Preparation and Release Profile of N8f-loaded Polylactide Scaffolds for Tissue Engineered Nerve Regeneration

조직공학적 신경재생을 위한 NGF를 함유한 PLA 담체의 제조 및 방출

  • 전은경 (한국화학연구원 생체의료고 분자팀) ;
  • 황혜진 (전북대학교 유기신물질공학과) ;
  • 강길선 (전북대학교 유기신물질공학과, 고분자공학과) ;
  • 이일우 (가톨릭의대 신경외과) ;
  • 이종문 (전북대학교 고분자공학과)
  • Published : 2001.11.01

Abstract

We developed the nerve growth factor (NGF) loaded poly (L - lactide) (PLA) scaffolds by means of emulsion freeze drying method to the possibility for the application of the nerve regeneration of spinal cord disease and the degeneration in Alzheimer's disease. The release amount of NGF from NGF loaded PLA scaffold were analyzed over a 4 week period in vitro at phosphate buffered saline (PBS), pH 7.4, at $37^{\circ}C$. It can be observed the open cell pore structure of porous scaffolds and can be easily controlled the pore structure by the controlling of formulation factors resulting in the controlling of the release rate and the release period. The stability of NGF during the preparation of PLA scaffold was evaluated by comparing the released amounts of total NGF, assayed NGF enzyme - linked immunosorbent assay (ELISA). Released NGF has been found to enhance the neurite sprouting and outgrowth from pheochromocytoma (PC-12) cells. These results suggest that the released NGF from NGF loaded PLA scaffold such as conduit type can be very useful for the nerve regeneration in the neural tissue engineering area.

조직공학적 신경재생 및 파킨슨씨병 등의 시경퇴행성 질환에서의 치료에 이용 목적으로 신경성장인자(nerve growth factor, NGF)를 생분해성 고분자 담체에 NGF를 서방화시키고자 PLA 담체에 함유시켜 유화동결건조법으로 제조하였다. 제조된 NGF의 방출량은 생체외 pH 7.4, 37$^{\circ}C$의 PBS 조건하에서 4주 동안 방출실험 하였으며, 함유된 NGF의 활성을 확인하기 위하여 PC-l2 세포에 직접 배양하여 확인하였다. 제조되어진 PLA 담체는 열린 셀 구조를 가졌으며, 초기 NGF의 함량이 많을수록 방출량도 증가를 보였으며, 제조과정에서의 NGF의 환성을 확인하기 위하여 PC-12 세포를 배양한 결과 신경돌기가 성장하였다. 본 연구는 생분해성 고분자 특정인 확산과 분해에 의해서 생물학적 활성물질인 NGF의 방출을 조절할 수 있으며, 조직공학적으로 서방화되어 3차원적인 신경재생을 가능케 할 것으로 기대된다.

