Article
  • Preparation and Release Profile of NGF-loaded Polylactide Scaffolds for Tissue Engineered Nerve Regeneration
  • Jeon EK, Whang HJ, Khang G, Lee I, Rhee JM, Lee HB
  • 조직공학적 신경재생을 위한 NGF를 함유한 PLA 담체의 제조 및 방출
  • 전은경, 황혜진, 강길선, 이일우, 이종문, 이해방
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 ℃. 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 신경퇴행성 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 ℃의 PBS 조건하에서 4주 동안 방출실험 하였으며, 함유된 NGF의 활성을 확인하기 위하여 PC-12 세포에 직접 배양하여 확인하였다. 제조되어진 PLA 담체는 열린 셀 구조를 가졌으며, 초기 NGF의 함량이 많을수록 방출량도 증가를 보였으며, 제조과정에서의 NGF의 활성을 확인하기 위하여 PC-12 세포를 배양한 결과 신경돌기가 성장하였다. 본 연구는 생분해성 고분자 특성인 확산과 분해에 의해서 생물학적 활성물질인 NGF의 방출을 조절할 수 있으며, 조직공학적으로 서방화되어 3차원적인 신경재생을 가능케 할 것으로 기대된다.

Keywords: tissue engineering; growth factor delivery; NGF; scaffold; nerve regeneration

