Skip to main content
SpringerLink
Log in

Microgravity and Microgravity Analogue Studies of Cartilage and Cardiac Tissue Engineering

  • Chapter
Effect of Spaceflight and Spaceflight Analogue Culture on Human and Microbial Cells

  • 796 Accesses

Abstract

Space is the ultimate frontier, and the International Space Station (ISS) has been serving as a platform for creative science, developing technologies, and testing materials, instruments and processes under extreme conditions. One of the areas of greatest interest is human health, due to the important changes in human physiology during spaceflight: cardiovascular deconditioning, loss of bone and muscle, changes in immune system and vision, among many others. Studies in astronauts are revealing some of the underlying mechanisms of these changes and helping develop new modalities to prevent or treat the adverse effects of the space environment. However, controllable studies of tissue function under the conditions of microgravity remain critical for understanding the effect of spaceflight on human health, and dissecting—under controllable conditions—the factors affecting the development and function of our tissues and organs. The ability of engineered tissue constructs to recapitulate some of the critical and physiological functions opened many exciting avenues of research.

In this chapter, we discuss representative ground-based analogue and spaceflight studies of tissue engineering relevant to understanding physiological changes in the environment of space. We focus on cartilage and myocardium as two of the most significant examples of tissues affected by the microgravity environment of spaceflight. In this context, we present the working principles and examples of application of biomaterial scaffolds and bioreactors for engineering cartilage and cardiac tissues. Finally, we discuss studies of tissue engineering on Earth, using systems that can model some aspects of microgravity, and in space, under the conditions of actual microgravity. We anticipate that future studies will lead to further increases in physiological relevance of the collected data, and catalyze creative thinking and the development of new products and technologies for improving human health.

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

Access this chapter

Log in via an institution
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

Institutional subscriptions

References

  1. Freed, L. E., & Vunjak-Novakovic, G. (1995). Cultivation of cell-polymer tissue constructs in simulated microgravity. Biotechnology and Bioengineering, 46(4), 306–313.

    Article  CAS  PubMed  Google Scholar 

  2. Freed, L. E., Langer, R., Martin, I., Pellis, N. R., & Vunjak-Novakovic, G. (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 

  3. Saltzman, W. M. (1997). Weaving cartilage at zero g: The reality of tissue engineering in space. Proceedings of the National Academy of Sciences of the United States of America, 94(25), 13380–13382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Vastag, B. (2001). Cell biology update: A decade of simulating space on earth. JAMA, 285(17), 2181–2182.

    Article  CAS  PubMed  Google Scholar 

  5. Freed, L. E., Hollander, A. P., Martin, I., Barry, J. R., Langer, R., & Vunjak-Novakovic, G. (1998). Chondrogenesis in a cell-polymer-bioreactor system. Experimental Cell Research, 240(1), 58–65.

    Article  CAS  PubMed  Google Scholar 

  6. Obradovic, B., Carrier, R. L., Vunjak-Novakovic, G., & Freed, L. E. (1999). Gas exchange is essential for bioreactor cultivation of tissue engineered cartilage. Biotechnology and Bioengineering, 63(2), 197–205.

    Article  CAS  PubMed  Google Scholar 

  7. Martin, I., Obradovic, B., Treppo, S., Grodzinsky, A. J., Langer, R., Freed, L. E., et al. (2000). Modulation of the mechanical properties of tissue engineered cartilage. Biorheology, 37(1–2), 141–147.

    CAS  PubMed  Google Scholar 

  8. Barzegari, A., & Saei, A. A. (2012). An update to space biomedical research: Tissue engineering in microgravity bioreactors. Bioimpacts, 2(1), 23–32.

    PubMed  PubMed Central  Google Scholar 

  9. Obradovic, B., Martin, I., Padera, R. F., Treppo, S., Freed, L. E., & Vunjak-Novakovic, G. (2001). Integration of engineered cartilage. Journal of Orthopaedic Research, 19(6), 1089–1097.

    Article  CAS  PubMed  Google Scholar 

  10. Conza, N., Mainil-Varlet, P., Rieser, F., Kraemer, J., Bittmann, P., Huijser, R., et al. (2001). Tissue engineering in space. Journal of Gravitational Physiology, 8(1), 17–20.

    Google Scholar 

  11. Lewis, M. L., & Hughes-Fulford, M. (1997). Response of living systems to spaceflight. In S. Churchill (Ed.), Fundamentals of space life sciences (pp. 21–39). Malabar: Krieger Publishing Company.

