跳到主要內容

臺灣博碩士論文加值系統

(3.229.142.104) 您好!臺灣時間:2021/07/28 13:24
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:顏榮信
研究生(外文):Jung-Hsing Yen
論文名稱:PLGA/TiO2敷料之生物相容性及組織反應之研究
論文名稱(外文):The study of biocompatibility and tissue response for PLGA/TiO2 dressing
指導教授:蔡肇基蔡肇基引用關係
學位類別:碩士
校院名稱:國立中興大學
系所名稱:生物醫學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:中文
論文頁數:58
中文關鍵詞:聚乳酸/聚甘醇酸共聚物二氧化鈦光觸媒生物相容性游離氧自由基抗菌效能
外文關鍵詞:PLGAtitanium dioxide(TiO2)photocatalyticbiocompatibilityfree oxygen radicalantimicrobial efficiency
相關次數:
  • 被引用被引用:0
  • 點閱點閱:282
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
聚乳酸/聚甘醇酸共聚物(PLGA)為逐漸普遍使用之生物可降解生醫材料,二氧化鈦(TiO2)光觸媒則是具備極佳之抗菌功能。本研究之主要目的是以PLGA為主成分,混合二氧化鈦光觸媒,製備成本低廉同時兼具通透性奈米抗菌光觸媒之新型人工敷料。如此材料能否在傷口癒合上發揮其功效,值得探討;再者此新型人工敷料的使用對生物體的相容性(biocompatibility),更是我們研究重點所在。
經由PLGA/TiO2光觸媒敷料的抗菌效能測試結果顯示,此光觸媒敷料相對於PLGA敷料及無敷料者,有明顯降低培養皿內&;#63754;黃色葡萄球菌的菌&;#63768;生成數目,達到抗菌效果,其抗菌活性值(R)值為0.516,雖然其抑菌率並非最高程度,但已能達到一般抗菌效果要求。
在細胞毒性試驗上,PLGA/TiO2光觸媒敷料在細胞形態上的變化及細胞附著定性評估,與對照組無顯著差異,對細胞數量的增減,所測定量評估,亦無顯著差異;證實PLGA/TiO2光觸媒敷料並無細胞毒性。在生物體反應上,對游離氧自由基及細胞激素檢測發現, PLGA/TiO2光觸媒敷的過氧化氫(H2O2)值在傷口癒合早期,傷口癒合晚期時相似,與PLGA敷料無顯著差異, 與對照組則有顯著差異。IL-6 值在癒合早期及晚期時,與PLGA敷料無顯著差異。傷口癒合效能測試結果顯示: 測量早期傷口大小時,PLGA敷料、PLGA/TiO2光觸媒敷料對對早期傷口癒合速率,遠優於對照組,對照組甚至於有負成長的情形,但一周後,傷口癒合速率就無明顯差異。傷口組織反應測試結果顯示: 在早期因傷口未癒合故表皮生長較少,發炎反應明顯,肉芽生成較少,在晚期,有些傷口已完全癒合,表皮生長較佳,發炎反應仍明顯,肉芽生成也快速長成,統計傷口組織評分,PLGA/TiO2光觸媒敷料在三項評分,皆與對照&;#32452;無明顯差異。
故PLGA/TiO2光觸媒敷料為無毒性,符合生物相容性敷料,並具抗菌性,提供醫療使用之可行性。


Poly-lactic-co-glycolic acid(PLGA)has been applied extensively for bio-medicine field due to its degrading property. Titanium dioxide(TiO2) have photocatalytic activity and antimicrobial efficacy. In this study, the PLGA/TiO2 dressing was created by mixing PLGA and TiO2. The wound healing effect was evaluated and the biocompatibility was tested. The results were presented in many methods.