References
  • 1. Nimni ME, Biomaterials, 18, 1201 (1997)
  •  
  • 2. Saltzman WM, MRS Bull., 21(11), 62 (1996)
  •  
  • 3. Rita LM, Microsc. Res. Tech., 45, 205 (1999)
  •  
  • 4. Isabel VN, Inmaculada SS, Microsc. Res. Tech., 45, 206 (1999)
  •  
  • 5. Khang G, Lee HB, Chem. World, 37(3), 46 (1997)
  •  
  • 6. Khang G, Lee HB, J. Biomed. Eng. Res., 20(1), 1 (1999)
  •  
  • 7. Khang G, Jo I, Lee JH, Lee I, Lee HB, Polym. Sci. Technol., 10(5), 640 (1999)
  •  
  • 8. Khang G, Lee HB, Bioindustry, 22, 32 (1999)
  •  
  • 9. Khang G, Lee JH, Lee HB, Polym. Sci. Technol., 10(6), 732 (1999)
  •  
  • 10. Lee I, Khang G, Lee HB, Polym. Sci. Technol., 10(6), 782 (1999)
  •  
  • 11. Khang G, Cho JC, Lee JW, Rhee JM, Lee HB, Bio-Med. Mater. Eng., 9(1), 49 (1999)
  •  
  • 12. Khang G, Jeon JH, Cho JC, Lee HB, Polym.(Korea), 23(3), 471 (1999)
  •  
  • 13. Khang G, Jeon JH, Cho JC, Rhee JM, Lee HB, Polym.(Korea), 23(6), 861 (1999)
  •  
  • 14. Khang G, Lee SJ, Jeon JH, Lee JH, Lee HB, Polym.(Korea), 24(6), 869 (2000)
  •  
  • 15. Lee SJ, Khang G, Lee JH, Lee YM, Lee HB, Polym.(Korea), 24(6), 877 (2000)
  •  
  • 16. Khang G, Rhee JM, Lee JH, Lee I, Lee HB, Korea Polym. J., 8(6), 276 (2000)
  •  
  • 17. Choi MG, Khang G, Lee IW, Rhee JM, Lee HB, Polym.(Korea), 25(3), 318 (2001)
  •  
  • 18. Khang G, Choi MK, Rhee JM, Lee SJ, Lee HB, Iwasaki Y, Nakabayashi N, Ishihara K, Korea Polym. J., 9(2), 107 (2001)
  •  
  • 19. Khang G, Lee I, Lee HB, Fiber Tech. Ind., 4, 1 (2000)
  •  
  • 20. Khang G, Lee HBMethods of Tissue Engineering, eds. by A. Atala and R. Lanza, chap. 20, Academic Press, N.Y., 2001 (2001)
  •  
  • 21. Khang G, Lee HBBiomedical Polymers, Korean Chemical Society, Munundang, 2001 (2001)
  •  
  • 22. Khang G, Rhee JM, Lee JS, Lee HB, Polym. Sci. Technol., 12(1), 4 (2001)
  •  
  • 23. Khang G, Lee I, Rhee JM, Lee HB, Polym. Sci. Technol., 12(2), 239 (2001)
  •  
  • 24. Khang G, Moon DS, Sung HS, Rhee JM, Lee JS, Lee HB, Biomater. Res., 4, 107 (2000)
  •  
  • 25. Khang G, Lee HB, Specialty Chem., 60, 5 (2001)
  •  
  • 26. Khang G, Lee HB, BioZineMay (2001)
  •  
  • 27. Yoo JJ, Lee ITissue Engineering: Concepts and Applications, Korea Med. Pub. Co., Seoul, 1998 (1998)
  •  
  • 28. Langer R, Vacanti JP, Science, 260, 920 (1993)
  •  
  • 29. Tabata Y, PSTT, 3(3), 80 (2000)
  •  
  • 30. Baldwin SP, Saltzman WM, Adv. Drug. Deliv. Rev., 33, 71 (1998)
  •  
  • 31. Haller MF, Saltzman WM, J. Control. Release, 53, 1 (1998)
  •  
  • 32. Saltzman WM, Mak MW, Mahoney MJ, Duenas ET, Cleland JL, Pharm. Res., 16(2), 232 (1999)
  •  
  • 33. Matsuzawa M, Tokumitsu S, Knoll W, Sasabe H, Langmuir, 14(18), 5133 (1998)
  •  
  • 34. Haller MF, Saltzman WM, Pharm. Res., 15(3), 377 (1998)
  •  
  • 35. Cao X, Shoichet MS, Biomaterials, 20, 329 (1999)
  •  
  • 36. Powell EM, Sobarzo MR, Saltzman WM, Brain Res., 515, 309 (1990)
  •  
  • 37. Pean JM, Venier-Julienne MC, Boury F, Menei P, Denizot B, Benoit JP, J. Control. Release, 56, 175 (1998)
  •  
  • 38. Eliaz RE, Kost J, J. Biomed. Mater. Res., 50, 388 (2000)
  •  
  • 39. King TW, Patrick CW, J. Biomed. Mater. Res., 51, 383 (2000)
  •  
  • 40. Patrick CW, Kukreti S, Mclntire LV, Exp. Neurol., 138, 277 (1996)
  •  
  • 41. Whang K, Thomas CH, Healy KE, Nuber G, Polymer, 36(4), 837 (1995)
  •  
  • 42. Whang K, Goldstick TK, Healy KE, Biomaterials, 21, 2545 (2000)
  •  
  • 43. Adamson AWPhysical Chemistry of Surfaces, p. 525, John Wiley, New York, 1990 (1990)
  •  
  • 44. Everett DHBasic Principles of Colloid Science, p. 115, The Royal Society of Chemistry, London, 1989 (1989)
  •  
  • 45. Schramm LL, Adv. Chem. Ser., 1, 231 (1992)
  •  
  • 46. Everett DHBasic Principles of Colloid Science, p. 130, The Royal Society of Chemistry, London, 1989 (1989)
  •  
  • 47. Khang G, Lee JH, Lee JW, Cho JC, Lee HB, Korea Polym. J., 8(2), 80 (2000)
  •  
  • 48. Choi HS, Khang G, Shin HC, Rhee JM, Lee HB, J. Control. Releasein press (2001)
  •  
  • 49. Li P, Matsunage K, Yamanoto K, Yoshikawa R, Kawashima K, Ohizumi Y, Neurosci. Lett., 273, 53 (1999)
  •  
  • 50. Ikeda T, Kitayama S, Morita K, Dohi T, Molecular Brain Res., 86, 90 (2001)
  •  
  • 51. Greene LA, Brain Res., 133, 350 (1977)
  •  
  • Polymer(Korea) 폴리머
  • Frequency : Bimonthly(odd)
    ISSN 0379-153X(Print)
    ISSN 2234-8077(Online)
    Abbr. Polym. Korea
  • 2022 Impact Factor : 0.4
  • Indexed in SCIE

This Article

  • 2001; 25(6): 893-901

    Published online Nov 25, 2001

  • Received on Aug 20, 2001