纯钛表面含辛伐他汀钙磷涂层的成骨活性研究
摘要
目的：创建一种含药仿生涂层,评估其的成骨效用。
材料与方法：本实验中,我们将不同浓度的辛伐他汀加入到放生溶液中,通过仿生法使药物与钙磷离子共沉积于钛片表面。应用扫描电子显微镜(SEM)、傅立叶红外光谱(FTIR)和X射线衍射仪(XRD)观察表面的形貌和结构。体外试验中,我们应用碱性磷酸酶(ALP),检测涂层对MC3T3-E1细胞的影响。
结果：通过扫描电子显微镜(SEM)、傅立叶红外光谱(FTIR)和X射线衍射仪(XRD),我们观察到低剂量的药物并没有改变钙磷涂层的宏观结构,而是掺入到晶体的结构中。在含药涂层表面培养MC3T3-E1细胞4天、7天和14天后,检测碱性磷酸酶的含量,发现涂层内的辛伐他汀能够释放出来,刺激MC3T3-E1细胞的分化,促进细胞功能的发挥,且1uM组作用效果最为明显。
结论：我们可以认为仿生法是携带药物极为有效的方法,它可以不改变药物的性质的同时将其混入晶体内,并能够将药物缓慢释放出来,发挥其应有的作用。另外,我们可以得出,低剂量的药物较高剂量更为安全,更能促进成骨细胞的功能。
Materials and Methods:In today's studies,we prepare simvastatin solustion with different concentration that be add into simulated body fluids which can be co-deposited onto the surface of titanium plates. By scanning electron microscope (SEM), X-ray diffraction apparatus(XRD) and fourier transform infrared spectroscopy(FTIR),we can observe the micostructure.In vitro,we can gain its influence on MEC3T3-E1 cells by detecting the alkaline phosphatase(ALP) activity.
Results:It is observed that in low-dose group,drugs had not only influenced the macrostructure of Ca-P coatings, but also became one part of Ca-P crystals.In vitro, MC3T3-E1 cells were inoculated onto the surface of biomimetic coatings in4,7 and 14 days, we found drugs could be released from the coatings and induce MC3T3-E1 cells differentiation in all groups especially in 1uM groups by alkaline phosphatase(ALP) detection.
Conclusion:We can conclude that biomimetic means is the most effective way to incorporate drugs into surfaces of implants without influencing drug's characteristics and make them released sustainedly to produce a marked effect.Meanwhile,it is found that low-dose drugs are more effective and safer than high-dose ones.
材料与方法：本实验中,我们将不同浓度的辛伐他汀加入到放生溶液中,通过仿生法使药物与钙磷离子共沉积于钛片表面。应用扫描电子显微镜(SEM)、傅立叶红外光谱(FTIR)和X射线衍射仪(XRD)观察表面的形貌和结构。体外试验中,我们应用碱性磷酸酶(ALP),检测涂层对MC3T3-E1细胞的影响。
结果：通过扫描电子显微镜(SEM)、傅立叶红外光谱(FTIR)和X射线衍射仪(XRD),我们观察到低剂量的药物并没有改变钙磷涂层的宏观结构,而是掺入到晶体的结构中。在含药涂层表面培养MC3T3-E1细胞4天、7天和14天后,检测碱性磷酸酶的含量,发现涂层内的辛伐他汀能够释放出来,刺激MC3T3-E1细胞的分化,促进细胞功能的发挥,且1uM组作用效果最为明显。
结论：我们可以认为仿生法是携带药物极为有效的方法,它可以不改变药物的性质的同时将其混入晶体内,并能够将药物缓慢释放出来,发挥其应有的作用。另外,我们可以得出,低剂量的药物较高剂量更为安全,更能促进成骨细胞的功能。
Materials and Methods:In today's studies,we prepare simvastatin solustion with different concentration that be add into simulated body fluids which can be co-deposited onto the surface of titanium plates. By scanning electron microscope (SEM), X-ray diffraction apparatus(XRD) and fourier transform infrared spectroscopy(FTIR),we can observe the micostructure.In vitro,we can gain its influence on MEC3T3-E1 cells by detecting the alkaline phosphatase(ALP) activity.
