現今的人工植體，多利用電漿熔射 (Plasma spray) 的方式，將氫氧基磷灰石 (Hydroxyapatite) 噴覆在金屬基材的表面上。研究指出，氫氧基磷灰石具有優良的生物相容性與生物活性，可與人體的骨組織直接產生化學鍵結，達到很好的整合性。但對於骨質疏鬆症的病人而言，其骨質密度偏低，骨組織無法與氫氧基磷灰石達到良好整合效果。人體中有98%的鍶存在於骨骼中，用鍶做治療可以促進骨細胞分化，抑制骨吸收，降低骨質流失的速率，因此在臨床上被用來治療骨質疏鬆症。氫氧基磷灰石中的鈣離子可被鍶離子所取代，形成鍶置換氫氧基磷灰石(Sr substituted HA) 材料，在體外與體內實驗中發現鍶置換氫氧基磷灰石骨水泥有聚骨的現象。本實驗的目的是利用電漿熔射的方式將鍶置換氫氧基磷灰石噴覆在鈦合金基材上，觀察骨母細胞於體外培養的表面生長情況，期望Sr-HA披覆在人工植體基材表面，將來可應用在骨質疏鬆的病人身上。在實驗中，先利用濕式化學法合成不同鍶離子濃度(0, 1, 3, 5與10 mole% Sr)取代氫氧基磷灰石中鈣離子的粉末，並針對合成溫度、煅燒溫度等作一些比較，之後藉由電漿熔射的方式將鍶置換氫氧基磷灰石噴覆在鈦六鋁四釩基材上。樣品的特性以X光繞射儀 (XRD) 、穿透式電子顯微鏡 (TEM)、感應耦合電漿原子發射光譜分析儀 (ICP-AES) 、掃描式電子顯微鏡/能量散佈光譜儀 (SEM/EDS)及熱差/熱重分析儀(DTA/TGA)等。由XRD實驗結果可以發現在高溫環境合成下，隨著鍶濃度的增加並沒有雜相的產生，且主峰會隨著鍶的增加而往低角度方向位移，電漿熔射前後其晶格常數a與c以及體積也隨著鍶濃度的增加而增加，晶粒大小則隨著鍶濃度的增加而減少。由TEM的結果也發現當鍶濃度的增加，其繞射圖譜之原子間距也會跟著增加。由ICP-AES的結果得知所合成之粉末幾乎與理想值接近。電漿熔射後其表面有許多未熔融的顆粒與熔融的薄餅，還有為結構與孔洞的存在，由XRD的結果發現有雜相的存在，隨著鍶含量的增加其結晶度與雜相的含量也越多。由EDS可知電漿熔射後其鈣鍶磷比會增加。為了瞭解樣品在體內的狀況，會浸泡模擬體液作測試，發現隨著浸泡的天數增加其雜相也隨之減少，其鈣鍶磷比也隨著天數的增加而降低，猜測可能是磷灰石(apatite)沉積所造成的。

Recently, the implants coated with hydroxyapatite (HA) by plasma spraying were widely used in orthopaedic applications. In previous study, HA has excellent biocompatibility and ability for bone tissue directly bonding and fixation. Because of the low bone density for the patients with osteoporosis, it was hard to achieve the great HA-bone tissue integration. There is 98 percent of strontium in the human’s normal bone. It had been investigated that strontium could promote the bone cell to differentiation, inhibit the bone absorption, and reduce the rate of bone loss. In the clinical usage, strontium can be used to cure osteoporosis. The Calcium atoms on HA can be substituted by strontium to form strontium substituted HA (Sr-HA). It was found that Sr-HA bone cement has the ability to bone aggregation in animal models. The aim of the study is to coat Sr-HA on the surface of metal implant, and it could be used for patients with osteoporosis. In this study, we plasma sprayed Sr-HA layers on titanium alloy substrate to observe the osteoblast cell morphology, proliferation, and differentiation in vitro. We formed the powders of different concentration of strontium (0, 1, 3, 5and 10 mole% Sr). Then the powders were coated on titanium alloy by plasma spraying. The samples were analyzed by X-ray Diffraction (XRD), Transmission Electron Microscope (TEM), Inductively coupled plasma-atomic emission spectrometer (ICP-AES), Scanning Electron Microscope/ Energy Dispersive Spectrometers (SEM/SEI/EDS), Thermal Differential / Thermal Gravimetric Analyzer (DTA/TGA) and etc. We formed the powders of different concentration of strontium. In the XRD for the phase of the powders, it was similar to HA pattern, and the peak shift was to low angle with Sr increase. The lattice constant and volume increase and grain size decrease with Sr increase. For TEM observation, the morphology of Sr-HA was resembled to HA. The interatomic distance increase with Sr increase. By ICP-AES, the CaSr/P was close to ideal value. Then, the Sr-HA layer was coated by plasma-spraying on titanium alloy. For SEM observation, the morphology of Sr-HA was has un-melted. particle, melted pellet, microcrack and pore. The XRD result showed the Sr-HA has mixed phase and the content increase with Sr increase. Then it was observed the mineralization level by the SBF immersion test. The result showed the apatite produced quickly with the content increase of Sr. Then we will to evaluate the influence of biocompatibility by HA of different Sr content substituted.

