Simple surface biofunctionalization of biphasic calcium phosphates for improving osteogenic activity and bone tissue regeneration

Kyu-Sik Shim; Hak-Jun Kim; Sung Eum Kim; Kyeongsoon Park

Journal of Industrial and Engineering Chemistry, Vol.68, 220-228, December, 2018

DOI10.1016/j.jiec.2018.07.048 Export Citation

Simple surface biofunctionalization of biphasic calcium phosphates for improving osteogenic activity and bone tissue regeneration

Kyu-Sik Shim, Hak-Jun Kim¹, Sung Eum Kim^{1, †}, and Kyeongsoon Park^{2, †}

Department of Biomedical Science, College of Medicine, Korea University,, Anam-dong, Seongbuk-gu, Seoul, 02841, Korea
¹Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Medical College, Guro Hospital 148, Guro-dong, Guro-gu, Seoul, 08308, Korea
²Department of Systems Biotechnology, Chung-Ang University, Anseong, Gyeonggi, 17546, Korea

E-mail:,

In this study, we found a simple surface biofunctionalization of biphasic calcium phosphate (BCP) based on the high affinity between alendronate and the calcium ions of BCP, and the strong interaction between heparin and bone morphogenic protein-2 (BMP-2). The biofunctionalized BCP did not be precipitated well and display a remarkable enhancement of osteogenic activity of human adipose-derived stem cells by showing increased alkaline phosphatase (ALP), calcium deposition and osteogenic-related genes (i.e., Runx-2, ALP, osteocalcin, and osteopontin), and bone regeneration in the calvarial defect model. Therefore, this simple surface technique can be used to easily functionalize various calcium phosphates.

Keywords:Surface biofunctionalization;Biphasic calcium phosphate;Alendronate;Heparin;Osteogenesis

[References]

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Muller KH, Motskin M, Philpott AJ, Routh AF, Shanahan CM, Duer MJ, Skepper JN, Biomaterials, 35, 1074 (2014)
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Xiong L, Zeng J, Yao A, Tu Q, Li J, Yan L, Tang Z, Int. J. Nanomed., 10, 517 (2015)
Shi X, Wang Y, Ren L, Gong Y, Wang DA, Pharm. Res., 26, 422 (2009)
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Lee H, Dellatore SM, Miller WM, Messersmith PB, Science, 318, 426 (2007)
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[1] Dorozhkin SV, Biomaterials, 31, 1465 (2010)

[2] Hong MH, Kim SM, Lee YK, J. Ceram. Sci. Technol., 8, 541 (2017)

[3] LeGeros RZ, Lin S, Rohanizadeh R, Mijares D, LeGeros JP, J. Mater. Sci. -Mater. Med., 14, 201 (2003)

[4] Suneelkumar C, Datta K, Srinivasan MR, Kumar ST, J. Conserv. Dent., 11, 92 (2008)

[5] Cheng L, Ye F, Yang R, Lu X, Shi Y, Li L, Fan H, Bu H, Acta Biomater., 6, 1569 (2010)

[6] Muller KH, Motskin M, Philpott AJ, Routh AF, Shanahan CM, Duer MJ, Skepper JN, Biomaterials, 35, 1074 (2014)

[7] Kim SE, Lee DW, Yun YP, Shim KS, Jeon DI, Rhee JK, Kim HJ, Park K, Biomed. Mater., 11, 025004 (2016)

[8] Shim KS, Kim SE, Yun YP, Choi S, Kim HJ, Park K, Song HR, Polymers, 9, 297 (2017)

[9] Xiong L, Zeng J, Yao A, Tu Q, Li J, Yan L, Tang Z, Int. J. Nanomed., 10, 517 (2015)

[10] Shi X, Wang Y, Ren L, Gong Y, Wang DA, Pharm. Res., 26, 422 (2009)

[11] Kim SE, Yun YP, Han YK, Lee DW, Ohe JY, Lee BS, Song HR, Park K, Choi BJ, Carbohydr. Polym., 99, 700 (2014)

