Growth Modelling Promoting Mechanical Stimulation of Smooth Muscle Cells of Porcine Tubular Organs in a Fibrin-PVDF Scaffold

  • Minh Tuấn Dương
  • Volker Seifarth
  • Ayşegül Artmann
  • Gerhard M. Artmann
  • Manfred Staat


Reconstructive surgery and tissue replacements like ureters or bladders reconstruction have been recently studied, taking into account growth and remodelling of cells since living cells are capable of growing, adapting, remodelling or degrading and restoring in order to deform and respond to stimuli. Hence, shapes of ureters or bladders and their microstructure change during growth and these changes strongly depend on external stimuli such as training. We present the mechanical stimulation of smooth muscle cells in a tubular fibrin-PVDFA scaffold and the modelling of the growth of tissue by stimuli. To this end, mechanotransduction was performed with a kyphoplasty balloon catheter that was guided through the lumen of the tubular structure. The bursting pressure was examined to compare the stability of the incubated tissue constructs. The results showed the significant changes on tissues with training by increasing the burst pressure as a characteristic mechanical property and the smooth muscle cells were more oriented with uniformly higher density. Besides, the computational growth models also exhibited the accurate tendencies of growth of the cells under different external stimuli. Such models may lead to design standards for the better layered tissue structure in reconstructing of tubular organs characterized as composite materials such as intestines, ureters and arteries.


Mechanical simulation Growth modelling Ureter Bladder Reconstruction Tissue engineering 



The focal cyclic intraluminal mechanical stimulation is based on suggestions by G. M. Artmann. This project was supported in part by the German Federal Ministry of Education and Research of Germany through the FHprofUnt project “BINGO” (03FH073PX2) and by the German Federal Ministry of Economics and Technology through the project “UREPLACE” (KF0634101SB8).

