Skip to main content

Principles of Analogue and True Microgravity Bioreactors to Tissue Engineering

  • Chapter

Abstract

Understanding the effects of microgravity per se on cultured cells is greatly advanced by the use of fluid physics and computational fluid dynamics. It is essential that the design and operation of cell culture systems for application in microgravity and microgravity analogue conditions are accompanied by thorough analysis of the physical environment in the context of gravity and fluid properties. This becomes critically important when assessing whether the cells are responding directly to microgravity as opposed to the indirect cell response to environmental (fluid) conditions created by microgravity, such as changes in fluid shear on the cell surface. The development of the rotating wall vessel (RWV) bioreactor systems that reproduce aspects of the microgravity environment was an orderly process of developing and optimizing models through iterative tests and validations. Without this deliberate approach, it would have been difficult to advance our understanding of low gravity and low fluid shear environments and their impact on cellular biology. This innovative approach to cell culture and tissue engineering enabled the development of three-dimensional (3-D) organotypic tissue aggregates that better recapitulate the form and function of the parental tissue in vivo when compared to cells cultured as conventional flat 2-D monolayers. In addition to culture of mammalian cells under low fluid shear stress, the RWV bioreactor has also been used to culture microbial pathogens under conditions of physiological low fluid shear that are relevant to those encountered in the infected host during the natural course of infection. These studies have revealed novel insight into pathogenic mechanisms used by microbes during the infection process, which are not observed during conventional culture.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Wolf, D.A., & Schwarz, R.P. (1991). Analysis of gravity-induced particle motion and fluid perfusion flow in the NASA-designed rotating zero-head-space tissue culture vessel. Washington, DC: National Aviation and Space Administration, NASA/TP-3143.

    Google Scholar 

  2. Wolf, D.A., & Schwarz, R.P. (1992). Experimental measurement of the orbital paths of particles sedimenting within a rotating viscous fluid as influenced by gravity. Washington, DC: National Aviation and Space Administration, NASA/TP-3200.

    Google Scholar 

  3. Martin, I., Wendt, D., & Heberer, M. (2004). The role of bioreactors in tissue engineering. Trends in Biotechnology, 22(2), 80–86.

    Article  CAS  PubMed  Google Scholar 

  4. Lyons, E., & Pandit, A. (2005). Design of bioreactors for cardiovascular applications. In N. Ashammakhi & R. L. Reis (Eds.), Tissue Engineering, 446(4), 408–420.

    Google Scholar 

  5. Unsworth, B. R., & Lelkes, P. I. (1998). Growing tissues in microgravity. Nature Medicine, 4(8), 901–907.

    Article  CAS  PubMed  Google Scholar 

  6. Freed, L. E., & Vunjak-Novakovic, G. (1997). Microgravity tissue engineering. In Vitro Cellular & Developmental Biology. Animal, 33(5), 381–385.

    Article  CAS  Google Scholar 

  7. Kleis, S. J., & Rivera-Solorio, I. (2003). Time scales for unsteady mass transfer from a sphere at low-finite Reynolds numbers. Journal of Heat Transfer, 125(4), 716–723.

    Article  Google Scholar 

  8. Rivera-Solorio, I., & Kleis, S. J. (2006). Model of the mass transport to the surface of animal cells cultured in a rotating bioreactor operated in micro gravity. Biotechnology and Bioengineering, 94(3), 495–504.

    Article  CAS  PubMed  Google Scholar 

  9. Ju, Z. H., et al. (2006). Numerical simulation of microcarrier motion in a rotating wall vessel bioreactor. Biomedical and Environmental Sciences, 19(3), 163–168.

    PubMed  Google Scholar 

  10. Tsao, Y.-M., et al. (1994). Fluid dynamics within a rotating bioreactor in space and Earth environments. Journal of Spacecraft and Rockets, 31(6), 937–943.

    Article  CAS  Google Scholar 

  11. Pollack, S. R., et al. (2000). Numerical model and experimental validation of microcarrier motion in a rotating bioreactor. Tissue Engineering, 6(5), 519–530.

    Article  CAS  PubMed  Google Scholar 

  12. Lappa, M. (2003). Organic tissues in rotating bioreactors: Fluid-mechanical aspects, dynamic growth models, and morphological evolution. Biotechnology and Bioengineering, 84(5), 518–532.

    Article  CAS  PubMed  Google Scholar 

  13. Botta, G. P., et al. (2006). Real-time assessment of three-dimensional cell aggregation in rotating wall vessel bioreactors in vitro. Nature Protocols, 1(4), 2116–2127.

    Article  CAS  PubMed  Google Scholar 

  14. Barrila, J., et al. (2010). Organotypic 3D cell culture models: Using the rotating wall vessel to study host-pathogen interactions. Nature Reviews Microbiology, 8(11), 791–801.

    Article  CAS  PubMed  Google Scholar 

  15. Duray, P. H., Hatfill, S. J., & Pellis, N. R. (1997). Tissue culture in microgravity. Science and Medicine, 4(3), 46–55.