Results:It is observed that in low-dose group,drugs had not only influenced the macrostructure of Ca-P coatings, but also became one part of Ca-P crystals.In vitro, MC3T3-E1 cells were inoculated onto the surface of biomimetic coatings in4,7 and 14 days, we found drugs could be released from the coatings and induce MC3T3-E1 cells differentiation in all groups especially in 1uM groups by alkaline phosphatase(ALP) detection.
Conclusion:We can conclude that biomimetic means is the most effective way to incorporate drugs into surfaces of implants without influencing drug's characteristics and make them released sustainedly to produce a marked effect.Meanwhile,it is found that low-dose drugs are more effective and safer than high-dose ones.
引文
[1]. Yeritxa E,Wen-hua R,Julia N,et al.Effect of ovariectomy andalendronate on implant osseointegration in rat maxillary bone. The Journal of Oral Implantology; 2008; 34(2):76-82.
[2]. Masataka Y, Tatsuo S, Yuki T,et al. Bone reactions to titanium screw implants in ovariectomized animals. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:411-418.
[3]. Jeffcoat MK, Chesnut CH III. Systemic osteoporosis and oral bone loss:evidence shows increased risk factors. J Am Dent Assoc 1993; 124:49-56.
[4]. Gabriela QDaniela QCelso ES,et al. Influence of estrogen deficiency and its treatment with alendronate and estrogen on bone density around osseointegrated implants:radiographic study in female rats. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008; 105:162-7
[5]. Lacoste L, Lam JY, Hung J, Letchacovski G, Solymoss CB, Waters D. Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction. Circulation.1995,92:3172-3177.
[6]. Istvan, E., Deisenhofer, J., Structural mechanism for statin inhibition of HMG-CoA reductase. Science,2001,292,1160-1164.
[7]. Mundy, G, Garrett, R., Harris, S., Chan, J., Chen, D., Rossini,G, Boyce, B., Zhao, M., and Gutierrez, G. Stimulation of bone formation in vitro and in rodents by statins. Science,1999,286,1946-1949.
[8]. Skoglund B, Forslund C, Aspenberg P. Simvastatin improves fracture healing in mice. J Bone Miner Res 2002,17:2004-8.
[9]. Thylin MR, McConnel JC, Schmid MJ, Reckling RR, Ojha J, Bhattacharyya I, et al. Effects of simvastatin gels on murine calvarial bone. J Periodontol 2002,73:1141-1148.
[10]. Chan KA, Andrade SE, Boles M, Buist DS, Chase GA, Donahue JG, et al. Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fractures among older women. Lancet 2000,355:2185-2188.
[11]. Ayukawa Y, Okamura A, Koyano K. Simvastatin promotes osteogenesis around titanium implants. A histological and histometrical study in rats. Clin Oral Implants Res 2004,15:346-350.
[12]. Du Z, Chen J, Yan F, Xiao Y. The effects of Simvastatin on bone healing around titanium implants in osteoporotic rats. Clin. Oral Impl. Res.2009,20:145-150.
[13]. Sugiyama M, Kodama T, Konishi K, Abe K, Asami S, Oikawa S.Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Biochem Biophys Res Commun 2002,71:688-692.
[14]. Pamela H, Florence B, Clemens A. van Blitterswijk. Biomimetic Hydroxyapatite Coating on Metal Implants. J. Am. Ceram. Soc.,2002 85(3):517-522.
[15]. Ju Hyeong J, Mark V. Thomasb,et al. Bioerodible devices for intermittent release of simvastatin acid. International Journal of Pharmaceutics.2007,340:6-12.
[16]. Habibovic P, Barrere F, Blitterswijk CA, Groot K, Layrolle P.Biomimetic hydroxyapatite coating on metal implants. J Am Ceram Soc 2002,85:517-522.
