Surface immobilization of biphasic calcium phosphate nanoparticles on 3D printed poly(caprolactone) scaffolds enhances osteogenesis and bone tissue regeneration

Kyu-Sik Shim; Sung Eun Kim; Young-Pil Yun; Daniel I. Jeon; Hak-Jun Kim; Kyeongsoon Park; Hae-Ryong Song

Journal of Industrial and Engineering Chemistry, Vol.55, 101-109, November, 2017

DOI10.1016/j.jiec.2017.06.033 Export Citation

Surface immobilization of biphasic calcium phosphate nanoparticles on 3D printed poly(caprolactone) scaffolds enhances osteogenesis and bone tissue regeneration

Kyu-Sik Shim^{1, 2}, Sung Eun Kim², Young-Pil Yun², Daniel I. Jeon³, Hak-Jun Kim², Kyeongsoon Park^{4, †}, and Hae-Ryong Song^{2, †}

¹Department of Biomedical Science, College of Medicine, Korea University, Anam-dong, Seongbuk-gu, Seoul, 02841, Republic of Korea
²Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Medical College, Guro Hospital, #80, Guro-dong, Guro-gu, Seoul, 08308, Republic of Korea
³Department of Biological Sciences, Western University, 1151 Richmond St., London, ON, N6A 3K7, Canada
⁴Department of Systems Biotechnology, College of Biotechnology and Natural Resources, Chung-Ang University, Anseong-si, Gyeonggi-do, 17546, Republic of Korea

E-mail:,

We fabricated biphasic calcium phosphate nanoparticles (BCP NPs)-immobilized on the surface of 3D printed PCL (BCP-IM-PCL) scaffolds, and evaluated in vitro osteogenesis and in vivo new bone formation in rat tibial defect model. In vitro and in vivo studies showed that BCP-IM-PCL significantly enhanced osteogenic markers (i.e., ALP activity, calcium deposition, and the expression of osteocalcin and osteopontin) and markedly increased new bone formation and mineralized bone tissues in tibial defect area, compared to unmodified PCL and BCP-mixed PCL scaffolds. This study demonstrated that BCP NPsimmobilized on the surface of PCL scaffolds are promising templates for bone tissue regeneration.

Keywords:Three-dimensional (3D) printed scaffolds;Biphasic calcium phosphate (BCP);MG-63 cells;Tibial defect model;New bone formation

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[Referenced By]

[1] germann M, Lill CA, Griesbeck K, Evans CH, Robbins PD, Schneider E, Baltzer AW, Gene Ther., 13, 1290 (2006)

[2] Nandi SK, Roy S, Mukherjee P, Kundu B, De DK, Basu D, Indian J. Med. Res., 132, 15 (2010)

[3] Oryan A, Alidadi S, Moshiri A, Maffulli N, J. Orthop. Surg. Res., 9, 18 (2014)

[4] Elsalanty ME, Genecov DG, Craniomaxillofac Trauma Reconstr, 2, 125 (2009)

[5] Athanasiou VT, Papachristou DJ, Panagopoulos A, Saridis A, Scopa CD, Megas P, Med. Sci. Monit., 16, BR24 (2010)

[6] Yazar S, Semin. Plast. Surg., 24, 255 (2010)

[7] Ehrler DM, Vaccaro AR, Clin. Orthop. Relat. Res., 38 (2000) .

[8] Do AV, Khorsand B, Geary SM, Salem AK, Adv. Healthc. Mater., 4, 1742 (2015)

[9] Peltola SM, Melchels FP, Grijpma DW, Kellomaki M, Ann. Med., 40, 268 (2008)

[10] Wust S, Muller R, Hofmann S, J. Funct. Biomater., 2, 119 (2011)

[11] Chen M, Le DQ, Baatrup A, Nygaard JV, Hein S, Bjerre L, Kassem M, Zou X, Bunger C, Acta Biomater., 7, 2244 (2011)

[12] Zhu Y, Gao C, Shen J, Biomaterials, 23, 4889 (2002)

[13] Kim SS, Park MS, Gwak SJ, Choi CY, Kim BS, Tissue Eng., 12, 2997 (2006)