The antimicrobial test of PLGA/TiO2 dressing reveals that it could significantly inhibit the growth of bacteria with antimicrobial activity (R) 0.516 . The antimicrobial efficiency has moderate ability. In cell toxicity test, PLGA/TiO2 dressing does not induce the cell morphologic change. The cell number was not influenced which confirms non-cytoxicity in the PLGA/TiO2 dressing. In free oxygen radical study, the H2O2 concentration level is the same in the early phase of wound healing and in the late phase of wound healing. There is no significant difference between PLGA and PLGA/TiO2 dressing. The SOD concentration level for PLGA/TiO2 dressing is the same level in the early phase and in the late phase. There is also no significant difference between the three groups. The wound healing efficiency reveals healing rate for PLGA dressing and PLGA/TiO2 is better than control in the early stage. The healing rate has no significant difference in the late phase. From histopathologic examination, the wound did not heal and no epithelization, few granulation, and markable inflammation response in the early stage. In the late phase of wound healing, the epithelization is complete and granulation formation is revealed. The scale for PLGA/TiO2 dressing has no significant difference in epidermis growing score, granulation score and inflammation score.
From this study, the PLGA/TiO2 dressing has non-toxicity properties and is biocompatible. It provides antibacterial efficiency and giving its feasibility of medicine application.


誌 謝…………………………………………………………………i
中文摘要……………………………………………………………… ii
英文摘要……………………………………………………………… iii
目 次……………………………………………………………………iv
圖目次………………………………………………………………… vii
表目次……………………………………………………………… viii
第一章. 緒論……………………………………………………………1
一. 傷口癒合機轉……………………………………………………1
(一) 傷口癒合過程…………………………………………………1
(二) 傷口癒合方式…………………………………………………2
(三) 傷口癒合結果…………………………………………………2
二. 傷口敷料 …………………………………………………………3
(一) 傷口覆蓋方式…………………………………………………3
(二) 生物性敷料……………………………………………………4
(三) 合成性敷料……………………………………………………5
三. 抗菌性敷料………………………………………………………5
四. PLGA/TiO2光觸媒敷料……………………………………………5
(一) PLGA生物降解性材料…………………………………………5
(二) 二氧化鈦( TiO2)光觸媒………………………………………7
(三) PLGA/TiO2光觸媒敷料…………………………………………8
五. 生物免疫及組織反應……………………………………………8
(一) 游離自由基檢測…………………………………………………8
(二) 細胞激素檢測………………………………………………9
六. 生物相容性 ……………………………………………………10
(一) 細胞毒性……………………………………………………11
(二) 刺激反應……………………………………………………12
(三) 過敏反應…………………………………………………………12
七. 研究方向及動機…………………………………………………13
第二章. 材料與方法……………………………………………………14
一. 聚乳酸/聚甘醇酸共聚物(PLGA)及二氧化鈦(TiO2)光觸媒敷料的製備
(一) PLGA的製備…………………………………………………14
(二) TiO2光觸媒的製……………………………………………14
(二) PLGA/TiO2光觸媒敷料的製備………………………………14
二. PLGA/TiO2光觸媒敷料的抗菌效能……………………………15
(一) 送測樣品規格及測試片製備程序…………………………15
(二) 抗菌測試準備事項…………………………………………16
(三) 抗菌測試步驟………………………………………………19
三. PLGA/TiO2光觸媒敷料的細胞毒性………………………22
(一) 細胞培養……………………………………………………22
(二) 試驗細胞的微觀組織觀察…………………… ………23
(三) 細胞計數……………………………………………………23
四. PLGA/TiO2光觸媒敷料的生物體反應…………………………25
(一) 游離自由基檢測……………………………………………25
(二) 細胞激素檢測………………………………………………27
五. PLGA/TiO2光觸媒敷料的傷口癒合效能………………………28
(一) 傷口癒合動物模式…………………………………………28
(二) 傷口大小之觀察……………………………………………28
六. PLGA/TiO2光觸媒敷料的傷口組織反應………………………29
(一) 組織切片製作………………………………………………29
(二) 顯微鏡觀察…………………………………………………33
(三) 組織病理特性………………………………………………33
第三章 結果與討論……………………………………………………36
一. PLGA/TiO2光觸媒敷料的抗菌效能……………………………36
(一) 二氧化鈦敷料的菌落生成數………………………………36
(二) 二氧化鈦敷料的抗菌活性值………………………………36
二. PLGA/TiO2光觸媒敷料的細胞毒性…………………………….37
(一) 二氧化鈦敷料的細胞毒性定性評估………………………37
(二) 二氧化鈦敷料的細胞毒性定量評估………………………38
三. PLGA/TiO2光觸媒敷料的生物體反應……………………………40
(一) 游離自由基…………………………………………………40
(二) 細胞激素……………………………………………………41
四. PLGA/TiO2光觸媒敷料的傷口癒合效能 ………………………42
(一) 傷口癒合動物模式…………………………………………42
(二) 傷口大小之觀察……………………………………………43
五. PLGA/TiO2光觸媒敷料的傷口組織反應…………………………44
(一) 組織病理變化觀察…………………………………………44
(二) 組織病理特徵評分…………………………………………45
第四章 結論……………………………………………………………49
第五章 未來展望………………………………………………………51
第六章 參考文獻………………………………………………………52


1.Singer, A.J. ,Clerk, R.A.(1999). Cutaneous wound healing. New England Journal Medicine , 341 (10) :738-746.
