Scientists sent a 3D bioprinter to space and demonstrated its ability to print living tissue while orbiting Earth. The findings, published in Advanced Materials, could one day lead better “space-based” medical treatments for astronauts on long missions.

Spaceflight poses unique risks to astronauts, including stressors to the human body such as G force, microgravity, and cosmic radiation. In fact, according to NASA, “astronauts who spend six months in space are exposed to roughly the same amount of radiation as 1,000 chest X-rays”.

These environmental factors put them at risk for central nervous system damage, bone loss, and cancer. It’s therefore not difficult to imagine a scenario where an astronaut on a long-haul mission might need medical treatment, including cancer therapy, aboard.

“The crew must be as autonomous as possible,” commented Nieves Cubo-Mateo, an industrial engineer and a 3D printing researcher at Nebrija University in Spain not involved in the current study.

Difficulty mimicking living tissue in space

To develop medical treatments in space, scientists first need to understand how the body behaves in this foreign environment. The team’s focus for this initial missions was to study how an anti-cancer therapy might affect a bioprinted tumor model in orbit.

“Tumor-related research in the space environment is a hot [topic] in space biology,” said Zhuo Xiong, professor in the Department of Mechanical Engineering in Tsinghua University, and the study’s lead author.

3D bioprinting has become an important technology for studying tissue regeneration and various diseases, such as cancer.  It allows scientists to build realistic models of organs and tissues, incorporating living cells, biomaterials, and other bioactive elements to imitate the real thing. The challenge when it comes to mimicking how tissues and organs will behave in space is building a 3D bioprinter that works in orbit, and as the Tsinghua University team pointed out, this is not an easy task. 

The printer and live cells need to survive the intense mechanical forces experienced during launch, not to mention the difficulty in maintaining living cells and biomaterials in fluctuating temperatures. To add complication, all the equipment must be scaled down and work “leak-free” in a microgravity environment. 

To solve these problems, Xiong and his team created a strong yet lightweight device optimized for 3D printing in space. The team wrote that to the best of their knowledge, this is the first time that on-orbit printing of this kind has been achieved via a satellite.

A light-weight, durable 3D bioprinter for orbit

To ensure efficient and effective space travel, the size and weight of items placed in a spacecraft must be minimized for better fuel efficiency. This made producing a scaled-down 3D printer quite the challenge, as those found in labs around the world are typically large machines that can occupy small rooms — much like the first computers. Shrinking them to fit the size constraints of the satellite’s cargo load required some innovative engineering.

The miniature 3D bioprinter the team developed ended up being the size of a shoebox, weighing six kilograms total, and designed to withstand the severe vibrations experienced during satellite launch.

It contains a printing unit, which consists of two motor-controlled syringes filled with cell-based bioinks, while the system’s “biological unit” contains two chambers filled with a medium in which the printed tissue can be embedded. The two units were linked and sealed from the outside environment via a soft latex film to prevent any leakage and maintain an internal differential pressure.

The device also incorporated a microscope to automatically capture images of the biological samples while in orbit and send them back for analysis on Earth. “To be able to fit a 3D bioprinter device and a confocal microscope under such dimensions [is an achievement] in bioprinting and space engineering,” said Cubo-Mateo.

With their equipment ready, on June 7, 2023, the device was launched from the Jiuquan Satellite Launch Center in China aboard a satellite designated for scientific experiments. Once in orbit 500 km above the Earth’s surface, initial tests via the 3D bioprinting of a lung cancer tumor model began.  

One small step for space medicine

Previous studies have shown that cancer cells are more sensitive to chemotherapies when administered in space, but sending intact biological samples into orbit is difficult. “Most research is carried out in microgravity-simulating devices or 2D culture systems, which can neither simulate the real space environment nor reflect the complex tumor microenvironment, greatly limiting the progress,” said Xiong.

To build a better model, the 3D printer the team sent to space contained two types of lung cancer cells: one “normal” and one known to be resistant to chemotherapy. The cells were stored in a specially designed bioink within the syringes. “It is challenging to maintain [conventional bioinks’ ideal] temperature at 4 °C due to volume and energy constraints,” wrote the scientists. “As a result, we needed to develop a bioink that can be stored at room temperature for at least 24h while maintaining satisfactory printability and cell viability.”

They therefore developed a microgel-based bioink that is heat responsive, resistant to bubble formation during launch, and mimics the tumor’s natural environment by including another cell type called CAF “to simulate a heterogeneous microenvironment typical of tumors”.

After printing the 3D tumor models, the team tested their ability to respond to a chemotherapy drug called cisplatin used to treat a number of different cancers. “We selected the widely used chemotherapy drug cisplatin as a representative example for more convincing conclusions,” said Xiong.

The automated system took pictures of the models at different time intervals over the course of the treatment. They then compared them to pictures of the same tumor models printed and treated on Earth. Their results confirmed previous experiments in which both normal and resistant cancer cells were more sensitive to the anti-cancer therapy in space than when treated on Earth.

Why this happens is still unclear. Further research is needed to determine if cosmic radiation and microgravity affect the tumor sensitivity to treatment. The team says they plan to conduct these experiments aboard the China’s Tiangong Space Station in the near future.

Beyond just tumor models

More experiments are also needed to understand how real tumors will respond when treated in space. “The measurements obtained [in the current study] were taken in a short time after printing (<60h), and the samples were cultures in space for a total of 5 days,” said Cubo-Mateo.

“The [3D] constructs do not [completely] resemble real tissue as cells did not have time to assemble and start forming the natural environment of the native tissue/tumor. Complete tissue or tumor maturation take longer (several weeks).”

Xiong is also optimistic that their 3D bioprinter will have practical use beyond just printing tumor models. Many studies have demonstrated 3D bioprinting’s potential to create personalized scaffolds to regrow tissues and organs.

Future experiments in space could determine if the same technology could be applied to astronauts who might suffer tissue damage while traveling a long way from home. “Our on-orbit 3D bioprinting technology could be used to print and regenerate damaged tissue in injured astronauts,” concluded Xiong.

Reference: Xingwu Mo, et. al., Satellite-Based On-Orbit Printing of 3D Tumor Models, Advanced Materials (2023). DOI: 10.1002/adma.202309618

Feature image credit: NASA