跳到主要內容

臺灣博碩士論文加值系統

(3.236.110.106) 您好!臺灣時間:2021/07/25 23:44
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:胡致遠
研究生(外文):Chih-Yuan Hu
論文名稱:雙相磷酸鈣人工骨移植材料之體內試驗
論文名稱(外文):In vivo studies of poor crystalline hydroxyapatite based biphasic calcium phosphate bone grafts
指導教授:楊正昌
學位類別:碩士
校院名稱:臺北醫學大學
系所名稱:口腔科學研究所
學門:醫藥衛生學門
學類:牙醫學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:81
中文關鍵詞:雙相磷酸鈣骨移植β-三鈣磷酸鹽動物實驗
外文關鍵詞:biphasic calcium phosphate (BCP)bone graftβ-tricalcium phosphate (β-TCP)in vivo
相關次數:
  • 被引用被引用:0
  • 點閱點閱:226
  • 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
在骨科與牙科臨床上針對大範圍骨缺損治療時,常使用骨移植材以促進癒合。在市售合成骨移植材中,由氫氧基磷灰石(hydroxyapatite, HA)與β-三鈣磷酸鹽(β-tricalcium phosphate, β-TCP)組成的雙相磷酸鈣(biphasic calcium phosphate, BCP)生醫陶瓷,為廣泛應用之合成骨移植材,但HA具有在體內吸收時間較長之問題。本研究以低結晶性氫氧基磷灰石(poor crystalline HA, PC-HA)與β-TCP組成雙相磷酸鈣骨移植材,藉由動物實驗評估比較不同比例移植材在骨缺損中新骨生成速率。本實驗室以濕式化學沈澱法分別反應生成PC-HA與β-TCP後,經過濾、混合、乾燥、壓錠、燒結、粉碎後以不同網目篩網控制顆粒大小,備製磷酸鈣骨移植材(PC-HA/β-TCP),藉由掃描式電子顯微鏡、傅氏紅外光譜儀與X光繞射分析儀進行材料之物化性分析。在動物實驗時,首先對四隻米格魯成犬拔除所有之小臼齒,等待16週癒合期後,對齒槽骨製造直徑3 mm,高6 mm之圓柱狀人工骨缺損,同時將三種不同比例之 (PC-HA/β-TCP 70/30, 60/40, and 0/100)材料植入缺損處為實驗組,以市售MBCP®(HA/β-TCP=60/40), Cerasorb®(β-TCP=100%)與未放置材料組別作為空白對照組。手術後8週在各區取出直徑5 mm,高8 mm圓柱狀區域進行組織切片觀察。切片結果顯示實驗室材料與市售商品在牙科骨缺損中,皆具備良好生物相容性,且能促進骨癒合。以one-way ANOVA分析新骨生成率(ratio of new bone formation),結果顯示組別間具有統計上差異(P<0.05),以Duncan multiple range test分析顯示有置放骨移植材料之各組之新骨生成率皆明顯優於空白對照組,另PC-HA/β-TCP= 70/30, 60/40之新骨生長率明顯大於β-TCP(100%)。由各組間之信度值(coefficient of variance, CV),可發現PC-HA/β-TCP= 70/30與60/40之新骨生成率較MBCP® 及Cerasorb®商品及空白對照組之分布均勻,推測較適於新生骨生長。結果顯示poor crystalline HA/β-TCP為適合骨缺損使用之新式雙相磷酸鈣骨移植材。
Bone substitute materials are widely used to accelerate healing process while suffering large bone defects in orthopedic and dental clinics. Commercial biphasic calcium phosphate (BCP), containing hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), is a widely used synthetic bone graft with the shortcoming of prolonged resorption time. In this study, poor crystalline hydroxyapatite (PC-HA) and β-TCP were mixed in different ratios to investigate which mixing ratio could be adapted to the resorption rate of clinical application for dental bony defect. After preparing PC-HA and β-TCP by wet chemical precipitation method separately , granular type bone grafts were collected by filtrating, freeze drying, tableting, sintering, mixing, and size screening. All the bone graft specimens were analyzed with scanning electric microscope (SEM), Fourier transform infrared spectrometer (FT-IR) and X-ray diffraction (XRD). Prior to the implantation experiments, all premolars of 4 beagles were extracted. After 16 weeks of healing period for stabilizing the wound sites in alveolar bone, 8 cylinder type of artificial bony defect (3 mm diameter, 6 mm length) were produced, and filled with disinfected BCP of (PC-HA/β-TCP= 70/30, 60/40, 0/100) as experimental groups and commercial products of MBCP® (HA/β-TCP= 60/40), Cerasorb®(β-TCP=100%), and empty defect as control groups. The cylinder type bone blocks (5 mm diameter, 8 mm length) were brought out at 8 weeks postoperatively for histological studies. There are significant differences of new bone formation ratio between all experimental and control groups (one-way ANOVA, P < 0.05). The results of Duncan multiple range test also showed significant differences between treatment groups compare to empty control groups, PC-HA/ β-TCP=70/30 to β-TCP, and PC-HA/ β-TCP=60/40 to β-TCP groups. Comparison of the coefficient variation (CV), the distribution in experimental groups of new bone formation show better evenness than groups of MBCP®, Cerasorb®, and empty controls. The results showed that BCP of experimental groups and commercial products are biocompatible and the healing effects are better than unfilled empty control groups, indicating BCP of PC-HA/β-TCP is a new choice for bone defects filling.