1. Wei, S. B., T. M. Shao, et al. (2010). "Study of CNx films on 316L stainless steel for orthodontic application." Diamond and Related Materials 19(5-6): 648-653.
2. Johns, S. M., T. Bell, et al. (1996). "Wear resistance of plasma immersion ion implanted Ti6Al4V." Surface & Coatings Technology 85(1-2): 7-14.
3. Li, Y. W., J. C. Leong, et al. (2000). "A novel injectable bioactive bone cement for spinal surgery: a developmental and preclinical study." Journal of Biomedical Materials Research 52(1): 164-170.
4. Oksiuta, Z., J. R. Dabrowski, et al. (2009). "Co-Cr-Mo-based composite reinforced with bioactive glass." Journal of Materials Processing Technology 209(2): 978-985.
5. Scott A. Guelcher and Jeffrey O. Hollinger (2006), “An Introduction to Biomaterials,” CRC Press, Taylor & Francis Group.
6. Shi D. (ed.) (2004), “Biomaterials and tissue engineering”, Berlin; New York: Springer.
7. Wang, D. G., C. Z. Chen, et al. (2008). "Hydroxyapatite coating on Ti6Al4V alloy by a sol-gel method." Journal of Materials Science-Materials in Medicine 19(6): 2281-2286.
8. Wolke, J. G. C., E. Vandenbulcke, et al. (2005). "A study to the surface characteristics of RF magnetron sputtered bioglass - and calcium phosphate coatings." Bioceramics 17 17: 187-190.
9. Meng, X. C., X. Y. Li, et al. (2005). "Effect of electrodeposited hydroxyapatite coatings on biomedical titanium by cathode revolving." High-Performance Ceramics Iii, Pts 1 and 2 280-283: 1525-1528.
10. Takahashi, N., T. Sasaki, et al. (2003). "S 12911-2 inhibits osteoclastic bone resorption in vitro." Journal of Bone and Mineral Research 18(6): 1082-108.
11. Grynpas, M. D., E. Hamilton, et al. (1996). "Strontium increases vertebral bone volume in rats at a low dose that does not induce detectable mineralization defect." Bone 18(3): 253-259.
12. Jha, L. J., S. M. Best, et al. (1997). "Preparation and characterization of fluoride-substituted apatites." Journal of Materials Science-Materials in Medicine 8(4): 185-191.
13. Xue, W. C., J. L. Moore, et al. (2006). "Osteoprecursor cell response to strontium-containing hydroxyapatite ceramics." Journal of Biomedical Materials Research Part A 79A(4): 804-814
14. Ni, G. X., K. Y. Chiu, et al. (2006). "Strontium-containing hydroxyapatite bioactive bone cement in revision hip arthroplasty." Biomaterials 27(24): 4348-4355.
15. Xue, W. C., H. L. Hosick, et al. (2007). "Preparation and cell-materials interactions of plasma sprayed strontium-containing hydroxyapatite coating." Surface & Coatings Technology 201(8): 4685-4693.
16. Albee, F. H. (1920). "Studies in Bonegrowth-triple Calcium Phosphate as a Stimulus to Osteogenesis." Ann. Surg.,71(32).
17. 王盈錦(2002)，”生物醫學材料”，合記圖書
18. 韓宗立(1986)，生醫用氫氧基磷灰石之研究， 國立成功大學礦冶及材料科學研究所碩士論文
19. Zhou, J. M., X. D. Zhang, et al. (1993). "High-Temperature Characteristics of Synthetic Hydroxyapatite." Journal of Materials Science-Materials in Medicine 4(1): 83-85.
20. 楊崇煒 (2006)，水熱法與高溫後處理對電漿熔射氫氧基磷灰石塗層微觀組織及結合強度之效應，國立成功大學材料科學及工程研究所博士論文
21. Correia, R. N., M. C. F. Magalhaes, et al. (1996). "Wet synthesis and characterization of modified hydroxyapatite powders." Journal of Materials Science-Materials in Medicine 7(8): 501-505
22. Delgado, J. A., L. Morejon, et al. (1999). "Zirconia-toughened hydroxyapatite ceramic obtained by wet sintering." Journal of Materials Science-Materials in Medicine 10(12): 715-719.
23. Afshar, A., M. Ghorbani, et al. (2003). "Some important factors in the wet precipitation process of hydroxyapatite." Materials & Design 24(3): 197-202
24. Saeri, M. R., A. Afshar, et al. (2003). "The wet precipitation process of hydroxyapatite." Materials Letters 57(24-25): 4064-4069.
25. Pretto, M., A. L. Costa, et al. (2003). "Dispersing behavior of hydroxyapatite powders produced by wet-chemical synthesis." Journal of the American Ceramic Society 86(9): 1534-1539.
