簡易檢索 / 詳目顯示

回結果列表
研究生： 郭于甄
Yu-Chen Kuo
論文名稱： 以冷凍乾燥法製備生醫玻璃/幾丁聚醣複合支架與性質鑑定
Characterization and preparation of freeze dried-bioactive glass/chitosan composite scaffolds
指導教授： 施劭儒
Shao-Ju Shih
口試委員: 施劭儒
王丞浩
周育任
鄭詠馨
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： 2020
畢業學年度： 108
語文別： 中文
論文頁數： 104
中文關鍵詞： 生醫玻璃 、骨組織工程 、噴霧乾燥法 、冷凍乾燥法
外文關鍵詞： bioactive glass, bone tissue engineering, spray drying, freeze drying
相關次數： 點閱：298  下載：11 
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報

    • 目前全球皆面臨高齡化社會的問題，當人的年齡超過三十歲，骨質密度就會開始下降，因罹患骨質疏鬆症而造成的骨折相當常見，為修復骨缺損，需使用骨填充材，但現今自體移植材料短缺，異體移植材料易造成疾病感染及排斥，因此人工合成的骨組織支架被列為考慮。
    幾丁聚醣具有優異的生物相容性、生物降解性、抗菌性以及促進傷口癒合的能力，其降解產物為無毒、非致癌性，同時又可幫助細胞貼附、增殖與分化；而生醫玻璃無毒，且擁有良好的生物相容性，亦具有生物降解性及生物活性，常被用來當作骨填充材，治療骨缺陷，因此本研究選取這兩者材料來製備骨組織複合支架。
    首先，利用噴霧乾燥法製備生醫玻璃與摻雜不同鍶濃度(2.5、5.0、7.5及10.0 mol%)之生醫玻璃，並透過掃描式電子顯微鏡、X光繞射儀、傅立葉轉換紅外線光譜儀分析其晶相結構、粉體顆粒形貌、元素組成以及鍶對體外生物活性的影響。接著，使用冷凍乾燥法製造生醫玻璃/幾丁聚醣之複合支架，並利用掃描式電子顯微鏡、萬能試驗機、微量盤分光光度計及X光繞射儀、分析其巨觀形貌、微觀結構、孔隙率、機械性質、膨潤度、降解行為、細胞存活率與體外生物活性。

    At present, the world is facing the problem of an aging society. When people are over 30 years old, bone density will start to decrease. Bone fractures caused by osteoporosis are quite common. To repair bone defects, bone filling materials are needed. For now, there is a shortage of autograft materials, and allograft materials are likely to cause disease infection and rejection. Therefore, synthetic tissue scaffolds are considered.
    Chitosan has good biocompatibility, biodegradability, antibacterial properties and the ability to accelerating wound healing. Its degradation products are non-toxic and non-carcinogenic. Also, it can enhance cell adhesion, proliferation and differentiation. Bioactive glass (BG) is non-toxic, has good biocompatibility, biodegradability and bioactivity. It is often used as a bone filling material to treat bone defects, so in this study, these two materials were chosen to fabricate bone tissue composite scaffolds.
    The first step, spray drying method was used to prepare 0.0, 2.5, 5.0, 7.5 and 10.0 mol% strontium-doped BG. Then using scanning electron microscope (SEM), X-ray diffractometer (XRD) and Fourier-transform infrared spectrometer (FTIR) to analyze the phase composition, morphology and in vitro bioactivity of BG and Sr-BG, respectively. Next step, freeze drying method was used to fabricate the Sr-BG/chitosan composite scaffolds, and the macroscopic morphology, elemental composition, microstructure, porosity, mechanical properties, swelling ratio, degradation behavior, cell viability and in vitro bioactivity were characterized by SEM, universal testing machine, microplate spectrophotometer and , XRD.

