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研究生: 黃芷翎
Huang, Chih-Ling
論文名稱: 以不同比例聚乳酸-聚甘醇酸共聚物製作多層孔隙之新型神經再生導管
Novel nerve regeneration conduits made by different ratios of poly (L-lactide-co-glycolide) forming with porous and multi-layered structure
指導教授: 廖峻德
Liao, Jiunn-Der
學位類別: 碩士
Master
系所名稱: 工學院 - 材料科學及工程學系
Department of Materials Science and Engineering
論文出版年: 2005
畢業學年度: 93
語文別: 中文
論文頁數: 66
中文關鍵詞: 聚乳酸聚乳酸-聚甘醇酸共聚物神經導管多層孔隙碳酸氫銨
外文關鍵詞: poly lactic acid, porous and multi-layered, poly lactide-co-glycolide, ammonium bicarbonate, nerve conduit
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  •   神經導管接合術是利用顯微手術將神經兩斷端縫入生醫材料所製備之神經導管以橋接神經斷裂的兩端,神經可藉由軸突的再生而重新連接缺口兩端的神經使功能恢復,導管可減少神經拉扯時造成的張力並引導軸突的再生,亦可承載神經生長因子促進神經再生,此外,也可以將阻礙神經再生的細胞及其分泌物阻擋在管外。本研究將以聚乳酸、聚乳酸-聚甘醇酸共聚合物(75:25)、聚乳酸-聚甘醇酸共聚合物(50:50)做為研究材料,以檸檬酸誘發碳酸氫銨發泡之氣泡成型法製作具有相連通孔隙之高分子薄膜,再將高分子薄膜捲製成特殊多層的導管,製作具有多層孔隙之新型神經再生導管,以電子能譜化學分析及減弱式全反射-傅立葉轉換紅外線光譜分析進行成份分析及化學元素測定;以電荷耦合元件攝影機、掃瞄式電子顯微鏡進行多層孔隙型神經導管巨觀及微觀形態結構觀察;以示差掃瞄熱量量測分析玻璃轉換溫度、奈米三維量測彈性模數及硬度;以及進行降解性質測定,並以掃瞄式電子顯微鏡進行降解後之導管微觀結構形態觀察。實驗結果顯示:聚乳酸、聚乳酸-聚甘醇酸共聚物(75:25)、聚乳酸-聚甘醇酸共聚物(50:50)三種材料經檸檬酸誘發碳酸氫銨發泡之氣泡成型法製程並不造成碳酸氫銨之殘留。聚乳酸-聚甘醇酸共聚物(50:50)的玻璃轉換溫度低於人體正常體溫,故降解28天後,導管的孔隙已融合成為緻密的表面,且於降解56天後完全降解;聚乳酸-聚甘醇酸共聚物(75:25)降解速率較慢,且降解56天後,孔隙略有融合的現象;而聚乳酸經檸檬酸誘發碳酸氫銨發泡再以捲製成型,可製造出具有較高的孔隙率及相連通的開孔結構之多層孔隙型神經導管,且降解56天後,仍可維持良好的孔隙率以維持導管的通透性質。

      Nerve bridging is suture a biomaterial-made conduit and to overpass the damaged nerve end to end with microsurgery. Peripheral nerve could be bridged between the proximal nerve and the distal stump to restore the function. Nerve conduits could eliminate tension at the healing site and induce the regeneration of axons. Nerve conduits also could permit neurobiological recovery to enhance neural regeneration and stop cells and their secretions from obstructing neural regeneration. In this study, we used poly L-latcide (PLLA), poly DL-latcide-co-glycolide 75:25 (PLGA7525) and poly DL-latcide-co-glycolide 50:50 (PLGA5050) during citric acid inducing ammonium bicarbonate gas forming process to form porous polymer film, and rolled the porous polymer film to make nerve conduits with pores and multi-layered. Electron Spectroscopy for Chemical Analyzer (ESCA) and Attenuated Total Reflectance – Fourier-Transform Infrared Spectrometer (ATR-FTIR) were employed for determining elements’ functionabilities and chemical compounds. Charge Coupled Device camera (CCD camera) and Scanning Electron Microscope (SEM) were employed for macroscopic and microscopic morphologies and structural observation. Differential Scanning Calorimetry (DSC) was employed for measuring glass-transition temperature (Tg). Nano-indentation system was employed for measuring elastic modulus and hardness. Biodegradation and water absorption ratios were measured to analyze their chemical properties and SEM was employed for microscopic morphology of the tested nerve conduit. Experiment results demonstrated that during citric acid inducing ammonium bicarbonate gas forming process, no salts (ammonium bicarbonate) remained, while Tg of PLGA5050 was lower than human body temperature. The porous structures of PLGA5050 conduit were dissolved into a condensed morphology after 28 testing days, while the material was completely degraded after 56 testing days. The degradation of PLGA7525 conduit was relatively slow, while the porous structures slightly changed their shapes after 56 testing days. Using citric acid inducing ammonium bicarbonate gas forming and unique rolling process, PLLA is relatively suitable to make multi-layered nerve conduits, which provide highly porous structures with many round openings. In addition, the porous structures with channeling characteristic can be preserved to 56 testing days.

