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研究生: 歐陽偉森
Ao-Ieong, Wai-Sam
論文名稱: 光聚合可吸收高分子PGSA之開發與分析
Synthesis and Characterization of Photocrosslinkable Biodegradable Elastomer PGSA
指導教授: 王潔
Wang, Jane,
口試委員: 陳俊太
劉大佼
學位類別: 碩士
Master
系所名稱: 工學院 - 化學工程學系
Department of Chemical Engineering
論文出版年: 2015
畢業學年度: 103
語文別: 英文
論文頁數: 98
中文關鍵詞: PGSA光交聯後處理3D 列印
外文關鍵詞: PGSA, 3D printing, photocrosslinking, post treatment
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  • 在過去十年中,具有彈性特性的可生物降解的材料的發展已經成為很流行的
    研究題目之一。同時,對於為了各種各樣的應用而大規模生產新的彈性體聚合物
    的需求已經日益增加。具有非常良生的生物相容性和生物降解性的新型彈性體聚
    癸二酸甘油酯(PGS)已經被應用於組織再生之中,成功重新生成老鼠動脈。但是
    PGS 的製造需要高溫低壓的環境,限制了其在醫學上和組織工程上的應用。在這
    篇論文裡,我們以PGS 為基礎,匯報一種可光固化、也可生物分解的的聚合物
    聚癸二酸甘油酯丙烯酸(PGSA)。在這裡,FT-IR 和NMR 分析是用於確認酰化的
    成功,固態NMR 是用來確認純化步驟的效率,而後建立完整的合成步驟。另外,
    熱性質的測試是用DSC 來確認交聯密度的行為。通過改變丙烯酸酯化的程度,
    我們得到範圍廣泛的機械性質,其中得到楊氏模數由0.12 到3.17MPa、最終拉
    力強度由0.1 到1.2MPa 和最終拉伸量由121%到39%。此外,當丙烯酸酯化的程
    度從15%提升到60%時,30 天後在酵素中降解程度從28%減少到5%,同時在這
    30 天中,降解趨勢呈現線性上升。在接觸中測試中,所有配方的PGSA 都呈現
    輕親水性。最後,一系列的細胞培養測試用來確認純化的效用以及在材料上表
    現。
    在 PGSA 光固化後,引入了後處理用以進一步提高交聯程度、提高機械性質
    和降解速率。同時,在處理過後的PGSA 上,發現了更好的細胞貼附性質。另一
    方面,我們把PGSA 引入到使用雙光子聚合技術的3D 列影上。這種材料目前仍
    處於初期開發的階段,但它們具有朝向再生醫學上應用的巨大潛力。


    The development of biodegradable materials with elastomeric properties had become one of the most popular research topics in the past decade, and the need to produce new elastomeric polymers in large scale for a wide variety of applications had been ever increasing. Poly(glycerol sebacate) (PGS) is a novel elastomer, containing very good biocompatibility and biodegradability, has been applied to soft tissue regeneration to regenerate arteries. However, the fabrication of PGS requires high temperature and low pressure which limit its application in medicine and tissue engineering. Here, we report on the synthesis of PGS-based photocurable biodegradable polymer, poly(glycerol sebacate) acrylate (PGSA). FT-IR and NMR analyses were employed for the confirmation of successful acylation and ssNMR were employed for to establish a full synthesis protocol along with the purification protocol. The behavior of crosslinking density was examined by testing the thermal properties using DSC. A wide range of mechanical properties are obtained with respect to their Young’s modulus from 0.12 to 3.17 MPa, ultimate tensile strength between 0.1 and 1.2 MPa and strain to failure from 121% to 39% by changing the degree of acrylation. Linearly degradation properties are observed and are degraded 28-8.5% in 30 days when increasing the degree of acrylation from 15% to 60%. The slightly hydrophilic properties of various forms of PGSA were confirmed by contact angle test. A series of cell culture were conducted for the confirmation of purification protocol and cell preference on the different PGSA products. Post treatment of photocured PGSA was introduced to further crosslink PGSA to increase the mechanical properties while facilitating degradation. Meanwhile, a great improvement of cell adhesion was found. PGSA was applied in 3D printing by two photon polymerization technology. Though the development of this material is still in the early stage, it is believed that they possess great potential in the applications toward
    regenerative medicine.

