For the first time, 3D human tissue has been assembled in the microgravity of space. Through a magnetic levitation device, researchers in Russia, led by Vladislav Parfenov at the Russian Academy of Sciences and 3D Bioprinting Solutions, enabled a cosmonaut aboard the International Space Station (ISS) to fabricate human cartilage from a few isolated cells. Their work could lead to crucial new techniques for regenerating tissues during long-term spaceflight.
Tissue engineering has seen a surge of interest in recent years. Traditionally, it involves seeding cells onto biocompatible “scaffolds”, which biodegrade once tissues have assembled themselves into 3D organs. However, more flexible, scaffold-free approaches are also emerging, which enable cells to assemble themselves without the need for structural biomaterials. To do this, researchers use techniques including removable supports, and guiding forces from acoustic and electrostatic fields.
One particularly promising approach involves magnetic levitation, through which strong field gradients can precisely guide tissue cells into place. To achieve strong enough gradients, however, cells must be suspended within a paramagnetic medium containing gadolinium ions. At the concentrations required for the technique to work, these ions are toxic to cells, and can cause dangerous pressure imbalances.
One potential solution to this problem is to perform levitated assemblies in microgravity. Recent studies have shown particular interest in doing this with cartilage – the smooth, elastic tissue found in human joints and intervertebral disks. Currently, it is poorly understood how cartilage is affected during long-term spaceflight, since space-based experiments are extremely expensive and time-consuming. In their study, Parfenov and collaborators designed a magnetic bioassembler for use on the ISS – which would only require a low, non-toxic concentration of gadolinium ions.
To do this, the researchers first fabricated tissue spheroids from human cartilage cells at the Baikonur Cosmodrome in Kazakhstan, which were embedded in heat-reversible hydrogel, then delivered to the ISS in hermetically sealed cuvettes. After gadolinium ions were injected by a cosmonaut aboard the space station, the cuvettes were cooled to release the cells from the hydrogel, then placed in a 37°C chamber within the bioassembler for two days. In these conditions, cell fusion and self-assembly could be sustained, and were recorded on a video camera. Finally, the assembled cartilage was stored at room temperature for two weeks, before being returned to Earth for analysis.
As Parfenov’s team hoped, the self-assembly process captured by the camera showed strong agreement with their mathematical models and computer simulations. The success of their experiment now represents a significant advance in our ability to fabricate 3D human tissues without the need for scaffolds, and with non-toxic levels of gadolinium ions. With the adverse effects of microgravity on human tissue already well known to researchers, their technique could prove critical in maintaining the health of astronauts during future manned space exploration.
The research is described in Science Advances.
