Bioreactors Drive Advances in Tissue Engineering

NASA Technology

It was an unlikely moment for inspiration. Engineers David Wolf and Ray Schwarz stopped by their lab around midday. Wolf, of Johnson Space Center, and Schwarz, with NASA contractor Krug Life Sciences (now Wyle Laboratories Inc.), were part of a team tasked with developing a unique technology with the potential to enhance medical research. But that wasn’t the focus at the moment: The pair was rounding up colleagues interested in grabbing some lunch.

altOne of the lab’s other Krug engineers, Tinh Trinh, was doing something that made Wolf forget about food. Trinh was toying with an electric drill. He had stuck the barrel of a syringe on the bit; it spun with a high-pitched whirr when he squeezed the drill’s trigger.

At the time, a multidisciplinary team of engineers and biologists—including Wolf, Schwarz, Trinh, and project manager Charles D. Anderson, who formerly led the recovery of the Apollo capsules after splashdown and now worked for Krug—was pursuing the development of a technology called a bioreactor, a cylindrical device used to culture human cells. The team’s immediate goal was to grow human kidney cells to produce erythropoietin, a hormone that regulates red blood cell production and can be used to treat anemia. But there was a major barrier to the technology’s success: Moving the liquid growth media to keep it from stagnating resulted in turbulent conditions that damaged the delicate cells, causing them to quickly die.

The team was looking forward to testing the bioreactor in space, hoping the device would perform more effectively in microgravity. But on January 28, 1986, the Space Shuttle Challenger broke apart shortly after launch, killing its seven crewmembers. The subsequent grounding of the shuttle fleet had left researchers with no access to space, and thus no way to study the effects of microgravity on human cells.

As Wolf looked from Trinh’s syringe-capped drill to where the bioreactor sat on a workbench, he suddenly saw a possible solution to both problems.

“It dawned on me that rotating the wall of the reactor would solve one of our fundamental fluid mechanical problems, specifically by removing the velocity gradient of the tissue culture fluid media near the reactor’s walls,” says Wolf. “It looked as though it would allow us to suspend the growing cells within the reactor without introducing turbulent fluid mechanical conditions.”

The three engineers skipped lunch. They quickly built a prototype from components lying around the lab and tested the bioreactor that night using hamster kidney cells (cheaper than their human counterparts). When the team returned in the morning, not much had changed; the cells were all dead. But after running chemical analyses, Wolf and his colleagues realized the cells had died from an altogether different reason than before: They had run out of nutrients because they grew too fast. The new bioreactor was, in a sense, too effective.

The bioreactor’s rotating wall eliminated the problematic mechanical forces that had damaged previous cell cultures, creating a constant free fall effect within the media and suspending the cells in a way very similar to microgravity. As the team discovered means of supplying nutrients and oxygen and removing waste at high enough rates to support the cell cultures, they noticed new structures forming within the bioreactor. While standard human cell cultures grown in Petri dishes settle into flat layers thanks to gravity, the NASA bioreactor’s microgravity mimicry produced very different results.

“These were three-dimensional structures that very accurately represented the way human tissue is structured in the body,” says Wolf. The bioreactor performed even better in space, as was later demonstrated by Wolf himself as an astronaut onboard the STS-86 mission to the Mir Space Station.

alt“When I first put the space-grown tissue samples under the microscope, I was astounded. With many years of experience culturing tissues, I had never seen any so well organized and with such fine structure,” Wolf says. It was another breakthrough moment, he says, similar to when the team first discovered the ability to assemble 3D tissue on Earth using the simulated microgravity of the NASA bioreactor. Wolf, Schwarz, and Trinh won NASA “Inventor of the Year” honors for their innovation.