[17]. Barrere F., Snel M.M., Blitterswijk C.A. van,et al.Nano-scale study of the nucleation and growth of calcium phosphate coating on titanium implants,Biomaterials 2004,25(14):2901-2901.
[18]. Habibovic P., van der Valk C.M., van Blitterswijk C.A., de Groot K., et al.3D microenvironment as essential element for osteoinduction by biomaterials. Biomaterials,26(17):3565-3575.
[19]. Kokubo T. Apatite Formation on surfaces of ceramics,metals and polymers in body environment,.Acta mater,1998,46(1).:2519-2527.
[20]. Qiyi Zhang, Yang Leng. Electrochemical activation of titanium for biomimetic coating of calcium phosphate. Biomaterials,2005,26:3853-3859.
[21]. Schliephake H, Scharnweber D, Dard M, et al. Biological performance of biomimetic calcium phosphate coating of titanium implants in the dog mandible. J Biomed Mater Res,2003,64A:225-34.
[22]. Liu Y, Groot K.de, Hunziker E.B.. BMP-2 liberated from biomimetic implant coatings induces and sustains direct ossification in an ectopic rat model.Bone,2005,36(5):745-757
[23]. Lenza R.F.S., Jones J.R., Vasconcelos W.L., Hench L.L.,.Surface-modified 3D scaffolds for tissue engineering. Journal of Materials Science: Materials in Medicine.2003,13(9):837-842.
[24]. Y Liu, J.P Li, E.B Hunziker and K de Groot. Incorporation of growth factors into medical devices via biomimetic coatings.Mathematical physical and engineering sciences,2006,364:233-248.
[25]. Haibo Q, Mei W. Improvement of Bonding Strength Between Biomimetic Apatite Coating and Substrate.2007,84(2):436-443.
[26]. Zhoujun W,Bo F, Jie W, et al. Biomimetic Apatite Coatings on Titanium Coprecipitated With Cephradine and Salviae Miltlorrhizae.2007,84(2):486-492.
[27]. Albrektsson T., Johansson C.. Osteoinduction,osteoconduction and osseointegration. Eur Spine J,2001,10:96-101.
[28]. Horiuch N, Maeda T. Statins and bone metabolism. Oral Diseases, 2006,12:85-101
[29]. Charras GT., Williams B.A., Sims S.M.,. Horton M.A,.Estimating the sensitivity of mechanosensitive ion channels to membrane strain and tension,J Biophys, 2004,87:2870-2884.
[30]. Garip S, Severcan F.Determination of simvastatin-induced changes in bone composition andstructure by Fourier transform infrared spectroscopy in rat animal model. Journal of Pharmaceutical and Biomedical Analysis xxx (2010) xxx-xxx
[1]. Kristin M. Hennessy a, Will C. Clem b, Matthew C. Phipps c, Amber A. Sawyer,et al. The effect of RGD peptides on osseointegration of hydroxyapatite biomaterials. Biomaterials 2008,29:3075-3083.
[2]. Maron DJ, Fazio S, Linton MF. Current perspectives on statins. Circulation,2000,101:207-213.
[3]. Lacoste L, Lam JY, Hung J, Letchacovski G, Solymoss CB, Waters D. Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction. Circulation 1995,92:3172-3177.
[4]. Kureishi Y, Luo Z, Shiojima I et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med 2000,6:1004-1010.
[5]. Istvan, E., Deisenhofer, J..Structural mechanism for statin inhibition of HMG-CoA reductase. Science,2001,292,1160-1164.
[6]. Riggs, B. L., and Melton, L. J. The prevention and treatment of osteoporosis. N. Engl. J. Med.1992,327:620-627.
[7]. Mundy, G., Garrett, R., Harris, S., Chan, J., Chen, D., Rossini, G., Boyce, B., Zhao, M., and Gutierrez, G. Stimulation of bone formation in vitro and in rodents by statins. Science 1999,286:1946-1949.
