Opportunities for Biomanufacturing in Low Earth Orbit: Current Status and Future Directions

Abstract

In humankind’s endeavor to explore beyond our planet and travel further into space, we are now at the threshold of an era in which it is possible to move to and from low Earth orbit (LEO) with increasing ease and reduced cost. Through the International Space Station (ISS) U.S. National Laboratory, investigators from industry, academia, and government can easily access the unique LEO environment on the ISS to conduct research and development (R&D) activities in ways not possible on Earth. A key advantage of the LEO environment for life sciences research is the ability to conduct experiments in sustained microgravity conditions. The ability to conduct long-term research in microgravity enables opportunities for novel, fundamental studies in tissue engineering and regenerative medicine, including research on stem cell proliferation and differentiation, biofabrication, and disease modeling using microphysiological systems (MPS) that build on prior research using simulated microgravity conditions (Grimm, D., et al. 2018). Over the last decade, space-based research has demonstrated that microgravity informs our knowledge of fundamental biology and accelerates advancements in health care and medical technologies (International Space Station 2019). The benefits provided by conducting biomedical research in LEO may lead to breakthroughs not achievable on Earth. We are now at a transition point, in which nations are changing their approach to space-based R&D. The focus is shifting from government-funded fundamental science toward the expansion of privately funded R&D with terrestrial application and economic value that will drive a robust marketplace for innovation and manufacturing in LEO. Making this long-term transition requires public-private participation and near-term funding to support critical R&D to leverage the benefits of the LEO environment and de-risk space-based research. Studies conducted on the ISS over the past several years have indicated that one area with potential significant economic value and benefit to life on Earth is space-based biomanufacturing, or the use of biological and nonbiological materials to produce commercially relevant biomolecules and biomaterials for use in preclinical, clinical, and therapeutic applications. We must take advantage of the remaining lifetime of the ISS as a valuable LEO platform to demonstrate this economic value and Earth benefit. By facilitating access to the space station, the ISS National Lab is uniquely positioned to enable the R&D necessary to bridge the gap between the initial discovery phase of space-based biomedical research and the development of a sustainable, investment-worthy biomanufacturing market in LEO supported by future commercial platforms. Through a joint effort, the Center for the Advancement of Science in Space (CASIS), which manages the ISS National Lab, and the University of Pittsburgh’s McGowan Institute for Regenerative Medicine brought together thought leaders from around the U.S. for a Biomanufacturing in Space Symposium that consisted of a series of working sessions to review data from past space-based tissue engineering and regenerative medicine research, discuss relevant current space-based R&D in this area, and consider potential future markets to address the questions: What are the most promising opportunities to leverage the ISS to advance space-based biomanufacturing moving forward? What are the current gaps or barriers that, if overcome, could clear pathways toward private investment in LEO as a valued site for research, development, and production activity? And, most importantly: For which opportunities do the most compelling value propositions exist? The goal of the Biomanufacturing in Space Symposium was to help identify the specific areas in which government and industry investment would be most likely to stimulate advancements that overcome barriers. This would lead to a more investment-ready landscape for private interests to enter the market and fuel exponential growth. The symposium was meant to serve as the first step in developing a roadmap to a sustainable market for biomanufacturing in space. The symposium identified and prioritized multiple key R&D opportunities to advance space-based biomanufacturing. These opportunities fall in the areas of disease modeling, stem cells and stem-cell-derived products, and biofabrication. Additionally, symposium participants highlighted the critical need for additional data to help validate and de-risk these opportunities and concluded that approaches such as automation, artificial intelligence (AI), and machine learning will be needed to produce and capture the required data. Symposium participants also came to a consensus that public-private partnerships and funding will be needed to advance the opportunities toward a biomanufacturing marketplace in LEO. This paper will summarize the current state of the science and technology on the ISS and in the fields of tissue engineering and regenerative medicine; provide an overview of biomanufacturing R&D in space to date; review the goals of the Biomanufacturing in Space Symposium; highlight the key commercial opportunities and gaps identified during the symposium; provide information on potential market sizes; and briefly discuss the next steps in developing a roadmap to biomanufacturing in space.

Stem cell therapy: Advances and future directions in regenerative medicine: A review

“…Furthermore, CRISPR/Cas9 has major ethical and technological constraints, despite its enormous promise. Application of this technique to cardiovascular diseases, for instance, necessitates changing DNA repair processes, enhancing genome editing tool designs, and analyzing the efficiency and safety of these methods [32].…”

Theoretical design of a space bioprocessing system to produce recombinant proteins

“…Protein-bound resin is separated from the lysate using the centrifuge, while the spent lysate is collected in a waste reservoir (8). The resin is washed with buffer (9). Wash buffer is separated by the centrifuge and collected into the waste reservoir.…”

“…Not all enzymes retain activity in low temperature storage and in situ production of enzymes would mitigate risks of relying solely on low temperature storage of proteins with limited stability. Space biomanufacturing systems have the potential to produce enzymes and other biological materials using in situ resources during a Mars mission [8][9][10][11][12][13] . Space systems must minimize cost and crew time, while assuring astronaut safety and addressing effects of increased radiation and reduced gravity [14][15][16][17] .…”

“…Crew will transfer the lysate to the lysate chamber (14) of a continuous loop affinity membrane purification system (15). Rollers (17) move the affinity membrane through buffer chambers for protein binding (14), wash (9), and elution (10). A 12 second wash chamber equilibrates the membrane for multiple cycles of protein binding.…”

Biomanufacturing for Space-Exploration – What to Take and When to Make

“…relying on the more complex, risky and time-intensive technologies of biomanufacturing. Also, due to the dearth of in situ resources on the Moon (Figure 1b) 34 , the scale of biomanufacturing will be constrained by the supply chain and capability for recycling these elements 35 . However, because of the well-supported environment, it is an ideal location to prove and improve technologies for biomanufacturing in space by testing automated and scaling operation of critical bioreactor systems for different bioprocess types (e.g., electro-and photo-autotrophic (gas) bioreactors for lithoautotrophic and/or saprotrophic fermentation of macronutrients 36 ), all of which are likely to have physiological and operational challenges in a low-gravity, resource-poor environment [37][38][39] .…”