    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. Ohyabu, Y., Kida, N., Kojima, H., Taguchi, T., Tanaka, J., & Uemura, T. (2006). Cartilaginous tissue formation from bone marrow cells using rotating wall vessel (RWV) bioreactor. Biotechnology and Bioengineering, 95(5), 1003–1008.

    Article  CAS  PubMed  Google Scholar 

  14. Sakai, S., Mishima, H., Ishii, T., Akaogi, H., Yoshioka, T., Ohyabu, Y., et al. (2009). Rotating three-dimensional dynamic culture of adult human bone marrow-derived cells for tissue engineering of hyaline cartilage. Journal of Orthopaedic Research, 27(4), 517–521.

    Article  PubMed  Google Scholar 

  15. Wu, X., Li, S. H., Lou, L. M., & Chen, Z. R. (2013). The effect of the microgravity rotating culture system on the chondrogenic differentiation of bone marrow mesenchymal stem cells. Molecular Biotechnology, 54(2), 331–336.

    Article  CAS  PubMed  Google Scholar 

  16. Rungarunlert, S., Klincumhom, N., Bock, I., Nemes, C., Techakumphu, M., Pirity, M. K., et al. (2011). Enhanced cardiac differentiation of mouse embryonic stem cells by use of the slow-turning, lateral vessel (STLV) bioreactor. Biotechnology Letters, 33(8), 1565–1573.

    Article  CAS  PubMed  Google Scholar 

  17. Nerem, R. M. (1992). Tissue engineering in the USA. Medical and Biological Engineering and Computing, 30(4), CE8–CE12.

    Article  CAS  PubMed  Google Scholar 

  18. Vunjak-Novakovic, G., & Scadden, D. T. (2011). Biomimetic platforms for human stem cell research. Cell Stem Cell, 8(3), 252–261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Vunjak-Novakovic, G., Bhatia, S., Chen, C., & Hirschi, K. (2013). HeLiVa platform: Integrated heart-liver-vascular systems for drug testing in human health and disease. Stem Cell Research & Therapy, 4(1 Suppl), S8. doi:10.1186/scrt369.

    Article  Google Scholar 

  20. Langer, R., & Vacanti, J. P. (1993). Tissue engineering. Science, 260(5110), 920–926.

    Article  CAS  PubMed  Google Scholar 

  21. Buckey, J. C., Jr., Lane, L. D., Levine, B. D., Watenpaugh, D. E., Wright, S. J., Moore, W. E., et al. (1996). Orthostatic intolerance after spaceflight. Journal of Applied Physiology, 81(1), 7–18.

    PubMed  Google Scholar 

  22. Lang, T., LeBlanc, A., Evans, H., Lu, Y., Genant, H., & Yu, A. (2004). Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. Journal of Bone and Mineral Research, 19(6), 1006–1012.

    Article  PubMed  Google Scholar 

  23. Vico, L., Collet, P., Guignandon, A., Lafage-Proust, M. H., Thomas, T., Rehaillia, M., et al. (2000). Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts. Lancet, 355(9215), 1607–1611.

    Article  CAS  PubMed  Google Scholar 

  24. Vaney, M. C., Maignan, S., Riès-Kautt, M., & Ducruix, A. (1996). High-Resolution Structure (1.33 Å) of a HEW Lysozyme Tetragonal Crystal Grown in the APCF Apparatus. Data and Structural Comparison with a Crystal Grown under Microgravity from SpaceHab-01 Mission. Acta Crystallographica. Section D, 52(3), 505–517.

    Article  CAS  Google Scholar 

  25. Jixiang, Z., Min, L., Rogers, R., Meyer, W., Ottewill, R. H., Crew, S.-S. S., et al. (1997). Crystallization of hard-sphere colloids in microgravity. Nature, 387, 883–885.

    Article  Google Scholar 

  26. Goree, J., Morfill, G. E., Tsytovich, V. N., & Vladimirov, S. V. (1999). Theory of dust voids in plasmas. Physical Review. E, Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics, 59(6), 7055–7067.

    CAS  PubMed  Google Scholar 

  27. Herlach, D. M., Cohrane, R. F., Egry, I., Fecht, H. J., & Greer, A. L. (1993). Containerless processing in the study of metallic melts and their solidification. International Materials Review, 38, 273–347.

