Manufacturing in Space

3D Bioprinting

 
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3D bioprinting holds the potential for fabrication of reproducible human tissue and whole organs for the purposes of pharmaceutical drug screening, disease research, and regenerative medicine applications. Current technology utilizes an additive manufacturing process that prints functional tissues through layered deposition of ‘bioinks’ that are composed of cells, growth factors, extracellular matrix components, and other biomaterial. The technology has come a long way, with successful implantation of functional 3D-bioprinted hyper-elastic bone and prosthetic ovaries in rodents. Construction of structural tissues such as bone and cartilage have seen great advancements, but there are challenges in the assembly of soft tissues such as blood vessels and muscles. This is due to terrestrial gravity and the forces imposed on printed tissues that cause structural collapse. 

To overcome these challenges, researchers have experimented with and tested a variety of bioinks to optimize physiochemical properties. To support the tissue’s 3D structure, viscosity of bioinks is increased to improve rigidity. However, as viscosity is increased, higher pressure is required for extrusion from the bioprinter, which increases shear stress on the cell thereby negatively affecting cell viability. 

Microgravity can function as a cofactor for 3D printing of tissues. In the absence of gravitational forces, lower-viscosity bioinks can be used, improving printability of bioinks and viability of cells. Maintenance of 3D organization allows for the creation of more complex tissue structures such as vascular tubes with retained internal lumens and spaces. Biotech companies are well on their way to developing the equipment and optimizing conditions for bioprinting tissue in microgravity, and several projects are in progress.

Emerging approaches in 3D bioprinting are being developed, which could enhance the precision of handling and assembly of cellular components, creating tissues with higher geometric resolution and improved reproducibility. Magnetic bioprinters, for example, use principles of formative biofabrication (instead of extrusion-based technology). This technology does not require a scaffold to direct cell position, but instead uses a controlled magnetic field to position magnetized tissue spheroids into 3D constructs. One key challenge of this technology results from the use of the paramagnetic medium (Gadolinium Gd3+) which is toxic to cells. In order to use lower concentrations of Gd3+, stronger magnets will need to be used or, alternatively, tissues can be constructed in microgravity which reduces the need for magnetic forces to manipulate cells. 

Recently, researchers have successfully used magnetic bioprinting technology to create 3D tissue constructs using chondrospheres at nontoxic concentration of paramagnetic medium, with the goal of constructing cartilage. Development of the technology will surely open up the possibility for biofabrication of other tissues.