臺灣博碩士論文加值系統

目的：本研究目的在評估使用不同骨取代物(硫酸鈣/非晶型磷酸鈣雙相複合材，低結晶型氫氧磷灰石/ s-三鈣磷酸鹽雙相複合材，膠原蛋白材料)填入下顎阻生第三大臼齒拔牙後窩洞，評估對於減少第二大臼齒牙周缺損的效益。

方法與材料：共20位受試者參與並完成試驗。共40個下顎阻生第三臼齒分成4組：硫酸鈣/非晶型磷酸鈣雙相複合材組，低結晶型氫氧磷灰石/ s-三鈣磷酸鹽雙相複合材組，膠原蛋白材料組及空白對照組。在拔牙前及拔牙試驗後3，6，12週測量下顎第二大臼齒臨床牙周囊袋深度。測量數值以平均值 ± 標準差計算及呈現。顯著差界值為P < 0.05。各組之差異以變異數分析(ANOVA)作統計，各組間不同時間點以配對t檢定進行統計分析。

結果：硫酸鈣/非晶型磷酸鈣雙相複合材組、低結晶型氫氧磷灰石/ s-三鈣磷酸鹽雙相複合材組、膠原蛋白材料組及空白對照組之下顎第二大臼齒遠心側牙周囊袋探測深度，在拔除阻生下顎第三大臼齒前分別為3.70 ± 1.16 mm、2.70 ± 0.82 mm、3.70 ± 1.49 mm、4.60 ± 0.82 mm；而在下顎第三大臼齒拔牙試驗後第12週，各組之第二大臼後遠心側牙周囊袋探測深度分別為2.80 ± 0.63 mm、2.50 ± 0.85 mm、4.90 ± 0.99 mm、4.50 ± 0.82 mm。各組於拔牙後第12週減少的牙周囊袋深度與術前探測值之比率則為24.3%、7.4%、-32.4%、2.2%。硫酸鈣/非晶型磷酸鈣雙相複合材組及低結晶型氫氧磷灰石/ s-三鈣磷酸鹽雙相複合材組在降低第二大臼齒牙周囊袋的成效優於膠原蛋白材料組及空白對照組，並有統計學上的意義(p < 0.05)。

結論： 本研究之結論支持合成骨取代物：硫酸鈣/非晶型磷酸鈣雙相複合材及低結晶型氫氧磷灰石/ s-三鈣磷酸鹽雙相複合材，填入下顎阻生第三大臼齒拔牙後窩洞，可以有效減少下顎第二大臼齒遠心側發生牙周囊袋發生的機會。

Purpose: The objective of this study was to evaluate the efficacy of different synthetic bone substitutes, calcium sulfate/amorphous calcium phosphate(CaSO4/ACP), poorly crystalline hydroxyapatite/ s-tricalcium sulfate (PC-HAp/ s-TCP), collagen sponge, for the prevention of second molar periodontal defects after extraction of an adjacent impacted mandibular third molar.

Method: Twenty patients (twelve male and eight female) patients with bilateral impacted mandibular third molars were selected to participate in the study. The forty extraction sockets were divided into 4 groups: empty control group, CaSO4/ACP group, PC-HAp/ s-TCP group, and collagen sponge group. Clinical pocket depth of the mandibular second molars were recorded at 3, 6, 12 weeks after the surgery. Data were calculated and reported as mean ± SD, and the significance level was set at p < 0.05. Repeated-measures analysis of variance (ANOVA) was used to detect the treatment and time effect among all groups. Paired t test was used to compare the result at different observation periods.

Results: The pocket depth measurements for the CaSO4/ACP, PC-HAp/ s-TCP, collagen sponge and empty control groups were 3.70 ± 1.16, 2.70 ± 0.82, 3.70 ± 1.49, 4.60 ± 0.82, respectively, before the surgery and 2.80 ± 0.63 mm, 2.50 ± 0.85 mm, 4.90 ± 0.99 mm, 4.50 ± 0.82 mm, respectively, at 12 weeks after the surgery. The pocket depth reduction/baseline pocket depth ratios were 24.3%, 7.4%, -32.4%, 2.2%, respectively, for the CaSO4/ACP, PC-HAp/s-TCP, collagen sponge, and empty control groups, at 12 weeks after surgery. CaSO4/ACP, PC-HAp/s-TCP as bone substitutes reduced the pocket depth more effectively than collagen sponge and empty control groups and the result is statistically significant.

