Skip to main content
Log in

Effect of cross-linking spacers on biocompatibility of chitosan-spacer-poly(ethylene oxide) hydrogel

  • Articles
  • Published:
Macromolecular Research Aims and scope Submit manuscript

Abstract

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 chitosan-spacer-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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. M. V. Risbud and M. Sittinger, Trends Biotechnol., 20, 351 (2002).

    Article  CAS  Google Scholar 

  2. M. Sittinger, D. W. Hutmacher, and M. V. Risbud, Curr. Opin. Biotechnol., 15, 411 (2004).

    Article  CAS  Google Scholar 

  3. R. Cortivo, P. Brun, A. Rastrelli, and G. Abatangelo, Biomaterials, 12, 727 (1991).

    Article  CAS  Google Scholar 

  4. J. Berger, M. Reist, J. M. Mayer, O. Felt, N. A. Peppas, and R. Gurny, Eur. J. Pharm. Biopharm., 57, 19 (2004).

    Article  CAS  Google Scholar 

  5. M. Rinaudo, Prog. Polym. Sci., 31, 603 (2006).

    Article  CAS  Google Scholar 

  6. K. Jeong, W. Lee, J. Cha, C. R. Park, Y. W. Cho, and I. C. Kwon, Macromol. Res., 16, 57 (2008).

    CAS  Google Scholar 

  7. G. I. Konishi and Y. Chujo, Macromol. Res., 16, 70 (2008).

    CAS  Google Scholar 

  8. J. H. You, S. W. Choi, J. H. Kim, and Y. T. Kwak, Macromol. Res., 16, 609 (2008).

    CAS  Google Scholar 

  9. T. Tsukagoshi, Y. Kondo, and N. Yoshino. Colloids Surf. B, 54, 82 (2007).

    Article  CAS  Google Scholar 

  10. S. J. Sofia and E. W. Merrill, J. Biomed. Mater. Res., 40, 153 (1998).

    Article  CAS  Google Scholar 

  11. Z. F. Li and E. Ruckenstein, J. Colloid Interface Sci., 269, 62 (2004).

    Article  CAS  Google Scholar 

  12. J. Kim, Y. Park, G. Tae, K. B. Lee, S. J. Hwang, I. S. Kim, I. Noh, and K. Sun, J. Biomed. Mater. Res., 88, 967 (2009).

    Article  Google Scholar 

  13. D. I. Zeugolis, R. G. Paul, and G. Attenburrow, Acta Biomater., 4, 1646 (2008).

    Article  CAS  Google Scholar 

  14. A. M. Rodriguez and C. A. Vacanti, Frontiers in Tissue Engineering, L. V. Mclntire, Ed., Elsevier Science, New York, 1998, pp 400–411.

    Chapter  Google Scholar 

  15. C. H. Chang, T. F. Kuo, C. C. Lin, C. H. Chou, K. H. Chen, F. H. Lin, and H. C. Liu, Biomaterials, 27, 1876 (2006).

    Article  CAS  Google Scholar 

  16. F. Boccafoschi, J. Habermehl, S. Vesentini, and D. Mantovani, Biomaterials, 26, 7410 (2005).

    Article  CAS  Google Scholar 

  17. M. Hanthamrongwit, W. H. Reid, and M. H. Grant, Biomaterials, 17, 775 (1996).

    Article  CAS  Google Scholar 

  18. A. Jayakrishnan and S. R. Jameela, Biomaterials, 17, 471 (1996).

    Article  CAS  Google Scholar 

  19. P. Tagliaferro, C. J. Tandler, A. J. Ramos, J. P. Saavedra, and A. Brusco, J. Neurosci. Methods, 77, 191 (1997).

    Article  CAS  Google Scholar 

  20. K. Weadock, R. M. Olson, and F. H. Silver, Biomater. Med. Devices Artif. Organs, 11, 293 (1984).

    CAS  Google Scholar 

  21. D. M. Simmons and J. N. Kearney, Biotechnol. Appl. Biochem., 17, 23 (1993).

    CAS  Google Scholar 

  22. P. B. van Wachem, M. J. A. van Luyn, L. H. H. Olde Damink, P. J. Dijkstra, J. Feijen, and P. Nieuwenhuis, J. Biomed. Mater. Res., 28, 353 (1994).