    Article  CAS  Google Scholar 

  28. Rhim, W.-K., Chung, S. K., Barber, D., Man, K. F., Gutt, G., Rulison, A., et al. (1993). An electrostatic levitator for high-temperature containerless materials processing in 1g. Review of Scientific Instruments, 64, 7055–7067.

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  30. Pellis, N. R., Goodwin, T. J., Risin, D., McIntyre, B. W., Pizzini, R. P., Cooper, D., 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 

  31. Freed, L. E., Rupnick, M. A., Schaefer, D., & Vunjak-Novakovic, G. (2003). Engineering functional cartilage and cardiac tissue: In vitro culture parameters. In F. Guilak, D. Butler, D. Mooney, & S. Goldstein (Eds.), Functional tissue engineering: The role of biomechanics (pp. 360–376). New York: Springer.

    Chapter  Google Scholar 

  32. Freed, L. E., & Vunjak-Novakovic, G. (2002). Spaceflight bioreactor studies of cells and tissues. In Advances in space biology and medicine (pp. 177–95). Elsevier Science.

    Google Scholar 

  33. Vunjak Novakovic, G., Eschenhagen, T., & Mummery, C. (2014). Myocardial Tissue Engineering: in vitro models. In The Biology of the Heart (textbook). Cold Spring Harbor Laboratories 4(3): a014076.

    Google Scholar 

  34. Grayson, W., Chao, P. G., Marolt, D., Radisic, M., Cannizzaro, C., Figallo, E., et al. (2007). Bioreactors for tissue engineering and regenerative medicine. In J. J. Mao, G. Vunjak-Novakovic, A. Mikos, & A. Atala (Eds.), Translational approaches in tissue engineering and regenerative medicine (pp. 353–374). Norwood: Artech House.

    Google Scholar 

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

    Article  CAS  Google Scholar 

  36. Burdick, J. A., & Vunjak-Novakovic, G. (2009). Engineered microenvironments for controlled stem cell differentiation. Tissue Engineering. Part A, 15(2), 205–219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Freed, L. E., Martin, I., & Vunjak-Novakovic, G. (1999). Frontiers in tissue engineering. In vitro modulation of chondrogenesis. In Clinical Orthopaedics and Related Research, (367 Suppl), S46–S58.

    Google Scholar 

  38. Kawamura, S., Wakitani, S., Kimura, T., Maeda, A., Caplan, A. I., Shino, K., et al. (1998). Articular cartilage repair. Rabbit experiments with a collagen gel-biomatrix and chondrocytes cultured in it. Acta Orthopaedica Scandinavica, 69(1), 56–62.

    Article  CAS  PubMed  Google Scholar 

  39. Radisic, M., Park, H., Shing, H., Consi, T., Schoen, F. J., Langer, R., et al. (2004). Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds. Proceedings of the National Academy of Sciences of the United States of America, 101(52), 18129–18134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhang, J., Wilson, G. F., Soerens, A. G., Koonce, C. H., Yu, J., Palecek, S. P., et al. (2009). Functional cardiomyocytes derived from human induced pluripotent stem cells. Circulation Research, 104(4), e30–e41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Moutos, F. T., Freed, L. E., & Guilak, F. (2007). A biomimetic three-dimensional woven composite scaffold for functional tissue engineering of cartilage. Nature Materials, 6(2), 162–167.

    Article  CAS  PubMed  Google Scholar 

  42. Engelmayr, G. C., Jr., Cheng, M., Bettinger, C. J., Borenstein, J. T., Langer, R., & Freed, L. E. (2008). Accordion-like honeycombs for tissue engineering of cardiac anisotropy. Nature Materials, 7(12), 1003–1010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Godier-Furnemont, A. F., Martens, T. P., Koeckert, M. S., Wan, L., Parks, J., Arai, K., et al. (2011). Composite scaffold provides a cell delivery platform for cardiovascular repair. Proceedings of the National Academy of Sciences of the United States of America, 108(19), 7974–7979.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bhumiratana, S., Bernhard, J., Cimetta, E., Vunjak-Novakovic, G. (2013). Principles of bioreactor design for tissue engineering. In: R. Lanza, R. Langer, & J. P. Vacanti (Eds.), Principles of tissue engineering (4th ed., pp. 261–78). Academic.

    Google Scholar 

  45. Jessup, J. M., Frantz, M., Sonmez-Alpan, E., Locker, J., Skena, K., Waller, H., 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. Hammond, T. G., Benes, E., O’reilly, K. C., Wolf, D. A., Linnehan, R. M., Taher, A., et al. (2000). Mechanical culture conditions effect gene expression: Gravity-induced changes on the space shuttle. Physiological Genomics, 3(3), 163–173.

