화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Macromolecular Research, Vol.23, No.10, 924-936, October, 2015
DOI10.1007/s13233-015-3126-x  Export Citation
Tri-layered silk fibroin and poly-ε-caprolactone small diameter vascular grafts tested in vitro and in vivo
A. Reum Park, Young-Hwan Park†, Hyun Jeong Kim1, Min-Keun Kim2, Seong-Gon Kim2, †, HaeYong Kweon3, and Subhas C. Kundu4
  • Department of Biosystems & Biomaterials Science and Engineering, Seoul National University, Seoul, 151-921, Korea
  • 1Department of Dental Anesthesiology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 110-768, Korea
  • 2Department of Oral and Maxillofacial Surgery, Gangneung-Wonju National University, Gangneung, Gangwon, 210-702, Korea
  • 3Sericultural and Apicultural Materials Division, National Academy of Agricultural Science,, Jeonju, Jeonbuk, 560-500, Korea
  • 4Department of Biotechnology, Indian Institute of Technology Kharagpur (IIT), West Bengal, 721302, India, Korea
E-mail:,
A silk fibroin (SF) and poly-ε-caprolactone (PCL) tri-layered nano-fibrous scaffold composed of an inner, middle, and outer layer is fabricated via sequential electrospinning. The middle layer of the SF/PCL blend nano-fiber is introduced to minimize delamination of each layer of the scaffold. The inner layer is composed of SF with Spirulina maxima extract (SP), and the outer is composed of PCL. The anti-thrombic effects of SP are tested first. The structure, mechanical properties, and cytocompatibility of the scaffold are evaluated. The tri-layered nano-fiber scaffold is implanted into a rat carotid artery, and the sample after 3 weeks of implantation is evaluated histologically. The SP exerts anti-thrombic activity, and the SF with SP inhibits platelet adhesion. The tri-layered scaffold with the middle layer composed of SF/PCL blend exhibits excellent tensile strengths, burst pressure strength, and suture retention strength. The fabricated material does not induce any cytotoxicity. The cells are well spread on the scaffold. Recipient vessel maintains patency 3 weeks after implantation. The inner lumen of the scaffold reveals regenerated endothelial cells. The results indicate that the tri-layered tubular SF/PCL vascular grafts can be used in vascular tissue engineering due to their excellent mechanical properties and good tissue regeneration capability.
Keywords:silk fibroin;poly-ε-caprolactone;nanofiber;tri-layers;scaffold;vascular tissue engineering
  1. Marelli B, Alessandrino A, Fare S, Freddi G, Mantovani D, Tanzi MC, Acta Biomater., 6, 4019 (2010)
  2. Bergmeister H, Schreiber C, Grasl C, Walter I, Plasenzotti R, Stoiber M, Bernhard D, Schima H, Acta Biomater., 9, 6032 (2013)
  3. van der Slegt J, Steunenberg SL, Donker JM, Veen EJ, Ho GH, de Groot HG, van der Laan L, J. Vasc. Surg., 1, 120 (2014)
  4. Dahl SL, Kypson AP, Lawson JH, Blum JL, Strader JT, Li Y, Manson RJ, Tente WE, DiBernardo L, Hensley MT, Carter R, Williams TP, Prichard HL, Dey MS, Bequlman KG, Niclason LE, Sci. Transl. Med., 3, 68 (2011)
  5. Lamm P, Juchem G, Milz S, Schuffenhauer M, Reichart B, Circulation., 104, I108 (2001)
  6. Rhodin JAG, in Architecture of the Vessel Wall, Comprehensive Physiology, John Wiley and Sons, Michigan, 2011, pp 10-31.