    目錄 摘要 I Abstract II 致謝 III 目錄 IV 圖目錄 VIII 表目錄 XII 第一章 緒論 1 1.1研究背景 1 1.2研究動機 2 第二章 文獻回顧 4 2.1組織工程 4 2.1.1骨組織工程支架需具備的條件 5 2.1.2常用於骨組織工程的生醫材料 5 2.2組織工程支架製備方法 8 2.2.1溶劑澆鑄/粒子過濾(Solvent casting/particulate leaching) 8 2.2.2靜電紡絲(Electrospinning) 9 2.2.3冷凍乾燥(Freeze drying) 10 2.3幾丁聚醣 13 2.4生醫玻璃 16 2.5鍶的基本特性 25 2.5.1鍶對骨細胞的影響 25 2.5.2鍶的抗菌能力 28 第三章 實驗方法 29 3.1實驗設計 29 3.2實驗藥品 31 3.3實驗儀器 33 3.4樣品製備 34 3.4.1生醫玻璃粉體製備 34 3.4.2生醫玻璃/幾丁聚醣複合支架製備 35 3.5樣品性質及分析方法 37 3.5.1 X光繞射儀 37 3.5.2場發射掃描式電子顯微鏡 38 3.5.3傅立葉轉換紅外線光譜儀 39 3.5.4體外生物活性試驗 41 3.5.5支架孔隙率測試 42 3.5.6壓縮試驗 42 3.5.7膨潤度測試(Swelling test) 43 3.5.8降解行為 44 3.5.9體外生物相容性試驗 45 第四章 實驗結果 47 4.1生醫玻璃性質分析 47 4.1.1晶相分析 47 4.1.2形貌觀察、元素及粒徑分析 48 4.2生醫玻璃之體外生物活性測試 52 4.2.1晶相分析 52 4.2.2官能基分析及生物活性比值 54 4.3生醫玻璃/幾丁聚醣複合支架性質分析 58 4.3.1巨觀形貌 58 4.3.2微結構觀察 59 4.3.3孔隙率(Porosity) 61 4.3.4抗壓強度 62 4.3.5膨潤度(Swelling ratio) 64 4.3.6降解行為 65 4.3.7生物相容性-細胞存活率分析 (MTT assay) 67 4.4生醫玻璃/幾丁聚醣複合支架之體外生物活性測試 68 4.4.1晶相分析 68 4.4.2形貌觀察 69 第五章 結果討論 71 5.1摻雜不同濃度鍶於生醫玻璃對體外生物活性之影響 71 5.2 Sr-BG/Chitosan複合支架中影響成型之因素 72 5.3 Sr-BG/Chitosan複合支架之孔隙率對於其他性質的影響 75 5.3.1支架孔隙率與機械強度的關係 75 5.3.2支架孔隙率與膨潤度的關係 76 5.3.3支架孔隙率與降解行為的關係 77 第六章 結論 78 第七章 未來工作 79 參考文獻 80

    參考文獻
    [1] K.J. Burg, S. Porter, J.F. Kellam, Biomaterial developments for bone tissue engineering, Biomaterials, 21 (2000) 2347-2359.
    [2] https://www.vitamk7.com/bone_health.php.
    [3] T.T. Madanagopal, S.V. Agarwalla, V. Rosa, Carbon nanocomposites for implant dentistry and bone tissue engineering, Applications of Nanocomposite Materials in Dentistry, (2019) 47-63.
    [4] R.L.J.P. Vacanti, Tissue Engineering, (1993) 920-926.
    [5] R. Tiruvannamalai-Annamalai, D.R. Armant, H.W. Matthew, A glycosaminoglycan based, modular tissue scaffold system for rapid assembly of perfusable, high cell density, engineered tissues, PLoS One, 9 (2014) e84287.
    [6] W.W. Thein-Han, R.D. Misra, Biomimetic chitosan-nanohydroxyapatite composite scaffolds for bone tissue engineering, Acta Biomater, 5 (2009) 1182-1197.
    [7] D. Vukajlovic, J. Parker, O. Bretcanu, K. Novakovic, Chitosan based polymer/bioglass composites for tissue engineering applications, Mater Sci Eng C Mater Biol Appl, 96 (2019) 955-967.
