In vitro Evaluation of Simvastatin Acid (SVA) Coated Beta-Tricalcium Phosphate (β-TCP) Particle on Bone Tissue Regeneration

Dae Hyeok Yang; Min Soo Bae; Lingjuan Qiao; Dong Nyoung Heo; Jung Bok Lee; Won Jun Lee; Jae Hong Park; Deok-Won Lee; Yu-Shik Hwang; Il Keun Kwon

Macromolecular Research, Vol.20, No.7, 754-761, July, 2012

DOI10.1007/s13233-012-0097-z Export Citation

In vitro Evaluation of Simvastatin Acid (SVA) Coated Beta-Tricalcium Phosphate (β-TCP) Particle on Bone Tissue Regeneration

Dae Hyeok Yang, Min Soo Bae, Lingjuan Qiao, Dong Nyoung Heo, Jung Bok Lee, Won Jun Lee¹, Jae Hong Park², Deok-Won Lee³, Yu-Shik Hwang, and Il Keun Kwon^†

Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, 130-701, Korea
¹Department of Chemical & Biomolecular Engineering, Interdisciplinary Program of Integrated Biotechnology, Sogang University, Seoul, 121-742, Korea
²Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University, Seoul, 130-701, Korea
³Department of Oral & Maxillofacial Surgery, Kyung Hee University Dental Hospital at Gang-dong, Seoul, 134-727, Korea

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The goal of this study was to evaluate the potential of beta-tricalcium phosphate (β-TCP) particles coated with difference concentrations (1 and 10 mM) of simvastatin acid (SVA) on bone formation in vitro. Changes in the surface morphologies and chemical compositions of SVA1-β-TCP and SVA10-β-TCP suggested that SVA was coated on their surface. These particles were further investigated by scanning electron microscopy (SEM) observations and X-ray photoelectron spectroscopy (XPS) measurements. By measuring ultraviolet/visible (UV/Vis) spectroscopy, we found that simvastatin acid (SVA) released in a sustained manner over the period of 28 days even though the initial burst happened within 1 day. These results verify that SVA1-β-TCP and SVA10-β-TCP can be useful as a biocompatible bone graft substitutes. Biocompatibility was evaluated by cytotoxicity tests, live/dead assay, and proliferation of preosteoblast cell-line (MC3T3-E1) cells culture. The results of assays for ALP activity, calcium deposition, and mRNA expressions of alkaline phosphatase (ALP) and osteopontin suggest that the amount of SVA plays an important role in accelerating bone formation in vitro.

Keywords:beta-tricalcium phosphate (β-TCP) particle;simvastatin acid (SVA);in vitro;ALP activity;calcium depostion.

[References]

Cypher TJ, Grossman JP, J. Foot Ankle Surg., 35, 413 (1996)
Carter G, AORN J., 70, 660 (1999)
Araujo M, ELinder E, Lindhe J, Clin. Oral Implants Res., 20, 1 (2009)
Khan SN, Tomin E, Lane JM, Orthop. Clin. N. Am., 31, 389 (2000)
Koo AN, Kwon IK, Lee SC, Lee SK, Kim HS, Woo YH, Jeon SH, Chae JH, Kang KW, Macromol. Res., 18(10), 1030 (2010)
Murugan R, Rao KP, Macromol. Res., 11(1), 14 (2003)
Cornell CN, Orthop. Clin. N. Am., 30, 591 (1999)
Kim HS, Kim JT, Jung YJ, Ryu SC, Son HJ, Kim YG, Macromol. Res., 15(1), 65 (2007)
Damien CJ, Parsons JR, J. Appl. Biomater., 2, 187 (1991)
Hooten JP, Engh CA, Heekin RD, Vinh TN, J. Bone Joint Surg. Br., 78, 270 (1996)
Schwarz N, Schlag G, Thurnher M, Eschberger J, Dinges HP, Redl H, J. Bone Joint Surg. Br., 73, 787 (1991)
Giannoudis PV, Dinopoulos H, Tsiridis E, Injury., 36S, S20 (2005)
Kondo N, Ogose A, Tokunaga K, Ito T, Arai K, Kudo N, Inoue H, Irie H, Endo N, Biomaterials., 26, 5600 (2005)
Yuan J, Cui L, Zhang WJ, Liu W, Cao Y, Biomaterials., 28, 1005 (2007)
Ogose A, Hotta T, Kawashima H, Kondo N, Gu W, Kamura T, Endo N, J. Biomed. Mater. Res. Part B: Appl. Biomater., 72B, 94 (2005)
Takahashi Y, Yamamoto M, Tabata Y, Biomaterials., 26, 4856 (2005)
Chazono M, Tanaka T, Komaki H, Fujii K, J. Biomed.Mater. Res., 70A, 542 (2004)
Carter TG, Brar PS, Tolas A, Beirne OR, J. Oral Maxillofac. Surg., 66, 1417 (2008)
Shields LB, Raque GH, Glassman SD, Campbell M, Vitaz T, Harpring J, Shields CB, Spine., 31, 542 (2006)
Sugiyama M, Kodama T, Konishi K, Abe K, Asami S, Oikawa S, Biochem. Biophys. Res. Commun., 271(3), 688 (2000)
Mundy G, Garrett R, Harris S, Chan J, Chen D, Rossini G, Boyce B, Zhao M, Gutierrez G, Science., 286, 1946 (1999)
Nyan M, Sato D, Kihara H, Machida T, Ohya K, Kasugai S, Clin. Oral Implants Res., 20, 280 (2009)
Kunze C, Freier T, Helwig E, Sandner B, Reif D, Wutzler A, Radusch HJ, Biomaterials., 24, 967 (2003)
Lee H, Dellatore SM, Miller WM, Messersmith PB, Science., 318, 426 (2007)
Lee H, Scherer NF, Messersmith PB, Proc. Natl. Acad. Sci. U.S.A., 103, 12999 (2006)
Kwon OS, Park SJ, Jang J, Biomaterials., 31, 4740 (2010)
Kim SE, Song SH, Yun YP, Choi BJ, Kwon IK, Bae MS, Moon HJ, Kwon YD, Biomaterials., 32, 366 (2011)
Boyd AR, Meenan BJ, Leyland NS, Surf. Coat. Technol., 200, 6002 (2006)
Kulhari H, Pooja D, Prajapati SK, Chauhan AS, Int.J. Pharm., 405, 203 (2011)
Nasu T, Takemoto M, Akiyama N, Fujibayashi S, Neo M, Nakamura T, J. Biomed. Mater. Res., 89A, 601 (2009)
Turksen K, Bhargava U, Moe HK, Aubin JE, J. Histochem.Cytochem., 40, 1339 (1999)
van den Beucken JJ, Walboomers XF, Boerman OC, Vos MR, Sommerdijk NA, Hayakawa T, Fukushima T, Okahata Y, J. Control. Release., 113, 63 (2006)