Conclusion: The results obtained in this study support the use of synthetic bone substitute, CaSO4/ ACP and PC-HAp/ s-TCP, to prevent future periodontal defects of the second molar adjacent to the third molar extraction socket.

標題………………………………………………………………………………i
審定書…………………………………………………………………………ii
上網授權書………………………………………………………………iii
誌謝……………………………………………………………………………iv
目錄………………………………………………………………………………v
表目錄……………………………………………………………………viii
圖目錄…………………………………………………………………………ix
中文摘要………………………………………………………………………xi
英文摘要…………………………………………………………………xiii
第一章 緒論…………………………………………………………………1
1.1. 背景……………………………………………………………1
1.2. 文獻回顧……………………………………………………2
1.3. 研究假說…………………………………………………15
1.4. 研究目的…………………………………………………16
第二章 研究材料與方法..……………………………………17
2.1. 人體試驗委員會……………………………………17
2.2. 研究對象…………………………………………………17
2.3. 研究設計…………………………………………………17
2.4. 材料…………………………………………………………18
2.5. 手術步驟…………………………………………………19
2.6. 資料收集…………………………………………………19
2.7. 統計分析…………………………………………………19
第三章 結果…………………………………………………………………21
第四章 討論…………………………………………………………………23
4.1. 導引骨再生術…………………………………………23
4.2. 再生膜於阻生下顎第三大臼齒拔牙後窩洞處導引骨再生術的功能……………………………………………………………………………………23
4.3. 預防性抗生素的使用……………………………24
4.4. 與動物實驗的比較…………………………………26
4.5. 合成骨取代物作為細胞支架的角色……27
第五章 結論與展望 …………………………………………………29
第六章 參考資料…………………………………………………………30
第七章 附錄…………………………………………………………………41
7.1 表…………………………………………………………………41
7.2 圖…………………………………………………………………51
7.3 人體試驗許可證明……………………………………77

1.Simon Z, Watson PA. Biomimetic dental implants--new ways to enhance osseointegration. J Can Dent Assoc 2002;68:286-8.
2.Blakey GH, Parker DW, Hull DJ, White RP, Jr., Offenbacher S, Phillips C, Haug RH. Impact of removal of asymptomatic third molars on periodontal pathology. J Oral Maxillofac Surg 2009;67:245-50.
3.Quee TA, Gosselin D, Millar EP, Stamm JW. Surgical removal of the fully impacted mandibular third molar. The influence of flap design and alveolar bone height on the periodontal status of the second molar. J Periodontol 1985;56:625-30.
4.Monaco G, Daprile G, Tavernese L, Corinaldesi G, Marchetti C. Mandibular third molar removal in young patients: an evaluation of 2 different flap designs. J Oral Maxillofac Surg 2009;67:15-21.
5.Chaves AJ, Nascimento LR, Costa ME, Franz-Montan M, Oliveira-Junior PA, Groppo FC. Effects of surgical removal of mandibular third molar on the periodontium of the second molar. Int J Dent Hyg 2008;6:123-8.
6.Elter JR, Offenbacher S, White RP, Beck JD. Third molars associated with periodontal pathology in older Americans. J Oral Maxillofac Surg 2005;63:179-84.
7.Sammartino G, Tia M, Bucci T, Wang HL. Prevention of mandibular third molar extraction-associated periodontal defects: a comparative study. J Periodontol 2009;80:389-96.
8.Kugelberg CF, Ahlstrom U, Ericson S, Hugoson A. Periodontal healing after impacted lower third molar surgery. A retrospective study. Int J Oral Surg 1985;14:29-40.