目錄
中文摘要 I
ABSTRACT III
目錄 V
第1章 緒論 1
1-1 研究動機與重要性 1
1-2 研究目的 2
1-3 研究假設 2
第2章 文獻回顧 4
2-1 骨骼的結構與機械特性 4
2-2骨骼缺損的治療方式與來源分類 6
2-3人工骨替代材的應用與選擇 8
2-4 磷酸鈣鹽類的介紹 10
2-5 雙相磷酸鈣陶瓷 13
2-6 骨移植材的體內測試 16
2-7 實驗動物的選擇與實驗設計 18
第3章 實驗材料與方法 20
3-1 實驗藥品 20
3-2實驗儀器 21
3-3 實驗架構圖 22
3-4 POOR CRYSTALLINE HA/Β-TCP雙相磷酸鈣複合材的製備 23
3-5 材料性質分析與檢測 24
3-5-1 SEM掃描式電子顯微鏡分析 24
3-5-2 XRD(X光繞射分析) 24
3-5-3 FTIR紅外線光譜分析 24
3-6 動物實驗 26
3-6-1 動物實驗材料置放組別 26
3-6-2 動物實驗手術步驟 26
3-6-3 骨組織切片製作 27
3-6-4 骨組織切片之觀察與評估方式 31
第4章 骨移植材料之物化性分析結果 32
4-1 SEM表面形態觀察 32
4-2 FTIR測試 33
4-3 X-RAY測試 34
第5章 動物實驗與組織切片結果 36
5-1 動物實驗組織切片定性觀察 36
5-2 動物實驗組織切片定量分析 40
第6章 討論 43
6-1物化性分析結果討論 43
6-2 動物實驗結果討論 45
第7章 結論與建議 48
7-1 結論 48
7-2 未來研究方向建議 49
表目錄
表2-1、骨頭的機械性質 55
表2-2、不同來源的骨移植材料優缺點比較 56
表2-3、骨移植材在骨科與牙科上之應用 57
表2-4、氫氧基磷灰石的物理與化學性質 58
表2-5、合成磷酸鈣骨移植材成分 59
表2-6、無機鹽類骨替代材與動物實驗模型 60
表3-1、動物試驗置放材料與位置 61
表3-2、不同植入材料的晶體顆粒大小計算........................................62
表3-3、各組新生骨面積比例與個體信度............................................63

圖目錄
圖2-1、海綿骨與緻密骨 64
圖2-2、氫氧基磷灰石晶體結構 65
圖3-1、冷凍乾燥機 66
圖3-2、噴霧乾燥機 67
圖3-3、材料製程與動物實驗架構圖 68
圖3-4、材料製備流程圖...…………………………………………….69
圖3-5、麻醉後以手術刀劃開,進行手術翻瓣 70
圖3-6、圓形鑽針鑽孔,鑽完取3 mm (直徑)x 6 mm(高度)骨缺損 70
圖3-7、將骨移植材料填入人工骨缺損處 71
圖3-8、將骨缺損處縫合並固定植入材料 71
圖4-1、顯微鏡(200倍)下顯示 72
圖4-2、顯微鏡(1000倍)下顯示 73
圖4-3、FTIR測試結果 74
圖4-4、X-ray繞射分析結果 75
圖5-1、植入PC-HA/β-TCP=70/30組別8週後取出組織切片觀察 76
圖5-2、植入PC-HA/β-TCP=60/40組別8週後取出組織切片觀察 77
圖5-3、植入市售商品MBCP®組別8週後取出組織切片觀察 78
圖5-4、植入β-TCP(100%)組別8週後取出組織切片觀察 79
圖5-5、植入市售商品Cerasorb®組別8週後取出組織切片觀察 80
圖5-6、未放置材料組別植入8週後取出組織切片觀察 81
1.Sullivan F. Strategic analysis of the European bone graft substitutes market. 2004.
