Thirty years ago, when the field of tissue engineering beginning to coalesce, experts predicted we were just a couple of decades away from creating brand-new organs for patients. After all, replacement parts made of plastic or metal had become a reality—just ask the millions of people living with knee or hip replacements.
So why aren’t we, in 2020, growing replacement lungs, livers and kidneys to fill the gap that donor organs can’t address?
“People asked that question back when tissue engineering was being defined in the ‘90s,” said Jordan Miller, Ph.D., an assistant professor of bioengineering at Rice University. “They said: ‘We’ve got a scaffold, we’ve got cells and we’ve got growth factors—so, give me a liver, then.’”
Growing new organs turned out to be a little further off than anyone thought, chiefly because “we’ve learned a lot that we didn’t know we didn’t know,” said Miller. But, thanks to advances in technology, he believes the field is in “striking distance” this decade.
Thousands of labs are working to make better cells that could eventually work the way natural organs do. But figuring out the best medium to grow cells in or the best recipe of nutrients to feed them are just pieces of the puzzle. Those cells need to be organized in the right way for them to work properly.
“You can grow billions of cells in a lab. You can grow hundreds of billions of cells, all flat at the bottom of a petri dish,” Miller said. “But put them in 3D, in a scaffold with factors, they will die if they’re any bigger than about half a millimeter.”
What’s missing, Miller says, is architecture: “If you don’t have it, you can’t get nutrients to cells and cells will die.”
And that’s where Volumetric, the startup Miller co-founded with Bagrat Grigoryan, Ph.D., comes in. While others work to solve the cell-sourcing question, as Miller puts it, Volumetric is focused on the architecture those cells will be put into to become tissues, and then organs. It started out with $150,000 in seed funding from Y Combinator and stands to reel in more after pitching its work to investors at the accelerator's Demo Day this week.
He likens building an organ to building a city. The same way cities need roadways to deliver food and remove waste, organs need blood vessels. And, depending on what they do, different organs have additional roadways: The lungs move air through their airways and the kidneys move urine through the urinary tree. Volumetric is using 3D bioprinting to create road maps for these organs.
Instead of 3D-printing hard plastics or metals, Volumetric is using water-based materials to make parts that are biocompatible with the body, mimicking the water content and stiffness of human organs.
“What we have been able to do is make the first vascular unit cell for lung tissue in a material that is mostly water,” Miller said. He means the smallest building block that, by itself, has organ-level function. In the lung, that’s the air sac. In a paper published in Science last May, Volumetric described a hydrogel with the roadways for an air sac and surrounding blood vessel network. It has worked with a small model of the liver lobule and is looking into pancreatic islets and kidney glomeruli.
There’s still some work between these unit cells and a functioning organ. For starters, Volumetric needs to scale up its single air sac to 600 million air sacs to reproduce the function of a lung. And, down the road, it will need to find the cells to put into its architecture to make these new organs.
“The beauty of doing architecture is we can give those architectures out to labs all around the world to do studies with. That way, the scientific community together can find the solution,” Miller said. “It’s not only less money we need to raise, but it’s better because we can try more things.”
And those labs aren’t the only avenue for collaboration: Volumetric’s technology could help companies improve the drug development process. Instead of testing their prospects in animal models that may not translate to humans, they could test them in engineered tissues and organs.
“We’re talking with pharma companies right now to identify their needs for 3D human-like architecture and their drug development pipeline. That is a very important problem because a lot of drugs fail at the phase 3 clinical trial. If you can’t get efficacy at that level, you can’t go to market,” Miller said.
Research applications aside, he figures the first therapeutic use of Volumetric’s technology may be in bridging treatments, which keep patients with failing organs alive long enough to receive a donor organ.
“An analogy we like is the left ventricular assist device (LVAD) for someone who needs a heart transplant but is not able to get one because supply is low. Sometimes, it may be appropriate to give them an LVAD,” Miller said. “It’s not a heart replacement, but it’s a heart assist device that buys them more time.”
Ultimately, though, Volumetric exists so that organ donation will become a thing of the past. A potential benefit of its technology would be to grow organs for patients using their own cells, resulting in a perfect match and eliminating the need for lifelong immunosuppressive therapy. And creating bespoke organs would solve multiple problems stemming from the shortage of donor organs.
“There are very difficult ethical issues that have to be wrestled with, with a limited supply,” Miller said.
“You have to be quite sick to be on the organ donation waitlist,” he said. But there is a whole class of conditions that would preclude someone from being on that list—people with cancer, for example, or those with alcohol-related liver damage who don’t meet certain criteria for a transplant.
The duo sees their work as the logical next step in the evolution of therapies for human disease. Treatments have evolved from small molecules to biologics, antibodies and cell therapies.
“At Volumetric, we are working on the next stages after that: tissue-level, then organ-level therapies … The potential is to make replacement organs for a patient from their own stem cells and in a way that the organ would be so compatible with their body that it would eventually become a part of their body and not have to be replaced,” Miller said.