of powerful proteins that regulate cell functions including self renewal, differentiation and proliferation, and thus they received much attention in wound healing applications. Heparin is a glycosaminoglycan with high affinity to a large variety of growth factors, and in this study, the hydrogel system composed of polycationic polypeptides is synthesized to complex with heparin and then to efficiently load growth factors. The natural and non-toxic ginipin is used to crosslink part of the amide groups on the side chain of poly(L-lysine) to fabricate polycationic hydrogels. These hydrogels can stably incorporate with heparin and carry growth factors with high efficiency. Besides, the swelling and mechanical properties of the poly(L-lysine) / heparin composite hydrogels can be tuned by changing the chain architectures or the degree of polymerization of polypeptides. These hydrogels is non-hemolytic and biocompatible. Furthermore, the VEGF-loaded composite can really promote the healing of wounds in the mice wound healing test.
論文目次 摘要 I
EXTENDED ABSTRACT II
誌謝 XII
目錄 XIII
表目錄 XVII
圖目錄 XVIII
第一章 緒論 1
1.1前言 1
1.2研究動機 1
第二章 文獻回顧 3
2.1 胺基酸 3
2.1.1 胺基酸的基本性質蛋白質結構 3
2.1.2蛋白質結構 4
2.2 胺基酸的聚合 5
2.2.1 NCAs合成 6
2.2.2 以一級氨為起始劑進行NCAs開環聚合 7
2.2.3 以一級醇為起始劑進行NCAs開環聚合 7
2.2.4 以金屬錯合物為起始劑進行NCAs開環聚合 9
2.3 非線性高分子 10
2.3.1樹枝狀聚合物(Dendrimer) 10
2.3.2星狀聚合物(Star polymer) 11
2.4水膠 12
2.4.1 水膠發展過程 12
2.4.2 聚胺基酸水膠形成機制 14
2.5肝素與生長因子之攜帶 16
2.5.1 生長因子 16
2.5.2 肝素(Heparin) 17
第三章 實驗方法與步驟 20
3.1 實驗藥品 20
3.2 實驗儀器與原理 22
3.2.1核磁共振光譜儀(nuclear magnetic resonance spectrophotometer) 22
3.2.2凝膠滲透層析儀(Gel Permeation Chromatography) 23
3.2.3圓二色光譜儀(Circular Dichroism Spectrum) 24
3.2.4紅外線光譜儀(Fourier Transform Infrared Spectroscopy, FTIR) 25
3.2.5場發射掃描式電子顯微鏡(Field Emission Scanning Electron Microscrope) 26
3.2.6 萬能材料試驗機 (MTS testing machine) 27
3.3溶劑之乾燥 28
3.4 N-羧酸酐(N-carbnhydrides)的合成 28
3.4線性聚合物(Linear polymer)的合成 29
3.4.1 以一級胺進行NCAs開環聚合 29
3.4.2 以鎳金屬錯合物進行NCAs開環聚合 29
3.5 星狀聚合物(Star polymer)的合成 30
3.5.1 合成3armed星狀聚合物 30
3.5.2 合成6armed星狀聚合物 31
3.6 去除聚賴胺酸之保護基Z group 31
3.7 聚賴胺酸水膠之製備 31
3.7.1純聚賴胺酸水膠之製備 31
3.7.2聚賴胺酸/肝素複合水膠之製備 32
3.7.3含生長因子的聚賴胺酸/肝素複合水膠之製備 32
3.8水膠物化性質之分析 32
3.8.1圓二色光譜鑑定交膠聯前聚賴胺酸高分子之二級結構 32
3.8.2紅外線光譜分析水膠與肝素之複合情形 33
3.8.3寧海準反應(ninhydrin reaction)定量交聯後水膠殘餘的氨基 33
3.8.4複合水膠澎潤性測試 34
3.8.5複合水膠機械性質測試 34
3.9水膠生化相關特性分析 34
3.9.1水膠攜帶生長因子能力試驗 34
3.9.2水膠溶血實驗 35
3.9.3水膠細胞毒性實驗 35
3.9.4水膠抗菌實驗 36
3.9.5小鼠傷口癒合模型 36
第四章 結果與討論 37
4.1 聚賴胺酸之合成與探討 37
4.1.1 線性短鏈聚賴氨酸合成分析 37
4.1.2 線性長鏈聚賴氨酸合成分析 39
4.1.3 星狀三枝化聚賴胺酸合成分析 40
4.1.4 星狀六枝化聚賴胺基酸合成分析 42
4.1.5以GPC確認聚賴胺酸之分子量 44
4.2高分子之二級結構探討 44
4.3水膠之製備 45
4.4聚賴氨酸水膠紅外線光譜分析 47
4.5 水膠之型態與構造 49
4.6複合水膠物化特性分析 51
4.6.1複合水膠中的氨基殘餘量 52
4.6.2複合水膠之固含量 54
4.6.3複合水膠之機械強度 54
4.6.4複合水膠之澎潤性質 56
4.7 複合水膠之生物降解性質 57
4.8水膠生化性質相關測試 58
4.8.1複合水膠攜帶生長因子能力探討 58
4.8.2水膠之溶血性質探討 59
4.8.3水膠之細胞相容性探討 60
4.8.4水膠之抗菌性質探討 62
4.8.5傷口癒合實驗 63
第五章 結論 65
參考文獻 67
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