Weightless Woes: Microgravity and Our Bones

As a means of studying accelerated aging, and thus an invaluable tool for longevity researchers, microgravity environments can have deleterious effects on human health. Among these are weaker bones and muscle atrophy (NASA, n.d.)  Weightlessness, pleasant as it may sound, is a shock to the system—one to which, it seems, we do not readily adapt. Astronauts experience potentially fatal fluid redistribution, hormonal shifts, and cardiovascular deconditioning (Wolfe, 1992). 

Their immune systems are also impacted. Although they experience a rise in overall white blood cell count, they display reduced immune function on long term missions (Crucian, 2015). To address this dilemma, astronauts must be prepared to handle health concerns and crises. Establishing these protocols takes time in space—which takes its toll. 

These issues are currently unavoidable. A distinctive focus should be conferred to tissue engineering and regenerative medicine. This may assist us in protecting and repairing the body in a variety of environments.  

Bones Loss: A Major Focal Point

Data from astronauts, along with studies on animals and cells in space reveal that microgravity substantially weakens bones. As astronauts stay in orbit, between 1–2% of their bone mass is stripped away each month. The most affected bones are those that usually bear weight on earth (Man, 2022).

Although bone loss on Earth and in space happen for different reasons, there are similarities for how it happens. In both cases, a lack of estrogen and reduced mechanical stress lead to lower bone density. 

Along with this comes more accelerated bone breakdown, weaker bones, and hormone imbalances. This makes spines, wrists, and hips especially vulnerable to fractures and breaks (Nelson, 2009). 

In microgravity, marrow cells tend to turn into fat cells instead of bone cells. This mimics the normal effects of aging by reducing the body’s ability to repair bone and adapt to physical stress (Juhl, 2021).

Moreover, decreased calcium absorption impedes new bone formation. Microgravity hinders osteoblasts (bone-forming cells) from forming and hastens cell death in bones (Caillot-Augusseau, 2000).

Research on the musculoskeletal system in space is facilitating the discovery of new interventions to prevent or halt age-related bone loss. In space, these methods (such as 3D bioprinting) may allow astronauts to deal with medical emergencies (Mochi, 2022).

Configuring material or bioprinters in microgravity in space is impractical, which is why simulation services provided by companies like Litegrav are indispensable. Large numbers of studies can be inexpensively conducted.

3D printing is finding an assortment of applications in healthcare. It is now possible to 3D print biocompatible materials, cells, and supporting parts to assemble increasingly complex, functional, and living tissues. It is being used in regenerative medicine to create organs and tissues for transplants. Understandably, it is being considered for long-term space missions and colonization (Ghidini, 2018).

Tissue engineering is a field that joins materials science, engineering, and medicine to repair damaged tissues. It bestows an alternative to grafts using the patient's own tissues (Berthiaume, 2011).

Specially designed scaffolds act like substitutes, imitating the properties of healthy tissue and providing a 3D space for cell growth, attachment and development. This assists in restoring the normal tissue function. The main components of tissue engineering are scaffolds, cells, and growth factors. These growth factors are frequently referred to as the tissue engineering triad (O’Brien, 2011).

In bone tissue engineering, an ideal scaffold should break down safely in the body. It should be constructed of biomaterials that imitate the structure and function of natural bone. It must work well with living tissues, encourage bone growth, and sustain new bone formation (Polo-Corrales, 2014). All of this must be even more carefully considered in microgravity. 

Engineering bone-tissue in simulated microgravity

Addressing bone loss in microgravity is pivotal to the future for both astronauts and patients on our planet. Scientists have conducted studies for understanding bone cell adaptation in microgravity. 

One study showed that implanted rat bone marrow cells cultivated in simulated microgravity struggled to form bone (Nishikawa, 2005). This indicates challenges for bone development in low-gravity conditions. 

Researchers implemented a device called a 3D clinostat, mimicking microgravity by rotating and canceling gravity’s effects. They grew rat bone cells in a scaffold of porous calcium hydroxyapatite for two weeks. Results revealed a 40% decrease in alkaline phosphatase, a marker for bone growth. Moreover, there was a reduction in matrix formation compared to cells grown in normal gravity. Implanted scaffolds still formed bone, but the volume was lower (Nishikawa, 2005).

In contrast, Jin et al. discovered enhanced bone repair when cells were grown on dynamic, rotating scaffolds. When implanted in defective rat skulls, the bone constructs repaired the defective bone more effectively. Stronger connections were observed in surrounding tissue (Jin, 2009). 

This finding suggests that movement in microgravity conditions can improve the development of lab-grown, functional bone. The implications for the medical industry are exciting and, more importantly, tangible.

Other studies on human cell models used advanced 3D scaffolds to promote bone formation. These scaffolds encourage cell differentiation. This was found even with limited mechanical stress, suggesting potential strategies to counter bone attrition during space missions (Mochi, 2022).

NASA Bone Engineering

Bone tissue engineering research on the ISS is geared towards understanding microgravity effects on bone density and health, particularly osteopenia (ISS, n.d.).

