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研究生:郭乃嘉
研究生(外文):Nai-Chia Kuo
論文名稱:骨內骨形態發生蛋白四腺病毒基因治療對牙科植體早期穩定度之影響
論文名稱(外文):The Effect of Intraosseous BMP4 Adenoviral Gene Therapy on Early Dental Implant Stability
指導教授:陳恆理陳恆理引用關係賴玉玲賴玉玲引用關係
指導教授(外文):Hen-Li ChenYu-Lin Lai
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:臨床牙醫學研究所
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:2009
畢業學年度:97
語文別:中文
論文頁數:51
中文關鍵詞:植體穩定度基因治療
外文關鍵詞:Implant stabilitygene therapy
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牙科植體目前已為臨床上具高成功率的治療方法,但研究顯示植體種植區若骨質不佳,易導致植體穩定度不佳而降低成功率。骨形態生成蛋白四(bone morphogenetic protein-4, BMP4)為有效促進骨再生之生長因子,先前本實驗室發現骨內給予帶有BMP4基因的腺病毒可增加局部骨密度,我們預期此種骨內BMP4腺病毒基因治療可透過促進植體周圍骨癒合,而有助於提升植體穩定度。本研究目的在探討骨內BMP4腺病毒基因治療對植體癒合及早期穩定度的影響。植體植入卵巢切除兔股骨時,在實驗組及對照組分別將攜有BMP4或半乳糖酶(LacZ)基因的腺病毒注入種植區骨內,於一週後以免疫組織染色顯示在實驗組植體鄰近周圍有BMP4表現;在0、4、8週進行共振頻率分析,發現隨時間而漸增的植體穩定度改善,在BMP4組較明顯;而微型電腦斷層掃描分析顯示BMP4 組的皮質骨增厚在4 及8 週均較多;組織學檢查可觀察到BMP4組在螺紋間有較佳骨整合現象。本研究顯示骨內骨形態生成蛋白4腺病毒基因治療可透過促進植體周圍骨癒合而改善植體的早期穩定度。
Nowadays implant therapy has become an accepted treatment modality in dentistry with high success rate. However, implant recipient site with poor bone quality often results in reduced implant stability and lower success rate. Bone morphogenetic protein-4 (BMP4) is a powerful osteogenic factor. Previously we found that the local bone density can be improved by intraosseous application of adenovirus vector carrying BMP4 gene (Ad-BMP4). We hypothesized that the intraosseous BMP4 adenoviral gene therapy can promote implant stability through enhancing peri-implant bone healing. The purpose of this study was to determine the effect of intraosseous BMP4 adenoviral gene therapy on implant healing and early implant stability. Intraosseous delivery of adenovirus carrying BMP4 or LacZ gene was performed respectively for experimental and control groups immediately followed by implant placement at femurs of ovariectomized rabbits. Immunohistochemistry staining one week postoperatively indicated that the BMP4 was expressed at the immediate peri-implant site in experimental group. Resonance frequency analysis at 0, 4, 8 weeks suggested that BMP4 gene therapy significantly increased the time-dependent improvement of implant stability at both 4 and 8 weeks. MicroCT data at 4 and 8 weeks showed that the thickness of peri-implant cortical bone increased more in BMP4 group. In addition, better osseointegration between threads was observed histologically in the BMP4 group. In conclusion, intraosseous BMP4 adenoviral gene therapy can improve early implant stability through enhancing peri-implant bone healing.
論文電子檔著作權授權書 i
口試委員審定書 ii
論文審定同意書 iii
致謝 iv
中文摘要 v
英文摘要 vi
目錄 viii
圖目錄 xi
第一章 緒論 1
1.1 研究動機 1
1.2 文獻回顧 2
1.2.1 植體周圍骨癒合 2
1.2.2 植體穩定度 3
1.2.3 植體穩定度之分析方法 4
1.2.4 促進植體周圍骨癒合 6
1.2.5 基因治療 7
1.2.6 骨形態生成蛋白 9
1.2.7 骨內給予方式 10
1.2.8 骨質疏鬆動物模型 11
1.3 研究目的 13
第二章 實驗材料及方法 14
2.1 實驗材料 14
2.1.1 試劑、溶液 14
2.1.2 儀器 16
2.1.3 動物實驗 16
2.2 實驗方法 19
2.2.1 細胞培養 19
2.2.2 腺病毒效價的測定 19
2.2.3 製備病毒/膠原蛋白混合物 20
2.2.4 骨內給予重組腺病毒及植入植體 20
2.2.5 免疫組織化學染色 21
2.2.6 蘇木紫-伊紅染色 22
2.2.7 植體穩定度測量 23
2.2.8 微型電腦斷層掃描儀之分析 23
2.2.9 未脫鈣硬組織切片之製作 24
2.2.10 統計方法 27
第三章 結果 28
3.1 腺病毒效價的測定 28
3.2 骨內給予Ad-BMP4對於植體周圍骨癒合及早期穩定度的影響 28
3.2.1 免疫組織化學染色 29
3.2.2 蘇木紫-伊紅染色 29
3.2.3 植體穩定度測量 29
3.2.4 微型電腦斷層掃描儀之分析 30
3.2.5 未脫鈣硬組織切片之觀察 31
第四章 討論 32
附錄 圖表 38
參考文獻 48

圖目錄

圖1、骨內給予重組腺病毒同時植入植體方法 38
圖2、免疫組織化學染色 39
圖3、組織蘇木紫 - 伊紅染色 40
圖4、癒合期間植體共振頻率之變化 41
圖5、癒合期間植體共振頻率變化量之百分比 41
圖6、股骨實驗標本與MicroCT不同切面之影像 42
圖7、癒合期間MicroCT之影像 43
圖8、MicroCT分析植體骨幹側皮質骨厚度之方法 44
圖9、MicroCT分析植體骨幹側皮質骨厚度之結果 45
圖10、柱狀圖表示MicroCT分析之皮質骨厚度改變量 46
圖11、未脫鈣硬組織切片 47
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