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Taulbut, M., Walsh, D., McCartney, G., Parcell, S., Hartmann, A., Poirier, G., et al. (2014). Spatial inequalities in life expectancy within postindustrial regions of Europe: A cross-sectional observational study. BMJ Open, 4(6), 1–9 (e004711).CrossRefGoogle Scholar
  2. 2.
    Wohland, P., Bees, P., Gillies, C., Alvanides, S., Matthews, F. E., O’neil, V., et al. (2014). Drivers of inequality in disability-free expectancy at birth and age 85 across space and time in Great Britain. Journal of Epidemiology and Community Health, 68, 826–833.CrossRefGoogle Scholar
  3. 3.
    Shalhav, A. L., Elbahnasy, A. M., Bercowsky, E., Kovacs, G., Brewer, A., Maxwell, K. L., et al. (1999). Laparoscopic replacement of urinary tract segments using biodegradable materials in a large-animal model. Journal of Endourology, 13, 241–244.CrossRefGoogle Scholar
  4. 4.
    El-Assmy, A., El-Sherbiny, A. T., El-Hamid, M. A., Mohsen, T., Nour, E. M., Bazeed, M., et al. (2004). Use of single layer small intestinal submucosa for long segment ureteral replacement: A pilot study. The Journal of Urology, 171, 1939–1942.CrossRefGoogle Scholar
  5. 5.
    Seifarth, V., Grosse, J. O., Gossmann, M., Janke, H. P., Arndt, P., Koch, S., et al. (2017). Mechanical induction of bi-directional orientation of primary porcine bladder smooth muscle cells in tubular fibrin-poly(vinylidene fluoride) scaffolds for ureteral and urethral repair using cyclic and focal balloon catheter stimulation. Journal of Biomaterials Applications, 32(3), 321–330.CrossRefGoogle Scholar
  6. 6.
    Filippo, R. E. D., Yoo, J. J., & Atala, A. (2002). Urethral replacement using cell seeded tubularized collagen matrices. The Journal of Urology, 168, 1789–1793.CrossRefGoogle Scholar
  7. 7.
    Orabi, H., AbouShwareb, T., Zhang, Y., Yoo, J. J., & Atala, A. (2013). Cell-seeded tubularized scaffolds for reconstruction of long urethral defects: A preclinical study. European Urology, 63, 531–538.CrossRefGoogle Scholar
  8. 8.
    Huang, A. H., & Niklason, L. E. (2011). Engineering biological-based vascular grafts using a pulsatile bioreactor. Journal of visualized experiments: JoVE, 52, 1–14.Google Scholar
  9. 9.
    Fu, Q., Deng, C. L., Zhao, R. Y., Wang, Y., & Cao, Y. (2014). The effect of mechanical extension stimulation combined with epithelial cell sorting on outcomes of implanted tissue-engineered muscular urethras. Biomaterials, 35, 105–112.CrossRefGoogle Scholar
  10. 10.
    Rodriguez, E. K., Hoger, A., & McCulloch, A. D. (1994). Stress-dependent finite growth in soft elastic tissues. Journal of Applied Biomechanics, 27(4), 455–467.CrossRefGoogle Scholar
  11. 11.
    Lubarda, V. A., & Hoger, A. (2002). On the mechanics of solids with a growing mass. International Journal of Solids and Structures, 39, 4627–4664.CrossRefGoogle Scholar
  12. 12.
    Himpel, G., Kuhl, E., Menzel, A., & Steinmann, P. (2005). Computational modelling of isotropic multiplicative growth. Computer Modeling in Engineering & Sciences, 8, 119–134.zbMATHGoogle Scholar
  13. 13.
    Kuhl, E., Mass, R., Himpel, G., & Menzel, A. (2006). Computational modeling of arterial wall growth. Biomechanics and Modeling in Mechanobiology, 6, 321–331.CrossRefGoogle Scholar
  14. 14.
    Holzapfel, G. A. (2000). Nonlinear solid mechanics, a continuum approach for engineering. Chichester: Wiley.zbMATHGoogle Scholar
  15. 15.
    Montzka, K., Läufer, T., Becker, C., Grosse, J., & Heidenreich, A. (2011). Microstructure and cytocompatibility of collagen matrices for urological tissue engineering. BJU International, 107, 1974–1981.CrossRefGoogle Scholar
  16. 16.
    Cornelissen, C. G., Dietrich, M., Krüger, S., Spillner, J., Schmitz-Rode, T., & Jockenhoevel, S. (2012). Fibrin gel as alternative scaffold for respiratory tissue engineering. Annual Review of Biomedical Engineering, 40, 679–687.CrossRefGoogle Scholar
  17. 17.
    Dellenback, R. J., & Chien, S. (1970). The extinction coefficient of fibrinogen from man, dog, elephant, sheep, and goat at 280 mμ. Proceedings of the Society for Experimental Biology and Medicine, 134, 353–355.CrossRefGoogle Scholar
  18. 18.
    Cholewinski, E., Dietrich, M., Flanagan, T. C., Schmitz-Rode, T., & Jockenhoevel, S. (2009). Tranexamic acid—An alternative to aprotinin in fibrin—Based cardiovascular tissue engineering. Tissue Engineering Part A, 15, 3645–3653.CrossRefGoogle Scholar
  19. 19.
    Eyrich, D., Brandl, F., Appel, B., Wiese, H., Maier, G., & Wenzel, M. (2007). Long-term stable fibrin gels for cartilage engineering. Biomaterials, 28, 55–65.CrossRefGoogle Scholar
  20. 20.
    Dorothea, L., Stollenwerk, K., Seifarth, V., Zraik, I. M., Vogt, M., Srinivasan, P. K., et al. (2016). Two differentially structured collagen scaffolds for potential urinary bladder augmentation: Proof of concept study in a Göttingen minipig model. Journal of Translational Medicine, 15, 1–16.Google Scholar
  21. 21.
    Seifarth, V. (2015). Ureteral tissue engineering: Development of a bioreactor system and subsequent characterization of the generated biohybrids (PhD Dissertation). University Duisburg-Essen, Germany.Google Scholar