2.Barbul, A.(1990).Immune aspects of wound repair. Clinic Plastic Surgery, 17(3):433-442.
3.Singer, A.J., Dagum, A.B.(2008). Current Management of Acute Cutaneous Wounds. New England Journal Medicine, 359(10): 1037-1046.
4.Kim,B.S. , Baez ,C.E., Atala, A.(2000). Biomaterials for tissue engineering, World Journal of Urology, 18:2-9.
5.Chen, G., Ushida, T., Tateishi, T.(2001). Development of biodegrade- able porous scaffolds for tissue engineering, Biomaterials, 17: 63-69.
6.Chen, G., Sato, T., Ohgushi, H., Ushida, T., Tateishi, T., Tanaka, J. (2005). Culturing of skin fibroblasts in a thin PLGA–collagen hybrid mesh. Biomaterials,6:2559-2566.
7.Choi, J. S., Leong, K. W. , Yoo, H. S.(2008). In vivo wound healing of diabetic ulcers using electrospun nanofibers immobilized with human epidermal growth factor(EGF). Biomaterials, 29:587-596.
8.Cai, R. , Kubota, Y. , Shuin, T., Sakai, H., Hashimoto, K., and Fujishima, A.(1992). Induction of cytotoxicity by photoexcited TiO2 particles. Cancer Research, 52:2346-2348.
9.Fujishima, A., Rao, T. N. , Tryk, D. A.(2000).Titanium dioxide photocatalysis. Journal of Photochemistry and Photobiology C: Photochemistry Reviews, 1:1-21.
10.Zhuang , W. , Liu , J., Zhang, J. H., Hu, B. X., Shen, J. (2008). Preparation, Characterization, and Properties of TiO2/PLA Nanocomposites by In Situ Polymerization. Polymer composites, 30:1074-1080.
11.Maness, P. C. , Smolinski, S., Blake, D. M., Huang, Z., Wolfrum, E. J.,and Jacoby, W. A.(1999). Bactericidal Activity of Photocatalytic TiO2 Reaction: toward an Understanding of Its Killing Mechanism. Applied and Environmental Microbiology, 65:4094-4098.
12.Chung, C. J. , Lin, H. I., Tsou, H. K., Shi , Z. Y. ,and He, J. L.(2008). An antimicrobial TiO2 coating for reducing hospital-acquired infection. Journal of Biomedical Materials Research Part B-Applied Biomaterials, 85B:220-224.
13.Fox, M.A, Dulay, M.T.(1993). Heterogeneous Photocatalysis. Chemical review, 93:341-357.
14.Suri, R.P.S, Lui,J., Hand,D.W, Crittenden,J.C., Perram,D.L., Mullins,M.M.(1993). Heterogeneous photocatalytic oxidation of hazardous organic contaminants in water. Water environment research, 65:665-673.