    第一章 緒論........................01 1-1研究背景.......................01 1-2研究動機與目的....................02 1-3文獻回顧.......................02 1-3-1神經導管之材料研究................03 1-3-1-1天然取得之可降解材料.............03 1-3-1-2人工合成高分子之可降解材料..........04 1-3-2神經導管之成型技術研究..............05 1-3-2-1滴塗成型及低溫乾燥法.............05 1-3-2-2擠製成型及鹽析法...............06 1-3-2-3圓筒編織法..................07 1-3-2-4氣泡成型法..................07 1-3-3神經導管之材料性質分析研究............08 1-3-3-1電子能譜化學分析...............08 1-3-3-2傅立葉轉換紅外線光譜分析...........08 1-3-3-3示差掃瞄熱量量測...............09 1-3-3-4降解性質分析.................09 1-4研究主題.......................09 第二章 理論基礎......................11 2-1生物可降解材料....................11 2-1-1聚乳酸、聚乳酸-聚甘醇酸共聚物之合成.......11 2-1-2聚乳酸、聚乳酸-聚甘醇酸共聚物之物理、化學性質..12 2-2示差掃瞄熱量量測...................13 2-3電子能譜化學分析...................14 2-4傅立葉轉換紅外線光譜分析...............15 第三章 材料與方法.....................16 3-1實驗材料.......................16 3-2實驗儀器及器材設備..................16 3-2-1多層孔隙型導管製備................16 3-2-2成份分析及化學元素測定..............17 3-2-3多層孔隙型導管形態觀察..............17 3-2-4熱性質及機械性質測定...............17 3-2-5降解性質測定...................18 3-3實驗方法.......................18 3-3-1多層孔隙型導管製備................18 3-3-2成份分析及化學元素測定..............21 3-3-3多層孔隙型導管形態觀察..............22 3-3-4熱性質及機械性質測定...............22 3-3-5降解性質測定...................24 第四章 結果與討論.....................25 4-1成份分析及化學元素測定................25 4-1-1電子能譜化學分析.................25 4-1-2減弱式全反射-傅立葉轉換紅外線光譜分析......32 4-2多層孔隙型導管形態觀察................37 4-2-1巨觀結構形態觀察.................37 4-2-2顯微結構形態及孔隙分布觀察............43 4-3熱性質及機械性質測定.................48 4-3-1示差掃瞄熱量量測.................48 4-3-2奈米三維量測...................49 4-4降解性質測定.....................53 4-4-1導管降解率及含水率量測..............53 4-4-2降解後之導管顯微結構形態觀察...........56 第五章 結論........................65 未來展望..........................66 參考文獻

    1.
    V. Maquet, D. Martin, B. Malgrange, “Peripheral nerve regeneration using bioresorbable macroporous polylactide scaffolds.”, Biomedical Materials Research, 52, 639–651, 2000.
    2.
    I. V. Yannas, “Synthesis of Tissues and Organs.”, Chemical Biological Chemistry, 5 , 26-39, 2004.
    3.
    M. F. Meek, J. H. Coert, “Clinical Use of Nerve Conduits in Peripheral – Nerve Repair : Review of the Literature.”, Reconstructive Microsurgery, 18, 97-109, 2002.
    4.
    C. A. Heath, G. E. Rutkowski, “The development of bioartificial nerve grafts for peripheral-nerve regeneration.”, Trends in Biotechnology, 16, 163-8, 1998.
