화학공학소재연구정보센터
Macromolecular Research, Vol.22, No.12, 1297-1305, December, 2014
Fabrication of recombinant human bone morphogenetic protein-2 coated porous biphasic calcium phosphate-sodium carboxymethylcellulose-gelatin scaffold and its In vitro evaluation
E-mail:
Fabrication of bone substitutes, which are a combination of bio-ceramics and bio-polymer, is performed to meet the demand for bone regeneration after fracture or disease. In this study, sodium carboxymethylcellulosegelatin (NaCMC-GEL) hydrogel scaffold where the ratio of NaCMC and GEL was 1:2 and biphasic calcium phosphate (BCP) loaded NaCMC-GEL where the ratio of BCP, NaCMC and GEL was 1:1:2 hydrogel scaffold were fabricated successfully by the freeze-drying method. These hydrogel scaffolds were crosslinked by 0.75wt% genipin solution to check the swelling and ensure optimum degradation. Then BCP-NaCMC-GEL hydrogel was coated with recombinant human bone morphogenetic protein-2 (rhBMP-2). Detailed morphological and material characterization, such as porosity, micro-structural analysis, and chemical constituents of NaCMC-GEL and BCP-NaCMC-GEL hydrogel scaffolds was carried out. The study demonstrates that these hydrogel scaffolds have a porous structure and the pore size is optimum for bone tissue regeneration. PBS uptake and degradation behavior of the NaCMC-GEL, BCP-NaCMC-GEL and BMP-2-BCP-NaCMC-GEL hydrogel scaffolds were also observed. BMP-2-BCP-NaCMCGEL hydrogel scaffold showed higher cell viability, cell attachment, and proliferation of pre-osteoblast MC3T3-E1 cells than the NaCMC-GEL, BCP-NaCMC-GEL scaffolds, which was confirmed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, live-dead assay, and immunofluorescence assay. The BMP-2 release profile from BMP-2-BCP-NaCMC-GEL scaffold was also shown. The observations show that BMP-2-coated BCPNaCMC-GEL hydrogel scaffold is a promising material for bone tissue regeneration.
  1. Kang SW, Yang HS, Seo SW, Han DK, Kim BS, J. Biomed. Mater. Res. A, 85, 747 (2008)
  2. Peter SJ, Lu L, Kim DJ, Mikos AG, Biomaterials, 21, 1207 (2000)
  3. Zhang R, Ma PX, J. Biomed. Mater. Res., 45, 285 (1999)
  4. Wei G, Ma PX, Biomaterials, 25, 4749 (2004)
  5. Thomson RC, Yaszemski MJ, Powers JM, Mikos AG, Biomaterials, 19, 1935 (1998)
  6. Guan L, Davies JE, J. Biomed. Mater. Res. A, 71, 480 (2004)
  7. Khan YM, Katti DS, Laurencin CT, J. Biomed. Mater. Res. A, 69, 728 (2004)
  8. Zhang R, Ma PX, J. Biomed. Mater. Res., 44, 446 (1999)
  9. Jang DW, Franco RA, Sarkar SK, Lee BT, Sci. Technol. Adv. Mater., 13, 035009 (2012)
  10. Ba Linh NT, Lee KH, Lee BT, J. Biomed. Mater. Res. A, 101, 2412 (2013)
  11. Nguyen TP, Lee BT, J. Biomater. Appl., 27, 311 (2012)
  12. Liu X, Ma PX, Ann. Biomed. Eng., 32, 477 (2004)
  13. Hench LL, Polak JM, Science, 295, 1014 (2002)
  14. Athanasiou KA, Niederauer GG, Agrawal CM, Biomaterials, 17, 93 (1996)
  15. Blackwood KA, Bock N, Dargaville TR, Woodruff MA, Int. J. Polym. Sci., 2012, 25 (2012)
  16. Slaughter BV, Khurshid SS, Fisher OZ, Khademhosseini A, Peppas NA, Adv. Mater., 21(32-33), 3307 (2009)
  17. Chang C, Zhang L, Carbohydr. Polym., 84, 40 (2011)
  18. Sannino A, Demitri C, Madaghiele M, Materials, 2, 353 (2009)
  19. Van Vlierberghe S, Dubruel P, Schacht E, Biomacromolecules, 12(5), 1387 (2011)
  20. Seo KH, You SJ, Chun HJ, Kim CH, Lee WK, Lim YM, Nho YC, Jang JW, Tissue Eng. Regen. Med., 6, 414 (2009)
  21. Dolz M, Roldan C, Herraez JV, Belda R, Sobrino P, J. Dispers. Sci. Technol., 13, 95 (1992)
  22. Lii CY, Tomasik P, Zaleska H, Liaw SC, Lai VMF, Carbohydr. Polym., 50, 19 (2002)
  23. Rathna GVN, Rao DVM, Chatterji PR, J. Macromol. Sci. A, 33, 1199 (1996)
  24. Rossi S, Boneferoni MC, Ferrari F, Caramella C, Pharm. Dev. Technol., 4, 55 (1999)
  25. Lee YT, Youn MH, Paul RK, Lee KH, Song HY, Mater. Chem. Phys., 104(2-3), 249 (2007)
  26. O’Brien FJ, Mater. Today, 14, 88 (2011)
  27. Pekor CM, Kisa P, Nettleship I, J. Am. Ceram. Soc., 91, 3185 (2008)
  28. Porter MM, Imperio R, Wen M, Meyers MA, McKittrick J, Adv. Funct. Mater., 24(14), 1978 (2014)
  29. Thomson RC, Shung AK, Yaszemski MJ, Mikos AG, in Principles of Tissue Engineering, Lanza R, Langer R, Vacanti J, Eds., Academic Press, San Diego, pp 251-262. (2007)
  30. Zhu W, Xiao J, Wang D, Liu J, Xiong J, Liu L, Zhang X, Zeng Y, Int. Orthop., 33, 567 (2009)
  31. Cortesi R, Nastruzzi C, Davis SS, Biomaterials, 19, 1641 (1998)
  32. Prystupa DA, Donald AM, Polym. Gels Net., 4, 87 (1996)
  33. Rosca C, Popa MI, Lisa G, Chitanu GC, Carbohydr. Polym., 62, 35 (2005)
  34. Linh NTB, Min YK, Lee BT, J. Mater. Sci., 48(12), 4233 (2013)
  35. Lu J, Descamps M, Dejou J, Koubi G, Hardouin P, Lemaitre J, Proust JP, J. Biomed. Mater. Res. A, 63, 408 (2002)
  36. Lim JY, Shaughnessy MC, Zhou Z, Noh H, Vogler EA, Donahue HJ, Biomaterials, 29, 1776 (2008)
  37. Ribeiro N, Sousa SR, Monteiro FJ, J. Colloid Interface Sci., 351(2), 398 (2010)
  38. Zhou H, Lee J, Acta Biomater., 7, 2769 (2011)
  39. dos Santos EA, Farina M, Soares GA, Anselme K, J. Biomed. Mater. Res. A, 89, 510 (2009)
  40. Wang J, Zhang H, Zhu X, Fan H, Fan Y, Zhang X, J. Biomed. Mater. Res. B: Appl. Biomater., 101, 1069 (2013)
  41. Yun YP, Kim SE, Kang EY, Kim HJ, Park K, Song HR, Tissue Eng. Regen. Med., 10, 122 (2013)