9.Kugelberg CF, Ahlstrom U, Ericson S, Hugoson A, Thilander H. The influence of anatomical, pathophysiological and other factors on periodontal healing after impacted lower third molar surgery. A multiple regression analysis. J Clin Periodontol 1991;18:37-43.
10.Chuang SK, Perrott DH, Susarla SM, Dodson TB. Age as a risk factor for third molar surgery complications. J Oral Maxillofac Surg 2007;65:1685-92.
11.Sammartino G, Tia M, Gentile E, Marenzi G, Claudio PP. Platelet-rich plasma and resorbable membrane for prevention of periodontal defects after deeply impacted lower third molar extraction. J Oral Maxillofac Surg 2009;67:2369-73.
12.Nazaroglou I, Stavrianos C, Kafas P, Matoulas E, Upile T, Barlas I, Jerjes W. Radiographic evaluation of bone regeneration after the application of plasma rich in growth factors in a lower third molar socket: a case report. Cases J 2009;2:9134.
13.Dodson TB. Is there a role for reconstructive techniques to prevent periodontal defects after third molar surgery? Oral Maxillofac Surg Clin North Am 2007;19:99-104, vii.
14.Aimetti M, Romano F. Use of resorbable membranes in periodontal defects treatment after extraction of impacted mandibular third molars. Minerva Stomatol 2007;56:497-508.
15.Szmyd L, Hester WR. Crevicular depth of the second molar in impacted third molar surgery. J Oral Surg Anesth Hosp Dent Serv 1963;21:185-9.
16.Pons-Vicente O, Valmaseda-Castellon E, Berini-Aytes L, Gay-Escoda C. Effect on pocket depth and attachment level of manual versus ultrasonic scaling of lower second molars following lower third molar extraction: a randomized controlled trial. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:e11-9.
17.Motamedi MH. A technique to manage gingival complications of third molar surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:140-3.
18.Kirtiloglu T, Bulut E, Sumer M, Cengiz I. Comparison of 2 flap designs in the periodontal healing of second molars after fully impacted mandibular third molar extractions. J Oral Maxillofac Surg 2007;65:2206-10.
19.Camelo M, Nevins ML, Schenk RK, Simion M, Rasperini G, Lynch SE, Nevins M. Clinical, radiographic, and histologic evaluation of human periodontal defects treated with Bio-Oss and Bio-Gide. Int J Periodontics Restorative Dent 1998;18:321-31.
20.Casati MZ, Sallum EA, Nociti FH, Jr., Caffesse RG, Sallum AW. Enamel matrix derivative and bone healing after guided bone regeneration in dehiscence-type defects around implants. A histomorphometric study in dogs. J Periodontol 2002;73:789-96.
21.Fugazzotto PA. GBR using bovine bone matrix and resorbable and nonresorbable membranes. Part 2: Clinical results. Int J Periodontics Restorative Dent 2003;23:599-605.
22.Fugazzotto PA. GBR using bovine bone matrix and resorbable and nonresorbable membranes. Part 1: histologic results. Int J Periodontics Restorative Dent 2003;23:361-9.
23.Aimetti M, Pigella E, Romano F. Clinical and radiographic evaluation of the effects of guided tissue regeneration using resorbable membranes after extraction of impacted mandibular third molars. Int J Periodontics Restorative Dent 2007;27:51-9.
24.Oxford GE, Quintero G, Stuller CB, Gher ME. Treatment of 3rd molar-induced periodontal defects with guided tissue regeneration. J Clin Periodontol 1997;24:464-9.
25.Dodson TB. Management of mandibular third molar extraction sites to prevent periodontal defects. J Oral Maxillofac Surg 2004;62:1213-24.
26.d''Aquino R, De Rosa A, Lanza V, Tirino V, Laino L, Graziano A, Desiderio V, Laino G, Papaccio G. Human mandible bone defect repair by the grafting of dental pulp stem/progenitor cells and collagen sponge biocomplexes. Eur Cell Mater 2009;18:75-83.
27.Barone A, Aldini NN, Fini M, Giardino R, Calvo Guirado JL, Covani U. Xenograft versus extraction alone for ridge preservation after tooth removal: a clinical and histomorphometric study. J Periodontol 2008;79:1370-7.
