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研究生: 武蔡金詩
Thai-Kim-Thi Vu
論文名稱: Poloxamer與幾丁聚醣之原位凝膠化及其應用於骨組織工程之評估
A poloxamer / chitosan in situ forming gel for bone tissue engineering
指導教授: 楊銘乾
Ming-Chien Yang
口試委員: 李振綱
Cheng-Kang Lee
蔡宏斌
Hong-Bing Tsai
學位類別: 碩士
Master
系所名稱: 工程學院 - 材料科學與工程系
Department of Materials Science and Engineering
論文出版年: 2012
畢業學年度: 100
語文別: 英文
論文頁數: 89
中文關鍵詞: F127幾丁聚醣黏彈性質原位凝膠化骨組織工程溫度敏感性凝膠黏膜黏著性
外文關鍵詞: F127, In situ forming gel, Thermosensitive gel, Mucoadhesion, Cell proliferation, Protein Adsorption, Complete Blood Count Test
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本研究旨在開發用於骨組織工程之原位凝膠支架,以恢復骨組織之功能。為達此目標,此一凝膠係由F127及幾丁聚醣構成。所得之溫度可逆性凝膠以流變儀測定其凝膠溫度(Tgel)、黏彈性質、黏膜黏著力,以便最佳化凝膠之組成。在特定比例下,該凝膠具有接近體溫之Tgel。添加幾丁聚醣不影響F127的自組裝特性,僅會提升其Tgel。此外,幾丁聚醣會強化凝膠的力學性質,可能係由於幾丁聚醣與F127微胞間有氫鍵作用而強化其結構。DSC結果顯示幾丁聚醣影響了水分子與F127之作用力。TGA的結果亦支持水分子與凝膠之相互作用。黏膜黏著實驗顯示F127/幾丁聚醣與黏液素(mucin)有流變學相乘效應,使其流動行為由牛頓流體轉變成為擬塑性。藥物釋放實驗顯示F127/幾丁聚醣凝膠可延緩羥乙氧甲鳥嘌呤(acyclovir)之釋放達20分鐘以上。此外,以細胞增生性、細胞貼附性、全血測試法證實F127/幾丁聚醣凝膠具有生物相容性。


This work is to develop an in situ gelation scaffold for bone tissue engineering to restore and maintain the function of human bone tissues. To meet this goal, the gel is comprised of F127 (a poloxamer) and chitosan. The gelation temperature (Tgel), viscoelastic properties and mucoadhesive force of the systems were investigated and optimized by means of rheological analyses. At specific concentrations, the resulting thermoreversible gel exhibited a Tgel close to the body temperature. The addition of chitosan did not hamper the self assembling process of F127, only elevating the gelation temperature. Furthermore, chitosan can improve the rheological properties of the gel, possibly due to the interaction between chitosan and F127 micelles through hydrogen bond, which reinforced the gel structure. The DSC results showed the interactions between water and F127 gels, indicating the influence of chitosan on the physicochemical features of gels. TGA results also indicated the interactions between the gels and water. Mucoadhesion experiments showed a rheological synergism between F127/chitosan gels and mucin dispersion, changing the flow behavior from a Newtonian fluid to a pseudoplastic fluid. In vitro release experiments indicated that the optimized gel was able to prolong and control acyclovir release for more than 20 min. Biocompatibility of the gel of F127 and chitosan was observed based on cell proliferation, protein adsorption and complete blood count test.

ABSTRACT I 中文摘要 II Acknowledgements III Table of Contents IV Table list VII Figure Captions VIII Chapter 1 Introduction 1 1.1 Bone Tissue Engineering 1 1.1.1. Motivation behind Bone Tissue Engineering 1 1.1.2. General Principles in Bone Tissue Engineering 3 1.2 Poloxamers 11 1.2.1. Uses of poloxamers 12 1.2.2. Biological Effect Of Poloxamers 12 1.3 Chitosan 14 1.3.1. Usage 15 1.3.2. Medical research 17 1.4 In situ forming hydrogel 18 1.5 Thermosensitive Hydrogels 18 1.5.1. Poly(N-isopropylacrylamide) 19 1.5.2. Hydroxypropyl cellulose 20 1.5.3. F127 21 1.6 Objectives of Thesis 22 Chapter 2 Materials and Methods 24 2.1. Chemicals 24 2.2. Methods 24 2.2.1. Preparation of gels 24 2.2.2. Rheological characterization 25 2.2.3. Thermal Analysis (DSC) 26 2.2.4. Thermogravimetric Analysis (TGA) 27 2.2.5. Mucoadhesion analysis 28 2.2.6. In vitro release study 28 2.2.7. Protein adsorption 29 2.2.8. Complete Blood Count 30 2.2.9. Cell proliferation 31 2.2.10. Statistical analysis 32 Chapter 3 Results and Discussion 33 3.1. Rheological characterization 33 3.2. Thermal Analysis (DSC) 42 3.3. Thermogravimetric Analysis (TGA) 46 3.4. Mucoadhesion analysis 48 3.5. In vitro release study 50 3.6. Protein adsorption 53 3.7. The complete blood count (CBC) assay 56 3.8. Cell Proliferation 61 Chapter 4 Conclusion 63 References 64

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