Journal of Artificial Organs

, Volume 16, Issue 1, pp 59–65

Implantation study of small-caliber “biotube” vascular grafts in a rat model

  • Masashi Yamanami
  • Hatsue Ishibashi-Ueda
  • Akihide Yamamoto
  • Hidehiro Iida
  • Taiji Watanabe
  • Keiichi Kanda
  • Hitoshi Yaku
  • Yasuhide Nakayama
Original Article


We developed autologous vascular grafts, called “biotubes,” by simple and safe in-body tissue architecture technology, which is a practical concept of regenerative medicine, without using special sterile conditions or complicated in vitro cell treatment processes. In this study, biotubes of extremely small caliber were first auto-implanted to rat abdominal aortas. Biotubes were prepared by placing silicone rods (outer diameter 1.5 mm, length 30 mm) used as a mold into dorsal subcutaneous pouches in rats for 4 weeks. After argatroban coating, the obtained biotubes were auto-implanted to abdominal aortas (n = 6) by end-to-end anastomosis using a custom-designed sutureless vascular connecting system under microscopic guidance. Graft status was evaluated by contrast-free time-of-flight magnetic resonance angiography (TOF-MRA). All grafts were harvested at 12 weeks after implantation. The patency rate was 66.7 % (4/6). MRA showed little stenosis and no aneurysmal dilation in all biotubes. The original biotube had wall thickness of about 56.2 ± 26.5 μm at the middle portion and mainly random and sparse collagen fibers and fibroblasts. After implantation, the wall thickness was 235.8 ± 24.8 μm. In addition, native-like vascular structure was regenerated, which included (1) a completely endothelialized luminal surface, (2) a mesh-like elastin fiber network, and (3) regular circumferential orientation of collagen fibers and α-SMA positive cells. Biotubes could be used as small-caliber vascular prostheses that greatly facilitate the healing process and exhibit excellent biocompatibility in vascular regenerative medicine.


Biotube Vascular grafts Autologous tissue In vivo tissue engineering Connective tissue 