28.Al Ruhaimi KA. Bone graft substitutes: a comparative qualitative histologic review of current osteoconductive grafting materials. Int J Oral Maxillofac Implants 2001;16:105-14.
29.Knabe C, Houshmand A, Berger G, Ducheyne P, Gildenhaar R, Kranz I, Stiller M. Effect of rapidly resorbable bone substitute materials on the temporal expression of the osteoblastic phenotype in vitro. J Biomed Mater Res A 2008;84:856-68.
30.Yuan H, Li Y, de Bruijn JD, de Groot K, Zhang X. Tissue responses of calcium phosphate cement: a study in dogs. Biomaterials 2000;21:1283-90.
31.Nilsson M, Wang JS, Wielanek L, Tanner KE, Lidgren L. Biodegradation and biocompatability of a calcium sulphate-hydroxyapatite bone substitute. J Bone Joint Surg Br 2004;86:120-5.
32.Urban RM, Turner TM, Hall DJ, Inoue N, Gitelis S. Increased bone formation using calcium sulfate-calcium phosphate composite graft. Clin Orthop Relat Res 2007;459:110-7.
33.Laiblin C, Jaeschke G. [Clinical chemistry examinations of bone and muscle metabolism under stress in the Gottingen miniature pig--an experimental study]. Berl Munch Tierarztl Wochenschr 1979;92:124-8.
34.Szmukler-Moncler S, Piattelli A, Favero GA, Dubruille JH. Considerations preliminary to the application of early and immediate loading protocols in dental implantology. Clin Oral Implants Res 2000;11:12-25.
35.Kawai T, Murakami S, Hiranuma H, Sakuda M. Healing after removal of benign cysts and tumors of the jaws. A radiologic appraisal. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79:517-25.
36.Kawai T, Murakami S, Hiranuma H, Sakuda M. Radiographic changes during bone healing after mandibular fractures. Br J Oral Maxillofac Surg 1997;35:312-8.
37.Peters CL, Hines JL, Bachus KN, Craig MA, Bloebaum RD. Biological effects of calcium sulfate as a bone graft substitute in ovine metaphyseal defects. J Biomed Mater Res A 2006;76:456-62.
38.Scarano A, Orsini G, Pecora G, Iezzi G, Perrotti V, Piattelli A. Peri-implant bone regeneration with calcium sulfate: a light and transmission electron microscopy case report. Implant Dent 2007;16:195-203.
39.Walsh WR, Morberg P, Yu Y, Yang JL, Haggard W, Sheath PC, Svehla M, Bruce WJ. Response of a calcium sulfate bone graft substitute in a confined cancellous defect. Clin Orthop Relat Res 2003:228-36.
40.Mesimeris V, Sade E, Baer PN. Calcium sulfate as a biodegradable barrier membrane--a preliminary report on the "Surgiplast" Technique. Periodontal Clin Investig 1995;17:13-6.
41.Benoit MA, Mousset B, Delloye C, Bouillet R, Gillard J. Antibiotic-loaded plaster of Paris implants coated with poly lactide-co-glycolide as a controlled release delivery system for the treatment of bone infections. Int Orthop 1997;21:403-8.
42.Bai MH, Liu XY, Ge BF, Yallg C, Chen DA. An implant of a composite of bovine bone morphogenetic protein and plaster of paris for treatment of femoral shaft nonunions. Int Surg 1996;81:390-2.
43.Strocchi R, Orsini G, Iezzi G, Scarano A, Rubini C, Pecora G, Piattelli A. Bone regeneration with calcium sulfate: evidence for increased angiogenesis in rabbits. J Oral Implantol 2002;28:273-8.
44.Coetzee AS. Regeneration of bone in the presence of calcium sulfate. Arch Otolaryngol 1980;106:405-9.
45.Lazary A, Balla B, Kosa JP, Bacsi K, Nagy Z, Takacs I, Varga PP, Speer G, Lakatos P. Effect of gypsum on proliferation and differentiation of MC3T3-E1 mouse osteoblastic cells. Biomaterials 2007;28:393-9.