2.Bai B, Jazrawi LM, Kummer FJ, Spivak JM. The use of an injectable, biodegradable calcium phosphate bone substitute for the prophylactic augmentation of osteoporotic vertebrae and the management of vertebral compression fractures. Spine 1999;24(15):1521-6.
3.Kwon S. Calcium phosphate bioceramics with various porosities and dissolution rates. J. Am. Ceram. Soc 2002;85(12):3129-3131.
4.van der Veere CN, Schoemaker B, van der Meer R, Groen AK, Jansen PL, Oude Elferink RP. Rapid association of unconjugated bilirubin with amorphous calcium phosphate. J Lipid Res 1995;36(8):1697-707.
5.Ryu HS, Hong KS, Lee JK, Kim DJ, Lee JH, Chang BS, Lee DH, Lee CK, Chung SS. Magnesia-doped HA/beta-TCP ceramics and evaluation of their biocompatibility. Biomaterials 2004;25(3):393-401.
6.Radin SR, Ducheyne P. Effect of bioactive ceramic composition and structure on in vitro behavior. III. Porous versus dense ceramics. J Biomed Mater Res 1994;28(11):1303-9.
7.Wang J, Chen W, Li Y, Fan S, Weng J, Zhang X. Biological evaluation of biphasic calcium phosphate ceramic vertebral laminae. Biomaterials 1998;19(15):1387-92.
8.Rao RR, Roopa HN, Kannan TS. Solid state synthesis and thermal stability of HAP and HAP - beta-TCP composite ceramic powders. J Mater Sci Mater Med 1997;8(8):511-8.
9.Lowe J. 組織學. 藝軒出版社 1995:233~271.
10.Riggs BL. 骨質疏鬆症:病因、診斷、治療. 合記圖書出版社 1997:1~15.
11.Hole JW J, Koos KA. Human Anatomy. WCB Press 1991:117-256.
12.Eichler J, Hutzschenreuter P, Rosenbladt I. [The behavior of biological parameters in experimental hyperthermia]. Anaesthesist 1969;18(7):210-5.
13.Coventry MB, Tapper EM. Pelvic instability: a consequence of removing iliac bone for grafting. J Bone Joint Surg Am 1972;54(1):83-101.
14.T. Kokubo HK, and M. Kawashita. Novel bioactive materials with different mechanical properties Biomaterials 2003;24:2161-2175.
15.Ikeda N. Quantitative comparison of osteoconduction of porous, dense A-W glass-ceramic and hydroxyapatite granules Biomaterials 1999;20:1087-1095.
16.Kokubo T. Bioactive glass ceramics: properties and applications. Biomaterials 1991;12(2):155-63.
17.Friedman CD, Costantino PD, Jones K, Chow LC, Pelzer HJ, Sisson GA, Sr. Hydroxyapatite cement. II. Obliteration and reconstruction of the cat frontal sinus. Arch Otolaryngol Head Neck Surg 1991;117(4):385-9.
18.Albrektsson T, Johansson C. Osteoinduction, osteoconduction and osseointegration. Eur Spine J 2001;10 Suppl 2:S96-101.
19.Whang K, Healy KE, Elenz DR, Nam EK, Tsai DC, Thomas CH, Nuber GW, Glorieux FH, Travers R, Sprague SM. Engineering bone regeneration with bioabsorbable scaffolds with novel microarchitecture. Tissue Eng 1999;5(1):35-51.
20.Salgado AJ, Coutinho OP, Reis RL. Bone tissue engineering: state of the art and future trends. Macromol Biosci 2004;4(8):743-65.
21.Leong KF, Cheah CM, Chua CK. Solid freeform fabrication of three-dimensional scaffolds for engineering replacement tissues and organs. Biomaterials 2003;24(13):2363-78.
22.Deramond H, Wright NT, Belkoff SM. Temperature elevation caused by bone cement polymerization during vertebroplasty. Bone 1999;25(2 Suppl):17S-21S.
23.Hench LL. From concept to clinic. J Mater Cera Soc 1991;74:1487-1510.
24.王正一. 醫學工程原理與應用. 正中書局 1996.
25.洪敏雄. "生醫陶瓷" 陶瓷技術手冊(下). 中華民國產業科技發展協進會 1994.
