화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Polymer(Korea), Vol.27, No.3, 226-234, May, 2003
Export Citation
조직공학적 골을 위한 이프리플라본을 함유한 다공성 지지체의 제조 및 그 특성
Preparation and Characterization of Ipriflavone-Loaded Poly(L-lactide-co-glycolide) Scaffold for Tissue Engineered Bone
장지욱, 이봉, 한창환1, 이일우2, 이해방3, 강길선4, †
  • 부경대학교 고분자공학과, 부산 608-739
  • 1가톨릭 의과대학 정형외과, 대전 301-723
  • 2가톨릭 의과대학 신경외과, 대전 301-723
  • 3한국화학연구원 생체고분자연구실, 대전 305-600
  • 4전북대학교 고분자공학과, 전주 561-756
Ji Wook Jang, Bong Lee, Chang Whan Han1, Il Woo Lee2, Hai Bang Lee3, and Gilson Khang4, †
  • Department of Polymer Engineering, Pukyong National University, San 100, Nam Ku, Busan 608-739, Korea
  • 1Department of Orthopedic Surgery, College of Medicine, The Catholic University of Korea, 520-2, Daeheung 2 Dong, Jung Ku, Daejeon 301-723, Korea
  • 2Department of Neurosurgery, College of Medicine, The Catholic University of Korea, 520-2, Daeheung 2 Dong, Jung Ku, Daejeon 301-723, Korea
  • 3Biomaterials Laboratory, Korea Research Institute of Chemical Technology, P. O. Box 107, Yuseong, Daejeon 305-600, Korea
  • 4Department of Polymer Science and Technology, Chonbuk National University, 664-14, Dukjin Dong 1Ga, Dukjin Ku, Jeonju 561-756, Korea
E-mail:
초록
이프리플라본은 이소플라본의 파생물로서 골의 재흡수를 방지하여 골의 재형성을 방해함으로써 골 형성에 도움을 준다. 이프리플라본은 칼슘의 양을 안정적으로 증가시킴과 함께 골수 줄기 세포의 작용으로 세포층에 칼슘을 침착시킨다. 조직공학적 골을 형성시키기 위해 락타이드-글리콜라이드 공중합체 (PLGA)에 이프리플라본을 함유시킨 지지체를 용매 캐스팅/염 추출법으로 제조하였다. 수은 다공도계, 주사 전자 현미경, 시차 주사 열량계, X선 회절기를 이용하여 특성결정을 수행하였고, 이프리플라본이 함유된 지지체와 이프리플라본이 함유되지 않은 지지체를 면역이 결핍된 쥐의 피하에 삽입하여 이들의 골 형성을 비교하였다. 조직을 hematoxylin & eosin, 본쿠사 염색과 면역화학적 염색법인 콜라겐 I 형과 오스테오칼신 염색을 하였다. 이프리플라본이 함유된 담체의 다공도는 91.7% 이상이었고 평균 다공 크기도 101 μm였다. PLGA로만 제조된 지지체와 이프리플라본을 50% 함유시킨 지지체를 동물 실험을 수행한 결과 이프리플라본은 피하 층과 다른 연조직에서 미분화 줄기 세포가 칼슘침착, 골아 세포, 골상으로의 유도에 더 많은 영향을 주는 것을 관찰하였다. 결론적으로 이프리플라본을 함유한 지지체에서 이프리플라본이 골형성에 중요한 요인으로 작용한다고 사료된다.
Ipriflavone (IP), a non-hormonal isoflavone derivative, has been shown to interfere with bone remodeling by inhibiting bone resorption and stimulating bone formation. IP consistently increased the amount of Ca incorporated into the cell layer by mesenchymal stem cells (MSCs). In this study, we developed the novel IP loaded poly(L-lactide-co-glycolide) (PLGA) scaffolds for the possibility of the application of the tissue engineered bone. IP/PLGA scaffolds were prepared by solvent casting/salt leaching method and were characterized by porosimeter, scanning electron microscopy, determination of residual salt amount, differential scanning calorimetry, and X-ray diffractometer, respectively. IP/PLGA scaffolds were implanted into the back of athymic nude mouse to observe the effect of IP on the osteoinduction compared with control PLGA scaffolds. Thin sections were cut from paraffin embedded tissues and histological sections were stained H&E, von Kossa, and immunohistochemical staining for TypeⅠcollagen and osteocalcin. It can be observed that the porosity was above 91.7% and the pore size was above 101 μm. Control scaffold and IP/PLGA scaffolds of 50% IP were implanted on the back of athymic nude mouse to observe the effect of IP on the induction of cells proliferation for 9 weeks. The evidence of calcification, osteoblast, and osteoid from the undifferentiated stem cells in the subcutaneous sites and other soft connective tissue sites having a preponderance of stem cells has been observed. From these results, it seems that IP plays an important role for bone induction in IP/PLGA scaffolds.