    CAS  PubMed  Google Scholar 

  16. Vunjak-Novakovic, G., et al. (2002). Microgravity studies of cells and tissues. Annals of the New York Academy of Sciences, 974, 504–517.

    Article  PubMed  Google Scholar 

  17. Margolis, L. B., et al. (1997). Lymphocyte trafficking and HIV infection of human lymphoid tissue in a rotating wall vessel bioreactor. AIDS Research and Human Retroviruses, 13(16), 1411–1420.

    Article  CAS  PubMed  Google Scholar 

  18. Schwarz, R. P., Goodwin, T. J., & Wolf, D. A. (1992). Cell culture for three-dimensional modeling in rotating-wall vessels: An application of simulated microgravity. Journal of Tissue Culture Methods, 14(2), 51–57.

    Article  CAS  PubMed  Google Scholar 

  19. Freed, L. E., et al. (1997). Tissue engineering of cartilage in space. Proceedings of the National Academy of Sciences of the United States of America, 94(25), 13885–13890.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Goodwin, T. J., Jessup, J. M., & Wolf, D. A. (1992). Morphologic differentiation of colon carcinoma cell lines HT-29 and HT-29KM in rotating-wall vessels. In Vitro Cellular & Developmental Biology, 28A(1), 47–60.

    Article  CAS  Google Scholar 

  21. Jessup, J. M., et al. (1997). Induction of carcinoembryonic antigen expression in a three-dimensional culture system. In Vitro Cellular & Developmental Biology. Animal, 33(5), 352–357.

    Article  CAS  Google Scholar 

  22. Zhau, H. E., et al. (1997). Establishment of a three-dimensional human prostate organoid coculture under microgravity-simulated conditions: Evaluation of androgen-induced growth and PSA expression. In Vitro Cellular & Developmental Biology. Animal, 33(5), 375–380.

    Article  CAS  Google Scholar 

  23. Wang, R., et al. (2005). Three-dimensional co-culture models to study prostate cancer growth, progression, and metastasis to bone. Seminars in Cancer Biology, 15(5), 353–364.

    Article  CAS  PubMed  Google Scholar 

  24. Lelkes, P. I., et al. (2001). Neuroendocrine tissue engineering in rotating wall vessel bioreactors under simulated microgravity conditions. In: 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society. Istanbul, Turkey: Engineering in Medicine and Biology Society.

    Google Scholar 

  25. Akins, R. E., et al. (1999). Cardiac organogenesis in vitro: Reestablishment of three-dimensional tissue architecture by dissociated neonatal rat ventricular cells. Tissue Engineering, 5(2), 103–118.

    Article  CAS  PubMed  Google Scholar 

  26. Khaoustov, V. I., et al. (1999). Induction of three-dimensional assembly of human liver cells by simulated microgravity. In Vitro Cellular & Developmental Biology. Animal, 35(9), 501–509.

    Article  CAS  Google Scholar 

  27. Doolin, E. J., et al. (1999). Effects of microgravity on growing cultured skin constructs. Tissue Engineering, 5(6), 573–582.

    Article  CAS  PubMed  Google Scholar 

  28. Chen, J., Chen, R., & Gao, S. (2007). Morphological characteristics and proliferation of keratocytes cultured under simulated microgravity. Artificial Organs, 31(9), 722–731.

    Article  PubMed  Google Scholar 

  29. Rauh, J., et al. (2011). Bioreactor systems for bone tissue engineering. Tissue Engineering. Part B, Reviews, 17(4), 263–280.

    Article  CAS  PubMed  Google Scholar 

  30. Hidaka, M., et al. (2007). Transplantation of engineered bone tissue using a rotary three-dimensional culture system. In Vitro Cellular & Developmental Biology. Animal, 43(2), 49–58.

    Article  CAS  Google Scholar 

  31. Low, H. P., Savarese, T. M., & Schwartz, W. J. (2001). Neural precursor cells form rudimentary tissue-like structures in a rotating-wall vessel bioreactor. In Vitro Cellular & Developmental Biology. Animal, 37(3), 141–147.

    Article  CAS  Google Scholar 

  32. Duke, J., et al. (1996). Chondrogenesis in aggregates of embryonic limb cells grown in a rotating wall vessel. Advances in Space Research, 17(6–7), 289–293.

    Article  CAS  PubMed  Google Scholar 

  33. Baker, T. L., & Goodwin, T. J. (1997). Three-dimensional culture of bovine chondrocytes in rotating-wall vessels. In Vitro Cellular & Developmental Biology. Animal, 33(5), 358–365.

    Article  CAS  Google Scholar 

  34. Freed, L. E., et al. (1998). Chondrogenesis in a cell-polymer-bioreactor system. Experimental Cell Research, 240(1), 58–65.