26.de Lange GL, Donath K. Interface between bone tissue and implants of solid hydroxyapatite or hydroxyapatite-coated titanium implants. Biomaterials 1989;10(2):121-5.
27.Krajewski A, Ravaglioli, A. A physico-chemical study of crystal growth of hydroxyapatite bioceramic. Biomaterials 1981;2(2):105-11.
28.Jinawath S, Pongkao D, Yoshimura M. Hydrothermal synthesis of hydroxyapatite from natural source. J Mater Sci Mater Med 2002;13(5):491-4.
29.Lin FH, Liao CJ, Chen KS, Sun JS. Preparation of high-temperature stabilized beta-tricalcium phosphate by heating deficient hydroxyapatite with Na4P2O7 x 10H2O addition. Biomaterials 1998;19(11-12):1101-7.
30.Kalkura SN, Anee TK, Ashok M, Betzel C. Investigations on the synthesis and crystallization of hydroxyapatite at low temperature. Biomed Mater Eng 2004;14(4):581-92.
31.陳文正. 氫氧基磷灰石複合骨水泥基本性質及植入結果研究. 國立成功大學材料科學及工程學系博士論文 2002.
32.Camire CL, Jegou Saint-Jean S, Mochales C, Nevsten P, Wang JS, Lidgren L, McCarthy I, Ginebra MP. Material characterization and in vivo behavior of silicon substituted alpha-tricalcium phosphate cement. J Biomed Mater Res B Appl Biomater 2005;76B(2):424-431.
33.Nery EB, LeGeros RZ, Lynch KL, Lee K. Tissue response to biphasic calcium phosphate ceramic with different ratios of HA/beta TCP in periodontal osseous defects. J Periodontol 1992;63(9):729-35.
34.Knaack D, Goad ME, Aiolova M, Rey C, Tofighi A, Chakravarthy P, Lee DD. Resorbable calcium phosphate bone substitute. J Biomed Mater Res 1998;43(4):399-409.
35.Ambrosio AM, Sahota JS, Khan Y, Laurencin CT. A novel amorphous calcium phosphate polymer ceramic for bone repair: I. Synthesis and characterization. J Biomed Mater Res 2001;58(3):295-301.
36.劉百栓. 以天然交聯劑綠梔子素交聯明膠結合三鈣磷酸鹽粉末之新骨科替代材料的研製與評估 國立中興大學化學工程學系博士論文 2004.
37.Ravaglioli A. KA. Bioceramics Materials, Properties, Applications. Chapman and Hall 1992.
38.黃國光. 動物實驗模型於牙周組織再生之運用-文獻回顧. 中華牙周醫誌 2003;8:153-168.
39.Malard O, Guicheux J, Bouler JM, Gauthier O, de Montreuil CB, Aguado E, Pilet P, LeGeros R, Daculsi G. Calcium phosphate scaffold and bone marrow for bone reconstruction in irradiated area: a dog study. Bone 2005;36(2):323-30.
40.Daculsi G, LeGeros RZ, Nery E, Lynch K, Kerebel B. Transformation of biphasic calcium phosphate ceramics in vivo: ultrastructural and physicochemical characterization. J Biomed Mater Res 1989;23(8):883-94.
41.Schmitz JP, Hollinger JO. The critical size defect as an experimental model for craniomandibulofacial nonunions. Clin Orthop Relat Res 1986(205):299-308.
42.Bosch C, Melsen B, Vargervik K. Importance of the critical-size bone defect in testing bone-regenerating materials. J Craniofac Surg 1998;9(4):310-6.
43.Prevéy PS, Lambda Research C, Ohio. X-ray diffraction characterization of crystalinity and phase composition in plasma-sprayed hydroxyapatite coatings. J Ther Spr Tech. 2000;9(3):369-376.
44.Leeuwenburgh SC, Wolke JG, Siebers MC, Schoonman J, Jansen JA. In vitro and in vivo reactivity of porous, electrosprayed calcium phosphate coatings. Biomaterials 2006;27(18):3368-78.
45.Zhou M, Lambert H, Landry J. Transient activation of a distinct serine protein kinase is responsible for 27-kDa heat shock protein phosphorylation in mitogen-stimulated and heat-shocked cells. J Biol Chem 1993;268(1):35-43.
46.Ravaglioli A, Krajewski A, Biasini V, Martinetti R, Mangano C, Venini G. Interface between hydroxyapatite and mandibular human bone tissue. Biomaterials 1992;13(3):162-7.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top