46.de Bruijn JD, Bovell YP, van Blitterswijk CA. Structural arrangements at the interface between plasma sprayed calcium phosphates and bone. Biomaterials 1994;15:543-50.
47.Petruskevicius J, Nielsen S, Kaalund S, Knudsen PR, Overgaard S. No effect of Osteoset, a bone graft substitute, on bone healing in humans: a prospective randomized double-blind study. Acta Orthop Scand 2002;73:575-8.
48.al Ruhaimi KA. Effect of adding resorbable calcium sulfate to grafting materials on early bone regeneration in osseous defects in rabbits. Int J Oral Maxillofac Implants 2000;15:859-64.
49.Bohner M. New hydraulic cements based on alpha-tricalcium phosphate-calcium sulfate dihydrate mixtures. Biomaterials 2004;25:741-9.
50.LeGeros RZ. Properties of osteoconductive biomaterials: calcium phosphates. Clin Orthop Relat Res 2002:81-98.
51.Nagano M, Nakamura T, Kokubo T, Tanahashi M, Ogawa M. Differences of bone bonding ability and degradation behaviour in vivo between amorphous calcium phosphate and highly crystalline hydroxyapatite coating. Biomaterials 1996;17:1771-7.
52.Posner AS, Blumenthal NC, Boskey AL, Betts F. Synthetic analogue of bone mineral formation. J Dent Res 1975;54 Spec No B:B88-93.
53.Boskey AL, Posner AS. Bone structure, composition, and mineralization. Orthop Clin North Am 1984;15:597-612.
54.Termine JD, Posner AS. Infrared analysis of rat bone: age dependency of amorphous and crystalline mineral fractions. Science 1966;153:1523-5.
55.Skrtic D, Antonucci JM, McDonough WG, Liu DW. Effect of chemical structure and composition of the resin phase on mechanical strength and vinyl conversion of amorphous calcium phosphate-based composites. J Biomed Mater Res A 2004;68:763-72.
56.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;58:295-301.
57.Ducheyne P, Cuckler JM. Bioactive ceramic prosthetic coatings. Clin Orthop Relat Res 1992:102-14.
58.Whited BM, Skrtic D, Love BJ, Goldstein AS. Osteoblast response to zirconia-hybridized pyrophosphate-stabilized amorphous calcium phosphate. J Biomed Mater Res A 2006;76:596-604.
59.Mao-Shuan Huang H-DW, Nai-Chia Teng, Bou-Yue Peng, Jia-Yo Wu, Wei-Jen Chang, Jen-Chang Yang, Chien-Chung Chen, Sheng-Yang Lee. In vivo evaluation of poorly crystalline hydroxyapatite-based biphasic calcium phosphate bone substitutes for treating dental bony defects. J Dent Sci 2010 5:100-108.
60.楊正昌 胡, 吳宏達, 楊沛青, 李勝揚. 提升植牙成功率的新型合成骨填補材BonaGraft之研發與應用. 臨床牙醫植體學精要/Synopsis of Clinical Implant Dentistry 2010:488-497.
61.Branemark PI. Osseointegration and its experimental background. J Prosthet Dent 1983;50:399-410.
62.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;63:729-35.
63.LeGeros RZ. Calcium phosphate-based osteoinductive materials. Chem Rev 2008;108:4742-53.
64.Martin JY, Schwartz Z, Hummert TW, Schraub DM, Simpson J, Lankford J, Jr., Dean DD, Cochran DL, Boyan BD. Effect of titanium surface roughness on proliferation, differentiation, and protein synthesis of human osteoblast-like cells (MG63). J Biomed Mater Res 1995;29:389-401.
65.Motomiya M, Ito M, Takahata M, Kadoya K, Irie K, Abumi K, Minami A. Effect of Hydroxyapatite porous characteristics on healing outcomes in rabbit posterolateral spinal fusion model. Eur Spine J 2007;16:2215-24.