Keywords:scaffold;ipriflavone;bone remodeling;bone resorption;tissue engineered bone
  1. Khang G, Lee SJ, Lee HB, "Polymer-cell Interaction," in Tissue Engineering; Concepts and Application, J.J. Yoo and I. Lee, Editors, Korean Med. Pub. Co., Seoul, p. 297 (2002)
  2. Khang G, Rhee JM, Lee I, Lee HB, Polym. Sci. Technol., 12(4), 527 (2001)
  3. Lee I, Khang G, Lee HB, Polym. Sci. Technol., 10(6), 782 (1999)
  4. Khang G, Jo I, Lee JH, Lee I, Lee JM, Lee HB, Polym. Sci. Technol., 10(5), 640 (1999)
  5. Wintermantel E, Mayer J, Blum J, Eckert KL, Luscher P, Mathey M, Biomaterials, 17, 83 (1996) 
  6. Baldwin SP, Saltzman WM, Adv. Drug Deliv. Rev., 33, 71 (1998) 
  7. Khang G, Rhee JM, Lee I, Lee HB, Polym. Sci. Technol., 13(2), 226 (2002)
  8. Wintermantel E, Bruinink A, Eckert KH, Ruffieux K, Petitmermet M, Mayer J, "Tissue Engineering Supported with Structured Biocompatible Materials; Goals and Achievements," M.O. Speidel and P. Uggowitzer, Editors, Mater. Med., p. 1 (1998)
  9. Putnam AJ, Mooney DJ, Nat. Med., 2, 824 (1996) 
  10. Minabe M, J. Periodontol, 53, 171 (1991)
  11. Khang G, Lee I, Lee HB, Lee SJ, Polym. Sci. Technol., 13(1), 4 (2002)
  12. Khang G, Lee HB, Regenerative Medicine, 1, 114 (2002)
  13. Whang K, Thomas CH, Healy KE, Nuber G, Polymer, 36(4), 837 (1995) 
  14. Sittinger M, Bujia J, Rotter N, Reitzel O, Minuth WW, Burmester GR, Biomaterials, 17, 237 (1996) 
  15. Athanasiou KA, Niederauer GG, Agrawal CM, Biomaterials, 17, 93 (1996) 
  16. Habal MB, Clin. Orthop., 188, 239 (1984)
  17. Lane JM, Sandhu HS, Orthop. Clin. North Am., 18, 213 (1997)
  18. Jergesen HE, Chua J, Kao RT, Kaban LB, Clin. Orthop., 268, 253 (1991)
  19. Rath NC, Reddi AH, Nature, 278, 855 (1979) 
  20. Khang G, Lee I, Rhee JM, Lee HB, Polym. Sci. Technol., 12(2), 239 (2001)
  21. Khang G, Park CS, Rhee JM, Lee SJ, Lee YM, Choi MK, Lee HB, Lee I, Korea Polym. J., 9(5), 267 (2001)
  22. Khang G, Rhee JM, Shin P, Kim IY, Lee B, Lee SJ, Lee YM, Lee HB, Lee I, Macromol. Res., 10(3), 158 (2002)
  23. Choi MG, Khang G, Lee IW, Rhee JM, Lee HB, Polym.(Korea), 25(3), 318 (2001)
  24. Jeon EK, Shim JY, Whang HJ, Khang G, Jo I, Lee I, Rhee JM, Lee HB, Biomater. Res., 5, 23 (2001)
  25. Jeon EK, Whang HJ, Khang G, Lee I, Rhee JM, Lee HB, Polym.(Korea), 25(6), 893 (2001)
  26. Kim HS, Lee I, Lee JM, Han CW, Sung JH, Park MY, Khang G, Lee HB, J. Korea Soc. Endocrinology, 17, 206 (2002)
  27. Lee SJ, Lee DH, Khang G, Lee YM, Lee HB, Macromol. Chem. Symp., 15, 201 (2002)
  28. Brandi MD, J. Medicine, 95, 593 (1993)
  29. Rondelli I, Acerbi D, Ventura P, J. Clin. Pharm. Res., 4, 183 (1991)
  30. Agnusdei D, Adami S, Cervetti R, Bone Miner., 19, S43 (1992) 
  31. Melis GB, Paoletti AM, Bartolini R, Bone Miner., 19(S), 49 (1992)
  32. Freed LE, Marquis JC, Nohria A, Emmanual J, Mikos AG, Langer R, J. Biomed. Mater. Res., 11, 27 (1993)
  33. Marques AP, Reis RL, Hunt JA, Biomaterials, 23, 1471 (2002) 
  34. Ritter HL, Drake LC, Ind. Eng. Chem., 17, 782 (1945) 
  35. Smith DM, hua DW, Earl WL, MRS Bull., 19, 44 (1994)
  36. Mikos AG, Sarakinos G, Leite SM, Vacanti JP, Langer R, Biomaterials, 14, 323 (1993) 
  37. Martini M, Formigli L, Tonelli P, Giannelli M, Amunni F, Naldi D, Bradi ML, Orlandini SZ, Orlandini GE, Calcif. Tissue Int., 63, 312 (1998)