[8]. Sugiyama M, Kodama T, Konishi K, Abe K, Asami S, Oikawa S. Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Biochem Biophys Res Commun 2000:271,688-692.
[9]. Lian JB, Stein GS, Boskey AL.2003. Bone formation:Maturation and functional activists osteoblast lineage cells. In:Favus MJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism.5th edition. Washington DC: The American Society for Bone and Mineral Research.2003,13-28.
[10]. Maeda T, Matsunuma A, Kurahashi I,et al. Induction of Osteoblast Differentiation Indices by Statins in MC3T3-E1 Cells. Journal of Cellular Biochemistry.2004,92:458-471.
[11]. Chunli S,Zhaoqing G, Qingjun M, Simvastatin induces osteoblastic differentiation and inhibits adipocytic differentiation in mouse bone marrow stromal cells. Biochemical and Biophysical Research Communications 2003,308:458-462.
[12]. Chunli Song, Jingying Wang,Quansheng Song,et al. Simvastatin induces estrogen receptor-alpha (ER-a) in murine bone marrow stromal cells. J Bone Miner Metab 2008,26:213-217.
[13]. Garip S, Severcan F.Determination of simvastatin-induced changes in bone composition andstructure by Fourier transform infrared spectroscopy in rat animal model. Journal of Pharmaceutical and Biomedical Analysis xxx (2010) xxx-xxx
[14]. Yeonju L, Marian J. Schmid, David B. Marx.et al. The effect of local simvastatin delivery strategies on mandibular bone formation in vivo. Biomaterials.2008,29:1940-1949.
[15]. Ayukawa Y, Yasukawa E, Moriyama Y,et al. Local application of statin promotes bone repair through the suppression of osteoclasts and the enhancement of osteoblasts at bone-healing sites in rats. Oral Surg Oral Med Oral Pathol Oral Radiol Endod.2009,107:336-342.
[16]. Ayukawa Y, Okamura A, Koyano K. Simvastatin promotes osteogenesis around titanium implants. A histological and histometrical study in rats. Clin. Oral Impl. Res.2004,15:346-350.
[17]. Ayukawa Y, Ogino Y, Moriyama Y,et al. Simvastatin enhances bone formation around titanium implants in rat tibiae. Journal of Oral Rehabilitation 2010,37:123-130.
[18]. Tomohiro Masuzaki*, Yasunori Ayukawa, Yasuko Moriyama,et al. The effect of a single remote injection of statin-impregnated poly (lactic-co-glycolic acid) microspheres on osteogenesis around titanium implants in rat tibia. Biomaterials.2010,31:3327-3334.
[19]. Moriyama Y, Ayukawa Y, Ogino Y, Atsuta I, Koyano K. Topical application ofstatin affects bone healing around implants. Clin. Oral Impl. Res. 2008,19:600-605.
[1]. Brdnemark P-I, Zarb GA, Albrektsson T. Tissue-integrated prosthesis osseointegration in clinical dentistry. Plastic and Reconstructive Surgery.1986,77(3):496-497.
[2]. Summers R B. The osteotome technique:Part 3-Less invasive methods of elevating the sinus floor. Compendium,1994,15(6):698-704.
[3]. Tanaka T. Lecture at the American Academy of Periodontology Annual Meeting, San Diego, California, October 6,1997.
[4]. Nedir R, Bischof M, Vazquez L, et al. Osteotome sinus floor eleva tion without grafting material:a 1·year prospective pilot study with ITI implants. Clin Oral hnplants Res,2006,17(6):679-86.
[5]. 张运昕 赖红昌 张志勇.上颌窦挤压提升术的临床应用及研究进展.口腔材料器械,2009,18(1)：43-45.
[6]. 邢汝东,王兴。上颌窦提升术移植材料的选择及使用。国外医学,2000,27(3)：1 59-161.