15.Wang, J.X., Fan, Y.B., Gao, Y., Hu, Q.H., Wang, T.C.(2009). TiO2 nanoparticles translocation and potential toxicological effect in rats after intraarticular injection. Biomaterials, 30(27):4590-4600.
16.Borm, P.J.A., Robins,D.,Haubold,S.,Huhlbusch, T.,Donaldson, K., Schins, R., Stone,V., Kreyling,W., Landemann,J., Krutmann,J., Warheit,D., Oberdorster,E.(2006). The potential risks of nanomaterials: A review carried out for ECETOC. Particle and Fibre Toxicology,3:11-46.
17.Ramsden,C.S., Smith,T.J., Shaw, B.J., Handy, R.D.(2009) Dietary exposure to titanium dioxide nanoparticles in rainbow trout, (Oncorhynchus mykiss): no effect on growth, but subtle biochemical disturbances in the brain. Ecotoxicology,18: 939-951.
18.Gamer, A.O., Leibold,E.,Ravenzwaay,S.(2006). The in vitro absorption of microfine zinc oxide and titanium dioxide through porcine skin. Toxicology in Vitro, 20(3): 301-307.
19.Chung, C.J., Lin, H.I., Chou, C.M., Hsiegh, C.H., Hsiao,C.H., Shi,Z.Y., He,J.L.(2009). Inactivation of of Staphylococcus aureus and Escherichia coli under various light sources on photocatalytic titanium dioxide thin film. Surface and Coatings Technology, 203(8):1081-1085.
20.ISO 10993-5.(1993),Biological evaluation of medical devices-part 5: tests for in vitro cytotoxicity, International Organization for Standardization, Switzerland.
21.Feng, Q. L. , Wu, J., Chen, G. Q., Cui, F. Z.,. Kim, T. N , Kim, J. O. (2000).A mechanistic study of the antibacterial effect of silver ions on Escherichia coli and Staphylococcus aureus. Journal of biomedical materials research, 52:662–668.
22.Evans, P. , Sheel, D. W. (2007).Photoactive and antibacterial TiO2 thin films on stainless steel. Surface and Coatings Technology, 201:9319-9324.
23.Kourai, H. (2001). Surface science and microbiology: Antimicrobial finishings. Journal of the Surface Science Society of Japan, 2:663-670.
24.Chungtsun,T.H., Tachiupao,C.J. , Kungnan,K.C.(1997). Antibacterial characteristic and material quality of ferrite antibacterial stainless steel "NSSAM-1". Nisshin Steel Technical Report, 76:48–55.
25.Kim, T.N. , Feng, Q.L., kim, J.O., Wu, J., Wang, H., Chen, G. C., Cui, F.Z. (1998). Antimicrobial effects of metal ions(Ag+, Cu2+, Zn2+) in hydroxyapatite. Journal of Materials Science: Materials in Medicine, 9:129-134.
26.Chung,C.J., Lin, H.I., He,J.L.(2007). Antimicrobial efficacy of photocatalytic TiO2 coatings prepared by arc ion plating. Surface and Coatings Technology, 202: 1302-1307.
27.Chung, C.J. , Lin, H. I. , He, J. L.(2007). Microstructural effect on the antimicrobial efficacy of arc ion plated TiO2. Journal of Materials Research, 22:3137-3143.
28.Shieh,K.J., Li,M., Lee,Y.H., Sheu,S.D., Liu,Y.T., Wang,Y.C. (2006). Antibacterial performance of photocatalyst thin film fabricated by defection effect in visible light. Nanomedicine: Nanotechnology, Biology, and Medicine, 2:121-126.
29.Chung, C.J., Lin, H.I., Tsou, H.K., Shi, Z.Y., He, J.L.(2007). An Antimicrobial TiO2 Coating for Reducing Hospital-Acquired Infection. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 25:220-224.
30.Peng,C.C., Yang,M.H., Chiu,W.T., Chiu,C.H., Yang,C.S., Chen,Y.W., Chen,K.C., Peng,R.Y.(2008). Composite nano-titanium oxide- chitosan artificial skin exhibits strong wound-healing effect- an approach with anti-inflammatory and bactericidal kinetics. Macromolecular Bioscience, 8:316-327.
