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Journal of Artificial Organs

, Volume 16, Issue 3, pp 294–304 | Cite as

A novel customizable modular bioreactor system for whole-heart cultivation under controlled 3D biomechanical stimulation

  • Jörn HülsmannEmail author
  • Hug Aubin
  • Alexander Kranz
  • Erhardt Godehardt
  • Hiroshi Munakata
  • Hiroyuki Kamiya
  • Mareike Barth
  • Artur Lichtenberg
  • Payam AkhyariEmail author
Original Article

Abstract

In the last decade, cardiovascular tissue engineering has made great progress developing new strategies for regenerative medicine applications. However, while tissue engineered heart valves are already entering the clinical routine, tissue engineered myocardial substitutes are still restrained to experimental approaches. In contrast to the heart valves, tissue engineered myocardium cannot be repopulated in vivo because of its biological complexity, requiring elaborate cultivation conditions ex vivo. Although new promising approaches—like the whole-heart decellularization concept—have entered the myocardial tissue engineering field, bioreactor technology needed for the generation of functional myocardial tissue still lags behind in the sense of user-friendly, flexible and low cost systems. Here, we present a novel customizable modular bioreactor system that can be used for whole-heart cultivation. Out of a commercially obtainable original equipment manufacturer platform we constructed a modular bioreactor system specifically aimed at the cultivation of decellularized whole-hearts through perfusion and controlled 3D biomechanical stimulation with a simple but highly flexible operation platform based on LabVIEW®. The modular setup not only allows a wide range of variance regarding medium conditioning under controlled 3D myocardial stretching but can also easily be upgraded for e.g. electrophysiological monitoring or stimulation, allowing for a tailor-made low-cost myocardial bioreactor system.

Keywords

Tissue engineering bioreactors Whole organ tissue engineering Biomechanical stimulation 3D stretching Process control system 

Notes

Acknowledgments

The authors are thankful to Antonio Pinto and Anja Vervoorts for the fruitful discussions and valuable comments throughout the progress of the project. Our very special thanks is due to Mrs. Susanne Bunnenberg for her generous donation that made our project possible in first place. The technical assistance of Gisela Müller and Martina Stuff is highly appreciated.

