Biomanufacturing in Microgravity: A New Frontier in Regenerative Medicine and Biotechnology

Biomanufacturing in microgravity is coming of age. These efforts are enabling foundational research into tissue engineering and regenerative medicine.

Microgravity, real and simulated, is a vital window into cellular behavior and tissue formation. The physiological changes that occur in microgravity—such as muscle atrophy, bone density loss, and immune system alterations—provide fast-tracked models for studying diseases that ordinarily take decades to progress (Shelhamer, 2020). 

Accelerated aging in space allows scientists to observe these changes within weeks, which is paramount for developing new longevity therapeutics in a timely manner (Sharma, 2022).

What Exactly is Biomanufacturing?

Biomanufacturing leverages living systems—such as microorganisms, enzymes, cells, and tissues—to create valuable products for medicine, agriculture, and materials science. These systems can be used in their natural form or modified for enhanced productivity and precision (Yi-Heng, 2017). 

End products typically come from cultivating cells in specialized equipment or extracting them from other natural sources. Engineering techniques are applied to these systems to boost efficiency, allowing for scalable production of biomaterials, cell lines, and therapeutic compounds (Vasic-Racki, 2006).

Why Microgravity?

Despite the costs associated with space-based research, these studies are contributing to numerous fields and subfields of biology. Weightlessness affects cell signaling, tissue formation, and metabolic processes, revealing novel insights that cannot be observed under normal gravitational conditions (Bradbury, 2020). 

Cells cultured in microgravity with rotating bioreactors or random positioning machines form complex 3D structures that resemble tissues in the body more closely than their Earth-grown counterparts. This is invaluable for studying cell growth, cancer development, and drug testing in realistic tissue models (Grimm, 2014).

Microgravity is useful for tissue engineering. By eliminating gravitational forces, biomechanical cues that guide tissue formation can be more precisely controlled. This facilitates the production of higher-quality 3D structures, such as blood vessels or organ tissues, which are crucial for medical research and drug development (Moroni, 2022).

More Benefits for Biomanufacturing

Microgravity is advancing biofabrication techniques by allowing for the ultra-thin layering of biomaterials, down to the atomic level, which is essential for creating high-precision medical devices. This extreme precision in material deposition brings new opportunities for bioengineering and personalized medicine (Sharma, 2022).

One recent breakthrough is the use of magnetic levitation to assemble 3D tissue structures without the need for scaffold support or labeling markers. By using magnetic tools approved for microgravity, scientists can cluster small cell groups, or spheroids, into larger, more organized tissues. This method was successfully applied in space to form human cartilage tissues, which exhibited strong cellular health and advanced fusion stages—a promising development for regenerative medicine (Parfenov, 2020).

Alongside scaffold-free tissue engineering, microgravity has facilitated the development of organ-on-a-chip systems. These devices mimic human organs on a microscale, letting researchers observe how tissues react under different conditions. Recently, the National Center for Advancing Translational Sciences (NCATS) and the ISS National Lab collaborated to send tissue chips to the ISS, where the effects of space on human biology can now be studied with unparalleled accuracy (Low, 2020). 

In the private sector, Litegrav has contributed to the advancement of organ-on-chip technologies by developing systems that offer continual flow in microgravity environments. Their research showed that cells grown with this flow experience showed improved growth, although viability challenges must be addressed. Such insights are improving our understanding of disease progression and refine cellular models for medical research.

The Future of Biomanufacturing in Microgravity

New advancements will continue to impact our understanding of human biology and drive the development of technologies that benefit humanity. Accelerated aging processes and altered physiological conditions make it substantially easier to study degenerative diseases, test regenerative therapies, and optimize biofabrication methods.

Using simulated microgravity devices like random positioning machines (RPMs) and rotating wall vessels, scientists can recreate certain aspects of microgravity on Earth. Litegrav’s 3d microgravity simulator allows researchers to simulate the low-shear, low-gravity environment in a controlled, terrestrial-based setting, making these experiments more accessible and reproducible than ever before.

References and Suggested Reading

• Baio, J., Martinez, A.F., Silva, I. et al. (2018). Cardiovascular progenitor cells cultured aboard the International Space Station exhibit altered developmental and functional properties. npj Microgravity, 4, 13. https://doi.org/10.1038/s41526-018-0048-x
• Bradbury, P., Wu, H., Choi, J.U., Rowan, A.E., Zhang, H., Poole, K., Lauko, J., & Chou, J. (2020). Modeling the impact of microgravity at the cellular level: Implications for human disease. Front Cell Dev Biol, 8, 96. https://doi.org/10.3389/fcell.2020.00096
• Cubo-Mateo, N., Podhajsky, S., Knickmann, D., Slenzka, K., Ghidini, T., & Gelinsky, M. (2020). Can 3D bioprinting be a key for exploratory missions and human settlements on the Moon and Mars? Biofabrication, 12(4), 043001. https://doi.org/10.1088/1758-5090/abb53a
• Grimm, D., Wehland, M., Pietsch, J., Aleshcheva, G., Wise, P., van Loon, J., Ulbrich, C., Magnusson, N. E., Infanger, M., & Bauer, J. (2014). Growing tissues in real and simulated microgravity: New methods for tissue engineering. Tissue Engineering Part B: Reviews, 20(6), 555–566.
• Low, L.A., & Giulianotti, M.A. (2020). Tissue Chips in Space: Modeling human diseases in microgravity. Pharm Res, 37, 8. https://doi.org/10.1007/s11095-019-2742-0
• Moroni, L., Tabury, K., Stenuit, H., Grimm, D., Baatout, S., & Mironov, V. (2022). What can biofabrication do for space and what can space do for biofabrication? Trends Biotechnol, 40(4), 398-411. https://doi.org/10.1016/j.tibtech.2021.08.008
• Parfenov, V.A., Khesuani, Y.D., Petrov, S.V., et al. (2020). Magnetic levitational bioassembly of 3D tissue construct in space. Sci Adv, 6(29), eaba4174. https://doi.org/10.1126/sciadv.aba4174
• Shelhamer, M., Bloomberg, J., LeBlanc, A., et al. (2020). Selected discoveries from human research in space that are relevant to human health on Earth. npj Microgravity, 6, 5. https://doi.org/10.1038/s41526-020-0095-y
• Sharma, A., Clemens, R.A., Garcia, O., et al. (2022). Biomanufacturing in low Earth orbit for regenerative medicine. Stem Cell Reports, 17(1), 1-13. https://doi.org/10.1016/j.stemcr.2021.12.001
• Space Quest Ventures. (n.d.). Litegrav enables organ-on-a-chip system microgravity simulation. Space Quest Ventures. Retrieved November 10, 2024, from https://spacequestventures.com/news/f/litegrav-enables-organ-on-a-chip-system-microgravity-simulation
• Vasic-Racki, D., Liese, A., Seebald, S., & Wandrey, C. (2006). History of industrial biotransformations—dreams and realities. In Industrial Biotransformations (pp. 1-37). Weinheim: Wiley-VCH, KGaA.
• Yi-Heng, P.Z., Jibin, S., & Yanhe, M. (2017). Biomanufacturing: History and perspective. Journal of Industrial Microbiology and Biotechnology, 44(4-5), 773–784. https://doi.org/10.1007/s10295-016-1863-2

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