Journal of Artificial Organs

, Volume 16, Issue 2, pp 176–184 | Cite as

In vivo evaluation of an in-body, tissue-engineered, completely autologous valved conduit (biovalve type VI) as an aortic valve in a goat model

  • Yoshiaki Takewa
  • Masashi Yamanami
  • Yuichiro Kishimoto
  • Mamoru Arakawa
  • Keiichi Kanda
  • Yuichi Matsui
  • Tomonori Oie
  • Hatsue Ishibashi-Ueda
  • Tsutomu Tajikawa
  • Kenkichi Ohba
  • Hitoshi Yaku
  • Yoshiyuki Taenaka
  • Eisuke Tatsumi
  • Yasuhide Nakayama
Original Article

Abstract

Using simple, safe, and economical in-body tissue engineering, autologous valved conduits (biovalves) with the sinus of Valsalva and without any artificial support materials were developed in animal recipients’ bodies. In this study, the feasibility of the biovalve as an aortic valve was evaluated in a goat model. Biovalves were prepared by 2-month embedding of the molds, assembled using two types of specially designed plastic rods, in the dorsal subcutaneous spaces of goats. One rod had three projections, resembling the protrusions of the sinus of Valsalva. Completely autologous connective tissue biovalves (type VI) with three leaflets in the inner side of the conduit with the sinus of Valsalva were obtained after removing the molds from both terminals of the harvested implants with complete encapsulation. The biovalve leaflets had appropriate strength and elastic characteristics similar to those of native aortic valves; thus, a robust conduit was formed. Tight valvular coaptation and a sufficient open orifice area were observed in vitro. Biovalves (n = 3) were implanted in the specially designed apico-aortic bypass for 2 months as a pilot study. Postoperative echocardiography showed smooth movement of the leaflets with little regurgitation under systemic circulation (2.6 ± 1.1 l/min). α-SMA–positive cells appeared significantly with rich angiogenesis in the conduit and expanded toward the leaflet tip. At the sinus portions, marked elastic fibers were formed. The luminal surface was covered with thin pseudointima without thrombus formation. Completely autologous biovalves with robust and elastic characteristics satisfied the higher requirements of the systemic circulation in goats for 2 months with the potential for valvular tissue regeneration.

Keywords

In vivo tissue engineering Heart valve Autologous tissue Aortic valve Systemic circulation 