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

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

[16] Kim SE, Yun YP, Shim KS, Kim HJ, Park K, Song HR, Biomed. Mater., 11, 055005 (2016)

[17] Dorozhkin SV, Biomaterials, 31, 1465 (2010)

[18] Stahli C, Bohner M, Bashoor-Zadeh M, Doebelin N, Baroud G, Acta Biomater., 6, 2760 (2010)

[19] Yuan H, van Blitterswijk CA, de Groot K, de Bruijn JD, Tissue Eng., 12, 1607 (2006)

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

[21] Rezwan K, Chen QZ, Blaker JJ, Boccaccini AR, Biomaterials, 27, 3413 (2006)

[22] Kim S, Kim SS, Lee SH, Ahn SE, Gwak SJ, Song JH, Kim BS, Chung HM, Biomaterials, 29, 1043 (2008)

[23] Zhang P, Hong Z, Yu T, Chen X, Jing X, Biomaterials, 30, 58 (2009)

[24] Luangphakdy V, Walker E, Shinohara K, Pan H, Hefferan T, Bauer TW, Stockdale L, Saini S, Dadsetan M, Runge MB, Vasanji A, Griffith L, Yaszemski M, Muschler GF, Tissue Eng., 19, 634 (2013)

[25] Mekala NK, Baadhe RR, Parcha SR, Yalavarthy PD, J. Biomed. Res., 27, 318 (2013)

[26] Maquet V, Boccaccini AR, Pravata L, Notingher I, Jerome R, Biomaterials, 25, 4185 (2004)

[27] Murphy WL, Kohn DH, Mooney DJ, J. Biomed. Mater. Res., 50, 50 (2000)

[28] Douglas T, Pamula E, Hauk D, Wiltfang J, Sivananthan S, Sherry E, Warnke PH, J. Mater. Sci. -Mater. Med., 20, 1909 (2009)

[29] Liu WY, Yeh YC, Lipner J, Xie JW, Sung HW, Thomopoulos S, Xia YN, Langmuir, 27(15), 9088 (2011)

[30] Meng ZX, Li HF, Sun ZZ, Zheng W, Zheng YF, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 33, 699 (2013)

[31] Wang DX, He Y, Bi L, Qu ZH, Zou JW, Pan Z, Fan JJ, Chen L, Dong X, Liu XN, Pei GX, Ding JD, Int. J. Nanomed., 8, 1855 (2013)

[32] Kim SE, Choi HW, Lee HJ, Chang JH, Choi J, Kim KJ, Lim HJ, Jun YJ, Lee SC, J. Mater. Chem., 18, 4994 (2008)

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

[34] Fan XW, Lin LJ, Dalsin JL, Messersmith PB, J. Am. Chem. Soc., 127(45), 15843 (2005)

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

[36] Owen TA, Aronow M, Shalhoub V, Barone LM, Wilming L, Tassinari MS, Kennedy MB, Pockwinse S, Lian JB, Stein GS, J. Cell. Physiol., 143, 420 (1990)

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

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

[39] Hofman S, Sidqui M, Abensur D, Valentini P, Missika P, Biomaterials, 20, 1155 (1999)

[40] Le Nihouannen D, Saffarzadeh A, Gauthier O, Moreau F, Pilet P, Spaethe R, Layrolle P, Daculsi G, J. Mater. Sci. -Mater. Med., 19, 667 (2008)

[41] Samavedi S, Whittington AR, Goldstein AS, Acta Biomater., 9, 8037 (2013)

[42] Tarafder S, Bose S, ACS Appl. Mater. Interfaces, 6, 9955 (2014)

[43] Coombes AG, Rizzi SC, Williamson M, Barralet JE, Downes S, Wallace WA, Biomaterials, 25, 315 (2004)

[44] Mattanavee W, Suwantong O, Puthong S, Bunaprasert T, Hoven VP, Supaphol P, ACS Appl. Mater. Interfaces, 1, 1076 (2009)

[45] Xin R, Leng Y, Chen J, Zhang Q, Biomaterials, 26, 6477 (2005)

[46] Barrere F, van Blitterswijk CA, de Groot K, Int. J. Nanomed., 1, 317 (2006)