  7. Huang C, Wang S, Qiu L, Ke Q, Zhai W, Mo X, ACS Appl. Mater. Interfaces, 5, 2220 (2013)
  8. Lee SJ, Liu J, Oh SH, Soker S, Atala A, Yoo JJ, Biomaterials, 29, 2891 (2008)
  9. Ghezzi CE, Marelli B, Muja N, Nazhat SN, Acta Biomater., 8, 1813 (2012)
  10. Vaz C, Van Tuijl S, Bouten C, Baaijens F, Acta Biomater., 1, 575 (2005)
  11. Omenetto FG, Kaplan DL, Science, 329(5991), 528 (2010)
  12. Kundu SC, Dash BC, Dash R, Kaplan DL, Prog. Polym. Sci, 33, 998 (2008)
  13. Kundu SC, Kundu B, Talukdar S, Bano S, Nayak S, Kundu J, Mandal BB, Bhardwaj N, Botlagunta M, Dash BC, Acharya C, Ghosh AK, Biopolymers, 97, 455 (2012)
  14. Kundu B, Rajkhowa R, Kundu SC, Wang X, Adv. Drug Deliv. Rev., 65, 457 (2013)
  15. Vepari C, Kaplan DL, Prog. Polym. Sci, 32, 991 (2007)
  16. Fukayama T, Takagi K, Tanaka R, Hatakeyama Y, Aytemiz D, Suzuki Y, Asakura T, Ann. Vasc. Surg., 29, 341 (2015)
  17. Yagi T, Sato M, Nakazawa Y, Tanaka K, Sata M, Itoh K, Takagi Y, Asakura T, J. Artif. Organs., 14, 89 (2011)
  18. Lovett M, Eng G, Kluge JA, Cannizzaro C, Vunjak- Novakovic G, Kaplan DL, Organometallics, 6, 217 (2010)
  19. Nakazawa Y, Sato M, Takahashi R, Aytemiz D, Takabayashi C, Tamura T, Enomoto S, Sata M, Asakura T, J. Biomater. Sci.-Polym. Ed., 22, 195 (2011)
  20. Enomoto S, Sumi M, Kajimoto K, Nakazawa Y, Takahashi R, Takabayashi C, Asakura T, Sata M, J. Vasc. Surg., 51, 155 (2010)
  21. Melchiorri AJ, Hibino N, Fisher JP, Tissue Eng. Part B: Rev., 19, 292 (2013)
  22. Maidoub H, Ben Mansour M, Chaubet F, Roudesli MS, Maaroufi RM, Biochim. Biophys. Acta, 1790, 1377 (2009)
  23. Son MH, Park KH, Choi AR, Yoo GJ, In MJ, Kim DH, Chae HJ, J. Kor. Soc. Food Sci. Nutr., 38, 136 (2009)
  24. Cha BG, Kwak HW, Park AR, Kim SH, Park SY, Kim HJ, Kim IS, Lee KH, Park YH, Biopolymers, 101, 307 (2014)
  25. Chu WL, Lim WL, Radhakrishnan AK, Lim PE, BMC Complement. Altern. Med., 21, 53 (2010)
  26. Bang CJ, Berstad A, Talstad I, Haemostasis, 21, 155 (1991)
  27. Han F, Jia X, Dai D, Yang X, Zhao J, Zhao Y, Fan Y, Yuan X, Biomaterials, 34, 7302 (2013)
  28. Nieponice A, Soletti L, Guan J, Deasy BM, Huard J, Wagner WR, Vorp DA, Biomaterials, 29, 825 (2008)
  29. Cha BG, Kwak HW, Park AR, Kim SH, Park SY, Kim HJ, Kim IS, Lee KH, Park YH, Biopolymers, 101, 307 (2014)
  30. Doshi H, Ray A, Kothari IL, Curr. Microbiol., 54(3), 213 (2007)
  31. Pugazhendy K, Int. J. Pharm. Biol. Arch., 3, 969 (2012)
  32. Elzein T, Nasser-Eddine M, Delaite C, Bistac S, Dumas P, J. Colloid Interface Sci., 273(2), 381 (2004)
  33. Zhou W, He J, Du S, Cui S, Gao W, Iran. Polym. J., 20, 389 (2011)
  34. Zoccola M, Aluigi A, Vineis C, Tonin C, Ferrero F, Piacentino MG, Biomacromolecules, 9(10), 2819 (2008)
  35. Nakazawa Y, Sato M, Takahashi R, Aytemiz D, Takabayashi C, Tamura T, Enomoto S, Sata M, Asakura T, J. Biomater. Sci.-Polym. Ed., 22, 195 (2011)
  36. Billiar K, Murray J, Laude D, Abraham G, Bachrach N, J. Biomed. Mater. Res., 56, 101 (2001)
  37. Konig G, Mcallister TN, Dusserre N, Garrido SA, Iyican C, Marini A, Fiorillo A, Avila H, Wystrychowski W, Zagalski K, Maruszewski M, Jones AL, Cierpka L, de la Fuente LM, L’Heureux N, Biomaterials, 30, 1542 (2009)
  38. Sarkar S, Salacinski H, Hamilton G, Seifalian A, Eur. J. Vasc. Endovasc. Surg., 31, 627 (2006)
  39. Stegemann JP, Kaszuba SN, Rowe SL, Tissue Eng., 13, 2601 (2007)
  40. Kottke-Marchant K, Veenstra AA, Marchant RE, J. Biomed. Mater. Res., 30, 209 (1996)
  41. Asran AS, Razghandi K, Aggarwal N, Michler GH, Groth T, Biomacromolecules, 11(12), 3413 (2010)
  42. Altankov G, Richau K, Groth T, Materwiss. Werksttech., 34, 1120 (2003)
  43. Murphy-Ullrich JE, J. Clin Invest., 107, 785 (2001)
  44. Liu S, Dong C, Lu G, Lu Q, Li Z, Kaplan DL, Zhu H, Acta Biomater., 9, 8991 (2013)
  45. Marelli B, Achilli M, Alessandrino A, Freddi G, Tanzi MC, Fare S, Mantovani D, Macromol. Biosci., 12, 1566 (2012)
  46. Liu HF, Li XM, Niu XF, Zhou G, Li P, Fan YB, Biomacromolecules, 12(8), 2914 (2011)
  47. Zhang X, Wang X, Keshav V, Wang X, Johanas JT, Leisk GG, Kaplan DL, Biomaterials, 30, 3213 (2009)