Between 2011 and 2021, experiments like EDOS examined bone microstructure changes and recovery post-flight. Meanwhile another experiment, ARED, evaluated the benefits of resistance exercises for maintaining osteal integrity and muscular strength. Studies such as IN VITRO BONE, OBLAST, and OBADIS investigated cell-level bone formation, growth, and structural changes (Mochi, 2022).

NASA’s STLV bioreactor grows cartilage for potential bone implants. Traditional bone repair methods involve cartilage formation before bone development. It is speculated that starting with cartilage might increase the rate of healing. The STLV obviates traditional challenges to growing cartilage by allowing cells effective and even growth by reducing turbulent forces. This makes it possible to produce larger tissue masses fit for implants (NASA, 1998).

The research being produced by the public and private sectors to address the health concerns of astronauts is coalescing into a future where interplanetary travel will be realized and diseases that have plagued us for countless millennia will be obviated or erased from memory. 

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References and Suggested Reading

Berthiaume F, Maguire TJ, Yarmush ML. Tissue engineering and regenerative medicine: history, progress, and challenges. Annu Rev Chem Biomol Eng. 2011;2:403-30. doi: 10.1146/annurev-chembioeng-061010-114257. PMID: 22432625.

Caillot-Augusseau A., Vico L., Heer M., Voroviev D., Souberbielle J.C., Zitterman A., Alexandre C., Lafage-Proust M.H. Space flight is associated with rapid decreases of undercarboxylated osteocalcin and increases of markers of bone resorption without changes in their circadian variation: Observations in two cosmonauts. Clin. Chem. 2000;46:1136–1143. doi: 10.1093/clinchem/46.8.1136.

Crucian, B., Stowe, R., Mehta, S. et al. Alterations in adaptive immunity persist during long-duration spaceflight. npj Microgravity 1, 15013 (2015). https://doi.org/10.1038/npjmgrav.2015.13

Ghidini T. Regenerative medicine and 3D bioprinting for human space exploration and planet colonisation. J Thorac Dis. 2018 Jul;10(Suppl 20)

. doi: 10.21037/jtd.2018.03.19. PMID: 30123576; PMCID: PMC6081368.

ISS National Lab. (n.d.). Skeletons in space: Studying bones in microgravity. ISS National Laboratory. Retrieved November 4, 2024, from https://issnationallab.org/iss360/skeletons-in-space-studying-bones-in-microgravity/

Jin F, Zhang Y, Xuan K, He D, Deng T, Tang L, Lu W, Duan Y. Establishment of three-dimensional tissue-engineered bone constructs under microgravity-simulated conditions. Artif Organs. 2010 Feb;34(2):118-25. doi: 10.1111/j.1525-1594.2009.00761.x. Epub 2009 Oct 10. PMID: 19817729.

Juhl, O.J., Buettmann, E.G., Friedman, M.A. et al. Update on the effects of microgravity on the musculoskeletal system. npj Microgravity 7, 28 (2021). https://doi.org/10.1038/s41526-021-00158-4

Man, J., Graham, T., Squires-Donelly, G. et al. The effects of microgravity on bone structure and function. npj Microgravity 8, 9 (2022). https://doi.org/10.1038/s41526-022-00194-8

Mochi, F., Scatena, E., Rodriguez, D. et al. Scaffold-based bone tissue engineering in microgravity: potential, concerns and implications. npj Microgravity 8, 45 (2022). https://doi.org/10.1038/s41526-022-00236-1

NASA. (1998). Use of NASA Bioreactor in engineering tissue for bone repair (NASA Technical Report No. 19990024866). NASA Technical Reports Server. https://ntrs.nasa.gov/citations/19990024866

NASA. (n.d.). Counteracting bone and muscle loss in microgravity. NASA. https://www.nasa.gov/missions/station/iss-research/counteracting-bone-and-muscle-loss-in-microgravity

Nelson, E.S., Lewandowski, B., Licata, A. et al. Development and Validation of a Predictive Bone Fracture Risk Model for Astronauts. Ann Biomed Eng 37, 2337–2359 (2009). https://doi.org/10.1007/s10439-009-9779-x

Nishikawa M, Ohgushi H, Tamai N, Osuga K, Uemura M, Yoshikawa H, Myoui A. The effect of simulated microgravity by three-dimensional clinostat on bone tissue engineering. Cell Transplant. 2005;14(10):829-35. doi: 10.3727/000000005783982477. PMID: 16454357.

O’Brien, F. J. (2011). Biomaterials & Scaffolds for Tissue Engineering. Materials Today.

Polo-Corrales L, Latorre-Esteves M, Ramirez-Vick JE. Scaffold design for bone regeneration. J Nanosci Nanotechnol. 2014 Jan;14(1):15-56. doi: 10.1166/jnn.2014.9127. PMID: 24730250; PMCID: PMC3997175.

Wolfe JW, Rummel JD. Long-term effects of microgravity and possible countermeasures. Adv Space Res. 1992;12(1):281-4. doi: 10.1016/0273-1177(92)90296-a. PMID: 11536970.

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