[7]. Lundgren S, Andersson S, Gualini F, Sennerby L. Bone reformation with sinus membrane elevation:a new surgical technique for maxillary sinus floor augmentation. Clin Implant Dent Relat Res 2004,6:165-173.
[8]. Naoki H,Lars S, Stefan L.Maxillary Sinus Augmentation Using Sinus Membrane Elevation and Peripheral Venous Blood for Implant-Supported Rehabilitation of the Atrophic Posterior Maxilla:Case Series, Clinical Implant Dentistry and Related Research,2007,9(3):150-155
[9]. Bjarni E. P, Claude R, Urs B, et al. Maxillary sinus floor elevation using the (transalveolar) osteotome technique with or without grafting material. Part Ⅰ: implant survival and patients' perception. Clinical Oral Implants Research,2009,20 (7):667-676
[10]. Lundgren S,Anderson S,Gualini F.Bone Reformation with Sinus Membrane Elevation:A New Surgical Technique for Maxillary Sinus Floor Augmentation. Clinical Implant Dentistry and Related Research,2006,6(3):165-173
[11]. Hatano N,SennerbyL, Lundgren S,et al.Maxillary Sinus Augmentation Using Sinus Membrane Elevation and Peripheral Venous Blood for Implant-Supported Rehabilitation of the Atrophic Posterior Maxilla:Case SeriesClinical Implant Dentistry and Related Research.9(3):150-155
[2]. Masataka Y, Tatsuo S, Yuki T,et al. Bone reactions to titanium screw implants in ovariectomized animals. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:411-418.
[3]. Jeffcoat MK, Chesnut CH III. Systemic osteoporosis and oral bone loss:evidence shows increased risk factors. J Am Dent Assoc 1993; 124:49-56.
[4]. Gabriela QDaniela QCelso ES,et al. Influence of estrogen deficiency and its treatment with alendronate and estrogen on bone density around osseointegrated implants:radiographic study in female rats. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008; 105:162-7
[5]. Lacoste L, Lam JY, Hung J, Letchacovski G, Solymoss CB, Waters D. Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction. Circulation.1995,92:3172-3177.
[6]. Istvan, E., Deisenhofer, J., Structural mechanism for statin inhibition of HMG-CoA reductase. Science,2001,292,1160-1164.
[7]. Mundy, G, Garrett, R., Harris, S., Chan, J., Chen, D., Rossini,G, Boyce, B., Zhao, M., and Gutierrez, G. Stimulation of bone formation in vitro and in rodents by statins. Science,1999,286,1946-1949.
[8]. Skoglund B, Forslund C, Aspenberg P. Simvastatin improves fracture healing in mice. J Bone Miner Res 2002,17:2004-8.
[9]. Thylin MR, McConnel JC, Schmid MJ, Reckling RR, Ojha J, Bhattacharyya I, et al. Effects of simvastatin gels on murine calvarial bone. J Periodontol 2002,73:1141-1148.
[10]. Chan KA, Andrade SE, Boles M, Buist DS, Chase GA, Donahue JG, et al. Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fractures among older women. Lancet 2000,355:2185-2188.
[11]. Ayukawa Y, Okamura A, Koyano K. Simvastatin promotes osteogenesis around titanium implants. A histological and histometrical study in rats. Clin Oral Implants Res 2004,15:346-350.
[12]. Du Z, Chen J, Yan F, Xiao Y. The effects of Simvastatin on bone healing around titanium implants in osteoporotic rats. Clin. Oral Impl. Res.2009,20:145-150.
[13]. Sugiyama M, Kodama T, Konishi K, Abe K, Asami S, Oikawa S.Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Biochem Biophys Res Commun 2002,71:688-692.
[14]. Pamela H, Florence B, Clemens A. van Blitterswijk. Biomimetic Hydroxyapatite Coating on Metal Implants. J. Am. Ceram. Soc.,2002 85(3):517-522.
[15]. Ju Hyeong J, Mark V. Thomasb,et al. Bioerodible devices for intermittent release of simvastatin acid. International Journal of Pharmaceutics.2007,340:6-12.