Keywords

References

  1. Biomaterials v.18 no.1201 M.E. Nimni
  2. MRS Bulletin v.21 no.11 W.M. Saltzman
  3. Microscopy Res. Tech. v.45 no.205 L.M. Rita
  4. Microscopy Res. Tech. v.45 no.206 V.N. Isabel;S.S. Inmaculada
  5. Chem. World v.37 no.3 G. Khang;H.B. Lee
  6. J. Biomed. Eng. Res. v.20 no.1 G. Khang;H.B. Lee
  7. Polymer Sci. Tech. v.10 no.640 G. Khang;I. Jo;J.H. Lee;I. Lee;H.B. Lee
  8. Bioindustry v.22 no.32 G. Khang;H.B. Lee
  9. Polymer Sci. Tech. v.10 no.732 G. Khang;J.H. Lee;H.B. Lee
  10. Polymer Sci. Tech. v.10 no.782 I. Lee;G. Khang;H.B. Lee
  11. Bio-Med. Mater. Eng. v.9 no.46 G. Khang;J.C. Cho;J.W. Lee;J.M. Rhee;H.B. Lee
  12. Polymer(Korea) v.23 no.3 G. Khang;J.H. Jeon;J.C. Cho;H.B. Lee
  13. Polymer(Korea) v.23 no.861 G. Khang;J.H. Jeon;J.C. Cho;J.M. Rhee;H.B. Lee
  14. Polymer(Korea) v.24 no.6 G. Khang;S.J. Lee;J.H. Jeon;J.H. Lee;H.B. Lee
  15. Polymer(Korea) v.24 no.877 S.J. Lee;G. Khang;J.H. Lee;Y.M. Lee;H.B. Lee
  16. Korea Polymer J. v.8 no.276 G. Khang;J.H. Lee;I. Lee;J.M. Rhee;H.B. Lee
  17. Polymer(Korea) v.3 no.318 M.K. Choi;G. Khang;I. Lee;J.M. Rhee;H.B. Lee
  18. Korea Polymer J. v.9 no.107 G. Khang;M.K. Choi;J.M. Rhee;S.J. Lee;H.B. Lee;Y. Iwasaki;N. Nakabayashi;K. Ishihara
  19. Fiber Tech. Ind. v.4 no.1 G. Khang;I. Lee;H.B. Lee
  20. Methods of Tissue Engineering G. Khang;H.B. Lee;A. Atala(ed.);R. Lanza(ed.)
  21. Biomedical Polymers G. Khang;H.B. Lee
  22. Polymer Sci. Tech. v.12 no.4 G. Khang;J.M. Rhee;J.S. Lee;H.B. Lee
  23. Polymer Sci. Tech. v.12 no.239 G. Khang;I. Lee;J.M. Rhee;H.B. Lee
  24. Biomater. Res. v.4 no.107 G. Khang;D.S. Moon;H.S. Sung;J.M. Rhee;J.S. Lee;H.B. Lee
  25. Specialty Chemicals v.60 no.5 G. Khang;H.B. Lee
  26. BioZine G. Khang;H.B. Lee
  27. Tissue Engineering : Concepts and Applications J.J. Yoo;I. Lee
  28. Science v.260 no.920 R. Langer;J.P. Vacanti
  29. PSTT v.3 no.3 Y. Tabata
  30. Adv. Drug Deliv. Rev. v.33 no.71 S.P. Baldwin;W.M. Saltzman
  31. J. Control. Rel. v.53 no.1 M.F. Haller;W.M. Saltzman
  32. Pharm. Res. v.16 no.2 W.M. Saltzman;M.W. Mak;M.J. Mahoney;E.T. Duenas;J.L. Cleland
  33. Langmuir v.14 no.5133 M. Matsuzawa;S. Tokumitsu;W. Knoll;H. Sasabe
  34. Pharm. Res. v.15 no.3 M.F. Haller;W.M. Saltzman
  35. Biomaterials v.20 no.329 X. Cao;M.S. Shoichet
  36. Brain Res. v.515 no.309 E.M. Powell;M.R. Sobarzo;W.M. Saltzman
  37. J. Control. Rel. v.56 no.175 J.M. Pean;M.C. Venier-Julienne;F. Boury;P. Menei;B. Denizot;J.P. Benoit
  38. J. Biomed. Mater. Res. v.50 no.388 R.E. Eliaz;J. Kost
  39. J. Biomed. Mater. Res. v.51 no.383 T.W. King;C.W. Patrick Jr.
  40. Exp. Neurol. v.138 no.277 C.W. Patrick Jr.;S. Kukreti;L.V. Mclntire
  41. Polymer v.36 no.837 K. Whang;C.K. Thomas;G. Nuber;K.E. Healy
  42. Biomaterials v.21 no.2545 K. Whang;T.K. Goldstick;K.E. Healy
  43. Physical Chemistry of Surfaces A.W. Adamson
  44. Basic Principles of Colloid Science D.H. Everett
  45. Adv. Chem. Ser. v.1 no.231 L.L. Schramm
  46. Basic Principles of Colloid Science D.H. Everett
  47. Korea Polymer J. v.8 no.80 G. Khang;J.H. Lee;J.W. Lee;J.C. Cho;H.B. Lee
  48. J. Control. Rel. H.S. Choi;G. Khang;H.C. Shin;J.M. Rhee;H.B. Lee
  49. Neurosci. Lett. v.273 no.53 P. Li;K. Matsunage;K. Yamanoto;R. Yoshikawa;K. Kawashima;Y. Ohizumi
  50. Molecular Brain Res. v.86 no.90 T. Ikeda;S. Kitayama;K. Morita;T. Dohi
  51. Brain Res. v.133 no.350 L.A. Greene