    CAS  PubMed  Google Scholar 

  47. 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 

  48. Freed, L. E., Marquis, J. C., Langer, R., & Vunjak-Novakovic, G. (1994). Kinetics of chondrocyte growth in cell-polymer implants. Biotechnology and Bioengineering, 43(7), 597–604.

    Article  CAS  PubMed  Google Scholar 

  49. Vunjak-Novakovic, G., Obradovic, B., Martin, I., & Freed, L. E. (2002). Bioreactor studies of native and tissue engineered cartilage. Biorheology, 39(1–2), 259–268.

    CAS  PubMed  Google Scholar 

  50. Wilson, J. W., Ramamurthy, R., Porwollik, S., McClelland, M., Hammond, T., Allen, P., et al. (2002). Microarray analysis identifies Salmonella genes belonging to the low-shear modeled microgravity regulon. Proceedings of the National Academy of Sciences of the United States of America, 99(21), 13807–13812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Duke, J., Daane, E., Arizpe, J., & Montufar-Solis, D. (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 

  52. Stamenkovic, V., Keller, G., Nesic, D., Cogoli, A., & Grogan, S. P. (2010). Neocartilage formation in 1 g, simulated, and microgravity environments: Implications for tissue engineering. Tissue Engineering. Part A, 16(5), 1729–1736.

    Article  CAS  PubMed  Google Scholar 

  53. Emin, N., Koc, A., Durkut, S., Elcin, A. E., & Elcin, Y. M. (2008). Engineering of rat articular cartilage on porous sponges: Effects of TGF-beta 1 and microgravity bioreactor culture. Artificial Cells, Blood Substitutes, and Immobilization Biotechnology, 36(2), 123–137.

    Article  CAS  PubMed  Google Scholar 

  54. Ulbrich, C., Westphal, K., Pietsch, J., Winkler, H. D., Leder, A., Bauer, J., et al. (2010). Characterization of human chondrocytes exposed to simulated microgravity. Cellular Physiology and Biochemistry, 25(4–5), 551–560.

    Article  CAS  PubMed  Google Scholar 

  55. Aleshcheva, G., Sahana, J., Ma, X., Hauslage, J., Hemmersbach, R., Egli, M., et al. (2013). Changes in morphology, gene expression and protein content in chondrocytes cultured on a random positioning machine. PLoS One, 8(11), e79057.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Akins, R. E., Schroedl, N. A., Gonda, S. R., & Hartzell, C. R. (1997). Neonatal rat heart cells cultured in simulated microgravity. In Vitro Cellular & Developmental Biology. Animal, 33(5), 337–343.

    Article  CAS  Google Scholar 

  57. Akins, R. E., Boyce, R. A., Madonna, M. L., Schroedl, N. A., Gonda, S. R., McLaughlin, T. A., 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 

  58. Papadaki, M., Bursac, N., Langer, R., Merok, J., Vunjak-Novakovic, G., & Freed, L. E. (2001). Tissue engineering of functional cardiac muscle: Molecular, structural, and electrophysiological studies. American Journal of Physiology. Heart and Circulatory Physiology, 280(1), H168–H178.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, Columbia University, New York, NY, USA

    Kacey Ronaldson & Gordana Vunjak-Novakovic (Mikati Foundation Professor of Biomedical Engineering and Medical Sciences)

  2. Laboratory for Stem Cells and Tissue Engineering, Columbia University, 622 West 168th Street, VC12-234, New York, NY, 10032, USA

    Gordana Vunjak-Novakovic (Mikati Foundation Professor of Biomedical Engineering and Medical Sciences)

Authors
  1. Kacey Ronaldson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gordana Vunjak-Novakovic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gordana Vunjak-Novakovic .

Editor information

Editors and Affiliations

  1. School of Life Sciences The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA

    Cheryl A. Nickerson

  2. Division of Space Life Science, Universities Space Research Association, Houston, Texas, USA

    Neal R. Pellis

  3. Biomedical Research and Environmental Sciences Division, NASA/Johnson Space Center, Houston, Texas, USA

    C. Mark Ott

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this chapter

Cite this chapter

Ronaldson, K., Vunjak-Novakovic, G. (2016). Microgravity and Microgravity Analogue Studies of Cartilage and Cardiac 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_9

Download citation

Publish with us

Policies and ethics

Search

Navigation