    Abstract .....................................................................................................................................I 摘要.........................................................................................................................................III Table of Content ....................................................................................................................IV List of Figures ...................................................................................................................... VII List of Tables..........................................................................................................................IX 1.1 Introduction to Tissue Engineering ............................................................................. 1 1.2 Biomaterials ................................................................................................................... 6 1.2.1 Traditional Biomaterials........................................................................................ 9 1.2.2 Polymeric Biomaterials ........................................................................................ 13 1.2.2.1 Biocompatible Polymers........................................................16 1.2.2.2 Biodegradable Polymers........................................................18 1.3 Fabrication of Polymeric Materials ........................................................................... 20 1.3.1 Physical Crosslinking in Thermoplastic Polymers ............................................ 21 1.3.2 Chemical Crosslinking in Thermoset Polymers ................................................ 23 1.3.3 Photocrosslinking in Thermoset Polymers......................................................... 25 1.4 Motivation .................................................................................................................... 27 Chapter 2 Experimental Method ......................................................................................... 29 2.1 Synthesis of PGSA....................................................................................................... 31 2.1.1 Chemicals and Instruments ................................................................................. 31 2.1.2 Synthesis and Formation of PGSA...................................................................... 33 2.1.3 Purification and Determination .......................................................................... 34 2.2 Characterization of PGSA.......................................................................................... 35 2.2.1 Polymer Characterization.................................................................................... 35 2.2.2 Mechanical Test .................................................................................................... 36 2.2.3 Thermal Test......................................................................................................... 362.2.4 Degradation Test .................................................................................................. 37 2.2.5 Swelling Test ......................................................................................................... 37 2.2.6 Contact Angle Test ............................................................................................... 38 2.2.7 Biocompatibility Test ........................................................................................... 39 2.3 Post Treatment of PGSA after UV Curing ............................................................... 40 Chapter 3 Result and Discussion.......................................................................................... 41 3.1 Synthesis of PGSA....................................................................................................... 41 3.1.1 Synthesis and Formation of PGSA...................................................................... 41 3.1.2 Removal of Impurities and the Efficacy of the Purification Process ............... 46 3.1.3.1 Confirmation of Purification Efficacy via Chemical Analyses ..............................................................................................48 3.1.2.2 Confirmation of Purification via In vitro Cell Viability Test ..............................................................................................................52 3.1.3 Conclusion............................................................................................................. 54 3.2 Characterization of PGSA.......................................................................................... 55 3.2.1 Polymer Characterization.................................................................................... 55 3.2.2 Mechanical Properties.......................................................................................... 58 3.2.3 Thermal Properties .............................................................................................. 60 3.2.5 Swelling Index....................................................................................................... 64 3.2.6 Contact Angle........................................................................................................ 66 3.2.7 Biocompatibility.................................................................................................... 68 3.3 Post Treatment Process Development ....................................................................... 70 3.4 Characterization of Post-treated PGSA.................................................................... 71 3.4.1 Mechanical Properties.......................................................................................... 71 3.4.2 Thermal Properties .............................................................................................. 74 3.4.3 Degradation Properties ........................................................................................ 75 3.4.4 Swelling Index....................................................................................................... 78 3.4.5 Biocompatibility.................................................................................................... 80Chapter 4 PGSA Microstructure Fabrication via Two-Photon Polymerization........ 82 4.1 Introduction to Two-Photon Polymerization............................................................ 82 4.2 Experimental Design ................................................................................................... 86 4.3 Result and Discussion of Laser Curing...................................................................... 87 Chapter 5 Conclusion and Future Work........................................................................ 89 5.1 Conclusion.................................................................................................................... 89 5.2 Future Work ................................................................................................................ 91 Chapter 6 Reference......................................................................................................... 92

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