臺灣博碩士論文加值系統

本研究的目的是利用具骨誘導能力之脫鈣冷凍乾燥異體移植骨(demineralized free-dried bone allograft)與多孔性氫氧磷灰石(porous hydroxyapatite) 混合使用並配合鈦金屬網托之應用來重建下顎骨大範圍缺損之後其骨癒合情形之狀況,並將結果和單獨填入多孔性氫氧磷灰石之缺損區比較,何者能縮短骨癒合時間 。
本實驗是以十隻成年的雜種狗作為研究對象，每隻實驗動物體重各為十公斤左右，將所有犬隻分為五組，每組二隻。實驗組利用多孔性氫氧磷灰石(porous HA)及脫鈣冷凍乾燥異體移植骨(DFDBA)混合置於鈦金屬網托內重建下顎骨缺損區，而對照組則單獨利用鈦金屬網托或僅以多孔性氫氧磷灰石(porous HA)置於鈦金屬網托內來重建下顎骨缺損區。分別於術後2週 ,4週(一個月),8週(二個月) ,12週(三個月),24週(六個月)將標本取下。利用掃描型電子顯微鏡 ( scanning electron microscopy，SEM ) 配合冷凍劈裂 ( freeze cracking )， EDTA-KOH特殊標本處理方式及血管鑄型( corrosive resin casting )技術觀察不同時期實驗組與對照組兩者骨再生及血管新生之差異。實驗結果發現在兩週實驗組的缺損區，近心、遠心鄰接面和上方三分之一均已出現排列較整齊的膠原纖維，有較多的造骨細胞附著。四週的實驗組，近心、遠心的鄰接面和上方三分之一則有較成熟的新生骨形成，在近遠心鄰接面則有織網骨沉積填滿。第十二週時，實驗組的骨缺損重建區內，近遠心的鄰接面和上方三分之一已出現哈維氏系統的構造，到二十四週時，骨缺損區四周新生骨組織生成量及骨成熟度，在實驗組與對照組己沒有差別，但是在骨缺損區中央區域，則還是以實驗組有較多的新生骨組織生成量及較好的骨成熟度，而在血管鑄型的標本發現兩週的實驗組有較多新生血管組織,並有血管長出及長入多孔性氫氧磷灰石的孔洞中,而八週的實驗組發現缺損區中央可觀察到纖細的血管網穿梭在多孔性氫氧磷灰石顆粒間，同時可見到血管網鑄型穿入多孔性氫氧磷灰石interpore 200的孔洞內，因此可將多孔性氫氧磷灰石interpore 200的顆粒穩定的固持住。其結果證實填入多孔性氫氧磷灰石混合脫鈣冷凍乾燥異體移植骨能達成早期骨癒合並可做為日後臨床應用之重要參考。

The purpose of this study was to investigate the changes of new bone ingrowth in porous hydroxyapatite-implanted or porous hydroxyapatite / DFDBA-implanted cavity by using scanning electron microscope (SEM) with EDTA-KOH method. Ten mongrel dogs were used as experimental animals. A 15mm × 7mm cavity was created on right mandible and left mandible with porous HA ( Interpore200, INTERPORE□ USA) implanted in left side and porous HA /DFDBA in right side and immobilized by titanium mesh. At the postoperative intervals of 2 week, 4 weeks, 8 weeks,12weeks, 24 weeks, the specimens were retrieved and proceeded for perfusion, fixation and were prepared by conventional preparatory procedures with the EDTA-KOH method and corrosion cast method and observed under SEM. Based upon the observation this study showed that porous HA mixed with DFDBA, due to both of the synergetic effect for revascularization of specific interconnected pores of porous HA and the osteoinductic ability of DFDBA, facilitated successive new bone ingrowth in bone defect after 2 weeks interval. And the results of 2 week group of corrosion cast showed the experimental group revealed more new-growth vessels. And these vessels penetrated into the pore of Interpore200. It gives the stability of these particles and facilitated the new bone growth. The results revealed the importance of the osteoinductic ability during the bone healing process in large bony defect. In the future , we must put efforts on the interaction of osteoinductic substances.

1. Lane, J.M., Bone graft substitutes. Western Journal of Medicine, 1995. 163(6): p. 565-6.
2. Misch, C.E. and F. Dietsh, Bone-grafting materials in implant dentistry. Implant Dentistry, 1993. 2(3): p. 158-67.
3. Frame, J.W., Hydroxyapatite as a biomaterial for alveolar ridge augmentation. International Journal of Oral & Maxillofacial Surgery, 1987. 16(6): p. 642-55.
