Synergistic effect of alginate/BMP-2/Umbilical cord serum-coated on 3D-printed PCL biocomposite for mastoid obliteration model

Chul Ho Jang; JiUn Lee; GeunHyung Kim

Journal of Industrial and Engineering Chemistry, Vol.72, 432-441, April, 2019

DOI10.1016/j.jiec.2018.12.046 Export Citation

Synergistic effect of alginate/BMP-2/Umbilical cord serum-coated on 3D-printed PCL biocomposite for mastoid obliteration model

Chul Ho Jang^†, JiUn Lee¹, and GeunHyung Kim^{1, †}

Department of Otolaryngology, Chonnam National University Medical School, Gwangju, South Korea
¹Department of Bio-Mechatronics, Tissue Engineering Laboratory, Sungkyunkwan University, Suwon, South Korea

E-mail:,

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been used widely in bone tissue regeneration; however, the use of rhBMP-2 can be limited clinically because extremely high doses can cause opposing effects on bone formation, such as high inflammation, edema, and even uncontrollable bone growth. To overcome the limitation of using BMP-2, we used an umbilical cord serum (UCS) that exhibits various growth factors (epidermal growth factor, transforming growth factor-β, nerve growth factor, etc.). To evaluate the effect of the UCS, we studied the synergistic effect of the composite scaffold using BMP-2/UCS/alginate coated on three-dimensional mesh-structured poly-ε-caprolactone (PCL), both in vitro and in vivo, using a rat mastoid obliteration model. The newly suggested biocomposite scaffold (BMP-2/UCS/alginate) demonstrates significantly rapid new bone formation (particularly, in the interstitial area of the scaffold) compared to those of two controls: PCL mesh structure coated with alginate, and BMP-2/alginate-coated PCL scaffold. Based on the in vitro and in vivo works, the present study demonstrates that the simultaneous use of low-dose BMP-2 and UCS increases osteogenesis significantly in a rat model compared to the control that uses only BMP-2.

Keywords:Polycaprolactone;Bone morphogenic protein;Umbilical cord serum;Osteogenesis

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[1] Jo SY, Eom TH, Yang HC, Cho YB, Jang CH, In Vivo, 28, 1207 (2014)

[2] Palva T, Karma P, Karja J, Palva A, Archiv. Otolaryngol., 101, 271 (1975)

[3] Linthicum FH, Laryngoscope, 112, 1777 (2002)

[4] Alves RD, Cabral F, Fonseca ACDO, Bento RF, Int. Arch. Otorhinolaryngol., 20, 76 (2016)

[5] Hamerschmidt R, dos Santos RF, Araujo JC, Stahlke HJ, Agulham MA, Moreira ATR, Mocellin M, Braz. J. Otorhinolar., 77, 315 (2011)

[6] Vos J, de Vey Mestdagh P, Colnot D, Borggreven P, Orelio C, Quak J, Eur. Arch. Otorhinolaryngol., 274, 4121 (2017)

[7] Yanagihara N, Komori M, Hinohira Y, Otol. Neurotol., 30, 766 (2009)

[8] Kim YJ, Park SG, Shin B, Kim J, Kim SW, Choo OS, Yin XY, Min BH, Choung YH, J. Biomed. Mater. Res. A, 105, 3493 (2017)

[9] Kim J, Kim HN, Lim KT, Kim Y, Pandey S, Garg P, Choung YH, Choung PH, Suh KY, Chung JH, Biomaterials, 34, 7257 (2013)

[10] Everts PA, Knape JT, Weibrich G, Schonberger JP, Hoffmann J, Overdevest EP, Box A, van Zundert A, J. Extra Corpor. Technol., 38, 174 (2006)

[11] Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR, Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 85, 638 (1998).