[1] Cypher TJ, Grossman JP, J. Foot Ankle Surg., 35, 413 (1996)

[2] Carter G, AORN J., 70, 660 (1999)

[3] Araujo M, ELinder E, Lindhe J, Clin. Oral Implants Res., 20, 1 (2009)

[4] Khan SN, Tomin E, Lane JM, Orthop. Clin. N. Am., 31, 389 (2000)

[5] Koo AN, Kwon IK, Lee SC, Lee SK, Kim HS, Woo YH, Jeon SH, Chae JH, Kang KW, Macromol. Res., 18(10), 1030 (2010)

[6] Murugan R, Rao KP, Macromol. Res., 11(1), 14 (2003)

[7] Cornell CN, Orthop. Clin. N. Am., 30, 591 (1999)

[8] Kim HS, Kim JT, Jung YJ, Ryu SC, Son HJ, Kim YG, Macromol. Res., 15(1), 65 (2007)

[9] Damien CJ, Parsons JR, J. Appl. Biomater., 2, 187 (1991)

[10] Hooten JP, Engh CA, Heekin RD, Vinh TN, J. Bone Joint Surg. Br., 78, 270 (1996)

[11] Schwarz N, Schlag G, Thurnher M, Eschberger J, Dinges HP, Redl H, J. Bone Joint Surg. Br., 73, 787 (1991)

[12] Giannoudis PV, Dinopoulos H, Tsiridis E, Injury., 36S, S20 (2005)

[13] Kondo N, Ogose A, Tokunaga K, Ito T, Arai K, Kudo N, Inoue H, Irie H, Endo N, Biomaterials., 26, 5600 (2005)

[14] Yuan J, Cui L, Zhang WJ, Liu W, Cao Y, Biomaterials., 28, 1005 (2007)

[15] Ogose A, Hotta T, Kawashima H, Kondo N, Gu W, Kamura T, Endo N, J. Biomed. Mater. Res. Part B: Appl. Biomater., 72B, 94 (2005)

[16] Takahashi Y, Yamamoto M, Tabata Y, Biomaterials., 26, 4856 (2005)

[17] Chazono M, Tanaka T, Komaki H, Fujii K, J. Biomed.Mater. Res., 70A, 542 (2004)

[18] Carter TG, Brar PS, Tolas A, Beirne OR, J. Oral Maxillofac. Surg., 66, 1417 (2008)

[19] Shields LB, Raque GH, Glassman SD, Campbell M, Vitaz T, Harpring J, Shields CB, Spine., 31, 542 (2006)

[20] Sugiyama M, Kodama T, Konishi K, Abe K, Asami S, Oikawa S, Biochem. Biophys. Res. Commun., 271(3), 688 (2000)

[21] Mundy G, Garrett R, Harris S, Chan J, Chen D, Rossini G, Boyce B, Zhao M, Gutierrez G, Science., 286, 1946 (1999)

[22] Nyan M, Sato D, Kihara H, Machida T, Ohya K, Kasugai S, Clin. Oral Implants Res., 20, 280 (2009)

[23] Kunze C, Freier T, Helwig E, Sandner B, Reif D, Wutzler A, Radusch HJ, Biomaterials., 24, 967 (2003)

[24] Lee H, Dellatore SM, Miller WM, Messersmith PB, Science., 318, 426 (2007)

[25] Lee H, Scherer NF, Messersmith PB, Proc. Natl. Acad. Sci. U.S.A., 103, 12999 (2006)

[26] Kwon OS, Park SJ, Jang J, Biomaterials., 31, 4740 (2010)

[27] Kim SE, Song SH, Yun YP, Choi BJ, Kwon IK, Bae MS, Moon HJ, Kwon YD, Biomaterials., 32, 366 (2011)

[28] Boyd AR, Meenan BJ, Leyland NS, Surf. Coat. Technol., 200, 6002 (2006)

[29] Kulhari H, Pooja D, Prajapati SK, Chauhan AS, Int.J. Pharm., 405, 203 (2011)

[30] Nasu T, Takemoto M, Akiyama N, Fujibayashi S, Neo M, Nakamura T, J. Biomed. Mater. Res., 89A, 601 (2009)

[31] Turksen K, Bhargava U, Moe HK, Aubin JE, J. Histochem.Cytochem., 40, 1339 (1999)

[32] van den Beucken JJ, Walboomers XF, Boerman OC, Vos MR, Sommerdijk NA, Hayakawa T, Fukushima T, Okahata Y, J. Control. Release., 113, 63 (2006)