Application of Bombyx mori Silk Fibroin as a Biomaterial for Vascular Grafts

  • Derya Aytemiz
  • Tetsuo AsakuraEmail author
Part of the Biologically-Inspired Systems book series (BISY, volume 5)


Although silk is known primarily as a textile material, silk fibroin from silkworm (Bombyx mori) has been used as a biomedical suture material for centuries. This review focuses on the application of B. mori silk fibroin to biomaterials, particularly vascular grafts with small diameter (<6 mm). The benefits of silk fibroin for use as a biomaterial are emphasized, especially with respect to the development of silk vascular grafts.


Bombyx mori silk fibroin Biomaterial Vascular graft 


  1. Altman GH, Horan RL, Lu HH, Moreau J, Martin I, Richmond JC, Kaplan DL (2002) Silk matrix for tissue engineered anterior cruciate ligaments. Biomaterials 23:4131PubMedCrossRefGoogle Scholar
  2. Altman GH, Diaz F, Jakuba C, Calabro T, Horan RL, Chen J, Lu H, Richmond J, Kaplan DL (2003) Silk-based biomaterials. Biomaterials 24:401PubMedCrossRefGoogle Scholar
  3. Asakura T, Kaplan DL (1994) Silk production and processing. In: Arutzen CJ (ed) Encyclopedia of agricultural science, vol 4. Academic Press, New York, p 1Google Scholar
  4. Asakura T, Yao J (2002) 13C CP/MAS NMR study on structural heterogeneity in Bombyx mori silk fiber and their generation by stretching. Protein Sci 11:2706PubMedCrossRefGoogle Scholar
  5. Asakura T, Watanabe Y, Uchida A, Minagawa H (1984a) NMR of silk fibroin. Carbon-13 NMR study of the chain dynamics and solution structure of Bombyx mori silk fibroin. Macromolecules 17:1075CrossRefGoogle Scholar
  6. Asakura T, Watanabe Y, Itoh T (1984b) NMR of silk fibroin. 3. Assignment of carbonyl carbon resonances and their dependence on sequence and conformation in Bombyx mori silk fibroin using selective isotopic labeling. Macromolecules 17:2421CrossRefGoogle Scholar
  7. Asakura T, Yoshimizu H, Kakizaki M (1990) An ESR study of spin-labeled silk fibroin membranes and spin-labeled glucose oxidase immobilized in silk fibroin membranes. Biotechnol Bioeng 35:511PubMedCrossRefGoogle Scholar
  8. Aytemiz D, Sakiyama W, Suzuki Y, Nakaizumi N, Tanaka R, Ogawa Y, Takagi Y, Nakazawa Y, Asakura T (2012) Development of small-diameter knitted silk vascular grafts coated with silk fibroin sponge. Adv Healthc Mater 5:2192Google Scholar
  9. Ayub ZH, Arai M, Hirabayashi K (1994) Quantitative structural analysis and physical properties of silk fibroin hydrogels. Polymer 35:2197CrossRefGoogle Scholar
  10. Ayutsede J, Gandhi M, Sukigara S, Micklus M, Chen H, Ko F (2005) Regeneration of Bombyx mori silk by electrospinning. Part 3: characterization of electrospun nonwoven mat. Polymer 46:1625CrossRefGoogle Scholar
  11. Bhat NV, Ahirrao SM (1983) Investigation of the structure of silk film regenerated with lithium thiocyanate solution. J Polym Sci Part A Polym Chem 21:1273CrossRefGoogle Scholar
  12. Bondar FS, Motta A, Migliaresi C, Kirkpatrick CJ (2008) Functionality of endothelial cells on silk fibroin nets: comparative study of micro- and nanometric fibre size. Biomaterials 29:561PubMedCrossRefGoogle Scholar
  13. Budd JS, Allen KE, Hartley G, Bell PR (1991) The effect of preformed confluent endothelial cell monolayers on the patency and thrombogenicity of small calibre vascular grafts. Eur J Vasc Surg 5:397PubMedCrossRefGoogle Scholar