4. Pinholt, E.M., G. Bang, and H.R. Haanaes, Alveolar ridge augmentation in rats by combined hydroxylapatite and osteoinductive material. Scandinavian Journal of Dental Research, 1991. 99(1): p. 64-74.
5. Pinholt, E.M., G. Bang, and H.R. Haanaes, Alveolar ridge augmentation in rats by Bio-Oss. Scandinavian Journal of Dental Research, 1991. 99(2): p. 154-61.
6. Linde, A., et al., Osteopromotion: a soft-tissue exclusion principle using a membrane for bone healing and bone neogenesis. Journal of Periodontology, 1993. 64(11 Suppl): p. 1116-28.
7. Manson, P.N., Facial bone healing and bone grafts. A review of clinical physiology. Clinics in Plastic Surgery, 1994. 21(3): p. 331-48.
8. Zanker , et al., Yamaguchi, K., et al., Degradation-resistant character of synthetic hydroxyapatite blocks filled in bone defects. Biomaterials, 1995. 16(13): p. 983-5.
9. Bucholz, R.W., A. Carlton, and R.E. Holmes, Hydroxyapatite and tricalcium phosphate bone graft substitutes. Orthopedic Clinics of North America, 1987. 18(2): p. 323-34.
10. Rosen, H.M., Porous, block hydroxyapatite as an interpositional bone graft substitute in orthognathic surgery. Plastic & Reconstructive Surgery, 1989. 83(6): p. 985-90; discussion 991-3.
11. Zitzmann, N.U., R. Naef, and P. Scharer, Resorbable versus nonresorbable membranes in combination with Bio-Oss for guided bone regeneration. International Journal of Oral & Maxillofacial Implants, 1997. 12(6): p. 844-52.
12. Oguchi, H., et al., Long-term histological evaluation of hydroxyapatite ceramics in humans. Biomaterials, 1995. 16(1): p. 33-8.
13. Uchida, A., et al., The use of calcium hydroxyapatite ceramic in bone tumour surgery. Journal of Bone & Joint Surgery - British Volume, 1990. 72(2): p. 298-302.
14. Salyer, K.E. and C.D. Hall, Porous hydroxyapatite as an onlay bone-graft substitute for maxillofacial surgery. Plastic & Reconstructive Surgery, 1989. 84(2): p. 236-44.
15. Cheng C. M, C.C.S., Su C. Y., A steremorphological Study of Bone Regeneration Following Hydroxyapatite or DFDBA Implantation using with EDTA-KOH method. Thesis of the master, NYMU Institute of Dental Science, 1997.
16. TC Lin, C.S., CS Chang, Stereomorphologic observation of bone tissue response to hydroxyapatite using SEM with the EDTA-KOH method. J Biomedical Materials Research, 1997. 36: p. 91-97.
17. Shu F Y, W.Y.J., Studies of the Bone Grafting Materials Based on Collagen Microspheres Containing Hydroxyapatite. Thesis of the PH. D, NYMU Institute of Biomedical Engineering, 1999.
18. Nyman, S., Bone regeneration using the principle of guided tissue regeneration. Journal of Clinical Periodontology, 1991. 18(6): p. 494-8.
19. Li, S.T., Biomaterials (collagen), in "The Biomedical Engineering Handbook" edit by J. D. Bronzino. 1995.
20. Younger, E.M. and M.W. Chapman, Morbidity at bone graft donor sites. Journal of Orthopaedic Trauma, 1989. 3(3): p. 192-5.
21. Heise, U., J.F. Osborn, and F. Duwe, Hydroxyapatite ceramic as a bone substitute. International Orthopaedics, 1990. 14(3): p. 329-38.
22. Kenney, E.B. and S.A. Jovanovic, Osteopromotion as an adjunct to osseointegration. International Journal of Prosthodontics, 1993. 6(2): p. 131-6.
23. Sandberg, E., C. Dahlin, and A. Linde, Bone regeneration by the osteopromotion technique using bioabsorbable membranes: an experimental study in rats. Journal of Oral & Maxillofacial Surgery, 1993. 51(10): p. 1106-14.
24. Dahlin, C., et al., Healing of maxillary and mandibular bone defects using a membrane technique. An experimental study in monkeys. Scandinavian Journal of Plastic & Reconstructive Surgery & Hand Surgery, 1990. 24(1): p. 13-9.
25. Seibert, J. and S. Nyman, Localized ridge augmentation in dogs: a pilot study using membranes and hydroxyapatite. Journal of Periodontology, 1990. 61(3): p. 157-65.
26. Dahlin, C., et al., Generation of new bone around titanium implants using a membrane technique: an experimental study in rabbits. International Journal of Oral & Maxillofacial Implants, 1989. 4(1): p. 19-25.