    [8] A. Kramschuster, L.-S. Turng, 17—Fabrication of tissue engineering scaf-folds, Handbook of Biopolymers and Biodegradable Plastics: Properties, Processing and Applications, 427 (2012).
    [9] 鄧珍波, 周長春, 樊渝江, 彭京平, 朱向東, 裴玄, 殷國富, 張興棟, 多孔鈦骨組織工程支架設計及孔結構表徵, 稀有金屬材料與工程, 45 (2016) 2287-2292.
    [10] K.C. Dee, D.A. Puleo, R. Bizios, An introduction to tissue-biomaterial interactions, (2003).
    [11] S. Yadav, S. Gangwar, An Overview on Recent progresses and future perspective of biomaterials, IOP Conference Series: Materials Science and Engineering, IOP Publishing, 404 (2018) 12-13.
    [12] V. Tarzia, T. Bottio, L. Testolin, G. Gerosa, Extended (31 years) durability of a Starr-Edwards prosthesis in mitral position, Interactive cardiovascular and thoracic surgery, 6 (2007) 570-571.
    [13] R. Huiskes, H. Weinans, B. Van Rietbergen, The relationship between stress shielding and bone resorption around total hip stems and the effects of flexible materials, Clinical orthopaedics and related research, (1992) 124-134.
    [14] J. Woodman, J. Jacobs, J. Galante, R. Urban, Metal ion release from titanium‐based prosthetic segmental replacements of long bones in baboons: A long‐term study, Journal of Orthopaedic Research, 1 (1983) 421-430.
    [15] P. Ducheyne, K.E. Healy, The effect of plasma‐sprayed calcium phosphate ceramic coatings on the metal ion release from porous titanium and cobalt‐chromium alloys, Journal of biomedical materials research, 22 (1988) 1137-1163.
    [16] T.W. Bauer, An overview of the histology of skeletal substitute materials, Archives of pathology & laboratory medicine, 131 (2007) 217-224.
    [17] L.S. Nair, C.T. Laurencin, Biodegradable polymers as biomaterials, Progress in polymer science, 32 (2007) 762-798.
    [18] S. Prasadh, R.C.W. Wong, Unraveling the mechanical strength of biomaterials used as a bone scaffold in oral and maxillofacial defects, Oral Science International, 15 (2018) 48-55.
    [19] A. Sáenz, E. Rivera, W. Brostow, V.M. Castaño, Ceramic biomaterials: an introductory overview, Journal of Materials Education, 21 (1999) 267-276.
    [20] F. Matassi, L. Nistri, D.C. Paez, M. Innocenti, New biomaterials for bone regeneration, Clinical cases in mineral and bone metabolism, 8 (2011) 21.
    [21] W. Bonfield, M. Wang, K. Tanner, Interfaces in analogue biomaterials, Acta Materialia, 46 (1998) 2509-2518.
    [22] L. Comuzzi, E. Ooms, J.A. Jansen, Injectable calcium phosphate cement as a filler for bone defects around oral implants: an experimental study in goats, Clinical Oral Implants Research, 13 (2002) 304-311.
    [23] K. Rezwan, Q. Chen, J.J. Blaker, A.R. Boccaccini, Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering, Biomaterials, 27 (2006) 3413-3431.
    [24] H. Niiranen, T. Pyhältö, P. Rokkanen, M. Kellomäki, P. Törmälä, In vitro and in vivo behavior of self‐reinforced bioabsorbable polymer and self‐reinforced bioabsorbable polymer/bioactive glass composites, Journal of Biomedical Materials Research Part A: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials, 69 (2004) 699-708.
    [25] S. Weiner, H.D. Wagner, The material bone: structure-mechanical function relations, Annual review of materials science, 28 (1998) 271-298.
    [26] H. Davis, J. Leach, Hybrid and composite biomaterials in tissue engineering, Topics in multifunctional biomaterials and devices, 10 (2008) 1-26.
    [27] S. Yunoki, T. Ikoma, A. Monkawa, E. Marukawa, S. Sotome, K. Shinomiya, J. Tanaka, Three-dimensional porous hydroxyapatite/collagen composite with rubber-like elasticity, Journal of Biomaterials Science, Polymer Edition, 18 (2007) 393-409.