66.Benoit PW, Hunt LM. Comparison of a microcrystalline collagen preparation and gelatin foam in extraction wounds. J Oral Surg 1976;34:1079-83.
67.Takahashi K. Effect of new bone substitute materials consisting of collagen and tricalcium phosphate. Bull Tokyo Dent Coll 2009;50:1-11.
68.McKay WF, Peckham SM, Badura JM. A comprehensive clinical review of recombinant human bone morphogenetic protein-2 (INFUSE Bone Graft). Int Orthop 2007;31:729-34.
69.Cardaropoli G, Araujo M, Hayacibara R, Sukekava F, Lindhe J. Healing of extraction sockets and surgically produced - augmented and non-augmented - defects in the alveolar ridge. An experimental study in the dog. J Clin Periodontol 2005;32:435-40.
70.Cochran DL, Jones AA, Lilly LC, Fiorellini JP, Howell H. Evaluation of recombinant human bone morphogenetic protein-2 in oral applications including the use of endosseous implants: 3-year results of a pilot study in humans. J Periodontol 2000;71:1241-57.
71.Fiorellini JP, Howell TH, Cochran D, Malmquist J, Lilly LC, Spagnoli D, Toljanic J, Jones A, Nevins M. Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation. J Periodontol 2005;76:605-13.
72.Hanisch O, Sorensen RG, Kinoshita A, Spiekermann H, Wozney JM, Wikesjo UM. Effect of recombinant human bone morphogenetic protein-2 in dehiscence defects with non-submerged immediate implants: an experimental study in Cynomolgus monkeys. J Periodontol 2003;74:648-57.
73.Howell TH, Fiorellini J, Jones A, Alder M, Nummikoski P, Lazaro M, Lilly L, Cochran D. A feasibility study evaluating rhBMP-2/absorbable collagen sponge device for local alveolar ridge preservation or augmentation. Int J Periodontics Restorative Dent 1997;17:124-39.
74.Guerrero JS. Use of Prophylactic Antibiotic Therapy in Oral Surgical Procedures: A Critical Review. Antibiotic therapy 2008.
75.Sancho-Puchades M, Herraez-Vilas JM, Berini-Aytes L, Gay-Escoda C. Antibiotic prophylaxis to prevent local infection in Oral Surgery: use or abuse? Med Oral Patol Oral Cir Bucal 2009;14:E28-33.
76.Sammartino G, Tia M, Marenzi G, di Lauro AE, D''Agostino E, Claudio PP. Use of autologous platelet-rich plasma (PRP) in periodontal defect treatment after extraction of impacted mandibular third molars. J Oral Maxillofac Surg 2005;63:766-70.
77.Dodson TB. Is there a role for reconstructive techniques to prevent periodontal defects after third molar surgery? J Oral Maxillofac Surg 2005;63:891-6.
78.Pearce AI, Pearce SG, Schwieger K, Milz S, Schneider E, Archer CW, Richards RG. Effect of surface topography on removal of cortical bone screws in a novel sheep model. J Orthop Res 2008;26:1377-83.
79.Burg KJ, LaBerge M, Shalaby SW. Change in stiffness and effect of orientation in degrading polylactide films. Biomaterials 1998;19:785-9.
80.Marei MK, Nouh SR, Saad MM, Ismail NS. Preservation and regeneration of alveolar bone by tissue-engineered implants. Tissue Eng 2005;11:751-67.
81.Trubiani O, Orsini G, Zini N, Di Iorio D, Piccirilli M, Piattelli A, Caputi S. Regenerative potential of human periodontal ligament derived stem cells on three-dimensional biomaterials: a morphological report. J Biomed Mater Res A 2008;87:986-93.
82.Hodde J. Naturally occurring scaffolds for soft tissue repair and regeneration. Tissue Eng 2002;8:295-308.
83.Graziano A, d''Aquino R, Cusella-De Angelis MG, De Francesco F, Giordano A, Laino G, Piattelli A, Traini T, De Rosa A, Papaccio G. Scaffold''s surface geometry significantly affects human stem cell bone tissue engineering. J Cell Physiol 2008;214:166-72.