화학공학소재연구정보센터
Macromolecular Research, Vol.19, No.3, 300-306, March, 2011
RGD-Conjugated In Situ Forming Hydrogels as Cell-Adhesive Injectable Scaffolds
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In this study, a bioactive hydrogel was prepared from a chitosan derivative and Arg-Gly-Asp (RGD)-conjugated polypseudorotaxane, which is a cell-adhesive extracellular matrix. Chitosan was modified with 4-hydroxy phenyl acetic acid to obtain a water-soluble product for enzymatic cross-linking. Tyramine-terminated polypseudorotaxane (PRx) was prepared from the inclusion complex of a tyramine-terminated poly(ethylene glycol) backbone, and α-cyclodextrin (α-CD). Gly-Arg-Gly-Asp-Ser (GRGDS) was conjugated to the PRx using 4-nitrophenyl chloroformate (NPC) and partially carboxylated with succinic anhydride. The structure of the PRx-RGD and 4-hydroxylphenylacetamide chitosan (CHPA) was characterized by 1H NMR and FTIR spectroscopy. The RGD content in PRx-RGD was determined to be 0.19%. PRx-RGD and CHPA solution was crosslinked to form a bioactive hydrogel in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2), which exhibited rapid gelation (~20 sec). An in vitro cell culture was carried out with L929 mouse fibroblasts for 1 and 3 days. The results showed that fibroblasts adhered better and appeared to be more biocompatible on the RGD-conjugated hydrogel than the hydrogel without RGD. The combined results highlight the potential use of this bioactive hydrogel as an injectable scaffold in tissue engineering applications.
  1. Joung YK, Choi JH, Park KM, Park KD, Biomed. Mater., 2, 269 (2007)
  2. Lee KY, Mooney DJ, Chem. Rev., 101(7), 1869 (2001)
  3. Van Tomme SR, Storm G, Hennink WE, Int. J. Pharm., 355, 1 (2008)
  4. Ito T, Yeo Y, Highley CB, Bellas E, Kohane DS, Biomaterials, 28, 3418 (2007)
  5. Lih E, Joung YK, Bae JW, Park KD, J. Bioact. Compat. Polym., 23, 444 (2008)
  6. Nguyen MK, Lee DS, Macromol. Res., 18(3), 284 (2010)
  7. Jin R, Hiemstra C, Zhong Z, Feijen J, Biomaterials, 28, 2791 (2007)
  8. Kurisawa M, Chung JE, Yang YY, Gao SJ, Uyama H, Chem. Commun., 14, 4312 (2005)
  9. Araki J, Ito K, Soft Matter, 3, 1456 (2007)
  10. Ooya T, Choi HS, Yamashita A, Yui N, Sugaya Y, Kano A, Maruyama A, Akita H, Ito R, Kogure K, Harashima H, J. Am. Chem. Soc., 128(12), 3852 (2006)
  11. Watanabe J, Ooya T, Park KD, Kim YH, Yui N, J. Biomater. Sci.-Polym. Ed., 11, 1333 (2000)
  12. Tran NQ, Joung YK, Lih E, Park KM, Park KD, Biomacromolecules, 11(3), 617 (2010)
  13. Kirsebom H, Aguilar MR, Roman JS, Fernandez M, Prieto MA, Bondar B, J. Bioact. Compat. Polym., 22, 621 (2007)
  14. Park KM, Joung YK, Park KD, Lee SY, Lee MC, Macromol. Res., 16(6), 517 (2008)
  15. Woo YI, Lee MH, Kim HL, Park JC, Han DW, Kim JK, Tsubaki K, Chung KH, Hyun SO, Yang YI, Macromol. Res., 18(1), 90 (2010)
  16. Choi WS, Bae JW, Joung YK, Park KD, Lee MH, Park JC, Kwon IK, Macromol. Res., 17(7), 458 (2009)
  17. Ehrbar M, Rizzi SC, Schoenmakers RG, San Miguel B, Hubbell JA, Weber FE, Lutolf MP, Biomacromolecules, 8(10), 3000 (2007)
  18. Joung YK, Sengoku Y, Ooya T, Park KD, Yui N, Sci. Tech. Adv. Mater., 6, 484 (2005)
  19. Ooya T, Ito A, Yui N, Macromol. Biosci., 5, 379 (2005)
  20. Park KM, Shin YM, Joung YK, Shin H, Park KD, Biomacromolecules, 11(3), 706 (2010)
  21. Jo S, Engel PS, Mikos AG, Polymer, 41(21), 7595 (2000)
  22. Ooya T, Eguchi M, Ozaki A, Yui N, Int. J. Pharm., 242, 47 (2002)
  23. Lin YS, Wang SS, Chung TW, Wang YH, Chiou SH, Hsu JJ, Chou NK, Hsieh KH, Chu SH, Artif. Organs, 25, 617 (2001)
  24. Zhang L, Hum M, Wang M, Li Y, Chen H, Chu C, Jiang H, J. Biomed. Mater. Res., 73A, 468 (2005)
  25. Hadara A, Coord. Chem. Rev., 148, 115 (1996)
  26. Wang LS, Chung JE, Chan PP, Kurisawa M, Biomaterials, 31, 1148 (2010)
  27. Bainbridge NJ, Harris KL, Jordan NR, Sharpe JR, Eur. Cell. Mater., 16, 36 (2008)
  28. Garcia AJ, Reyes CD, J. Dent. Res., 84, 407 (2005)
  29. Jeschke B, Meyer J, Jonczyk A, Kessler H, Adamietz P, Meenen NM, Kantlehner M, Goepfert C, Nies B, Biomaterials, 23, 3455 (2002)
  30. Rowley JA, Sun ZX, Goldman D, Mooney DJ, Adv. Mater., 14(12), 886 (2002)