Skip to main content


Log in

Development of an in vivo tissue-engineered vascular graft with designed wall thickness (biotube type C) based on a novel caged mold

  • Original Article
  • Blood Vessel Prosthesis
  • Published:
Journal of Artificial Organs Aims and scope Submit manuscript


Small-diameter biotube vascular grafts developed by in-body tissue architecture had high patency at implantation into rabbit carotid arteries or rat abdominal aortas. However, the thin walls (34 ± 14 μm) of the original biotubes made their implantation difficult into areas with low blood flow volumes or low blood pressure due to insufficient mechanical strength to maintain luminal shape. In this study, caged molds with several windows were designed to prepare more robust biotubes. The molds were assembled with silicone tubes (external diameter 2 mm) and cylindrical covers (outer diameter 7 mm) with 12 linear windows (1 × 9 mm). After the molds were embedded into beagle dorsal subcutaneous pouches for 4 weeks, type C (cage) biotubes were obtained by completely extracting the surrounding connective tissues from the molds and removing the molds. The biotube walls (778 ± 31 μm) were formed at the aperture (width 1 mm) between the silicone rods and the covers by connective cell migration through the windows of the covers. Excellent mechanical properties (external pressure resistance, approximately 4 times higher than beagle native femoral arteries; burst strength, approximately 2 times higher than original biotubes) were obtained. In the acute phase of implantation of the biotubes into beagle femoral arteries, perfect patency was obtained with little stenosis and no aneurysmal dilation. The type C biotubes may be useful for implantation into peripheral arteries or veins in addition to aortas.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others


  1. Esquivel CO, Blaisdell FW. Why small vascular grafts fail: a review of clinical and experimental experience and the significance of the interaction of blood at the interface. J Surg Res. 1986;41:1–15.

    Article  CAS  PubMed  Google Scholar 

  2. 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;98:120–6.

    Article  PubMed  Google Scholar 

  3. Yamanami M, Ishibashi-Ueda H, Yamamoto A, Iida H, Watanabe T, Kanda K, Yaku H, Nakyama Y. Implantation study of small-caliber “biotube” vascular grafts in a rat model. J Artif Organs. 2013;16:59–65.

    Article  CAS  PubMed  Google Scholar 

  4. Sakai O, Kanda K, Takamizawa K, Sato T, Yaku H, Nakayama Y. Faster and stronger vascular “Biotube” graft fabrication in vivo using a novel nicotine-containing mold. J Biomed Mater Res B Appl Biomater. 2009;90:412–20.

    PubMed  Google Scholar 

  5. Nakayama Y, Tsujinaka T. Acceleration of robust “biotube” vascular graft fabrication by in-body tissue architecture technology using novel eosin Y-releasing mold. J Biomed Mater Res B Appl Biomater. 2014;102:231–8.

    Article  PubMed  Google Scholar 

  6. 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.

    Article  PubMed  Google Scholar 

  7. Oie T, Yamanami M, Ishibahi-Ueda H, Kanda K, Yaku H, Nakayama Y. In-body optical stimulation formed connective tissue vascular grafts, “biotubes”, with many capillaries and elastic fibers. J Artif Organs. 2010;13:235–40.

    Article  CAS  PubMed  Google Scholar 

  8. Hayashi K, Handa H, Nagasawa S, Okumura A, Moritake K. Stiffness and elastic behavior of human intracranial and extracranial arteries. J Biomech. 1980;13:175–84.

    Article  CAS  PubMed  Google Scholar 

  9. Hayashi K, Nakamura T. Material test system for the evaluation of mechanical properties of biomaterials. J Biomed Mater Res. 1985;19:133–44.

    Article  CAS  PubMed  Google Scholar 

  10. Hayashi K, Igarashi Y, Takamizawa K. Mechanical properties and hemodynamics in coronary arteries. In: Kitamura K, Abe H, Sagawa K, editors. New approaches in cardiac mechanics. Tokyo: Japan Scientific Societies Press; 1986. p. 285–94.

    Google Scholar 

  11. Nakayama Y, Takewa Y, Sumikura H, Yamnami M, Matui Y, Oie T, Kishimoto Y, Arakawa M, Ohmura K, Kajikawa T, Kanda K, Tatsumi E. In-body tissue-engineered aortic valve (Biovalve type VII) architecture based on 3D printer molding. J Biomed Mater Res B Appl Biomater. 2015;103:1–11.

    Article  PubMed  Google Scholar 

  12. Funayama M, Takewa Y, Oie T, Matsui Y, Tatsumi E, Nakayama Y. In situ observation and enhancement of leaflet tissue formation in bioprosthetic “biovalve”. J Artif Organs. 2015;18:40–7.

    Article  PubMed  Google Scholar 

  13. Madras PN, Ward CA, Johnson WR, Singh PI. Anastomotic hyperplasia. Surgery. 1981;90:922–3.

    CAS  PubMed  Google Scholar 

  14. 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.

    Article  PubMed  Google Scholar 

  15. Klinkert P, van Dijk PJ, Breslau PJ. Polytetrafluoroethylene femorotibial bypass grafting: 5-year patency and limb salvage. Ann Vasc Surg. 2003;17:486–91.

    Article  CAS  PubMed  Google Scholar 

  16. Arena FJ. Arterial kink and damage in normal segments of the superficial femoral and popliteal arteries abutting nitinol stents-a common cause of late occlusion and restenosis? A single-center experience. J Invasive Cardiol. 2005;17:482–6.

    PubMed  Google Scholar 

  17. Campbell GR, Campbell JH. Development of tissue engineered vascular grafts. Curr Pharm Biotechnol. 2007;8:43–50.

    Article  CAS  PubMed  Google Scholar 

Download references


The authors thank Ms. Mami Sone for her participation in this study.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Yasuhide Nakayama.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Furukoshi, M., Moriwaki, T. & Nakayama, Y. Development of an in vivo tissue-engineered vascular graft with designed wall thickness (biotube type C) based on a novel caged mold. J Artif Organs 19, 54–61 (2016).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: