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系統識別號 U0007-2007201017080600
論文名稱(中文) A Novel Resorbable Composite of Calcium Sulfate and Amorphous Calcium Phosphate Bone Substitute for Dental Implants
論文名稱(英文) A Novel Resorbable Composite of Calcium Sulfate and Amorphous Calcium Phosphate Bone Substitute for Dental Implants
校院名稱 臺北醫學大學
系所名稱(中) 牙醫學系碩博士班
系所名稱(英) School of Dentistry
學年度 98
學期 2
出版年 99
研究生(中文) 柏馬
研究生(英文) Malosi Poma
學號 M204095014
學位類別 碩士
語文別 英文
口試日期 2010-07-05
論文頁數 104頁
口試委員 指導教授-李勝揚
共同指導教授-楊正昌
共同指導教授-王敦正
委員-王錫福
委員-陳建中
中文關鍵字 合成骨材質  擴增  硫酸鈣  無定形磷酸鈣  吸收速率 
英文關鍵字 Synthetic bone substitutes  augmentation  calcium sulfate  amorphous calcium phosphate  resorption rate 
學科別分類
中文摘要 目的: 本篇研究的目的在於製造一種新的可吸收性α型半水硫酸鈣骨填補材料,特別是可用於齒槽骨缺損的移植物,這種移植物可以在三到六個月之間產生吸收與替代,仿造人類下顎骨自然再生的速率。本研究使用一犬齒的模型以研究這種新的骨填補材其於體內之生物相容性,生物代謝性與骨傳導性。
材料與方法: 本研究使用一種創新的單一過程來製備這種α-CSH/ACP的合成骨移植替代物。不同的含水α-CSH/ACP合成物的固化測試,是以Vicat針頭來偵測其粒狀區塊的合成穩定度。體外溶解測試是將樣本(α-CSH/ACP 60/40, 70/30, 80/20與 CS/β-TCP 60/40, 70/30, 80/20的顆粒,TMU CS, Osteoset®)浸泡於磷酸緩衝液中(PBS),並以每分鐘30轉與37度C水浴搖晃。在米格魯犬的雙側下顎骨製備出骨缺損,骨缺損的半徑為5mm,深8mm,並種植入α-CSH/ACP (60/40),CS/β-TCP (60/40) 與 (40/60),CS,Osteoset®(CS)與一個缺損不作任何處理做為控制組。在三週與六週進行觀察,樣本使用環鋸取下,以H.E染色後,在光學顯微鏡與Image J電腦軟體進行組織與組織形態分析。統計方式以不成雙與單側student t test進行統計,並使用ANOVA與pos hoc tukey’s測試,以P值小於0.05具有意義。
結果: 結果顯示了高純度α-CSH與ACP的種種特性。α-CSH與ACP合成物的固化時間隨者ACP成分的增加而縮短。由於硫酸鈣其具有不良於結晶的氫氧磷灰石形成,因此以緩慢溶解著名,所有的材料皆顯示了早期於PBS中快速溶解。α-CSH/ACP與 CS/β-TCP的合成物,其溶解速度較單獨的TMU CS來得緩慢。α-CSH/ACP與CS/β-TCP的吸收速率隨著ACP或β-TCP的比率增加而漸減。當α-CSH/ACP合成物的吸收比CS/β-TCP合成物來得快時,TMU CS與Osteoset顆粒顯示了相似的吸收速率。三週後的組織測試顯示所有的植体骨填補材料並無顯著的發炎或是免疫抗拒反應產生。六週後,編織骨被層狀骨以及空腔取代,進而顯現了許多大的空間。於三週後,α-CSH/ACP的骨再生率為21.1 ±9.5%,CS/β-TCP (60/40) 為23.0 ±9.9,Osteoset (CS)為29.0 ±16.0,CS/β-TCP (40/60)為 33.1 ±12.0%,控制組為13.6 ±9.5%。而在六周時,新骨形成的比率在α-CSH/ACP,CS/β-TCP (60/40),CS/β-TCP (40/60),Osteoset®(100%CS),CS組與控制組則分別為62.2 ±6.8%,48.9 ±8.1%,52.7 ±6.7%,53.3 ±4.6%,42.4 ±8.8%以及40.1 ±7.2%。所有的骨填補物質組別中,除了CS組之外,都比對照組顯現了較多的新骨形成。當α-CSH/ACP比起其他骨填補材質有較多的新骨形成,Osteoset®(CS)與CS/β-TCP 40/60組別比起TMU CS組別也有較多的骨再生現像產生,並且P值都小於0.05。推斷接近這種新的α-CSH/ACP材質的合成物,其將會於三到四個月內在人類下顎骨中被吸收並置換成新的骨骼。
結論: 所有實驗的SBGS都是可吸收的,生物相容的,並且具備骨傳導性。基於新骨形成速率的推斷,α-CSH/ACP (60/40)合成物可在三六個月內被骨骼所吸收並替代,這也意味著其接近並相似於自然骨再生速率。新的α-CSH/ACP合成物可以縮短植體治療期間的癒合期,因此可以作為牙科植體未來理想的骨填補材質。
英文摘要 Objectives: The purpose of this study was to develop a novel resorbable α-calcium sulfate hemihydrate/amorphous calcium phosphate (α-CSH/ACP) bone graft substitute specifically for alveolar ridge augmentation that could mimic the natural regeneration rate of human jaw bone by resorbing and substituted by bone within three to six months. A canine model was used to investigate the in vivo biocompatibility, biodegradation and osteoconductivity of the novel bone substitute.
Materials and Methods: An innovative single process was used to produce synthetic bone graft substitute (SBGS) of α-CSH/ACP. Setting test for various hydrated α-CSH/ACP compositions was conducted by the Vicat needle to determine formulation good for granular particles preparation. In vitro dissolution was conducted by immersing of specimens (granules of, α-CSH/ACP 60/40, 70/30, 80/20 and CS/β-TCP 60/40, 70/30, 80/20, pellets of TMU CS and Osteoset®) in phosphate buffered solution (PBS) and incubated in a shaking bath operated at 30 rpm and 37oC. Bone defects of φ 5mm x 8 mm depth were created bilaterally in mandibles of beagle dogs and implanted with α-CSH/ACP (60/40), CS/β-TCP (60/40) as well as (40/60), CS, Osteoset®(CS) and one defect was left empty as a control. After three weeks and six weeks, specimens were harvested with trephine burs and prepared with H.E staining for histological and histomorphometrical analysis under microscope and Image J computer software. Unpaired and one tailed student t test, ANOVA and pos hoc tukey’s test were used for statistical interpretation of data. P value < 0.05 was stated as significance.
Results: The results displayed high purity manufactured α-CSH and ACP. Setting time of α-CSH/ACP composites was shortened as the ACP content increasing. All materials displayed early rapid dissolution in PBS due to calcium sulfate followed by remarkable slow dissolution as a result of poor crystalline hydroxyapatite formation. Composites of α-CSH/ACP and CS/β-TCP resorbed slower than TMU CS alone. Resorption rate of composites α-CSH/ACP and CS/β-TCP reduced as the amount of ACP or β-TCP increasing. TMU CS and Osteoset pellets demonstrated similar resorption rates, while composites of α-CSH/ACP dissolute faster than CS/β-TCP composites. Histological examination after three weeks revealed no obvious presence of inflammation or immune rejection for all implanted SBGS. After six weeks, woven bone were replaced by lamellae bone and empty defects showed presence of big empty spaces. After three weeks, bone regeneration were α-CSH/ACP 21.1 ±9.5%, CS/β-TCP (60/40) 23.0 ±9.9, Osteoset (CS) 29.0 ±16.0, CS/β-TCP (40/60) 33.1 ±12.0% and empty control 13.6 ±9.5%. At six weeks, ratio of new bone formation for α-CSH/ACP, CS/β-TCP (60/40), CS/β-TCP (40/60), Osteoset®(100%CS),CS, and empty control were 62.2 ±6.8%, 48.9 ±8.1%, 52.7 ±6.7%, 53.3 ±4.6%, 42.4 ±8.8%, and 40.1 ±7.2%, respectively. All SBGS except CS exhibited more new bone formation than the control. Osteoset®(CS) and CS/β-TCP 40/60 regenerated more bone than TMU CS, while α-CSH/ACP yielded more new bone than all the other SBGS, p value < 0.05. Extrapolation graph approximated this novel composite of α-CSH/ACP to be resorbed and substituted by new bone within three to four months in human jaw bone.