31.JIS Z2801:2000, (2001). Antimicrobial products – Test for antimicrobial activity and efficacy, Japanese Industrial Standard.
32.Ehrlich, H.P., Tarver, H., Hunt, T.K.(1973). Effects of vitamin A and glucocorticoids upon inflammation and collagen synthesis. Annal Surgery, 177(2):222-227.
33.Phillips, J.D., Kim, C.S., Fonkalsrud, E.W., Zeng, H., Dinda,r H. (1992). Effects of chronic corticosteroid and vitamin A on the healing of intestinal anastomoses. American west Journal Surgery, 163:71-77.
34.Mahmut,D., Karaaslan,E., Ozturk,E.(2003).The Effects of Single- Dose Dexamethasone on Wound Healing in Rats. Anesthesia Analgesia,97 :1377-1380.
35.Gercek,A., Yildirim,O., Konya,D.(2007). Effects of parenteral fish-oil emulsion (Omegaven) on cutaneous wound healing in rats treated with dexamethasone. Journal of Parenteral and Enteral Nutrition, 31(3):161-166.
36.Liu, S.A, Tung, K.C., Cheng, C.C, Chiu,Y.T.(2007).The impact of different closure materials on pharyngeal wound healing: an experiemental anaimal study. European Archives of. Otorhino Laryngology, 265:227-231.
37.Peter, J., Winterswijk, V., Nout, E.(2007). Tissue Engineering and Wound Healing: An Overview of the Past, Present, and Future
38.Wounds, 19(10):277-284 Zahedi, P., Rezaeiana , I., Ranaei-Siadatb , S.O., Jafaria, S.H., Supapholc, P.(2010).A review on wound dressings with an emphasis on electrospun nanofibrous polymeric bandages. Polymers Advances Technologies, 21: 77–95
39.Amy,M.P., Michelle, L.R., Kevin, R. B., Daniel,E.S., Michael,O., Barry,N.K., Eric,P.S., Frank,R.D.(2008). Neutrophil microbicides induce a pathogen survival response in community-associated methicillin-resistant Staphylococcus aureus. Journal of Immunology, 180:500-509.
40.Maness, P. C. , Smolinski, S., Blake, D. M., Huang, Z., Wolfrum, E. J., Jacoby, W. A.(1999). Bactericidal activity of photocatalytic TiO2 reaction: Toward an understanding of its killing mechanism. Applied and Environmental Microbiology, 65:4094-4098.
41.Wong, M. S., Chu, W. C., Sun, D. S. , Huang, H. S., Chen, J. H., Tsai, P. J. , Lin, N. T. , Yu, M. S. ,. Hsu, S. F, Wang, S. L. , Chang, H. H. (2006).Visible-light–induced bactericidal activity of a nitrogen-doped titanium photocatalyst against human pathogens. Applied and Environmental Microbiology,72:6111-6116.
42.Block, S. S. , Goswami, D. Y. (1997).Chemically enhanced sunlight for killing bacteria. Journal of Solar Energy Engineering: Transactions of the ASME, 119:85-91.
43.Raad,I., Darouiche, R. O., Hachem, R., Sacilowski, M., Bodey, G. P. (1995). Antibiotics and prevention of microbial colonization of catheters. Antimicrobial Agents and Chemotherapy, 39:2397-2400.
44.Popov, A.P., Priezzhev, A.V., Lademann, L., Myllyia,R.(2005). TiO2 nanoparticles as an effective UV-B radiation skin-protective compound in sunscreens. Journal of Physics D: Applied Physics , 38(15): 2564-2570.
45.Wei,C., Lin,W.Y., Zainal,Z., Williams, N.E., Zhu, K., Kruzic, A.P., Smith, R.L., Rajeshwar, K.(1994). Bactericidal activity of TiO2 photocatalyst in aqueous media: Toward a solar-assisted water disinfection system. Environmental Science and Technology, 28:934-938.


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top