  14. Cao Z, Chen X, Yao J, Huang L, Shao Z (2007) The preparation of regenerated silk fibroin microspheres. Soft Matter 3:910CrossRefGoogle Scholar
  15. Causin F, Pascarella R, Pavesi G, Marasco R, Zambon G, Battaglia R, Munari M (2011) Acute endovascular treatment (<48 hours) of uncoilable ruptured aneurysms at non-branching sites using silk flow-diverting devices. Interv Neuroradiol 17:357PubMedGoogle Scholar
  16. Chao PH, Yodmuang S, Wang X, Sun L, Kaplan DL, Vunjak-Novakovic G (2010) Silk hydrogel for cartilage tissue engineering. J Biomed Mater Res Part B 95B:84CrossRefGoogle Scholar
  17. Chen K, Iura K, Aizawa R, Hirabayashi K (1991) The digestion of silk fibroin by rat. J Seric Sci Jpn 60:402Google Scholar
  18. Chen X, Li W, Zhong W, Lu Y, Yu T (1997) pH sensitivity and ion sensitivity of hydrogels based on complex-forming chitosan/silk fibroin interpenetrating polymer network. J Appl Polym Sci 65:2257CrossRefGoogle Scholar
  19. Demiri EC, Iordanidis EC, Mantinaos CF (1999) Experimental use of prosthetic grafts in microvascular surgery. Handchir Mikrochir Plast Chir 31:102PubMedCrossRefGoogle Scholar
  20. Demura M, Asakura T (1989) Immobilization of glucose oxidase with Bombyx mori silk fibroin by only stretching treatment and its application to glucose sensor. Biotechnol Bioeng 33:598PubMedCrossRefGoogle Scholar
  21. Demura M, Asakura T (1991) Porous membrane of Bombyx mori silk fibroin: structure characterization, physical properties and application to glucose oxidase- immobilization. J Membr Sci 59:39CrossRefGoogle Scholar
  22. Demura M, Asakura T, Kuroo T (1989a) Immobilization of biocatalysts with Bombyx mori silk fibroin by several kinds of physical treatment and its application to glucose sensor. Biosensors 4:361CrossRefGoogle Scholar
  23. Demura M, Asakura T, Nakamura E (1989b) Immobilization of peroxidase with Bombyx mori silk fibroin membrane and its application to biophotosensor. J Biotechnol 10:113CrossRefGoogle Scholar
  24. Demura M, Komura T, Asakura T (1991) Membrane potential of Bombyx mori silk fibroin membrane induced by an immobilized enzyme reaction. Bioelectrochem Bioenerg 26:167CrossRefGoogle Scholar
  25. Enomoto S, Sumi M, Kajimoto K, Nakazawa Y, Takahashi R, Takabayashi C, Asakura T, Sata M (2010) Long-term patency of small-diameter vascular graft made from fibroin, a silk-based biodegradable material. J Vasc Surg 51:155PubMedCrossRefGoogle Scholar
  26. Fan H, Liu H, Wong EJW, Toh SL, Goh JCH (2008) In vivo study of anterior cruciate ligament regeneration using mesenchymal stem cells and silk scaffold. Biomaterials 29:3324PubMedCrossRefGoogle Scholar
  27. Fan H, Liu H, Toh SL, Goh JCH (2009) Anterior cruciate ligament regeneration using mesenchymal stem cells and silk scaffold in large animal model. Biomaterials 30:4967PubMedCrossRefGoogle Scholar
  28. Goujon N, Wang X, Rajkowa R, Byrne N (2012) Regenerated silk fibroin using protic ionic liquids solvents: towards an all-ionic-liquid process for producing silk with tunable properties. Chem Commun 48:1278CrossRefGoogle Scholar
  29. Gupta MK, Khokhar SK, Phillips DM, Sowards LA, Drummy LF, Kadakia MP, Naik RR (2006) Patterned silk films cast from ionic liquid solubilized fibroin as scaffolds for cell growth. Langmuir 23:1315CrossRefGoogle Scholar