    Article  CAS  PubMed  Google Scholar 

  35. Goodwin, T. J., et al. (1993). Rotating-wall vessel coculture of small intestine as a prelude to tissue modeling: Aspects of simulated microgravity. Proceedings of the Society for Experimental Biology and Medicine, 202(2), 181–192.

    Article  CAS  PubMed  Google Scholar 

  36. Radtke, A. L., et al. (2010). Analysis of interactions of Salmonella type three secretion mutants with 3-D intestinal epithelial cells. PLoS One, 5(12), e15750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Suderman, M. T., et al. (2006). Three-dimensional human bronchial-tracheal epithelial tissue-like assemblies as hosts for severe acute respiratory syndrome-COV infection. Houston, TX: National Aviation and Space Administration.

    Google Scholar 

  38. Crabbe, A., et al. (2011). Alveolar epithelium protects macrophages from quorum sensing-induced cytotoxicity in a three-dimensional co-culture model. Cellular Microbiology, 13(3), 469–481.

    Article  CAS  PubMed  Google Scholar 

  39. Crabbe, A., et al. (2015). Recellularization of decellularized lung scaffolds is enhanced by dynamic suspension culture. PLoS One, 10(5), e0126846.

    Article  PubMed  PubMed Central  Google Scholar 

  40. LaMarca, H. L., et al. (2005). Three-dimensional growth of extravillous cytotrophoblasts promotes differentiation and invasion. Placenta, 26(10), 709–720.

    Article  CAS  PubMed  Google Scholar 

  41. Hjelm, B. E., et al. (2010). Development and characterization of a three-dimensional organotypic human vaginal epithelial cell model. Biology of Reproduction, 82(3), 617–627.

    Article  CAS  PubMed  Google Scholar 

  42. Swan, K. F., et al. (2015). [317-POS]: In vitro model of placental trophoblast differentiation and cytomegalovirus infection. Pregnancy Hypertens, 5(1), 155–156.

    Google Scholar 

  43. Smith, Y. C., et al. (2006). Novel three-dimensional organoid model for evaluation of the interaction of uropathogenic Escherichia coli with terminally differentiated human urothelial cells. Infection and Immunity, 74(1), 750–757.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Cortiella, J., et al. (2010). Influence of acellular natural lung matrix on murine embryonic stem cell differentiation and tissue formation. Tissue Engineering Part A, 16(8), 2565–2580.

    Article  CAS  PubMed  Google Scholar 

  45. Jessup, J. M., et al. (2000). Microgravity culture reduces apoptosis and increases the differentiation of a human colorectal carcinoma cell line. In Vitro Cellular & Developmental Biology. Animal, 36(6), 367–373.

    Article  CAS  Google Scholar 

  46. Fitzgerald, W., et al. (2009). Immune suppression of human lymphoid tissues and cells in rotating suspension culture and onboard the International Space Station. In Vitro Cellular & Developmental Biology. Animal, 45(10), 622–632.

    Article  Google Scholar 

  47. Pellis, N. R., et al. (1997). Changes in gravity inhibit lymphocyte locomotion through type I collagen. In Vitro Cellular & Developmental Biology. Animal, 33(5), 398–405.

    Article  CAS  Google Scholar 

  48. Chen, J., et al. (2011). The simulated microgravity enhances the differentiation of mesenchymal stem cells into neurons. Neuroscience Letters, 505(2), 171–175.

    Article  CAS  PubMed  Google Scholar 

  49. Cooper, D., & Pellis, N. R. (1998). Suppressed PHA activation of T lymphocytes in simulated microgravity is restored by direct activation of protein kinase C. Journal of Leukocyte Biology, 63(5), 550–562.

    CAS  PubMed  Google Scholar 

  50. Taylor, G. R. (1993). Immune changes in humans concomitant with space flights of up to 10 days duration. Physiologist, 36(1 Suppl), S71–S74.

    CAS  PubMed  Google Scholar 

  51. Martin, I., et al. (2000). Modulation of the mechanical properties of tissue engineered cartilage. Biorheology, 37(1–2), 141–147.

    CAS  PubMed  Google Scholar 

  52. Nauman, E. A., et al. (2007). Novel quantitative biosystem for modeling physiological fluid shear stress on cells. Applied and Environmental Microbiology, 73(3), 699–705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Rivera-Solorio, I. (2001). Local mass transfer for bioreactors in microgravity, in mechanical engineering. Houston, TX: University of Houston.

    Google Scholar 

  54. Velasco Fuentes, O. U. (2009). Kelvin’s discovery of Taylor columns. European Journal of Biomechanics - B/Fluids, 28(3), 469–472.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David A. Wolf .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this chapter

Cite this chapter

Wolf, D.A., Kleis, S.J. (2016). Principles of Analogue and True Microgravity Bioreactors to Tissue Engineering. In: Nickerson, C., Pellis, N., Ott, C. (eds) Effect of Spaceflight and Spaceflight Analogue Culture on Human and Microbial Cells. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3277-1_2

Download citation

Publish with us

Policies and ethics