27. Hedner, E. and A. Linde, Efficacy of bone morphogenetic protein (BMP) with osteopromotive membranes--an experimental study in rat mandibular defects. European Journal of Oral Sciences, 1995. 103(4): p. 236-41.
28. Damien, C.J., et al., Investigation of a hydroxyapatite and calcium sulfate composite supplemented with an osteoinductive factor. Journal of Biomedical Materials Research, 1990. 24(6): p. 639-54.
29. Newman, S.A., Lineage and pattern in the developing vertebrate limb. Trends in Genetics, 1988. 4(12): p. 329-32.
30. Hall, B.K. and T. Miyake, The membranous skeleton: the role of cell condensations in vertebrate skeletogenesis. Anatomy & Embryology, 1992. 186(2): p. 107-24.
31. Wozney, J.M., et al., Growth factors influencing bone development. Journal of Cell Science - Supplement, 1990. 13: p. 149-56.
32. Wozney, J.M., The bone morphogenetic protein family and osteogenesis. Molecular Reproduction & Development, 1992. 32(2): p. 160-7.
33. Reddi, A.H., Regulation of cartilage and bone differentiation by bone morphogenetic proteins. Current Opinion in Cell Biology, 1992. 4(5): p. 850-5.
34. Kingsley, D.M., What do BMPs do in mammals? Clues from the mouse short-ear mutation. Trends in Genetics, 1994. 10(1): p. 16-21.
35. Tickle, C., Vertebrate development. On making a skeleton. Nature, 1994. 368(6472): p. 587-8.
36. Hogan, B.L., Bone morphogenetic proteins in development. Current Opinion in Genetics & Development, 1996. 6(4): p. 432-8.
37. Edwards, C.J. and P.H. Francis-West, Bone morphogenetic proteins in the development and healing of synovial joints. Seminars in Arthritis & Rheumatism, 2001. 31(1): p. 33-42.
38. Urist, M.R., Bone: formation by autoinduction. Science, 1965. 150(698): p. 893-9.
39. Urist, M.R. and B.S. Strates, Bone morphogenetic protein. Journal of Dental Research, 1971. 50(6): p. 1392-406.
40. Urist, M.R., et al., A bovine low molecular weight bone morphogenetic protein (BMP) fraction. Clinical Orthopaedics & Related Research, 1982(162): p. 219-32.
41. Takagi, K. and M.R. Urist, The role of bone marrow in bone morphogenetic protein-induced repair of femoral massive diaphyseal defects. Clinical Orthopaedics & Related Research, 1982(171): p. 224-31.
42. Takagi, K. and M.R. Urist, The reaction of the dura to bone morphogenetic protein (BMP) in repair of skull defects. Annals of Surgery, 1982. 196(1): p. 100-9.
43. Mizutani, H. and M.R. Urist, The nature of bone morphogenetic protein (BMP) fractions derived from bovine bone matrix gelatin. Clinical Orthopaedics & Related Research, 1982(171): p. 213-23.
44. Wang, E.A., et al., Bone morphogenetic protein-2 causes commitment and differentiation in C3H10T1/2 and 3T3 cells. Growth Factors, 1993. 9(1): p. 57-71.
45. Owen, M., The origin of bone cells in the postnatal organism. Arthritis & Rheumatism, 1980. 23(10): p. 1073-80.
46. Owen, M., Lineage of osteogenic cells and their relationship to the stromal system. Bone and Mineral Research. Amsterdam: Elservier, 1985. 1.
47. Friedenstein, A., Determined and inducible osteogenic precursor cells. Hard Tissue Growth, Repair, and Remineralization. Amsterdam: Associated Scientific Publishers., 1973: p. 169.
48. PD Delmas, L.M., The proteins of bone. Physiology and Pharmacology of Bone. New York:Springer, 1993: p. 673.
49. Parfitt, A.M., The cellular basis of bone remodeling: the quantum concept reexamined in light of recent advances in the cell biology of bone. Calcified Tissue International, 1984. 36(Suppl 1): p. S37-45.
50. Guyton, A., Text book of Medical Physiology. Philadelphia: Saunders, 1991.
51. Alvarez, J.I., et al., Osteoclast precursors circulate in avian blood. Calcified Tissue International, 1992. 51(1): p. 48-53.
52. Athanasou, N., Current concepts review: Cellular biology of bone resorbing cells. J Bone Joint Surg Am, 1996. 78(A): p. 1096.
53. Sorensen, M.S., Temporal bone dynamics, the hard way. Formation, growth, modeling, repair and quantum type bone remodeling in the otic capsule. Acta Oto-Laryngologica - Supplement, 1994. 512: p. 1-22.
54. Raisz, L.G., Recent advances in bone cell biology: interactions of vitamin D with other local and systemic factors. Bone & Mineral, 1990. 9(3): p. 191-7.
55. Watrous, D.A. and B.S. Andrews, The metabolism and immunology of bone. Seminars in Arthritis & Rheumatism, 1989. 19(1): p. 45-65.
56. Young, M.F., et al., Structure, expression, and regulation of the major noncollagenous matrix proteins of bone. Clinical Orthopaedics & Related Research, 1992(281): p. 275-94.
57. Hauschka, P., Growth factor effects in bone. The Osteoblast and Osteocyte. Caldwell, NJ: Telfor Press, 1990: p. 103.
58. Buckwalter, J.A., et al., Bone biology. I: Structure, blood supply, cells, matrix, and mineralization. Instructional Course Lectures, 1996. 45: p. 371-86.
59. Buckwalter, J.A., et al., Bone biology. II: Formation, form, modeling, remodeling, and regulation of cell function. Instructional Course Lectures, 1996. 45: p. 387-99.
60. JO Hollinger, B.M., Bone and its repair. Bioceramics.London: Pergamon-Elservier Science, 1995: p. 3.
61. Jarcho, M., et al., Tissue, cellular and subcellular events at a bone-ceramic hydroxylapatite interface. Journal of Bioengineering, 1977. 1(2): p. 79-92.
62. Frost, H.M., The biology of fracture healing. An overview for clinicians. Part II. Clinical Orthopaedics & Related Research, 1989(248): p. 294-309.
63. Frost, H.M., The biology of fracture healing. An overview for clinicians. Part I. Clinical Orthopaedics & Related Research, 1989(248): p. 283-93.
64. Simmons, D.J., Fracture healing perspectives. Clinical Orthopaedics & Related Research, 1985(200): p. 100-13.
65. Oni, O.O., Fracture healing perspectives. Clinical Orthopaedics & Related Research, 1987(220): p. 304-8.
66. Ohta, Y., Comparative changes in microvasculature and bone during healing of implant and extraction sites. Journal of Oral Implantology, 1993. 19(3): p. 184-98.
67. Goodman, S.B., J.A. Davidson, and V.L. Fornasier, Histological reaction to titanium alloy and hydroxyapatite particles in the rabbit tibia. Biomaterials, 1993. 14(10): p. 723-8.
68. Koole, R., H. Bosker, and F.N. van der Dussen, Late secondary autogenous bone grafting in cleft patients comparing mandibular (ectomesenchymal) and iliac crest (mesenchymal) grafts. Journal of Cranio-Maxillo-Facial Surgery, 1989. 17(Suppl 1): p. 28-30.
69. Buser, D., et al., Lateral ridge augmentation using autografts and barrier membranes: a clinical study with 40 partially edentulous patients. Journal of Oral & Maxillofacial Surgery, 1996. 54(4): p. 420-32; discussion 432-3.
70. Hislop, W.S., P.M. Finlay, and K.F. Moos, A preliminary study into the uses of anorganic bone in oral and maxillofacial surgery. British Journal of Oral & Maxillofacial Surgery, 1993. 31(3): p. 149-53.
71. Rummelhart, J.M., et al., A comparison of freeze-dried bone allograft and demineralized freeze-dried bone allograft in human periodontal osseous defects. Journal of Periodontology, 1989. 60(12): p. 655-63.
72. Buck, B.E., et al., Human immunodeficiency virus cultured from bone. Implications for transplantation. Clinical Orthopaedics & Related Research, 1990(251): p. 249-53.
73. Buck, B.E., T.I. Malinin, and M.D. Brown, Bone transplantation and human immunodeficiency virus. An estimate of risk of acquired immunodeficiency syndrome (AIDS). Clinical Orthopaedics & Related Research, 1989(240): p. 129-36.
74. Ashman, A., The use of synthetic bone materials in dentistry. Compendium - Supplement, 1992. 13(11): p. 1020, 1022, 1024-6, passim.
75. Jarcho, M., Biomaterial aspects of calcium phosphates. Properties and applications. Dental Clinics of North America, 1986. 30(1): p. 25-47.
76. White, E. and E.C. Shors, Biomaterial aspects of Interpore-200 porous hydroxyapatite. Dental Clinics of North America, 1986. 30(1): p. 49-67.
77. Frame, J.W., A convenient animal model for testing bone substitute materials. Journal of Oral Surgery, 1980. 38(3): p. 176-80.
78. Zaner, D.J. and R.A. Yukna, Particle size of periodontal bone grafting materials. Journal of Periodontology, 1984. 55(7): p. 406-9.