    [28] N. Thadavirul, P. Pavasant, P. Supaphol, Development of polycaprolactone porous scaffolds by combining solvent casting, particulate leaching, and polymer leaching techniques for bone tissue engineering, Journal of Biomedical Materials Research Part A, 102 (2014) 3379-3392.
    [29] N. Zhu, X. Chen, Biofabrication of tissue scaffolds, Advances in biomaterials science and biomedical applications, (2013) 315-328.
    [30] H. Janik, M. Marzec, A review: Fabrication of porous polyurethane scaffolds, Materials Science and Engineering: C, 48 (2015) 586-591.
    [31] S. Chahal, A. Kumar, F.S.J. Hussian, Development of biomimetic electrospun polymeric biomaterials for bone tissue engineering. A review, Journal of Biomaterials Science, Polymer Edition, (2019) 1-51.
    [32] Q.P. Pham, U. Sharma, A.G. Mikos, Electrospinning of polymeric nanofibers for tissue engineering applications: a review, Tissue engineering, 12 (2006) 1197-1211.
    [33] D. Liang, B.S. Hsiao, B. Chu, Functional electrospun nanofibrous scaffolds for biomedical applications, Advanced drug delivery reviews, 59 (2007) 1392-1412.
    [34] Z.M. Huang, Y.Z. Zhang, M. Kotaki, S. Ramakrishna, A review on polymer nanofibers by electrospinning and their applications in nanocomposites, Composites science and technology, 63 (2003) 2223-2253.
    [35] W.J. Li, C.T. Laurencin, E.J. Caterson, R.S. Tuan, F.K. Ko, Electrospun nanofibrous structure: a novel scaffold for tissue engineering, Journal of Biomedical Materials Research: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials, 60 (2002) 613-621.
    [36] N. Bhardwaj, S.C. Kundu, Electrospinning: a fascinating fiber fabrication technique, Biotechnology advances, 28 (2010) 325-347.
    [37] A. Liapis, R. Bruttini, A theory for the primary and secondary drying stages of the freeze-drying of pharmaceutical crystalline and amorphous solutes: comparison between experimental data and theory, Separations Technology, 4 (1994) 144-155.
    [38] P. Courtney, B. Forbes, P.G. Royall, A. Alqurshi, J. Strang, Freeze-dried formulations: a new perspective on reformulating naloxone, European Pharmaceutical Review, 22 (2017) 32-36.
    [39] S.L. Nail, L.A. Gatlin, Freeze-drying: principles and practice, Pharmaceutical Dosage Forms-Parenteral Medications, 2 (2016) 367-396.
    [40] G. Turnbull, J. Clarke, F. Picard, P. Riches, L. Jia, F. Han, B. Li, W. Shu, 3D bioactive composite scaffolds for bone tissue engineering, Bioactive materials, 3 (2018) 278-314.
    [41] T. Garg, O. Singh, S. Arora, R. Murthy, Scaffold: a novel carrier for cell and drug delivery, Critical Reviews™ in Therapeutic Drug Carrier Systems, 29 (2012).
    [42] S.V. Madihally, H.W. Matthew, Porous chitosan scaffolds for tissue engineering, Biomaterials, 20 (1999) 1133-1142.
    [43] S. Hudson, C. Smith, Polysaccharides: chitin and chitosan: chemistry and technology of their use as structural materials, Biopolymers from renewable resources, (1998) 96-118.
    [44] M. Rinaudo, Chitin and chitosan: properties and applications, Progress in polymer science, 31 (2006) 603-632.
    [45] N. Alves, J. Mano, Chitosan derivatives obtained by chemical modifications for biomedical and environmental applications, International journal of biological macromolecules, 43 (2008) 401-414.
    [46] P.J. VandeVord, H.W. Matthew, S.P. DeSilva, L. Mayton, B. Wu, P.H. Wooley, Evaluation of the biocompatibility of a chitosan scaffold in mice, Journal of Biomedical Materials Research: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials, 59 (2002) 585-590.