[12] Ang LPK, Do TP, Thein ZM, Reza HM, Tan XW, Yap C, Tan DT, Beuerman RW, Invest. Ophth. Vis. Sci., 52, 6138 (2011)

[13] Jang CH, Cho YB, Yeo M, Lee H, Min EJ, Lee BH, Kim GH, Int. J. Biol. Macromol., 62, 232 (2013)

[14] Jang YS, Jang CH, Cho YB, Kim M, Kim GH, Int. J. Pediatr. Otorhinolaryngol., 78, 2237 (2014)

[15] Jang CH, Cho YB, Choi CH, Jang YS, Jung WK, Lee H, Kim GH, Int. J. Pediatr. Otorhinolaryngol., 78, 1061 (2014)

[16] Huang KH, Lin YH, Shie MY, Lin CP, J. Formos. Med. Assoc. (2018).

[17] Tannoury CA, An HS, J. Spine, 14, 552 (2014)

[18] Hsu WK, Wang JC, J. Spine, 8, 419 (2008)

[19] Kaewsrichan J, Wongwitwichot P, Chandarajoti K, Chua K, Ruszymah B, Arch. Oral Biol., 56, 90 (2011)

[20] Kim BR, Nguyen TBL, Min YK, Lee BT, Tissue Eng. A, 20, 3279 (2014)

[21] Liu HW, Chen CH, Tsai CL, Hsiue GH, Bone, 39, 825 (2006)

[22] Kim M, Jung WK, Kim G, Bioprocess Biosyst. Eng., 36, 1725 (2013)

[23] Martins A, Pinho ED, Faria S, Pashkuleva I, Marques AP, Reis RL, Neves NM, Small, 5, 1195 (2009)

[24] Schmidt-Bleek K, Willie BM, Schwabe P, Seemann P, Duda GN, Cytokine Growth F. R., 27, 141 (2016)

[25] Yoon KC, Choi W, You IC, Choi J, Cornea, 30, 744 (2011)

[26] Yoon KC, You IC, Im SK, Jeong TS, Park YG, Choi J, Ophthalmology, 114, 1637e2 (2007)

[27] Shetty P, Bharucha K, Tanavde V, Cell Biol. Int., 31, 293 (2007)

[28] Rungsiwiwut R, Ingrungruanglert P, Numchaisrika P, Virutamasen P, Phermthai T, Pruksananonda K, Stem Cells Int., 2016 (2016)

[29] Gronowicz G, Jacobs E, Peng T, Zhu L, Hurley M, Kuhn LT, Tissue Eng. A, 23, 1490 (2017)

[30] Kempen DH, Lu L, Heijink A, Hefferan TE, Creemers LB, Maran A, Yaszemski MJ, Dhert WJ, Biomaterials, 30, 2816 (2009)

[31] Schmid GJ, Kobayashi C, Sandell LJ, Ornitz DM, Dev. Dyn., 238, 766 (2009)

[32] Gerstenfeld LC, Einhorn TA, J. Musculoskelet. Neuronal Interact., 3, 297 (2003)

[33] Oh HJ, Jang JY, Li Z, Park SH, Yoon KC, Curr. Eye Res., 37, 1084 (2012)

[34] Erdem E, Yagmur M, Harbiyeli I, Taylan-Sekeroglu H, Ersoz R, Int. J. Ophthalmol., 7, 807 (2014)

[35] Jia L, Zhou X, Huang X, Xu X, Jia Y, Wu Y, Yao J, Wu Y, Wang K, Faseb J., 32, 4534 (2018)

[36] James AW, LaChaud G, Shen J, Asatrian G, Nguyen V, Zhang X, Ting K, Soo C, Tissue Eng. B Rev., 22, 284 (2016)

[37] Yoon KC, Im SK, Park YG, Jung YD, Yang SY, Choi J, Cornea, 25, 268 (2006)

[38] Vajpayee R, Mukerji N, Tandon R, Sharma N, Pandey R, Biswas N, Malhotra N, Melki S, Brit. J. Opthalmol., 87, 1312 (2003)

[39] Sharma N, Goel M, Velpandian T, Titiyal JS, Tandon R, Vajpayee RB, Invest. Ophthalmol. Vis. Sci., 52, 1087 (2011)

[40] Jang CH, Lee H, Kim M, Kim G, Int. J. Biol. Macromol., 93, 1575 (2016)