화학공학소재연구정보센터
Polymer(Korea), Vol.34, No.3, 253-260, May, 2010
조직 확장기용 생분해성 하이드로젤의 제조 및 특성분석
Preparation and Characterization of Biodegradable Hydrogels for Tissue Expander Application
E-mail:,
초록
본 연구에서는 조직확장 응용을 위한 생체적합성 생분해성 하이드로젤을 제조하고, 그 기본특성을 분석하였다. 친수성 고분자인 poly(ethylene glycol)의 양 말단에 다양한 몰비의 D,L-lactide와 glycolide를 개환 중합시켜 PLGAPEG-PLGA 삼중공중합체를 합성한 뒤 비닐기를 도입하여 하이드로젤 제조 시 swelling/degradation controllers(SDC) 로 사용하였다. 합성한 SDC와 PEG diacrylate를 사용하여 라디칼 중합으로 제조한 하이드로젤은 건조된 상태에서도 유연하고 탄성을 보였으며 분해테스트에서는 SDC의 조성과 SDC/PEG의 몰비에 따라 다양한 팽윤지연시간과 분해기간을 갖는 것으로 나타났다. 그 밖에 기계적 물성과 팽윤압력을 측정하였고, 이식시험을 통해 이식용 하이드로젤을 사용목적에 맞게 이식하거나 삽입하였을 때의 생체 조직의 국소적인 병리적 양상을 육안관찰과 현미경적 관찰을 통하여 평가하였다.
In this study, we prepared and evaluated a series of biocompatible and biodegradable block copolymer hydrogels with a delayed swelling property for tissue expander application. The hydrogels were synthesized via a radical crosslinking reaction of poly(ethylene glycol) (PEG) diacrylate and poly(D,L-lactide-coglycolide)-poly(ethylene glycol)-poly(D,L-lactide-co-glycolide)(PLGA-PEG-PLGA) triblock copolymer diacrylate as a swelling/degradation controller (SDC). For the synthesis of various SDCs that can lead to different degradation and swelling properties, various PLGA-PEG-PLGA triblock copolymers with different LA/GA ratios and different PLGA block lengths were synthesized and modified to have terminal acrylate groups. The resultant hydrogels were flexible and elastic even in the dry state. The in vitro degradation tests showed that the delayed swelling properties of the hydrogels could be modulated by varying the chemical composition of the biodegradable crosslinker (SDC) and the block ratio of SDC/PEG. The histopathologic observation after implantation of hydrogels in mice was performed and evaluated by macrography and microscopy. Any significant inflammation or necrosis was not observed in the implanted tissues. Due to their biocompatibility, elasticity, sufficient swelling pressure, delayed swelling and controllable degradability, the hydrogels could be useful for tissue expansion and other biomedical applications.
  1. Hennink WE, van Nostrum CF, Adv. Drug Deliv. Rev., 54, 13 (2002)
  2. Kopecek J, Biomaterials, 28, 5185 (2007)
  3. Hoffman AS, Adv. Drug Deliv. Rev., 54, 3 (2002)
  4. Wang B, Zhu W, Zhang Y, Yang Z, Ding J, React. Funct. Polym., 66, 509 (2006)
  5. Pitarresi G, Saiano F, Cavallaro G, Mandracchia D, Palumbo FS, Int. J. Pharm., 335, 130 (2007)
  6. Nair LS, Laurencin CT, Prog. Polym. Sci., 32, 762 (2007)
  7. Kim SY, Kim HY, Korean J. Rheol., 5(1), 1 (1993)
  8. Gunatillake P, Mayadunne R, Adhikari R, Biotechnol. Annu. Rev., 12, 301 (2006)