  30. Ha SW, Tonelli AE, Hudson SM (2005) Structural studies of Bombyx mori silk fibroin during regeneration from solutions and wet fiber spinning. Biomacromolecules 6:1722PubMedCrossRefGoogle Scholar
  31. Harris JR, Seikaly H (2002) Evaluation of polytetrafluoroethylene micrografts in microvascular surgery. J Otolaryngol 31:89PubMedCrossRefGoogle Scholar
  32. Harris LD, Kim BS, Mooney DJ (1998) Open pore biodegradable matrices formed with gas foaming. J Biomed Mater Res 42:396PubMedCrossRefGoogle Scholar
  33. Higuchi A, Yoshida M, Ohno T, Asakura T, Hara M (2000) Production of interferon-β in a culture of fibroblast cells on some polymeric films. Cytotechnology 34:165PubMedCrossRefGoogle Scholar
  34. Hines DJ, Kaplan DL (2011) Mechanisms of controlled release from silk fibroin films. Biomacromolecules 12:804PubMedCrossRefGoogle Scholar
  35. Hino T, Tanimoto M, Shimabayashi S (2003) Change in secondary structure of silk fibroin during preparation of its microspheres by spray-drying and exposure to humid atmosphere. J Colloid Interface Sci 266:68PubMedCrossRefGoogle Scholar
  36. Hino R, Tomita M, Yoshizato K (2006) The generation of germline transgenic silkworms for the production of biologically active recombinant fusion proteins of fibroin and human basic fibroblast growth factor. Biomaterials 27:5715PubMedCrossRefGoogle Scholar
  37. Hu X, Shmelev K, Sun L, Gil ES, Park SH, Cebe P, Kaplan DL (2011) Regulation of silk material structure by temperature-controlled water vapor annealing. Biomacromolecules 12:1686PubMedCrossRefGoogle Scholar
  38. Kambe Y, Yamamoto K, Kojima K, Tamada Y, Tomita N (2010) Effects of RGDS sequence genetically interfused in the silk fibroin light chain protein on chondrocyte adhesion and cartilage synthesis. Biomaterials 31:7503PubMedCrossRefGoogle Scholar
  39. Kim UJ, Park J, Li C, Jin HJ, Valluzzi R, Kaplan DL (2004) Structure and properties of silk hydrogels. Biomacromolecules 5:786PubMedCrossRefGoogle Scholar
  40. Kim UJ, Park J, Kim HJ, Wada M, Kaplan DL (2005) Three-dimensional aqueous-derived biomaterial scaffolds from silk fibroin. Biomaterials 26:2775PubMedCrossRefGoogle Scholar
  41. Kinahan ME, Filippidi E, Köster S, Hu X, Evans HM, Pfohl T, Kaplan DL, Wong J (2011) Tunable silk: using microfluidics to fabricate silk fibers with controllable properties. Biomacromolecules 12:1504PubMedCrossRefGoogle Scholar
  42. Kojima K, Kuwana Y, Sezutsu H, Kobayashi I, Uchino K, Tamura T, Tamada Y (2007) A new method for the modification of fibroin heavy chain protein in the transgenic silkworm. Biosci Biotechnol Biochem 71:2943PubMedCrossRefGoogle Scholar
  43. Kuzuhara A, Asakura T, Tomoda R, Matsunaga T (1987) Use of silk fibroin for enzyme membrane. J Biotechnol 5:199CrossRefGoogle Scholar
  44. Lammel AS, Hu X, Park SH, Kaplan DL, Scheibel TR (2010) Controlling silk fibroin particle features for drug delivery. Biomaterials 31:4583PubMedCrossRefGoogle Scholar
  45. Leonardi M, Cirillo L, Toni F, Dall'olio M, Princiotta C, Stafa A, Simonetti L, Agati R (2011) Treatment of intracranial aneurysms using flow-diverting silk stents (BALT): a single centre experience. Interv Neuroradiol 17:306PubMedGoogle Scholar