  1. 1.
    Tomizawa Y. Vascular protheses for aortocoronary bypass grafting: a review. Artif Organs. 1995;19:39–45.PubMedCrossRefGoogle Scholar
  2. 2.
    Ferrari ER, von Segesser LK. Arterial grafting for myocardial revascularization: how better is it? Curr Opin Cardiol. 2006;21(6):584–8.PubMedGoogle Scholar
  3. 3.
    Faries PL, LoGerfo FW, Arora S, Hook S, Pulling MC, Akbari CM, Campbell DR, Pomposelli FB Jr. A comparative study of alternative conduits for lower extremity revascularization: all-autogenous conduit versus prosthetic grafts. J Vasc Surg. 2000;32:1080–90.PubMedCrossRefGoogle Scholar
  4. 4.
    Daenens K, Schepers S, Fourneau I, Hounthoofd S, Nevelsteen A. Heparin-bonded ePTFE grafts compared with vein grafts in femoropopliteal and femorocrural bypass: 1- and 2-year results. J Vasc Surg. 2009;49:1210–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Ao PY, Hawthorne WJ, Vicaretti M, Fletcher JP. Development of intimal hyperplasia in six different vascular prostheses. Eur J Vasc Endovascu Surg. 2000;20:241–9.CrossRefGoogle Scholar
  6. 6.
    Isenberg BC, Williams C, Tranquillo RT. Small-diameter artificial arteries engineered in vitro. Circ Res. 2006;98(1):25–35.PubMedCrossRefGoogle Scholar
  7. 7.
    Nakayama Y, Ishibashi-Ueda H, Takamizawa K. In vivo tissue-engineered small-caliber arterial graft prosthesis consisting of autologous tissue (biotube). Cell Transpl. 2004;13:439–49.CrossRefGoogle Scholar
  8. 8.
    Watanabe T, Kanda K, Ishibashi-Ueda H, Yaku H, Nakayama Y. Development of biotube vascular grafts incorporating cuffs for easy implantation. J Artif Organs. 2007;10:10–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Sakai O, Kanda K, Ishibashi-Ueda H, Takamizawa K, Ametani A, Yaku H, Nakayama Y. Development of the wing-attached rod for acceleration of “Biotube” vascular grafts fabrication in vivo. J Biomed Mater Res B Appl Biomater. 2007;83:240–7.PubMedGoogle Scholar
  10. 10.
    Watanabe T, Kanda K, Ishibashi-Ueda H, Yaku H, Nakayama Y. Autologous small-caliber “Biotube” vascular grafts with argatroban loading: a histomorphological examination after implantation to rabbits. J Biomed Mater Res B Appl Biomater. 2010;92:236–42.PubMedGoogle Scholar
  11. 11.
    Watanabe T, Kanda K, Yamanami M, Ishibashi-Ueda H, Yaku H, Nakayama Y. Long-term animal implantation study of biotube—autologous small-caliber vascular graft fabricated by in-body tissue architecture. J Biomed Mater Res B Appl Biomater. 2011;98(1):120–6.PubMedGoogle Scholar
  12. 12.
    Hayashida K, Kanda K, Yaku H, Ando J, Nakayama Y. Development of an in vivo tissue-engineered, autologous heart valve (the biovalve): preparation of a prototype model. J Thorac Cardiovasc Surg. 2007;134:152–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Yamanami M, Yahata Y, Uechi M, Fujiwara M, Ishibashi-Ueda H, Kanda K, Watanabe T, Tajikawa T, Ohba K, Yaku H, Nakayama Y. Development of a completely autologous valved conduit with the sinus of Valsalva using in-body tissue architecture technology: a pilot study in pulmonary valve replacement in a beagle model. Circulation. 2010;122:S100–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Sakai O, Nakayama Y, Nemoto Y, Okamoto Y, Watanabe T, Kanda K, Yaku H. Development of sutureless vascular connecting system for easy implantation of small-caliber artificial grafts. J Artif Organs. 2005;8:119–24.PubMedCrossRefGoogle Scholar
  15. 15.
    Lopez-Soler RI, Brennan MP, Goyal A, Wang Y, Fong P, Tellides G, Sinusas A, Dardik A, Breuer C. Development of a mouse model for evaluation of small diameter vascular grafts. J Surg Res. 2007;139:1–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Narita Y, Kagami H, Matsunuma H, Murase Y, Ueda M, Ueda Y. Decellularized ureter for tissue-engineered small-caliber vascular graft. J Artif Organs. 2008;11:91–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Pektok E, Nottelet B, Tille JC, Gurny R, Kalangos A, Moeller M, Walpoth BH. Degradation and healing characteristics of small-diameter poly(epsilon-caprolactone) vascular grafts in the rat systemic arterial circulation. Circulation. 2008;118:2563–70.PubMedCrossRefGoogle Scholar
  18. 18.
    Shin’oka T, Imai Y, Ikada Y. Transplantation of a tissue-engineered pulmonary artery. N Engl J Med. 2001;15:532–3.CrossRefGoogle Scholar
  19. 19.
    Campbell JH, Efendy JE, Campbell GR. Novel vascular graft grown within recipient’s own peritoneal cavity. Circ Res. 1999;85:1173–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Watanabe T, Kanda K, Yamanami M, Yaku H, Nakayama Y. Biotubes designed for large animals: auto-implantation to the carotid artery of the beagle dogs. Int J Artif Organs. 2008;31:601.Google Scholar
  21. 21.
    Watanabe T, Yamanami M, Kanda K, Ishibashi-Ueda H, Yaku H, Nakayama Y. Application of biotube vascular grafts to abcominal region in a beagle model. Int J Artif Organs. 2010;33:466.Google Scholar
  22. 22.
    Shindo S, Takagi A, Whittemore AD. Improved patency of collagen-impregnated grafts after in vitro autogenenous endothelial cell seeding. J Vasc Surg. 1987;6:325–32.PubMedGoogle Scholar
  23. 23.
    Kuwabara F, Narita Y, Yamawaki-Ogata A, Kanie K, Kato R, Satake M, Kaneko H, Oshima H, Usui A, Ueda Y. Novel small-caliber vascular grafts with trimeric Peptide for acceleration of endothelialization. Ann Thorac Surg. 2012;93(1):156–63.PubMedCrossRefGoogle Scholar
  24. 24.
    Hibino N, Villalona G, Pietris N, Duncan DR, Schoffner A, Roh JD, Yi T, Dobrucki LW, Mejias D, Sawh-Martinez R, Harrington JK, Sinusas A, Krause DS, Kyriakides T, Saltzman WM, Pober JS, Shin’oka T, Breuer CK. Tissue-engineered vascular grafts form neovessels that arise from regeneration of the adjacent blood vessel. FASEB J. 2011;25(8):2731–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Yamanami M, Yamamoto A, Iida H, Watanabe T, Kanda K, Yaku H, Nakayama Y. 3-Tesla magnetic resonance angiographic assessment of a tissue-engineered small-caliber vascular graft implanted in a rat. J Biomed Mater Res B Appl Biomater. 2010;92:156–60.PubMedGoogle Scholar

Copyright information

© The Japanese Society for Artificial Organs 2012

Authors and Affiliations

  • Masashi Yamanami
    • 1
    • 2
  • Hatsue Ishibashi-Ueda
    • 3
  • Akihide Yamamoto
    • 4
    • 5
  • Hidehiro Iida
    • 4
    • 5
  • Taiji Watanabe
    • 1
    • 2
  • Keiichi Kanda
    • 2
  • Hitoshi Yaku
    • 2
  • Yasuhide Nakayama
    • 1
  1. 1.Division of Medical Engineering and MaterialsNational Cerebral and Cardiovascular Center Research InstituteSuitaJapan
  2. 2.Department of Cardiovascular SurgeryKyoto Prefectural University of MedicineKyotoJapan
  3. 3.Department of PathologyNational Cerebral and Cardiovascular CenterOsakaJapan
  4. 4.Department of Biomedical ImagingNational Cerebral and Cardiovascular Center Research InstituteOsakaJapan
  5. 5.Department of Medical Physics and Engineering, Division of Health Sciences, Graduate School of MedicineOsaka UniversityOsakaJapan

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