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References

  1. 1.
    Lichtenberg A, Tudorache I, Cebotari S, et al. Preclinical testing of tissue-engineered heart valves re-endothelialized under simulated physiological conditions. Circulation. 2006;114:I559–65. doi: 10.1161/CIRCULATIONAHA.105.001206.PubMedCrossRefGoogle Scholar
  2. 2.
    Cebotari S, Tudorache I, Ciubotaru A, et al. Use of fresh decellularized allografts for pulmonary valve replacement may reduce the reoperation rate in children and young adults: early report. Circulation. 2011;124:S115–23. doi: 10.1161/CIRCULATIONAHA.110.012161.PubMedCrossRefGoogle Scholar
  3. 3.
    Akhyari P, Kamiya H, Gwanmesia P, et al. In vivo functional performance and structural maturation of decellularised allogenic aortic valves in the subcoronary position. Eur J Cardiothorac Surg. 2010;38:539–46. doi: 10.1016/j.ejcts.2010.03.024.PubMedCrossRefGoogle Scholar
  4. 4.
    Chiu LLY, Iyer RK, Reis LA, et al. Cardiac tissue engineering: current state and perspectives. Front Biosci. 2012;17:1533–50.CrossRefGoogle Scholar
  5. 5.
    Akhyari P, Fedak PWM, Weisel RD, et al. Mechanical stretch regimen enhances the formation of bioengineered autologous cardiac muscle grafts. Circulation. 2002;106:I137–42.PubMedCrossRefGoogle Scholar
  6. 6.
    Eschenhagen T, Zimmermann WH. Engineering myocardial tissue. Circ Res. 2005;97:1220–31. doi: 10.1161/01.RES.0000196562.73231.7d.PubMedCrossRefGoogle Scholar
  7. 7.
    Kensah G, Gruh I, Viering J, et al. A novel miniaturized multimodal bioreactor for continuous in situ assessment of bioartificial cardiac tissue during stimulation and maturation. Tissue Eng Part C Methods. 2011;17:463–73. doi: 10.1089/ten.TEC.2010.0405.PubMedCrossRefGoogle Scholar
  8. 8.
    Zhang T, Wan LQ, Xiong Z, et al. Channelled scaffolds for engineering myocardium with mechanical stimulation. J Tissue Eng Regen Med. 2011;. doi: 10.1002/term.481.Google Scholar
  9. 9.
    Au HTH, Cheng I, Chowdhury MF, et al. Interactive effects of surface topography and pulsatile electrical field stimulation on orientation and elongation of fibroblasts and cardiomyocytes. Biomaterials. 2007;28:4277–93. doi: 10.1016/j.biomaterials.2007.06.001.PubMedCrossRefGoogle Scholar
  10. 10.
    Ott HC, Matthiesen TS, Goh S, et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med. 2008;14:213–21. doi: 10.1038/nm1684.PubMedCrossRefGoogle Scholar
  11. 11.
    Akhyari P, Aubin H, Gwanmesia P, et al. The quest for an optimized protocol for whole-heart decellularization: a comparison of three popular and a novel decellularization technique and their diverse effects on crucial extracellular matrix qualities. Tissue Eng Part C Methods. 2011;17:915–26. doi: 10.1089/ten.TEC.2011.0210.PubMedCrossRefGoogle Scholar
  12. 12.
    Badylak SF, Taylor D, Uygun K. Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds. Annu Rev Biomed Eng. 2011;13:27–53. doi: 10.1146/annurev-bioeng-071910-124743.PubMedCrossRefGoogle Scholar
  13. 13.
    Aubin H, Kranz A, Hülsmann A, Lichtenberg A, Akhyari A. Decellularized whole heart for bioartificial heart. In: Kao RL, editor. Cellular cardiomyoplasty: methods and protocols. In: Walker J, editor. Methods in molecular biology. Humana Press, a part of Springer Science + Business Media (in press).Google Scholar
  14. 14.
    Aubin H, Nichol JW, Hutson CB, et al. Directed 3D cell alignment and elongation in microengineered hydrogels. Biomaterials. 2010;31:6941–51. doi: 10.1016/j.biomaterials.2010.05.056.PubMedCrossRefGoogle Scholar
  15. 15.
    Xu F, Beyazoglu T, Hefner E, et al. Automated and adaptable quantification of cellular alignment from microscopic images for tissue engineering applications. Tissue Eng Part C Methods. 2011;17:641–9. doi: 10.1089/ten.TEC.2011.0038.PubMedCrossRefGoogle Scholar
  16. 16.
    Song JJ, Ott HC. Bioartificial lung engineering. Am J Transpl. 2012;12:283–8. doi: 10.1111/j.1600-6143.2011.03808.x.CrossRefGoogle Scholar
  17. 17.
    Schmitz-Spanke S, Seyfried E, Schwanke U, et al. Das isolierte Kaninchenherz: ein Vergleich zwischen fünf Varianten (The isolated rabbit heart: comparison between five different modifications). Herz. 2002;27:803–13. doi: 10.1007/s00059-002-2419-y.PubMedCrossRefGoogle Scholar
  18. 18.
    Tandon N, Cannizzaro C, Chao PG, et al. Electrical stimulation systems for cardiac tissue engineering. Nat Protoc. 2009;4:155–73. doi: 10.1038/nprot.2008.183.PubMedCrossRefGoogle Scholar
  19. 19.
    Koning M, Werker PMN, van Luyn MJA, et al. Hypoxia promotes proliferation of human myogenic satellite cells: a potential benefactor in tissue engineering of skeletal muscle. Tissue Eng Part A. 2011;17:1747–58. doi: 10.1089/ten.tea.2010.0624.PubMedCrossRefGoogle Scholar
  20. 20.
    Fink C, Ergün S, Kralisch D, et al. Chronic stretch of engineered heart tissue induces hypertrophy and functional improvement. FASEB J. 2000;14:669–79.PubMedGoogle Scholar
  21. 21.
    Gonen-Wadmany M, Gepstein L, Seliktar D. Controlling the cellular organization of tissue-engineered cardiac constructs. Ann N Y Acad Sci. 2004;1015:299–311. doi: 10.1196/annals.1302.025.PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society for Artificial Organs 2013

Authors and Affiliations

  • Jörn Hülsmann
    • 1
    Email author
  • Hug Aubin
    • 1
  • Alexander Kranz
    • 1
  • Erhardt Godehardt
    • 1
  • Hiroshi Munakata
    • 1
    • 2
  • Hiroyuki Kamiya
    • 1
  • Mareike Barth
    • 1
  • Artur Lichtenberg
    • 1
  • Payam Akhyari
    • 1
    Email author
  1. 1.Research Group for Experimental Surgery, Department of Cardiovascular Surgery, Medical FacultyHeinrich Heine University Medical School, Duesseldorf University HospitalDuesseldorfGermany
  2. 2.Division of Cardiovascular Surgery, Department of SurgeryKobe University Graduate School of MedicineKobeJapan

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