26. Sergey V (2007). Dorozhkin. Calcium orthophosphates. J Mater Sci 42:1061–95.
27. Heijligers, H. J. M., F. C. M. Driessens, et al. (1979). "Lattice-Parameters and Cation Distribution of Solid-Solutions of Calcium and Strontium Hydroxyapatite." Calcified Tissue International 29(2): 127-131
28. Yang, Z. W., Y. S. Jiang, et al. (2005). "Preparation and characterization of magnesium doped hydroxyapatite gelatin nanocomposite." Journal of Materials Chemistry 15(18): 1807-1811
29. Nordstrom, E. G. and K. H. Karlsson (1990). "Carbonate-Doped Hydroxyapatite." Journal of Materials Science-Materials in Medicine 1(3): 182-184.
30. Webster, T. J., E. A. Massa-Schlueter, et al. (2004). "Osteoblast response to hydroxyapatite doped with divalent and trivalent cations." Biomaterials 25(11): 2111-2121.
31. Balamurugan, A., G. Balossier, et al. (2009). "Sol-gel synthesis and spectrometric structural evaluation of strontium substituted hydroxyapatite." Materials Science & Engineering C-Biomimetic and Supramolecular Systems 29(3): 1006-1009.
32. Nielsen, S. P. (2004). "The biological role of strontium." Bone 35(3): 583-588
33. Ammann, P., V. Shen, et al. (2004). "Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats." J Bone Miner Res 19(12): 2012-2020
34. Qiu, K., X. J. Zhao, et al. (2006). "Effect of strontium ions on the growth of ROS17/2.8 cells on porous calcium polyphosphate scaffolds." Biomaterials 27(8): 1277-1286.
35. Capuccini, C., P. Torricelli, et al. (2008). "Strontium-substituted hydroxyapatite coatings synthesized by pulsed-laser deposition: In vitro osteoblast and osteoclast response." Acta Biomaterialia 4(6): 1885-1893.
36. Ni, G. X., Y. S. Choy, et al. (2006). "Nano-mechanics of bone and bioactive bone cement interfaces in a load-bearing model." Biomaterials 27(9): 1963-1970.
37. Tian, M., F. Chen, et al. (2009). "In vivo study of porous strontium-doped calcium polyphosphate scaffolds for bone substitute applications." Journal of Materials Science-Materials in Medicine 20(7): 1505-1512
38. Li, Z. Y., W. M. Lam, et al. (2007). "Chemical composition, crystal size and lattice structural changes after incorporation of strontium into biomimetic apatite." Biomaterials 28(7): 1452-1460
39. Pan, H. B., Z. Y. Li, et al. (2009). "Solubility of strontium-substituted apatite by solid titration." Acta Biomaterialia 5(5): 1678-1685.
40. 楊永欽 (2003)，殘留應力對電漿熔射氫氧基磷灰石塗層與鈦鋁釩合金基材間結合強度之影響研究，國立成功大學材料科學及工程研究所博士論文
41. D. Matejka and B Benko, (1989) ”Plasma Spraying of Metallic and Ceramic Materials” John Wiley and Sons Ltd
42. R. Suryanarayanan (Ed.), (1993), “Plasma Spraying: Theory and Application”, pp. 1-7, World Scientific Publishing Co. Pte. Ltd., London, Printed in Singapore.
43. Brossa, F., A. Cigada, et al. (1996). "Tribological behaviour of Ti6Al4V modified by surface treatments." Journal of Materials Science-Materials in Medicine 7(8): 471-474
44. Sun, L. M., C. C. Berndt, et al. (2001). "Material fundamentals and clinical performance of plasma-sprayed hydroxyapatite coatings: A review." Journal of Biomedical Materials Research 58(5): 570-592.
45. Lai, K. A., W. J. Shen, et al. (2002). "Failure of hydroxyapatite-coated acetabular cups - Ten-year follow-up of 85 Landos Atoll arthroplasties." Journal of Bone and Joint Surgery-British Volume 84B(5): 641-646.
46. 周邦彥，添加氧化鋯顆粒強化相與引入氧化鋯介層對電漿熔射氫氧基磷灰石塗層性質的影響，國立成功大學材料科學及工程研究所博士論文
47. 王寶琪，電漿熔射氫氧基磷灰石披覆於鈦鋁釩合金基材生醫塗層之塗層特性與生物反應研究，國立成功大學材料科學及工程研究所博士論文
48. H. S. Ingham, A.Mecto Pshepard. Flame Spray Handbook. 3:17. 1965
49. O'Donnell, M. D., Y. Fredholm, et al. (2008). "Structural analysis of a series of strontium-substituted apatites." Acta Biomaterialia 4(5): 1455-1464
50. Djosic, M. S., V. B. Miskovic-Stankovic, et al. (2008). "Electrochemical synthesis and characterization of hydroxyapatite powders." Materials Chemistry and Physics 111(1): 137-142
51. Pankaj Vadgama (2005), ‘Surfaces and interfaces for biomaterials”, Boca Raton :CRC Press