References

  1. 1.
    Cosgrove DM, Lytle BW, Taylor PC, Camacho MT, Stewart RW, McCarthy PM, Miller DP, Piedmonte MR, Loop FD. The Carpentier-Edwards pericardial aortic valve. Ten-year results. J Thorac Cardiovasc Surg. 1995;110:651–62.PubMedCrossRefGoogle Scholar
  2. 2.
    Shin’oka T, Ma PX, Shum-Tim D, Breuer CK, Cusick RA, Zund G, Langer R, Vacanti JP, Mayer JE. Tissue-engineered heart valves. Autologous valve leaflet replacement study in a lamb model. Circulation. 1996;94:164–8.Google Scholar
  3. 3.
    Dohmen PM, Ozaki S, Nitsch R, Yperman J, Flameng W, Konertz W. A tissue engineered heart valve implanted in a juvenile sheep model. Med Sci Monit. 2003;9:97–104.Google Scholar
  4. 4.
    Vesely I. Heart valve tissue engineering. Circ Res. 2005;97:743–55.PubMedCrossRefGoogle Scholar
  5. 5.
    Baraki H, Tudorache I, Braun M, Höffler K, Görler A, Lichtenberg A, Bara C, Calistru A, Brandes G, Hewicker-Trautwein M, Hilfiker A, Haverich A, Cebotari S. Orthotopic replacement of the aortic valve with decellularized allograft in a sheep model. Biomaterials. 2009;30:6240–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Nakayama Y, Ishibashi-Ueda H, Takamizawa K. In vivo tissue-engineered small-caliber arterial graft prosthesis consisting of autologous tissue (biotube). Cell Transplant. 2004;13:439–49.PubMedCrossRefGoogle Scholar
  7. 7.
    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
  8. 8.
    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. J Biomed Mater Res B Appl Biomater. 2007;83:240–7.PubMedGoogle Scholar
  9. 9.
    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
  10. 10.
    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
  11. 11.
    Hayashida K, Kanda K, Oie T, Okamoto Y, Ishibashi-Ueda H, Onoyama M, Tajikawa T, Ohba K, Yaku H, Nakayama Y. Architecture of an in vivo-tissue engineered autologous conduit “Biovalve”. J Biomed Mater Res B Appl Biomater. 2008;86:1–8.PubMedGoogle Scholar
  12. 12.
    Nakayama Y, Yamanami M, Yahata Y, Tajikawa T, Ohba K, Watanabe T, Kanda K, Yaku H. Preparation of a completely autologous trileaflet valve-shaped construct by in-body tissue architecture technology. J Biomed Mater Res B Appl Biomater. 2009;91:813–8.PubMedGoogle 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.
    Nakayama Y, Yahata Y, Yamanami M, Tajikawa T, Ohba K, Kanda K, Yaku H. A completely autologous valved conduit prepared in the open form of trileaflet (type VI biovalve): mold design and valve function in vitro. J Biomed Mater Res Part B Appl Biomater. 2011;99B:135–41.CrossRefGoogle Scholar
  15. 15.
    Conconi MT, Rocco F, Spinazzi R, Tommasini M, Valfrè C, Busetto R, Polesel E, Albertin G, Dei Tos A, Iacopetti I, Cecchetto A, Zussa C, Grigioni M, Parnigotto PP, Nussdorfer GG. Biological fate of tissue-engineered porcine valvular conduits xenotransplanted in the sheep thoracic aorta. Int J Mol Med. 2004;14:1043–8.PubMedGoogle Scholar
  16. 16.
    Gulbins H, Pritisanac A, Pieper K, Goldemund A, Meiser BM, Reichart B, Daebritz S. Successful endothelialization of porcine glutaraldehyde-fixed aortic valves in a heterotopic sheep model. Ann Thorac Surg. 2006;81:1472–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Van Nooten G, Somers P, Cornelissen M, Bouchez S, Gasthuys F, Cox E, Sparks L, Narine K. Acellilar porcine and kangaroo aortic valve scaffolds show more intense immune-mediated calcification than cross-linked Toronto SPV valves in the sheep model. Interact Cardiovasc Thorac Surg. 2006;5:544–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Duran CMG, Alonso J, Gaite L, Alonso C, Cagigas JC, Marce L, Fleitas MG, Revuelta JM. Long-term results of conservative repair of rheumatic aortic valve insufficiency. Eur J Cardiothorac Surg. 1988;2:217–23.PubMedCrossRefGoogle Scholar
  19. 19.
    Duran CM, Gometza B, Kuma N, Gallo R, Bjonastad K. From aortic cusp extension to valve replacement with stentless pericardium. Ann Thorac Surg. 1995;60:S428–32.PubMedCrossRefGoogle Scholar
  20. 20.
    Duran CMG, Gometza B, Kuma N. Aortic valve replacement with freehand autologous pericardium. J Thorac Cardiovasc Surg. 1995;110:511–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Duran C, Gometza B, Kuma N, Gallo R, Bjonastad K. Treated bovine and autologous pericardium: surgical technique. J Cardiac Surg. 1995;10:1–9.CrossRefGoogle Scholar
  22. 22.
    Ozaki S, Kawase I, Yamashita H, Uchida S, Nozawa Y, Matsuyama T, Takatoh M, Hagiwara S. Aortic valve reconstruction using self-developed aortic valve plasty system in aortic valve disease. Interact Cardiovasc Thorac Surg. 2011;12:550–3.PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society for Artificial Organs 2012

Authors and Affiliations

  • Yoshiaki Takewa
    • 1
  • Masashi Yamanami
    • 2
    • 3
  • Yuichiro Kishimoto
    • 1
  • Mamoru Arakawa
    • 1
  • Keiichi Kanda
    • 3
  • Yuichi Matsui
    • 2
    • 4
  • Tomonori Oie
    • 2
    • 5
  • Hatsue Ishibashi-Ueda
    • 6
  • Tsutomu Tajikawa
    • 4
  • Kenkichi Ohba
    • 4
  • Hitoshi Yaku
    • 3
  • Yoshiyuki Taenaka
    • 1
  • Eisuke Tatsumi
    • 1
  • Yasuhide Nakayama
    • 2
  1. 1.Department of Artificial OrgansNational Cerebral and Cardiovascular Center Research InstituteSuitaJapan
  2. 2.Division of Medical Engineering and MaterialsNational Cerebral and Cardiovascular Center Research InstituteSuitaJapan
  3. 3.Department of Cardiovascular SurgeryKyoto Prefectural University of MedicineKyotoJapan
  4. 4.Department of Mechanical and Systems EngineeringKansai UniversityOsakaJapan
  5. 5.Shinkan Kogyo Co.OsakaJapan
  6. 6.Department of PathologyNational Cerebral and Cardiovascular Center HospitalOsakaJapan

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