    Article  Google Scholar 

  23. S. Jo, D. Kim, J. Woo, Y. D. Park, G. Tae, G. Yoon, and I. Noh, Macromol. Res., 19, 147 (2011).

    Article  CAS  Google Scholar 

  24. M. F. Cote and C. F. Doillon, Biomaterials, 13, 612 (1992).

    Article  CAS  Google Scholar 

  25. R. Marchand, S. Woerly, L. Bertrand, and N. Valdes, Brain Res. Bull., 39, 415 (1993).

    Article  Google Scholar 

  26. S. C. Chena, Y. C. Wua, F. L. Mib, Y. H. Lina, L. C. Yua, and H. W. Sung, J. Control. Release, 96, 285 (2004).

    Article  Google Scholar 

  27. H. Arslan, B. Hazer, and S. C. Yoon, J. Appl. Polym. Sci., 103, 81 (2007).

    Article  CAS  Google Scholar 

  28. Y. Y. Li, X. Z. Zhang, G. C. Kim, H. Cheng, S. X. Cheng, and R. X. Zhuo, Small, 2, 917 (2006).

    Article  CAS  Google Scholar 

  29. X. L. Niu, L. Y. Liu, M. L. Hu, and X. Chen, J. Mol. Cell. Cardiol., 27, 531 (1995).

    Article  CAS  Google Scholar 

  30. C. G. Liu, K. G. Desai, X. G. Chen, and H. J. Park, J. Agric. Food Chem., 53, 437 (2005).

    Article  CAS  Google Scholar 

  31. H. Arslan, B. Hazer, and S. C. Yoon, J. Appl. Polym. Sci., 103, 81 (2007).

    Article  CAS  Google Scholar 

  32. M. E. Nimni, D. Cheung, B. Strates, M. Kodama, and K. Sheikh, J. Biomed. Mater. Res., 21, 741 (1987).

    Article  CAS  Google Scholar 

  33. J. N. Gade, J. H. Fellman, and J. P. Bentley, J. Biomed. Mater. Res., 25, 799 (1991).

    Article  CAS  Google Scholar 

  34. H. Petite, V. Frei, A. Hut, and D. Herbage, J. Biomed. Mater. Res., 28, 159 (1994).

    Article  CAS  Google Scholar 

  35. K. B. Hey, C. M. Laths, M. J. Raxworthy, and E. J. Wood, Biotechnol. Appl. Biochem., 12, 85 (1990).

    CAS  Google Scholar 

  36. M. Koide, K. Osaki, J. Konishi, K. Oyamada, T. Katakura, and A. Takahashi, J. Biomed. Mater. Res., 27, 79 (1993).

    Article  CAS  Google Scholar 

  37. M. C. Wang, G. D. Pins, and F. H. Silver, Biomaterials, 15, 507 (1994).

    Article  CAS  Google Scholar 

  38. M. S. Kim, Y. J. Choi, I. Noh, and G. Tae, J. Biomed. Mater. Res., 83A, 674 (2007).

    Article  CAS  Google Scholar 

  39. T. T. Minh, W. Y. Baek, and J. O. Lim, J. Tissue Eng. Regen. Med., 6, 119 (2009).

    Google Scholar 

  40. K. H. Seo, S. J. You, H. J. Chun, C. H. Kim, W. K. Lee, Y. M. Lim, Y. C. Nho, and J. W. Jang, J. Tissue Eng. Regen. Med., 6, 414 (2009).

    Google Scholar 

  41. S. J. Park, S. M. Yu, M. H. Chun, H. J. Chun, and C. H. Kim, J. Tissue Eng. Regen. Med., 6, 438 (2009).

    Google Scholar 

  42. M. S. Bae, S. E. Kim, J. S. Na, and I. K. Kwon, J. Tissue Eng. Regen. Med., 7, 184 (2010).

    Google Scholar 

  43. Y. Pan, X. Luo, A. Zhu, and S. Dai, J. Biomater. Sci., Polym. Ed., 20, 981 (2009).

    Article  CAS  Google Scholar 

  44. L. Yin, X. Zhao, L. Cui, J. Ding, M. He, C. Tang, and C. Yin, Food Chem. Toxicol., 47, 1139 (2009).

    Article  CAS  Google Scholar 

  45. E. Borenfreund and J. A. Puerner, Toxicol. Lett., 24, 119 (1985).

    Article  CAS  Google Scholar 

  46. D. Triglia, S. S. Braa, C. Yonan, and G. K. Naughton, In Vitro Cell. Dev. Biol. Anim., 27, 239 (1991).

    Article  Google Scholar 

  47. F. George and A. T. John, Toxicol. Lett., 160, 171 (2006).

    Article  Google Scholar 

  48. Y. Jang, H. K. Song, D. C. Jeong, and S. H. Lee, Korean J. Anesthesiol., 55, 467 (2008).

    Article  Google Scholar 

  49. Y. Li, X. Zhang, G. Kim, H. Cheng, S. Cheng, and R. Zhuo, Small, 2, 917 (2006).

    Article  CAS  Google Scholar 

  50. T. Wu, Y. Zhang, X. Wang, and S. Liu, Chem. Mater., 20, 101 (2008).

    Article  CAS  Google Scholar 

  51. J. Shan, M. Nuopponen, H. Jiang, T. Viitala, E. Kauppinen, K. Kontturi, and H. Tenhu, Macromolecules, 38, 2918 (2005).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Insup Noh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, D., Kim, S., Jo, S. et al. Effect of cross-linking spacers on biocompatibility of chitosan-spacer-poly(ethylene oxide) hydrogel. Macromol. Res. 19, 573–581 (2011). https://doi.org/10.1007/s13233-011-0606-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13233-011-0606-5

Keywords

Navigation