  46. Li M, Wu Z, Zhang C, Lu S, Yan H, Huang D, Ye H (2001) Study on porous silk fibroin materials. II. Preparation and characteristics of spongy porous silk fibroin materials. J Appl Polym Sci 79:2192CrossRefGoogle Scholar
  47. Li M, Ogiso M, Minoura N (2003) Enzymatic degradation behavior of porous silk fibroin sheets. Biomaterials 24:357PubMedCrossRefGoogle Scholar
  48. Losi P, Lombardi S, Briganti E, Soldani G (2004) Luminal surface microgeometry affects platelet adhesion in small-diameter synthetic grafts. Biomaterials 25:4447PubMedCrossRefGoogle Scholar
  49. Lovett M, Cannizzaro C, Daheron L, Messmer B, Vunjak-Novakovic G, Kaplan DL (2007) Silk fibroin microtubes for blood vessel engineering. Biomaterials 28:5271PubMedCrossRefGoogle Scholar
  50. Lovett M, Eng G, Kluge JA, Cannizzaro C, Vunjak-Novakovic G, Kaplan DL (2010) Tubular silk scaffolds for small diameter vascular grafts. Organogenesis 6:217PubMedCrossRefGoogle Scholar
  51. Lu Q, Hu X, Wang X, Kluge JA, Lu S, Cebe P, Kaplan DL (2010) Water-insoluble silk films with silk I structure. Acta Biomater 6:1380PubMedCrossRefGoogle Scholar
  52. Makaya K, Terada S, Ohgo K, Asakura T (2009) Comparative study of silk fibroin porous scaffolds derived from salt/water and sucrose/hexafluoroisopropanol in cartilage formation. J Biosci Bioeng 108:68PubMedCrossRefGoogle Scholar
  53. Meinel L, Fajardo R, Hofmann S, Langer R, Chen J, Snyder B, Vunjak-Novakovic G, Kaplan DL (2005) Silk implants for the healing of critical size bone defects. Bone 37:688PubMedCrossRefGoogle Scholar
  54. Minoura N, Tsukada M, Nagura M (1990) Physico-chemical properties of silk fibroin membrane as a biomaterial. Biomaterials 11:430PubMedCrossRefGoogle Scholar
  55. Motta A, Migliaresi C, Faccioni F, Torricelli P, Fini M, Giardino R (2004) Fibroin hydrogels for biomedical applications: preparation, characterization and in vitro cell culture studies. J Biomater Sci Polym Ed 15:851PubMedCrossRefGoogle Scholar
  56. Nagano A, Tanioka Y, Sakurai N, Sezutsu H, Kuboyama N, Kiba H, Tanimoto Y, Nishiyama N, Asakura T (2011) Regeneration of the femoral epicondyle on calcium-binding silk scaffolds developed using transgenic silk fibroin produced by transgenic silkworm. Acta Biomater 7:1192PubMedCrossRefGoogle Scholar
  57. Nazarov R, Jin HJ, Kaplan DL (2004) Porous 3-D scaffolds from regenerated silk fibroin. Biomacromolecules 5:718PubMedCrossRefGoogle Scholar
  58. Nishibe T, Kondo Y, Muto A, Dardik A (2007) Optimal prosthetic graft design for small diameter vascular grafts. Vascular 15:356PubMedCrossRefGoogle Scholar
  59. Numata K, Cebe P, Kaplan DL (2010) Mechanism of enzymatic degradation of beta sheet crystals. Biomaterials 31:2926PubMedCrossRefGoogle Scholar
  60. Numata K, Katashima T, Sakai T (2011) The state of water, molecular structure and cytotoxicity of silk hydrogels. Biomacromolecules 12:2137PubMedCrossRefGoogle Scholar
  61. Ohgo K, Zhao C, Kobayashi M, Asakura T (2003) Preparation of non-woven nanofibers of Bombyx mori silk, Samia Cynthia ricini silk and recombinant hybrid silk with electrospinning method. Polymer 44:846CrossRefGoogle Scholar
  62. Orban JM, Wilson LB, Kofroth JA, El-Kurdi MS, Maul TM, Vorp DA (2004) Crosslinking of collagen gels by transglutaminase. J Biomed Mater Res A 68:756PubMedCrossRefGoogle Scholar
