使用人工牙根作為缺牙患者的治療方式，自1970年發展至今，已經相當普及且有極高的成功率。然而作為目前主流的鈦金屬材料受限於本身的顏色，在植體周圍會有顏色暗沉的現象，而使得美觀不佳，造成發展上的瓶頸。因此與牙齒本身顏色相近的陶瓷材料被提出使用在人工牙根上，目前陶瓷人工牙根的發展以氧化鋯為主。另外植牙的成功與否視骨整合而定，因此本實驗目的為評估自行研發之氧化鋯陶瓷人工牙根在動物實驗模式下，與國外市面上之氧化鋯陶瓷人工牙根之骨整合的比較；另外藉由未脫鈣磨片的標本處理技術，輔以骨螢光標定，探討氧化鋯植體的骨癒合模式。
本研究實驗組為自行研發，經由粒徑60μm二氧化鋯顆粒噴砂(Sandblasted)表面處理之氧化鋯人工牙根，對照組為市面上販售之Z-Look3之氧化鋯人工牙根。在本實驗中，共使用了3隻beagle dog，兩種不同植體分為4、9、13週組時間點，隨機植入下顎骨雙側無牙區。另於九週組時間點，於其中一隻狗脛骨植入兩種氧化鋯植體及一隻鈦金屬植體(Ti-Unite)作為移除扭力測試使用，在植牙時間點以不同顏色骨螢光標定，以觀察不同時間點之骨新生。在觀察期間以植體搖動度分析儀Periotest作非侵入性植體搖動度測試，並同時觀察臨床植體狀況。在動物犧牲後取得標本，以醫學X光機拍攝計算骨吸收，切片觀察各組骨-植體接觸比(BIC)，以及骨標定螢光的觀察。
以X光片計算近遠心側骨吸收比率，4週實驗組與對照組分別為2.7±1.6%與2.2±1.3%；9週實驗組與對照組分別為2.2±1.3%與3.1±2.3%；13週實驗組與對照組分別為2.7±1.5%與4.5±2.5%，各組間均無差異。在植體搖動度測試數據(PTV)中，在4週、9週與13週組各個時間點，實驗組與對照組的數值分別為4週0.73±5.29與0.42±0.78；9週0.92±2.45與2.05±1.91；13週2.11±2.01與2.19±0.83，兩組間各時間點數值皆相當接近，沒有統計上的差異，且數值都顯示出良好的骨整合，具有足夠的穩定度。而在骨-植體接觸比(BIC)數據上，4週、9週與13週組各個時間點，實驗組與對照組的數值分別為4週52.0%±1.7%與51.5%±2.1%，9週64.0%±11.2%與62.5%±8.1%，13週61.73%±6.0%與64.1%±5.2%，兩組間各時間點數值皆相當接近，沒有統計上的差異，都達到相當的骨整合。於同組植體不同時間之比較中，實驗組4週與13週間有統計上的差異(P = 0.045)，顯示隨時間增加，骨整合程度有上升的趨勢，其餘各組間則沒有差異。移除扭力測試中，實驗組得到較相對組高的移除扭力(實驗組為127N-cm，對照組為99N-cm、110N-cm，鈦金屬為106 N-cm)，但因為樣本數量不足，不具有統計上的意義。在骨新生螢光標定以及未脫鈣組織磨片及脫鈣組織切片的觀察中，實驗組與對照組呈現出相似的骨新生沉積，表示骨整合的過程中有相似的癒合反應。
以目前的實驗結果，本研究中所使用之自行開發氧化鋯陶瓷人工牙根在此動物實驗中達到與對照組相近的實驗結果。另外建立出未脫鈣磨片輔以骨螢光標定的處理技術，可觀察到本實驗中的氧化鋯植體於各時間點之骨新生模式。

