화학공학소재연구정보센터
Macromolecular Research, Vol.19, No.6, 573-581, June, 2011
Effect of Cross-Linking Spacers on Biocompatibility of Chitosan-Spacer-Poly(ethylene oxide) Hydrogel
E-mail:
A cross-linking spacer molecule in biomaterials is an important factor in controlling their biocompatibility. The effects of various cross-linking spacers on the biocompatibility of chitosan-spacer-poly(ethylene oxide) (PEO) hydrogel were evaluated by various cytotoxicity assays and by targeting to specific cell organs. The chitosanspacer-PEO hydrogel was synthesized using a Michael type addition reaction by employing chitosan-acrylate and PEO-thiols. Chitosan-acrylates have been synthesized employing three different cross-linking spacers such as 2-carboxyethyl acrylate, linoleic acid and oleic acid. This study verified the grafting of the spacer molecules to the amine groups of chitosan side chains with FTIR by comparing the peaks of the chitosan-acrylates with those of the unmodified chitosan. After evaluating the cytotoxicity of the chitosan-acrylates in solution with a live a dead assay, the cytotoxicity of the chitosan-spacer-PEO gels was compared with each other by testing them with CCK-8 for their effects on cell proliferation, with a MTT assay for their effects on mitochondria damage, with BrdU assay for their effects on DNA damages and with the neutral red assay for their effects on lysosome damages. The degrees of cytotoxicity of the chitosan-spacer-PEO hydrogels were compared with those of Teflon and Latex, positive and negative control, respectively, using neural cells, such as PC-12 cells. The chitosan-2-carboxyethyl acrylate-PEO hydrogels demonstrated the best cell compatibility among the hydrogels employed in this study.
  1. Risbud MV, Sittinger M, Trends Biotechnol., 20, 351 (2002)
  2. Sittinger M, Hutmacher DW, Risbud MV, Curr. Opin. Biotechnol., 15, 411 (2004)
  3. Cortivo R, Brun P, Rastrelli A, Abatangelo G, Biomaterials, 12, 727 (1991)
  4. Berger J, Reist M, Mayer JM, Felt O, Peppas NA, Gurny R, Eur. J. Pharm. Biopharm., 57, 19 (2004)
  5. Rinaudo M, Prog. Polym. Sci, 31, 603 (2006)
  6. Jeong K, Lee W, Cha J, Park CR, Cho YW, Kwon IC, Macromol. Res., 16(1), 57 (2008)
  7. Konishi GI, Chujo Y, Macromol. Res., 16(1), 70 (2008)
  8. You JH, Choi SW, Kim JH, Kwak YT, Macromol. Res., 16(7), 609 (2008)
  9. Tsukagoshi T, Kondo Y, Yoshino N, Colloids Surf. B: Biointerfaces, 54, 82 (2007)
  10. Sofia SJ, Merrill EW, J. Biomed. Mater. Res., 40, 153 (1998)
  11. Li ZF, Ruckenstein E, J. Colloid Interface Sci., 269(1), 62 (2004)
  12. Kim J, Park Y, Tae G, Lee KB, Hwang SJ, Kim IS, Noh I, Sun K, J. Biomed. Mater. Res., 88, 967 (2009)
  13. Zeugolis DI, Paul RG, Attenburrow G, Acta Biomater., 4, 1646 (2008)
  14. Rodriguez AM, Vacanti CA, Frontiers in Tissue Engineering, Mclntire LV, Ed., Elsevier Science, New York, 1998, pp 400-411.
  15. Chang CH, Kuo TF, Lin CC, Chou CH, Chen KH, Lin FH, Liu HC, Biomaterials, 27, 1876 (2006)
  16. Boccafoschi F, Habermehl J, Vesentini S, Mantovani D, Biomaterials, 26, 7410 (2005)
  17. Hanthamrongwit M, Reid WH, Grant MH, Biomaterials, 17, 775 (1996)
  18. Jayakrishnan A, Jameela SR, Biomaterials, 17, 471 (1996)
  19. Tagliaferro P, Tandler CJ, Ramos AJ, Saavedra JP, Brusco A, J. Neurosci. Methods, 77, 191 (1997)
  20. Weadock K, Olson RM, Silver FH, Biomed. Microdevices Artif. Organs, 11, 293 (1984)
  21. Simmons DM, Kearney JN, Biotechnol. Appl. Biochem., 17, 23 (1993)
  22. van Wachem PB, van Luyn MJA, Olde Damink LHH, Dijkstra PJ, Feijen J, Nieuwenhuis P, J. Biomed. Mater. Res., 28, 353 (1994)
  23. Jo S, Kim D, Woo J, Yoon G, Park YD, Tae G, Noh I, Macromol. Res., 19(2), 147 (2011)
  24. Cote MF, Doillon CF, Biomaterials, 13, 612 (1992)
  25. Marchand R, Woerly S, Bertrand L, Valdes N, Brain Res. Bull., 39, 415 (1993)
  26. Chena SC, Wua YC, Mib FL, Lina YH, Yua LC, Sung HW, J. Control. Release, 96, 285 (2004)
  27. Arslan H, Hazer B, Yoon SC, J. Appl. Polym. Sci., 103(1), 81 (2007)
  28. Li YY, Zhang XZ, Kim GC, Cheng H, Cheng SX, Zhuo RX, Small, 2, 917 (2006)
  29. Niu XL, Liu LY, Hu ML, Chen X, J. Mol. Cell. Cardiol., 27, 531 (1995)
  30. Liu CG, Desai KG, Chen XG, Park HJ, J. Agric. Food Chem., 53, 437 (2005)
  31. Arslan H, Hazer B, Yoon SC, J. Appl. Polym. Sci., 103(1), 81 (2007)
  32. Nimni ME, Cheung D, Strates B, Kodama M, Sheikh K, J. Biomed. Mater. Res., 21, 741 (1987)
  33. Gade JN, Fellman JH, Bentley JP, J. Biomed. Mater. Res., 25, 799 (1991)
  34. Petite H, Frei V, Hut A, Herbage D, J. Biomed. Mater. Res., 28, 159 (1994)
  35. Hey KB, Laths CM, Raxworthy MJ, Wood EJ, Biotechnol. Appl. Biochem., 12, 85 (1990)
  36. Koide M, Osaki K, Konishi J, Oyamada K, Katakura T, Takahashi A, J. Biomed. Mater. Res., 27, 79 (1993)
  37. Wang MC, Pins GD, Silver FH, Biomaterials, 15, 507 (1994)
  38. Kim MS, Choi YJ, Noh I, Tae G, J. Biomed. Mater. Res., 83A, 674 (2007)
  39. Minh TT, Baek WY, Lim JO, J. Tissue Eng Regen. Med., 6, 119 (2009)
  40. Seo KH, You SJ, Chun HJ, Kim CH, Lee WK, Lim YM, Nho YC, Jang JW, J. Tissue Eng. Regen. Med., 6, 414 (2009)
  41. Park SJ, Yu SM, Chun MH, Chun HJ, Kim CH, J. Tissue Eng. Regen. Med., 6, 438 (2009)
  42. Bae MS, Kim SE, Na JS, Kwon IK, J. Tissue Eng. Regen. Med., 7, 184 (2010)
  43. Pan Y, Luo X, Zhu A, Dai S, J. Biomater. Sci.-Polym. Ed., 20, 981 (2009)
  44. Yin L, Zhao X, Cui L, Ding J, He M, Tang C, Yin C, Food Chem. Toxicol., 47, 1139 (2009)
  45. Borenfreund E, Puerner JA, Toxicol. Lett., 24, 119 (1985)
  46. Triglia D, Braa SS, Yonan C, Naughton GK, In Vitro Cell. Dev. Biol. Anim., 27, 239 (1991)
  47. George F, John AT, Toxicol. Lett., 160, 171 (2006)
  48. Jang Y, Song HK, Jeong DC, Lee SH, Korean J. Anesthesiol., 55, 467 (2008)
  49. Li Y, Zhang X, Kim G, Cheng H, Cheng S, Zhuo R, Small, 2, 917 (2006)
  50. Wu T, Zhang Y, Wang X, Liu S, Chem. Mater., 20, 101 (2008)
  51. Shan J, Nuopponen M, Jiang H, Viitala T, Kauppinen E, Kontturi K, Tenhu H, Macromolecules, 38(7), 2918 (2005)