  9. Gupta B, Revagade N, Hilborn JS, Prog. Polym. Sci., 32, 455 (2007)
  10. Kim TK, Yoon JJ, Lee DS, Park TG, Biomaterials, 27, 152 (2006)
  11. Maurus PB, Kaeding CC, Oper. Tech. Sports Med., 12, 158 (2004)
  12. Im SJ, Choi YM, Subramanyam E, Park K, Huh KM, Macromol. Res., 15, 7 (2007)
  13. Storey RF, Warren SC, Allison CJ, Puckett AD, Polymer, 38(26), 6295 (1997)
  14. Ge Z, Zhang X, Dai J, Li W, Luo Y, Eur. Polym. J., 45, 530 (2009)
  15. Zhang H, He Y, Li S, Liu X, Polym. Degrad. Stabil., 88, 309 (2005)
  16. Heller J, Barr J, Ng SY, Abdellauoi KS, Gurny R, Adv. Drug Deliv. Rev., 54, 1015 (2002)
  17. Attawia MA, Uhrich KE, Botchwey E, Langer R, Laurencin CT, J. Orthop. Res., 14, 10 (1995)
  18. Vauthier C, Dubernet C, Chauvierre C, Brigger I, Couvreur P, J. Control. Release, 93, 151 (2003)
  19. Timmer MD, Ambrose CG, Mikos AG, Biomaterials, 24, 571 (2003)
  20. Vauthier C, Dubernet C, Fattal E, Pinto-Alphandary H, Couvreur P, Adv. Drug Deliv. Rev., 55, 519 (2003)
  21. Lakshmi S, Katti DS, Laurencin CT, Adv. Drug Deliv. Rev., 55, 467 (2003)
  22. Penczek S, Pretula J, Kaluzynski K, Biomacromolecules, 6, 5 (2005)
  23. Jeong JH, Lim DW, Han DK, Park TG, Colloids Surf. B: Biointerfaces, 18, 371 (2000)
  24. Liu C, et al., Colloids Surf. A: Physicochem. Eng. Aspects, 302, 430 (2007)
  25. Loh XJ, Colin Sng KB, Li J, Biomaterials, 29, 3185 (2008)
  26. Zhou S, Deng X, Yang H, Biomaterials, 24, 3563 (2003)
  27. Aamer KA, Sardinha H, Bhatia SR, Tew GN, Biomaterials, 25, 1087 (2004)
  28. Mothe CG, Drumond WS, Wang SH, Thermochim. Acta, 445(1), 61 (2006)
  29. Chen S, Pieper R, Webster DC, Singh J, Int. J. Pharm., 288, 207 (2005)
  30. Duvvuri S, Janoria KG, Mitra AK, J. Control. Release, 108, 282 (2005)
  31. Qiao M, Chen D, Ma X, Liu Y, Int. J. Pharm., 294, 103 (2005)
  32. O'Brien MM, Trauma., 7, 7 (2005)
  33. Kobus KF, J. Plast. Reconstr. Aesthet. Surg., 60, 414 (2007)
  34. Neumann CG, Plast. Reconstr. Surg., 19, 7 (1957)
  35. Wiese KG, Heinemann DEH, Ostermeier D, Peters JH, J. Biomed. Mater. Res., 54, 179 (2001)
  36. Chevray PM, Breast Dis.: A Year Book Quarterly, 16, 200 (2005)
  37. Khan KKPTA, Ch'ng HS, J. Pharm. Pharm. Sci., 3, 9 (2000)
  38. ISO10993-12 (2007)
  39. ISO10993-6 (2007)
  40. Azab AK, et al., J. Biomed. Mater. Res. Part A, 83A, 414 (2007)
  41. Tienhoven EAEV, Korbee D, Schipper L, Verharen HW, Jong WHD, J. Biomed. Mater. Res. Part A, 78A, 175 (2006)
  42. Fu K, Pack DW, Klibanov AM, Langer R, Pharm. Res., 17, 7 (2000)
  43. Harris JM, Poly(ethylene glycol) Chemistry: Biotechnical and Biomedical Applications, Plenum Press, New York (1992)
  44. Min Z, Svensson H, Svedman P, Annals of Plastic Surgery, 21, 6 (1988)