    5.
    D. Ceballos, X. Navarro, N. Dubey, “Magnetically Aligned Collagen Gel Filling a Collagen Nerve Guide Improves Peripheral Nerve Regeneration.”, Experimental Neurology, 158, 290–300, 1999.
    6.
    S. Yoshii, M. Oka, “Collagen filaments as a scaffold for nerve regeneration.”, Biomedical Materials Research, 56, 400-405 , 2001.
    7.
    S. Yoshii, M. Oka, M. Shima, A. Taniguchi, M. Akagi, “Bridging a 30-mm nerve defect using collagen filaments.”, Biomedical Materials Research, 67, 467– 474, 2003.
    8.
    M. Suzuki, S. Itoh, I. Yamaguchi, “Tendon Chitosan Tubes Covalently Coupled With Synthesized Laminin Peptides Facilitate Nerve Regeneration In Vivo.”, Neuroscience Research, 72, 646–659, 2003.
    9.
    M. Hakkarainen, A. C. Albertsson, S. Karlsson, “Weight losses and molecular weight changes correlated with the evolution of hydroxyacids in simulated in vivo degradation of homo- and copolymers of PLA and PGA.”, Polymer Degradation and Stability, 52, 283-291, 1996.
    10.
    M. S. Widmer, P. K. Gupta, Lichun Lu, “Manufacture of porous biodegradable polymer conduits by an extrusion process for guided tissue regeneration.”, Biomaterials, 19, 1945-1955, 1998.
    11.
    N. N. Aldini, G. Perego, G.D. Cella, “Effectiveness of a bioabsorbable conduit in the repair of peripheral nerves.”, Biomaterials, 17, 959-962, 1996.
    12.
    G. R. D. Evans, K. Brandt, M.S. Widmer, “In vivo evaluation of poly(L-lactic acid) porous conduits for peripheral nerve regeneration.”, Biomaterials, 20, 1109-1115, 1999.
    13.
    K. Matsumoto, K. Ohnishi, T. Kiyotani, “Peripheral nerve regeneration across an 80-mm gap bridged by a polyglycolic acid (PGA) – collagen tube filled with laminin-coated collagen fibers: a histological and electrophysiological evaluation of regenerated nerves.”, Brain Research, 868, 315-328, 2000.
    14.
    J. J. Yoon, T. G. Park, “Degradation behaviors of biodegradable macroporous scaffolds prepared by gas foaming of effervescent salts.”, Biomedical Materials Research, 55, 401-408, 2001.
    15.
    Y. J. Choi, I. Noh, “Media tissue regeneration of the hybrid expanded polytetra.uoroethylene vascular graft via gelatin coating.”, Current Applied Physics, 5, 463–467, 2005.
    16.
    K. M. Shakesheff, C. Evora, I. Soriano, R. Langer, “The Adsorption of Poly(vinyl alcohol) to Biodegradable Microparticles Studied by X-Ray Photoelectron Spectroscopy (XPS).”, Colloid and Interface Science, 185, 538–547, 1997.
    17.
    E. Kiss, I. Bertoti, E.I. Vargha-Butler, “XPS and Wettability Characterization of Modified Poly(lactic acid) and Poly(lactic/glycolic acid) Films.”, Colloid and Interface Science, 245, 91–98, 2002.
    18.
    L. Mu, S. S. Feng, “Vitamin E TPGS used as emulsifier in the solvent evaporation/extraction technique for fabrication of polymeric nanospheres for controlled release of paclitaxel.”, Controlled Release, 80, 129-144, 2002.
    19.
    K. Fu, K. Griebenow, L. Hsieh, A. M. Klibanov, R. Langer, “FTIR characterization of the secondary structure of proteins encapsulated within PLGA microspheres.”, Controlled Release, 58, 357-366, 1999.
    20.
    T. Yotoriyama, Y. Sushiaki, T. Mise,m T. Tsukamoto, “Surface characterization of thin film induced by He+ ion-besm irradiation into PLLA.”, Surface & Coatings Technology, 196, 383-388, 2004.
    21.
    J. S. C. Loo, C. P. Ooi, F. Y. C. Boey, “Degradation of poly(lactide-co-glycolide)(PLGA) and poly(L-lactide)(PLLA) by electron beam radiation.”, Biomaterials, 26, 1359-1367, 2005.