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

[13] Lee DW, Yun YP, Park K, Kim SE, Bone, 50, 974 (2012)

[14] Kim SE, Yun YP, Shim KS, Park K, Choi SW, Suh DH, Colloids Surf. B: Biointerfaces, 122, 457 (2014)

[15] Kim SE, Yun YP, Lee JY, Park K, Suh DH, Colloids Surf. B: Biointerfaces, 123, 191 (2014)

[16] Shim KS, Kim SE, Yun YP, Jeon DI, Kim HJ, Park KS, Song HR, J. Ind. Eng. Chem., 55, 101 (2017)

[17] Wang D, Miller S, Sima M, Kopeckova P, Kopecek J, Bioconjug. Chem., 14, 853 (2003)

[18] Uludag H, Curr. Pharm. Des., 8, 1929 (2002)

[19] Uludag H, Gao TJ, Wohl GR, Kantoci D, Zernicke RF, Biotechnol. Prog., 16(6), 1115 (2000)

[20] Chen H, Li G, Chi H, Wang D, Tu C, Pan L, Zhu L, Qiu F, Guo F, Zhu X, Bioconjugate Chem., 23, 1915 (2012)

[21] Thamake SJ, Raut SL, Gryczynski Z, Ranjan AP, Vishwanatha JK, Biomaterials, 33, 7164 (2012)

[22] Kim SE, Kim CS, Yun YP, Yang DH, Park K, Kim SE, Jeong CM, Huh JB, Carbohydr. Polym., 114, 123 (2014)

[23] Kim SE, Yun YP, Shim KS, Park K, Choi SW, Shin DH, Suh DH, Colloids Surf. B: Biointerfaces, 134, 453 (2015)

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

[25] Yun YP, Kim SJ, Lim YM, Park K, Kim HJ, Jeong SI, Kim SE, Song HR, J. Biomed. Nanotechnol., 10, 1080 (2014)

[26] Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH, Tissue Eng., 7, 211 (2001)

[27] Winter A, Breit S, Parsch D, Benz K, Steck E, Hauner H, Weber RM, Ewerbeck V, Richter W, Arthritis Rheum., 18, 418 (2003)

[28] Strem BM, Hicok KC, Zhu M, Wulur I, Alfonso Z, Schreiber RE, Fraser JK, Hedrick MH, Keio J. Med., 54, 132 (2005)

[29] Yoon E, Dhar S, Chun DE, Gharibjanian NA, Evans GR, Tissue Eng., 13, 619 (2007)

[30] Ravichandran R, Venugopal JR, Sundarrajan S, Mukherjee S, Ramakrishna S, Biomaterials, 33, 846 (2012)

[31] Heinemann C, Heinemann S, Bernhardt A, Worch H, Hanke T, Biomacromolecules, 9(10), 2913 (2008)

[32] Senarath-Yapa K, McArdle A, Renda A, Longaker MT, Quarto N, Int. J. Mol. Sci., 15(6), 9314 (2014)

[33] Rice DP, Front. Oral Biol., 12, 1 (2008)

[34] Kim YJ, Lee MH, Wozney JM, Cho JY, Ryoo HM, J. Biol. Chem., 279, 50773 (2004)

[35] Liu T, Gao Y, Sakamoto K, Minamizato T, Furukawa K, Tsukazaki T, Shibata Y, Bessho K, Komori T, Yamaguchi A, J. Cell Physiol., 211, 728 (2007)

[36] Zhang YW, Yasui N, Ito K, Huang G, Fujii M, Hanai J, Nogami H, Ochi T, Miyazono K, Ito Y, Proc. Natl. Acad. Sci. U. S. A., 97, 10549 (2000)

[37] Dragoo JL, Choi JY, Lieberman JR, Huang J, Zuk PA, Zhang J, Hedrick MH, Benhaim P, J. Orthop. Res., 21, 622 (2003)

[38] Dragoo JL, Lieberman JR, Lee RS, Deugarte DA, Lee Y, Zuk PA, Hedrick MH, Benhaim P, Plast. Reconstr. Surg., 115, 1665 (2005)