Characterization of Lactide/Hyaluronic Acid Polymer Cross-Linked by 1,3-Butadiene Diepoxide

1,3-Butadiene Diepoxide에 의해 가교된 락타이드/히아루론산 고분자의 특성

  • Han, Gwang-Seon (Department of Chemical Engineering and Nano-Bio Technology, Hannam University) ;
  • Bae, Jung-Eun (Department of Biological Sciences, Hannam University) ;
  • Kim, In-Seop (Department of Biological Sciences, Hannam University) ;
  • Cheong, Seong-Ihl (Department of Chemical Engineering and Nano-Bio Technology, Hannam University)
  • 한광선 (한남대학교 나노생명화학공학과) ;
  • 배정은 (한남대학교 생명과학과) ;
  • 김인섭 (한남대학교 생명과학과) ;
  • 정성일 (한남대학교 나노생명화학공학과)
  • Published : 2008.07.31

Abstract

The hyaluronic acid (HA) polymers cross-linked with lactide (LA) using the crosslinking agent, 1,3-butadiene diepoxide (BD), were prepared in order to develop a biomedical material for tissue engineering. The degree of lactide and BD reaction of the crosslinked polymer was determined by the analysis of nuclear magnetic resonance spectroscopy. Both degree of reaction and swelling ratio increased with BD concentration or LA/HA mole ratio. Tensile modulus decreased with increasing BD concentration or decreasing LA/HA mole ratio. Degradation was shown to be progressed at two different stages and became slow with increasing BD concentration. It was shown that the first stage degradation was mainly due to the decomposition of ester linkage in the crosslinked structure. The cell growth inhibition increased with BD concentration. Although cytotoxicity was slightly observed in the high BD concentration, the value was very low (below 6%) enough not to affect the cell growth.

조직공학용 생체재료로 사용하고자 가교제 1,3-butadiene diepoxide(BD)를 사용하여 락타이드(LA)와 가교시킨 히아루론산(HA) 고분자를 제조하였다. 가교된 고분자의 락타이드 및 BD 반응도는 핵자기 공명 분광법으로 결정하였다. 반응도와 팽윤도는 LA/HA 몰비 혹은 가교제 농도를 증가시킴에 따라 증가하였다. 탄성률은 가교제 농도가 증가하거나 HA/LA 몰비가 감소함에 따라 감소하였다. 생분해는 2단계로 진행되었으며 BD 농도가 증가할수록 서서히 진행되었다. 첫 단계 분해는 주로 가교구조에 존재하는 에스테르기의 분해에 기인한 것으로 나타났다. 세포 성장 저해는 BD 농도가 증가함에 따라 증가하였다. 세포 독성은 BD 농도가 클 경우 약간 나타났으나 그 값은 6% 미만으로 세포 성장에 큰 문제는 없는 것으로 나타났다.

Keywords

References

  1. Y. D. Park, N. Tirelli, and J. A. Hubbell, Biomaterials, 24, 893 (2003) https://doi.org/10.1016/S0142-9612(02)00420-9
  2. G. D. Prestwitch, D. M. Marecak, and J. F. Marecek, J. Control. Rel., 53, 93 (1998) https://doi.org/10.1016/S0168-3659(97)00242-3
  3. Y. Luo, K. R. Kirker, and G. D. Prestwich, J. Control. Rel., 69, 169 (2000) https://doi.org/10.1016/S0168-3659(00)00300-X
  4. S. N. Park, H. J. Lee, K. H. Lee, and H. Suh, Biomaterials, 22, 1205 (2002)
  5. S. N. Park, H. J. Lee, K. H. Lee, and H. Suh, Biomaterials, 24, 1631 (2003) https://doi.org/10.1016/S0142-9612(02)00550-1
  6. H. S. Nam, J. H. Kim, J. H. An, and D. J. Jung, Polymer(Korea), 25, 476 (2001)
  7. J. A. Hunt, H. N. Joshi, V. J. Stella, and E. M. Topp, J. Control. Rel., 12, 159 (1990) https://doi.org/10.1016/0168-3659(90)90092-8
  8. L. Benedetti, R. Cortivo, T. Berti, A. Berti, F. Pea, M. Marzzo, M. Moras, and G. Abatangel, Biomateials, 14, 1154 (1993)
  9. J. Aigner, J. Tegeler, P. Hutzler, D. Campoccia, A. Pavesio, C. Hammer, E. Kastenbauer, and A. Naurnann, J. Biomed. Mater. Res., 42, 172 (1998) https://doi.org/10.1002/(SICI)1097-4636(199811)42:2<172::AID-JBM2>3.0.CO;2-M
  10. G. P. Chen, Y. Ito, Y. Imanishi, A. Magnani, S. Lamponi, and R. Barbucci, Bioconjugate Chem., 8, 730 (1997) https://doi.org/10.1021/bc9700493
  11. J. S. Lee, D. J. Choo, S. H. Kim, and Y. H. Kim, Polymer (Korea), 22, 880 (1998)
  12. C. Grandfils, P. Flandroy, and R. Jerome, J. Control. Rel., 38, 109 (1996) https://doi.org/10.1016/0168-3659(95)00102-6
  13. H. Fukuzaki, M. Yoshida, M. Asano, and M. Kumakura, Eur. Polym. J., 25, 1019 (1989) https://doi.org/10.1016/0014-3057(89)90131-6
  14. S. Li, M. Tenon, H. Garreau, C. Braud, and M. Vert, Polym. Degrad. Stab., 67, 85 (2000) https://doi.org/10.1016/S0141-3910(99)00091-9
  15. J. Y. Kwon and S. I. Cheong, Polymer(Korea), 29, 445 (2005)
  16. J. Y. Kwon and S. I. Cheong, Membrane J.(Korea), 15, 8 (2005)
  17. J. Y. Kwon and S. I. Cheong, Polymer(Korea), 29, 599 (2005)
  18. M. S. Kim, J. Y. Kwon, and S. I. Cheong, Membrane J.(Korea), 15, 281 (2005)
  19. W. J. Kim, J. Y. Kwon, S. I. Cheong, and I. S. Kim, Korean J. Biotechnol. Bioeng., 21, 255 (2006)
  20. K. Sakurai, Y. Ueno, and T. Okuyama, U.S. Patent 4,716,224 (1987)
  21. T. Malson, L. G. Ahrgren, and A. N. Belder, U.S. Patent 4,772,419 (1988)
  22. J. D. Yang, S. W. Tsai, J. H. Chen, C. L. Chen, and Y. L. Hsieh, U.S. Patent 6,852,255 (2002)
  23. T. C. Laurent, K. Hellsing, and B. Gelotte, Acta Chem. Scand., 18, 274 (1964) https://doi.org/10.3891/acta.chem.scand.18-0274
  24. B. Ronnebeger, W. J. Kao, J. M. Anderson, and T. Kissel, J. Biomed. Mater. Res. Part A, 30, 31 (1996) https://doi.org/10.1002/(SICI)1097-4636(199601)30:1<31::AID-JBM5>3.0.CO;2-S
  25. H. R. Allcock and F. W. Lampe, Contemporary Polymer Chemistry, 2nd ed., Prentice-Hall, Inc., New Jersey, NJ, 1981
  26. S. H. Oh, J. Y. Lee, S. H. Ghil, S. S. Lee, S. H. Yuk, and J. H. Lee, Biomaterials, 27, 1936 (2006) https://doi.org/10.1016/j.biomaterials.2005.09.030