[16]. Habibovic P, Barrere F, Blitterswijk CA, Groot K, Layrolle P.Biomimetic hydroxyapatite coating on metal implants. J Am Ceram Soc 2002,85:517-522.
[17]. Barrere F., Snel M.M., Blitterswijk C.A. van,et al.Nano-scale study of the nucleation and growth of calcium phosphate coating on titanium implants,Biomaterials 2004,25(14):2901-2901.
[18]. Habibovic P., van der Valk C.M., van Blitterswijk C.A., de Groot K., et al.3D microenvironment as essential element for osteoinduction by biomaterials. Biomaterials,26(17):3565-3575.
[19]. Kokubo T. Apatite Formation on surfaces of ceramics,metals and polymers in body environment,.Acta mater,1998,46(1).:2519-2527.
[20]. Qiyi Zhang, Yang Leng. Electrochemical activation of titanium for biomimetic coating of calcium phosphate. Biomaterials,2005,26:3853-3859.
[21]. Schliephake H, Scharnweber D, Dard M, et al. Biological performance of biomimetic calcium phosphate coating of titanium implants in the dog mandible. J Biomed Mater Res,2003,64A:225-34.
[22]. Liu Y, Groot K.de, Hunziker E.B.. BMP-2 liberated from biomimetic implant coatings induces and sustains direct ossification in an ectopic rat model.Bone,2005,36(5):745-757
[23]. Lenza R.F.S., Jones J.R., Vasconcelos W.L., Hench L.L.,.Surface-modified 3D scaffolds for tissue engineering. Journal of Materials Science: Materials in Medicine.2003,13(9):837-842.
[24]. Y Liu, J.P Li, E.B Hunziker and K de Groot. Incorporation of growth factors into medical devices via biomimetic coatings.Mathematical physical and engineering sciences,2006,364:233-248.
[25]. Haibo Q, Mei W. Improvement of Bonding Strength Between Biomimetic Apatite Coating and Substrate.2007,84(2):436-443.
[26]. Zhoujun W,Bo F, Jie W, et al. Biomimetic Apatite Coatings on Titanium Coprecipitated With Cephradine and Salviae Miltlorrhizae.2007,84(2):486-492.
[27]. Albrektsson T., Johansson C.. Osteoinduction,osteoconduction and osseointegration. Eur Spine J,2001,10:96-101.
[28]. Horiuch N, Maeda T. Statins and bone metabolism. Oral Diseases, 2006,12:85-101
[29]. Charras GT., Williams B.A., Sims S.M.,. Horton M.A,.Estimating the sensitivity of mechanosensitive ion channels to membrane strain and tension,J Biophys, 2004,87:2870-2884.
[30]. Garip S, Severcan F.Determination of simvastatin-induced changes in bone composition andstructure by Fourier transform infrared spectroscopy in rat animal model. Journal of Pharmaceutical and Biomedical Analysis xxx (2010) xxx-xxx
[1]. Kristin M. Hennessy a, Will C. Clem b, Matthew C. Phipps c, Amber A. Sawyer,et al. The effect of RGD peptides on osseointegration of hydroxyapatite biomaterials. Biomaterials 2008,29:3075-3083.
[2]. Maron DJ, Fazio S, Linton MF. Current perspectives on statins. Circulation,2000,101:207-213.
[3]. Lacoste L, Lam JY, Hung J, Letchacovski G, Solymoss CB, Waters D. Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction. Circulation 1995,92:3172-3177.
[4]. Kureishi Y, Luo Z, Shiojima I et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med 2000,6:1004-1010.
[5]. Istvan, E., Deisenhofer, J..Structural mechanism for statin inhibition of HMG-CoA reductase. Science,2001,292,1160-1164.
[6]. Riggs, B. L., and Melton, L. J. The prevention and treatment of osteoporosis. N. Engl. J. Med.1992,327:620-627.