  63. Phillips DM, Drummy LF, Naik RR, Long HCD, Fox DM, Trulove PC, Mantz RA (2005) Regenerated silk fiber wet spinning from an ionic liquid solution. J Mater Chem 15:4206CrossRefGoogle Scholar
  64. Rajkhowa R, Gil ES, Kluge J, Numata K, Wang L, Wang X, Kaplan DL (2010) Reinforcing silk scaffolds with silk particles. Macromol Biosci 10:599PubMedCrossRefGoogle Scholar
  65. Rockwood DN, Gil ES, Park SH, Kluge JA, Grayson W, Bhumiratana S, Rajkhowa R, Wang X, Kim SJ, Vunjak-Novakovic G, Kaplan DL (2011) Ingrowth of human mesenchymal stem cells into porous silk particle reinforced silk composite scaffolds: an in vitro study. Acta Biomater 7:144PubMedCrossRefGoogle Scholar
  66. Sarkar S, Sales KM, Hamilton G, Seifalian AM (2007) Addressing thrombogenicity in vascular graft construction. J Biomed Mater Res B Appl Biomater 82B:100CrossRefGoogle Scholar
  67. Sato M, Nakazawa Y, Takahashi R, Tanaka K, Sata M, Aytemiz D, Asakura T (2010) Small-diameter vascular grafts of Bombyx mori silk fibroin prepared by a combination of electrospinning and sponge coating. Mater Lett 64:1786CrossRefGoogle Scholar
  68. Schmedlen RH, Elbjeirami WM, Gobin AS, West JL (2003) Tissue engineered small-diameter vascular grafts. Clin Plast Surg 30:507PubMedCrossRefGoogle Scholar
  69. Seal BL, Otero TC, Panitch A (2001) Effects of chitosan on properties of novel human-like collagen/chitosan hybrid vascular scaffold. Mater Sci Eng R Rep 34:147CrossRefGoogle Scholar
  70. Soffer L, Wang X, Zhang X, Kluge J, Dorfmann L, Kaplan DL, Leisk G (2008) Silk-based electrospun tubular scaffolds for tissue-engineered vascular grafts. J Biomater Sci Polym Ed 19:653PubMedCrossRefGoogle Scholar
  71. Sukigara S, Gandhi M, Ayutsede J, Micklus M, Ko F (2004) Regeneration of Bombyx mori silk by electrospinning-part 1: processing parameters and geometric properties. Polymer 45:3701CrossRefGoogle Scholar
  72. Tamada Y (2005) New process to form a silk fibroin porous 3-D structure. Biomacromolecules 6:3100PubMedCrossRefGoogle Scholar
  73. Tamura T, Thibert C, Royer C, Kanda T, Abraham E, Kamba M, Komoto N, Thomas JL, Mauchamp B, Chavancy G, Shirk P, Fraser M, Prudhomme JC, Couble P (2000) Germline transformation of the silkworm Bombyx mori L. using a piggyBac transposon-derived vector. Nat Biotechnol 18:81PubMedCrossRefGoogle Scholar
  74. Teebken OE, Haverich A (2002) Tissue engineering of small-diameter vascular grafts. Graft 5:14CrossRefGoogle Scholar
  75. Teebken OE, Pichlmaier AM, Haverich A (2001) Cell seeded decellularised allogeneic matrix grafts and biodegradable polydioxanone-prostheses compared with arterial autografts in a porcine model. Eur J Vasc Endovasc Surg 22:139PubMedCrossRefGoogle Scholar
  76. Tomita M, Munetsuna H, Sato T, Adachi T, Hino R, Hayashi M, Shimizu K, Nakamura N, Tamura T, Yoshizato K (2003) Transgenic silkworms produce recombinant human type III procollagen in cocoons. Nat Biotechnol 21:52PubMedCrossRefGoogle Scholar
  77. Tsukada M, Freddi G, Minoura N, Allara G (1994) Preparation and application of porous silk fibroin materials. J Appl Polym Sci 54:507CrossRefGoogle Scholar
  78. Um IC, Kweon H, Park YH, Hudson S (2001) Structural characteristics and properties of the regenerated silk fibroin prepared from formic acid. Int J Biol Macromol 29:91PubMedCrossRefGoogle Scholar