  22. 22.
    Ternifi, R., Gennisson, J. L., Tanter, M., & Beillas, P. (2013). Effects of storage temperature on the mechanical properties of porcine kidney estimated using Shear Wave Elastography. Journal of the Mechanical Behavior of Biomedical Material, 28, 86–93.CrossRefGoogle Scholar
  23. 23.
    Janmey, P. A., & McCulloch, C. A. (2007). Cell mechanics: Integrating cell responses to mechanical stimuli. Annual Review of Biomedical Engineering, 9, 1–34.CrossRefGoogle Scholar
  24. 24.
    Murphy, S. V., & Atala, A. (2013). Organ engineering—Combining stem cells, biomaterials, and bioreactors to produce bioengineered organs for transplantation. BioEssays, 35, 163–172.CrossRefGoogle Scholar
  25. 25.
    Nishi, M., Matsumoto, R., Dong, J., & Uemura, T. (2013). Engineered bone tissue associated with vascularization utilizing a rotating wall vessel bioreactor. Journal of Biomedical Materials Research—Part A, 101, 421–427.CrossRefGoogle Scholar
  26. 26.
    Seliktar, D., Black, R. A., Vito, R. P., & Nerem, R. M. (2000). Dynamic mechanical conditioning of collagen-gel blood vessel constructs induces remodeling in vitro. Annual Review of Biomedical Engineering, 28, 351–362.CrossRefGoogle Scholar
  27. 27.
    Tschoeke, B., Flanagan, T. C., Cornelissen, A., Koch, S., Roehl, A., Sriharwoko, M., et al. (2008). Development of a composite degradable/nondegradable tissue-engineered vascular graft. Artificial Organs, 32, 800–809.Google Scholar
  28. 28.
    Jockenhoevel, S., & Flanagan, T. C. (2011). In D. Eberli (Ed.), Tissue engineering for tissue and organ regeneration. InTech.Google Scholar
  29. 29.
    Geutjes, P., Roelofs, L., Hoogenkamp, H., Walraven, M., Kortmann, B., de Gier, R., et al. (2012). Tissue engineered tubular construct for urinary diversion in a preclinical porcine model. The Journal of Urology, 188, 653–660.CrossRefGoogle Scholar
  30. 30.
    Wei, X., Li, D. B., Xu, F., Wang, Y., Zhu, Y. C., Li, H., et al. (2011). A novel bioreactor to simulate urinary bladder mechanical properties and compliance for bladder functional tissue engineering. Chinese Medical Journal (Engl), 124, 568–573.Google Scholar
  31. 31.
    Davis, N. F., Mooney, R., Piterina, A. V., Callanan, A., McGuire, B. B., Flood, H. D., et al. (2011). Construction and evaluation of urinary bladder bioreactor for urologic tissue-engineering purposes. Urology, 78, 954–960.CrossRefGoogle Scholar
  32. 32.
    Wang, C., Cen, L., Yin, S., Liu, Q., Liu, W., Cao, Y., et al. (2010). A small diameter elastic blood vessel wall prepared under pulsatile conditions from polyglycolic acid mesh and smooth muscle cells differentiated from adipose-derived stem cells. Biomaterials, 31, 621–630.CrossRefGoogle Scholar
  33. 33.
    Kanda, K., Matsuda, T., & Oka, T. (1993). Mechanical stress induced cellular orientation and phenotypic modulation of 3-D cultured smooth muscle cells. ASAIO Journal, 39(3), M668–M690.Google Scholar
  34. 34.
    Taber, L. A. (1998). Biomechanical growth laws for muscle tissue. Journal of Theoretical Biology, 193, 201–213.CrossRefGoogle Scholar
  35. 35.
    Humphrey, J. D. (2002). Cardiovascular solid mechanics-cells, tissues, and organs. New York: Springer.CrossRefGoogle Scholar
  36. 36.
    Kuhl, E. (2004). Theory and numerics of open system continuum thermodynamics-Spatial and material settings (Habilitation thesis). Technical University of Kaiserslautern, Germany.Google Scholar
  37. 37.
    Kuhl, E., Menzel, A., & Steinmann, P. (2003). Computational modeling of growth: A critical review, a classification of concepts and two new consistent approaches. Computational Mechanics, 32, 71–88.CrossRefGoogle Scholar
  38. 38.
    Menzel, A. (2007). A fibre reorientation model for orthotropic multiplicative growth: Configurational driving stresses, kinematics-based reorientation, and algorithmic aspects. Biomechanics and Modeling in Mechanobiology, 6, 303–320.CrossRefGoogle Scholar
  39. 39.
    Duong, M. T., & Staat, M. (2014). A face-based smoothed finite element method for hyperelastic models and tissue growth. In E. Oñate, J. Oliver & A. Huerta (Eds.), Proceedings 11th World Congress on Computational Mechanics (WCCM XI), 5th European Conference on Computational Mechanics (ECCM V), 6th European Conference on Computational Fluid Dynamics (ECFD VI) (pp. 2657–2668), Barcelona, Spain.Google Scholar
  40. 40.
    Duong, M. T. (2014). Hyperelastic modeling and soft-tissue growth integrated with the smoothed finite element method—SFEM (PhD Dissertation). RWTH Aachen University, Germany.Google Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Minh Tuấn Dương
    • 1
    • 2
    • 3
  • Volker Seifarth
    • 1
  • Ayşegül Artmann
    • 1
  • Gerhard M. Artmann
    • 1
  • Manfred Staat
    • 1
  1. 1.Institute for BioengineeringUniversity of Applied Sciences AachenJülichGermany
  2. 2.University of Erlangen-NurembergErlangenGermany
  3. 3.Hanoi University of Science and TechnologyHanoiVietnam

Personalised recommendations