[7]. Mundy, G., Garrett, R., Harris, S., Chan, J., Chen, D., Rossini, G., Boyce, B., Zhao, M., and Gutierrez, G. Stimulation of bone formation in vitro and in rodents by statins. Science 1999,286:1946-1949.
[8]. Sugiyama M, Kodama T, Konishi K, Abe K, Asami S, Oikawa S. Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Biochem Biophys Res Commun 2000:271,688-692.
[9]. Lian JB, Stein GS, Boskey AL.2003. Bone formation:Maturation and functional activists osteoblast lineage cells. In:Favus MJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism.5th edition. Washington DC: The American Society for Bone and Mineral Research.2003,13-28.
[10]. Maeda T, Matsunuma A, Kurahashi I,et al. Induction of Osteoblast Differentiation Indices by Statins in MC3T3-E1 Cells. Journal of Cellular Biochemistry.2004,92:458-471.
[11]. Chunli S,Zhaoqing G, Qingjun M, Simvastatin induces osteoblastic differentiation and inhibits adipocytic differentiation in mouse bone marrow stromal cells. Biochemical and Biophysical Research Communications 2003,308:458-462.
[12]. Chunli Song, Jingying Wang,Quansheng Song,et al. Simvastatin induces estrogen receptor-alpha (ER-a) in murine bone marrow stromal cells. J Bone Miner Metab 2008,26:213-217.
[13]. Garip S, Severcan F.Determination of simvastatin-induced changes in bone composition andstructure by Fourier transform infrared spectroscopy in rat animal model. Journal of Pharmaceutical and Biomedical Analysis xxx (2010) xxx-xxx
[14]. Yeonju L, Marian J. Schmid, David B. Marx.et al. The effect of local simvastatin delivery strategies on mandibular bone formation in vivo. Biomaterials.2008,29:1940-1949.
[15]. Ayukawa Y, Yasukawa E, Moriyama Y,et al. Local application of statin promotes bone repair through the suppression of osteoclasts and the enhancement of osteoblasts at bone-healing sites in rats. Oral Surg Oral Med Oral Pathol Oral Radiol Endod.2009,107:336-342.
[16]. Ayukawa Y, Okamura A, Koyano K. Simvastatin promotes osteogenesis around titanium implants. A histological and histometrical study in rats. Clin. Oral Impl. Res.2004,15:346-350.
[17]. Ayukawa Y, Ogino Y, Moriyama Y,et al. Simvastatin enhances bone formation around titanium implants in rat tibiae. Journal of Oral Rehabilitation 2010,37:123-130.
[18]. Tomohiro Masuzaki*, Yasunori Ayukawa, Yasuko Moriyama,et al. The effect of a single remote injection of statin-impregnated poly (lactic-co-glycolic acid) microspheres on osteogenesis around titanium implants in rat tibia. Biomaterials.2010,31:3327-3334.
[19]. Moriyama Y, Ayukawa Y, Ogino Y, Atsuta I, Koyano K. Topical application ofstatin affects bone healing around implants. Clin. Oral Impl. Res. 2008,19:600-605.
[1]. Brdnemark P-I, Zarb GA, Albrektsson T. Tissue-integrated prosthesis osseointegration in clinical dentistry. Plastic and Reconstructive Surgery.1986,77(3):496-497.
[2]. Summers R B. The osteotome technique:Part 3-Less invasive methods of elevating the sinus floor. Compendium,1994,15(6):698-704.
[3]. Tanaka T. Lecture at the American Academy of Periodontology Annual Meeting, San Diego, California, October 6,1997.
[4]. Nedir R, Bischof M, Vazquez L, et al. Osteotome sinus floor eleva tion without grafting material:a 1·year prospective pilot study with ITI implants. Clin Oral hnplants Res,2006,17(6):679-86.
[5]. 张运昕 赖红昌 张志勇.上颌窦挤压提升术的临床应用及研究进展.口腔材料器械,2009,18(1)：43-45.
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