  79. van Det RJ, Vriens BHR, van der Palen J, Geelkerken RH (2009) Dacron or ePTFE for femoro-popliteal above-knee bypass grafting: short- and long-term results of a multicentre randomised trial. Eur J Endovasc Surg 37:457CrossRefGoogle Scholar
  80. Vepari C, Kaplan DL (2007) Silk as a biomaterial. Prog Polym Sci 32:991PubMedCrossRefGoogle Scholar
  81. Wang X, Kim HJ, Xu P, Matsumoto A, Kaplan DL (2005) Biomaterial coatings by stepwise deposition of silk fibroin. Langmuir 21:11335PubMedCrossRefGoogle Scholar
  82. Wang Y, Rudym DD, Walsh A, Abrahamsen L, Kim HJ, Kim HS, Kirker-Head C, Kaplan DL (2008) In vivo degradation of three-dimensional silk fibroin scaffolds. Biomaterials 29:3415PubMedCrossRefGoogle Scholar
  83. Wenk E, Wandrey AJ, Merkle HP, Meinel L (2008) Silk fibroin spheres as a platform for controlled drug delivery. J Control Release 132:26PubMedCrossRefGoogle Scholar
  84. Yagi T, Sato M, Nakazawa Y, Tanaka K, Sata M, Itoh K, Takagi Y, Asakura T (2011) Preparation of double-raschel knitted silk vascular grafts and evaluation of short-term function in a rat abdominal aorta. J Artif Organs 14:89PubMedCrossRefGoogle Scholar
  85. Yanagisawa S, Zhu Z, Kobayashi I, Uchino K, Tamada Y, Tamura T, Asakura T (2007) Improving cell-adhesive properties of recombinant Bombyx mori silk by incorporation of collagen or fibronectin derived peptides produced by transgenic silkworms. Biomacromolecules 8:3487PubMedCrossRefGoogle Scholar
  86. Yang C, Bochu W (2009) Biodegradation of silk biomaterials. Int J Mol Sci 10:1514CrossRefGoogle Scholar
  87. Yao JM, Asakura T (2004) Silks. In: Wnek GE, Bowlin GL (eds) Encyclopedia of biomaterials and biomedical engineering, vol. 2. Marcel Dekker, New York, p 1363Google Scholar
  88. Yeo JH, Lee KG, Lee YW, Kim SY (2003) Simple preparation and characteristics of silk fibroin microsphere. Eur Polym J 39:1195CrossRefGoogle Scholar
  89. Yoshimizu H, Asakura T (1990a) The structure of Bombyx mori silk fibroin membrane swollen by water studied with ESR, 13C-NMR, and FT-IR spectroscopies. J Appl Polym Sci 40:1745CrossRefGoogle Scholar
  90. Yoshimizu H, Asakura T (1990b) Preparation and characterization of silk fibroin powder and its application to enzyme immobilization. J Appl Polym Sci 40:127CrossRefGoogle Scholar
  91. Zhang YQ, Wei-De S, Ru-Li X, Zhuge LJ, Gao WJ, Wang WB (2007) Formation of silk nanoparticles in water-miscible organic solvent and their characterization. J Nanopart Res 9:885CrossRefGoogle Scholar
  92. Zhang X, Baughman CB, Kaplan DL (2008) In vitro evaluation of electrospun silk fibroin scaffolds for vascular cell growth. Biomaterials 29:2217PubMedCrossRefGoogle Scholar
  93. Zhang X, Reagan MR, Kaplan DL (2009a) Electrospun silk biomaterial scaffolds for regenerative medicine. Adv Drug Deliv Rev 61:988PubMedCrossRefGoogle Scholar
  94. Zhang X, Wang X, Keshav V, Wang X, Johanas JT, Leisk GG, Kaplan DL (2009b) Dynamic culture conditions to generate silk-based tissue-engineered vascular grafts. Biomaterials 30:3213PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Department of BiotechnologyTokyo University of Agriculture and TechnologyTokyoJapan
  2. 2.Institute for Molecular ScienceOkazakiJapan

Personalised recommendations