Titanium dental implant has become a more popular treatment modality for edentulous patients since 1970s. However, metal exposure of titanium implant in cervical area has become a major concerning in anterior esthetic. Therefore, ceramic materials such as zirconia with the advantage of natural look color have been advocated as an alternate material for dental implant. So far the clinical efficacy of zirconia dental implant and the healing process of osteointgration between zirconium and bone have not been well demonstrated. Since the osteointgration is a crucial factor for successful implant therapy, the purpose of this study are to fabricate new zirconia dental implants with self-developed surface treatment modality and to compare such a self-developed zirconia implant with commercial zirconia implants in healing pattern and clinical efficacy by canine model.
In this study, self-developed zirconia implants in which were sandblasted with 60μm zirconium dioxide particles for surface treatment were enrolled in experimental group and commercial dental implants, Z-Look3 (Z-Systems AG, Konstanz, Germany) were enrolled in the control group. Implants in each group were subgroup according to different observation intervals (4, 9 and 13 weeks) with randomly distribution at bilateral mandible edentulous area in three beagle dogs. Furthermore, one additional titanium implant (Ti-Unite) compare to both self-developed and commercial zirconia implant by implanted in tibia bone for removal torque test in nine weeks subgroup. A bone-labeling technique with dyes injected at 4, 9 and 13week was used to observe new bone formation at different time points. Non-invasive evaluation including clinical observation on the implant status and implant stability analyzer, Periotest was used for accessment of degree of osteointgration in the observation period. After animal sacrificed and specimens harvested, rate of bone resorption was calculated by radiographic analysis. Grinding slides and decalcified sections observed histology and histomorphometry by calculated bone-implant contact (BIC). Calculated rate of bone resorption was listed as followings, 4 weeks experimental and control group were 2.7 ± 1.6% and 2.2 ± 1.3%; 9 weeks experimental and control group were 2.2 ± 1.3% and 3.1 ± 2.3%; 13 weeks experimental and the control group were 2.7 ± 1.5% and 4.5 ± 2.5%, there was no significant differences between the groups. Periotest values were listed as followings, the experimental group and the control group values were 0.73 ± 5.29 and 0.42 ± 0.78 for the 4 weeks group; 0.92 ± 2.45 and 2.05 ± 1.91 for the 9 weeks group; 2.11 ± 2.01 and 2.19 ± 0.83 for the 13 weeks group, there were no difference between the two groups, and the values were showed good osteointgration and sufficient stability. In the bone implant contact ratio, the experimental and control group BIC were 52.0% ± 1.7% and 51.5% ± 2.1% for the 4 weeks group; 64.0% ± 11.2% and 62.5% ± 8.1% for the 9 weeks group; 61.73% ± 6.0% and 64.1% ± 5.2% for the 13 weeks group, between the two groups at each time point values were very close, there were no significant difference. Removal torque test, the experimental group got a higher removal torque value (experimental group was 127N-cm, the control group were 99N-cm, 110N-cm and the titanium implant was 106 N-cm), due to small sample size, current results failed to demonstrate statistical significance. Undecalcified and decalcified tissue sections and labeling fluorochrome observation, both experimental and control groups showed similar new bone deposition, which means that the process of osteointgration have similar healing response.
In present animal study, healing pattern and clinical efficacy in new zirconia dental implants with self-developed surface treatment modality has been throughout investigated and evaluated, furthermore, new self-made zirconia implant owe equivalent ability in osteointgration as compare to commercial zirconia implant.

口試委員會審定書 i
誌謝 ii
中文摘要 iii
Abstract v
目錄 viii
圖目錄 xii
表目錄 xv
第一章 緒論 1
1.1 前言 1
1.2 研究動機 1
1.3 本文架構 2
第二章 文獻回顧 3
2.1 人工牙根發展 3
2.2 骨整合機制-植牙傷口骨癒合 5
2.3 鈦金屬植體 6
2.4 鈦金屬植體缺陷 6
2.5 氧化鋁植體 7
2.6 氧化鋯植體 8
2.6.1 氧化鋯發展歷史 8
2.6.2 材料性質 8
2.6.3 生物相容性 10
2.7 鈦金屬與氧化鋯植體之比較回顧 11
2.8 氧化鋯人工牙根臨床研究 14
2.9 非侵入性植體評估方式-Periotest 14
第三章 實驗材料與方法 16
3.1 實驗植體 16
3.1.1 植體外型 16
3.1.2 植體表面形貌觀察 17
3.2 實驗動物 17
3.2.1 實驗動物選擇 17
3.2.2 實驗動物狀況 18
3.3 實驗分組 18
3.4 實驗手術 19
3.4.1 麻醉與拔牙 19
3.4.2 植牙手術 20
3.4.3 術後動物照護 22
3.4.4 非侵入性評估-植體動搖度Periotest 23
3.4.5 骨頭螢光標定 23
3.5 動物犧牲及標本取得 24
3.5.1 動物犧牲灌流 25
3.5.2 移除扭力測試(Removal torque test) 25
3.5.3 標本取得 26
3.6 標本處理及染色 27
3.6.1 標本處理 27
3.6.2 標本X光片評估 27
3.6.3 未脫鈣(Undecalcified)標本製備 28
3.6.4 染色- Stevenel’s blue and Alizarin red S stain 31
3.6.5 脫鈣(Decalcified)標本製備 32
3.6.6 染色- H&E stain 32
3.7 掃描式電子顯微鏡標本觀察 33
3.8 骨-植體接觸比BIC計算 34
3.9 骨螢光標定觀察 35
3.10 實驗統計方式 35
第四章 實驗結果 36
4.1 植體表面掃描式電子顯微鏡SEM觀察 36
4.2 動物觀察 37
4.3 植體排除標準 37
4.4 植體動搖度Periotest Value 38
4.5 醫學用X光影像結果 42
4.6 脫鈣染色影像 45
4.7 未脫鈣磨片染色影像 47
4.8 骨-植體接觸比(BIC) 53
4.9 移除扭力值(RTQ) 54
4.10 骨螢光標定影像 55
4.11 骨整合SEM觀察 62
4.12 失敗骨整合之組織型態 64
第五章 討論與結論 67
5.1 實驗討論 67
5.1.1 骨吸收比率之探討 67
5.1.2 植體動搖度之探討 67
5.1.3 骨-植體接觸比之探討 68
5.1.4 移除扭力值之探討 69
5.1.5 骨癒合機制之探討 70
5.2 實驗檢討 71
5.3 結論 72
參考文獻 73

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