    [47] M. Pourhaghgouy, A. Zamanian, M. Shahrezaee, M.P. Masouleh, Physicochemical properties and bioactivity of freeze-cast chitosan nanocomposite scaffolds reinforced with bioactive glass, Mater Sci Eng C Mater Biol Appl, 58 (2016) 180-186.
    [48] Y. Zhang, M. Zhang, Synthesis and characterization of macroporous chitosan/calcium phosphate composite scaffolds for tissue engineering, Journal of Biomedical Materials Research: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials, 55 (2001) 304-312.
    [49] R. LogithKumar, A. KeshavNarayan, S. Dhivya, A. Chawla, S. Saravanan, N. Selvamurugan, A review of chitosan and its derivatives in bone tissue engineering, Carbohydrate polymers, 151 (2016) 172-188.
    [50] F. Shahidi, J.K.V. Arachchi, Y.-J. Jeon, Food applications of chitin and chitosans, Trends in food science & technology, 10 (1999) 37-51.
    [51] G. Kravanja, M. Primožič, Ž. Knez, M. Leitgeb, Chitosan-based (Nano) materials for novel biomedical applications, Molecules, 24 (2019) 1960.
    [52] A. Ahmed, A.R. Sofy, A. Sharaf, Effectiveness of chitosan as naturally-derived antimicrobial to fulfill the needs of today’s consumers looking for food without hazards of chemical preservatives, Microbiol RES J, 7 (2017) 55-67.
    [53] L.L. Hench, Ö. Andersson, Bioactive glasses, An introduction to bioceramics, (1993) 41-62.
    [54] L.L. Hench, Bioceramics: from concept to clinic, Journal of the american ceramic society, 74 (1991) 1487-1510.
    [55] R. Li, A. Clark, L. Hench, An investigation of bioactive glass powders by sol‐gel processing, Journal of Applied Biomaterials, 2 (1991) 231-239.
    [56] T.A. Lin, Influence of Si concentration on cytotoxicity and bioactivity of spray dried bioactive glass, Department of Materials Science and Engineering, National Taiwan University of Science and Technology, 2018.
    [57] L.L. Hench, R.J. Splinter, W. Allen, T. Greenlee, Bonding mechanisms at the interface of ceramic prosthetic materials, Journal of biomedical materials research, 5 (1971) 117-141.
    [58] J.R. Jones, Review of bioactive glass: from Hench to hybrids, Acta biomaterialia, 9 (2013) 4457-4486.
    [59] S.J. Shih, Y.J. Chou, I.C. Chien, One-step synthesis of bioactive glass by spray pyrolysis, Journal of Nanoparticle Research, 14 (2012) 1299.
    [60] P.T. HSU, Synthesis of Cu@Ag core-shell particles using one-step spray pyrolysis, Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei, 2016.
    [61] R. Vehring, W.R. Foss, D. Lechuga-Ballesteros, Particle formation in spray drying, Journal of Aerosol Science, 38 (2007) 728-746.
    [62] D. Santos, A.C. Maurício, V. Sencadas, J.D. Santos, M.H. Fernandes, P.S. Gomes, Spray Drying: An Overview, Biomaterials-Physics and Chemistry-New Edition, (2017).
    [63] S.P. Nielsen, The biological role of strontium, Bone, 35 (2004) 583-588.
    [64] P.C. D’haese, G.F. Van Landeghem, L.V. Lamberts, V.A. Bekaert, I. Schrooten, M.E. De Broe, Measurement of strontium in serum, urine, bone, and soft tissues by Zeeman atomic absorption spectrometry, Clinical chemistry, 43 (1997) 121-128.
    [65] S. Dahl, P. Allain, P. Marie, Y. Mauras, G. Boivin, P. Ammann, Y. Tsouderos, P. Delmas, C. Christiansen, Incorporation and distribution of strontium in bone, Bone, 28 (2001) 446-453.
    [66] M. Sila-Asna, A. Bunyaratvej, S. Maeda, H. Kitaguchi, N. Bunyaratavej, Osteoblast differentiation and bone formation gene expression in strontium-inducing bone marrow mesenchymal stem cell, Kobe J Med Sci, 53 (2007) 25-35.