Conclusion: All experimented SBGS were resorbable, biocompatible and osteoconductive. Based on the extrapolation of ratio of new bone formation with time, the α-CSH/ACP (60/40) composite could be resorbed and substituted by bone within three to six months implying the resorption rate closely mimics the natural bone regeneration rate. Novel composite of α-CSH/ACP could shorten the healing and implant treatment period, therefore it could be an ideal SBGS for dental implants in the future.
論文目次 CONTENTS
Abstracts…………………………………………………………………………..I
Acknowledgements……………………………………………………………VIII
Abbreviations…………………………………………………………………….X
Glossary of terms………………………………………………………………...XI
Contents………………………………………………………………………….XII
1 Introduction………………………………………………………………………1
1-1 Background…………………………………………………………………...1
1-2 Motivation………………………………………………………………….....3
1-3 Purpose……………………………………………………………………......5
1-4 Hypothesis………………………………………………………………….....6
2 Literature Review………………………………………………………………...9
2-1 Demand for Dental Implants and Bone Grafts…………………………….....9
2-2 Ideal Properties of Bone Graft Substitutes for Dental Implants…………….10
2-3 Proposed Ideal Resorption Period…………………………………………..11
2-4 Resorption Rate of Bone Substitutes………………………………………..13
2-5 Calcium Sulfate bone substitute…………………………………………….14
2-6 Composite of Calcium Sulfate with Calcium Phosphate…………………...16
2-7 Amorphous Calcium Phosphate…………………………………………….20
2-8 Animal Study………………………………………………………………..23
2-8-1 In-Vitro Study vs. Animal Model……………………………………23
2-8-2 Canine Model………………………………………………………...24
2-8-3 Critical Defect Size…………………………………………………..25
3Materials and Method…………………………………………………………....27
3-1 Materials…………………………………………………………………….27
3-2 Equipments………………………………………………………………….27
3-3 Study Structure……………………………………………………………...29
3-4 Material Production and Characterization…………………………………..31
3-4-1 TMU Novel Manufacturing Process…………………………………31
3-4-2 Manufacturing Process for α-Calcium Sulfate Hemihydrate………...32
3-4-3 Manufacturing Process of Amorphous Calcium Phosphate…………33
3-5 Setting Test………………………………………………………………….34
3-6 In-Vitro Dissolution Test…………………………………………………...34
3-7 Animal Study………………………………………………………………..35
3-7-1 Purpose……………………………………………………………….35
3-7-2 Animals………………………………………………………………36
3-7-3 Study Design…………………………………………………………36
3-7-4 Anesthesia……………………………………………………………37
3-7-5 Surgical Procedures………………………………………………….38
3-7-6 Histological and Histomorphometrical Analysis…………………….39
3-8 Statistical Analysis…………………………………………………………40
4 Results…………………………………………………………………………..41
5 Discussion……………………………………………………………………….45
6 Conclusion………………………………………………………………………57
References………………………………………………………………………...58
Figures…………………………………………………………………………….73
Table……………………………………………………………………………....90

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