3D Bioprinting in Microgravity: Opportunities, Challenges, and Possible Applications in Space

Abstract

3D bioprinting has developed tremendously in the last couple of years and enables the fabrication of simple, as well as complex, tissue models. The international space agencies have recognized the unique opportunities of these technologies for manufacturing cell and tissue models for basic research in space, in particular for investigating the effects of microgravity and cosmic radiation on different types of human tissues. In addition, bioprinting is capable of producing clinically applicable tissue grafts, and its implementation in space therefore can support the autonomous medical treatment options for astronauts in future long term and far-distant space missions. The article discusses opportunities but also challenges of operating different types of bioprinters under space conditions, mainly in microgravity. While some process steps, most of which involving the handling of liquids, are challenging under microgravity, this environment can help overcome problems such as cell sedimentation in low viscous bioinks. Hopefully, this publication will motivate more researchers to engage in the topic, with publicly available bioprinting opportunities becoming available at the International Space Station (ISS) in the imminent future.

Keywords: additive manufacturing; biofabrication; low Earth orbit - LEO; space.

Figure 1

Different opportunities to use EBB. Adapted with permission under the temrs of the CC–BY license.^{[ 39 ]} Copyright 2018, the Author(s). Published by IOP Publishing. A) Direct writing. B) Printing in coagulation bath. C) Printing in support bath. D) Co–axial extrusion.

Figure 2

A) Resolution and size of the objects produced by liquid deposition modeling (LDM, also referred to as extrusion bioprinting or EBB), inkjet printing, and laser bioprinting. B) Differential behavior of inkjet bioprinting expected on Earth (left) and space (right). Differences are expected due to microgravity at (B1) the cell (B2) droplet and (B3) construct levels.

Figure 3

A) Schematic overview of the MEW process; B) Concept of the critical translation speed (CTS) and relation to collector speed v _c and speed of the jet v _jet. (A) Adapted with permission under the terms of the CC–BY license.^{[ 70 ]} Copyright 2015, the Authors. Published by IOP Publishing. (B) Adapted with permission under the terms of the CC–BY license.^{[ 74 ]} Copyright 2018, the Authors. Published by Wiley–VCH GmbH.

Figure 4

A–L) Deposition patterns used to influence fiber deposition and to generate different constructs with defined pores and properties; structure shown in (L) was collected on a tubular collector; scale bars = 100 µm (A)–(D), 500 µm (E)–(H), 50 µm (I), 200 µm (J)–(L); M–P) Influence of pattern and fiber deposition on cell orientation and filling of pores. (A−L) Reproduced under terms of the CC‐BY license. ^{[ 71 ]} Copyright 2019, the Authors. Published by Wiley–VCH GmbH. (M–P) Reproduced with permission.^{[ 81 ]} Copyright 2019, Elsevier.

Figure 5

Demonstration of horizontal and vertical MEW printing. The minimal effect of gravity on the MEW jet during printing shown in A) in horizontal and B) upside‐down orientation followed by the translation into C) a scale‐up MEW printer capable of fabricating 1024 scaffolds per print and D) a single 80 cm × 80 cm fabric. E) Image showing a CAD model of the scale‐up prototype configuration with 8 print heads evenly spaced on a horizontal configuration to a large translating collector and F) a computer rendering envisioning how the small footprint permits multiple systems to operate in unison. Reproduced under terms of the CC‐BY license.^{[ 71 ]} Copyright 2019, the Authors Published by WileyVCH GmbH.

Figure 6

A) SLA, B) DLP, C) MPL. Generally, all three technologies can be executed in top‐down or inverted configurations; the latter is usually employed for 3D bioprinting. In addition, with the dawn of novel light sources and photoinitiators, wavelengths in the visible range are increasingly used. Reproduced with permission.^{[ 95 ]} Copyright 2021, Elsevier.

Figure 7

Graphical representation of the capabilities of several bioprinting techniques discussed in this work, regarding the throughput and resolution: digital light processing (DLP), stereolithography (SLA), extrusion bioprinting (EBP), melt electrowriting (MEW), multiphoton lithography (MPL), and volumetric printing (VP). With both MPL and EW, features within the scale of cells and smaller can be produced, allowing it to control the microenvironment at the cellular level. However, these techniques are limited in their throughput to a few mm³ h⁻¹. DLP, SLA, VP, and EBP enable the realization of constructs of several cm³ with a minimal feature size in the range of capillaries, cell spheroids, or blood vessels. Acell‐shaped datapoint indicates studies that involved cell encapsulation during printing. Adapted with permission.^{[ 101 ]} Copyright 2023, Elsevier.

Figure 8

Concept of integrated vials and perfusion system involving terrestrial procedures – Resin constitution and printing vial preparation for tomographic projections, Xolography or FLight biofabrication, and extra‐terrestrial procedures – printing of the tissue constructs and media circulation within a pressurized reactor system. Note: After preparation, the resin may be stored under normal refrigeration at 4 °C or cryopreserved (using cryo‐protectants).

Figure 9

In situ data mining for intelligent bioprinting (system proposed by Politecnico di Milano).

Figure 10

Adapting postprinting maturation and tissue characterization to space. All‐in‐one integrated and specifically designed bioprinting and cultivation instrumented device.