    [67] E. Bonnelye, A. Chabadel, F. Saltel, P. Jurdic, Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro, Bone, 42 (2008) 129-138.
    [68] P. Marie, Strontium ranelate: a physiological approach for optimizing bone formation and resorption, Bone, 38 (2006) 10-14.
    [69] A. Moghanian, S. Firoozi, M. Tahriri, Characterization, in vitro bioactivity and biological studies of sol-gel synthesized SrO substituted 58S bioactive glass, Ceramics International, 43 (2017) 14880-14890.
    [70] P.J. Meunier, C. Roux, E. Seeman, S. Ortolani, J.E. Badurski, T.D. Spector, J. Cannata, A. Balogh, E.-M. Lemmel, S. Pors-Nielsen, The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis, New England Journal of Medicine, 350 (2004) 459-468.
    [71] P. Marie, P. Ammann, G. Boivin, C. Rey, Mechanisms of action and therapeutic potential of strontium in bone, Calcified tissue international, 69 (2001).
    [72] N.D. Ravi, R. Balu, T. Sampath Kumar, Strontium‐substituted calcium deficient hydroxyapatite nanoparticles: Synthesis, characterization, and antibacterial properties, Journal of the American Ceramic Society, 95 (2012) 2700-2708.
    [73] T. Kokubo, H. Kushitani, S. Sakka, T. Kitsugi, T. Yamamuro, Solutions able to reproduce in vivo surface‐structure changes in bioactive glass‐ceramic A‐W3, Journal of biomedical materials research, 24 (1990) 721-734.
    [74] S. Srinivasan, R. Jayasree, K. Chennazhi, S. Nair, R. Jayakumar, Biocompatible alginate/nano bioactive glass ceramic composite scaffolds for periodontal tissue regeneration, Carbohydrate Polymers, 87 (2012) 274-283.
    [75] A.d.S. Scari, B.C. Pockszevnicki, J. Landre Junior, M. Junior, P.A. Almeida, Stress-strain compression of AA6082-T6 aluminum alloy at room temperature, Journal of structures, 2014 (2014).
    [76] L. Ma, Collagen/chitosan porous scaffolds with improved biostability for skin tissue engineering, 24 (2003) 4833-4841.
    [77] E.J. Chong, T.T. Phan, I.J. Lim, Y. Zhang, B.H. Bay, S. Ramakrishna, C.T. Lim, Evaluation of electrospun PCL/gelatin nanofibrous scaffold for wound healing and layered dermal reconstitution, Acta biomaterialia, 3 (2007) 321-330.
    [78] Z. Li, W. Lam, C. Yang, B. Xu, G. Ni, S. Abbah, K. Cheung, K. Luk, W. Lu, Chemical composition, crystal size and lattice structural changes after incorporation of strontium into biomimetic apatite, Biomaterials, 28 (2007) 1452-1460.
    [79] Y.C. Fredholm, N. Karpukhina, R.V. Law, R.G. Hill, Strontium containing bioactive glasses: glass structure and physical properties, Journal of Non-Crystalline Solids, 356 (2010) 2546-2551.
    [80] M. O’donnell, R. Hill, Influence of strontium and the importance of glass chemistry and structure when designing bioactive glasses for bone regeneration, Acta Biomaterialia, 6 (2010) 2382-2385.
    [81] H. Pan, X. Zhao, X. Zhang, K. Zhang, L. Li, Z. Li, W. Lam, W. Lu, D. Wang, W. Huang, Strontium borate glass: potential biomaterial for bone regeneration, Journal of the Royal Society Interface, 7 (2009) 1025-1031.
    [82] S. Hesaraki, M. Gholami, S. Vazehrad, S. Shahrabi, The effect of Sr concentration on bioactivity and biocompatibility of sol–gel derived glasses based on CaO–SrO–SiO2–P2O5 quaternary system, Materials Science and Engineering: C, 30 (2010) 383-390.

    QR CODE