    22.
    M. Ramchandani, M. pankaskie, D. Robinson, “The influence of manufacturing procedure on the degradation of poly(lactide-co-glycolide)85:15 and 50:50 implants.”, Controlled Release, 43, 161-173, 1997.
    23.
    D. Bendix, “Chemical synthesis of polylactide and its copolymers for medical applications.”, Polymer Degradation and Subility, 59, 129-135, 1998.
    24.
    D. M. Schachter, J. Kohn, “A synthetic polymer matrix for the delayed or pulsatile release of water-soluble peptides.”, Controlled Release, 78, 143-153, 2002.
    25.
    G. Lombardl, “For better thermal analysis.”, 2nd, ICTA, 1980.
    26.
    D. Briggs, M. P. Seah, “Practical surface analysis by Auger and X-ray Photoelectron Spectroscopy.”, John Wiley & Sons, New York, 1994.
    27.
    P. R. Griffiths, J.A. Haseth, “Fourier transform infrared spectrometry.”, John Wiley, New York, 1986.
    28.
    A. E. Fournier, S. M. Strittmatter, “Regenerating nerves follow the road more traveled.”, Nature neuroscience, 5, 9, 2002.
    29.
    B. Palsson, S. N. Bhatia, “Tissue Engineering.”, Pearson Prentice Hall, USA, 2004.
    30.
    B. D. Ratner, A. S. Hoffman, F. J. Schoen, “Biomaterials Science – An Introduction to Material in Medicine.”, Academic Press, USA, 1996.
    31.
    F. J. Rodriguez, N. Gomez, G. Perego, “Highly permeable polylactide-caprolactone nerve guides enhance peripheral nerve regeneration through long gaps.”, Biomaterials, 20, 1489-1500, 1999.
    32.
    G. R. D. Evans, “Challenges to nerve regeneration.”, Seminars in Surgical Oncology, 19, 312-318, 2000.
    33.
    L. G. Griffith, G. Naughton, “Tissue Engineering – Current Challenges and Expanding Opportunities.”, Science, 295, 2002.
    34.
    R. Nazarov, H. J. Jin, D. L. Kaplan, “Porous 3-D Scaffolds from Regenerated Silk Fibroin.”, Biomacromolecules, 5, 718-726, 2004.
    35.
    S. C. J. Loo, C. P. Ooi, Y. C. F. Boey, “Radiation of poly(lactide-co-glycolide)(PLGA) and poly(L-lactide)(PLLA).”, Polymer Degradation and Stability, 83, 259-265, 2004.
    36.
    T. Kiyotani, M. Teramachi, Y. Takimoto, “Nerve regeneration across a 25 mm gap bridged by a polyglycolic acid collagen tube, a histological and electrophysiological evaluation of regenerated nerves.”, Brain Research, 140, 66, 1996.
    37.
    T. Sato, G. Chen, T. Ushida, ”Evaluation of PLLA–collagen hybrid sponge as a scaffold for cartilage tissue engineering.”, Materials Science and Engineering, 24, 365–372, 2004.
    38.
    王光林, “周圍神經組織工程材料的預構”, 中國修復重建外科雜志, 第14卷, 第2期, 2000。
    39.
    沈欣欣, 謝侑霖, 陳瑞祥, “神經修復導管發展的歷史”, 生技與醫療器材報導雜誌, 28, 2001。
    40.
    吳侑峻, “骨的組織工程研究-利用聚乳酸-聚乙醇酸共聚物當作支架”,國立成功大學生物科技研究所碩士論文, 2003。
    41.
    徐善慧, 陳俊宇, “巧奪天工的人類智慧-組織工程”, 科學發展, 356期, 2002。
    42.
    陳悅生, “想換條新的神經嗎?- 神經再生”, 科學發展, 356期, 2002。
    43.
    張根源, “生物吸收性高分子合成及表面生物活性改質技術”, 化工科技與商情, 第36期, 2000。
    44.
    曾清秀, 呂綜, 李永全, “幫細胞蓋一個家 組織工程用支架”, 科學發展, 356期, 2002。
    45.
    楊炯琳, “周邊神經再生研究的發展與展望”, 化工資訊與商情, 第2期, 2003。

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