As mission statements go, Vital3D’s is bold: to create all the necessary technology and know-how needed to print a functional kidney, ready for human transplant.
“There are a lot of people who don’t believe this is possible and that we should print something smaller and do something more tangible,” says Vidmantas Šakalys, CEO of the three-year-old Lithuanian startup.
“Lots of different groups are doing lots of research into bioengineering and living tissues to understand how cells are growing, and there’s still a lot of work to be done before this becomes a reality, but that’s our mission — to bring bioprinting of large-scale organs into being, starting with the kidney.”
3D bioprinting, the method Šakalys’s fledgling company is using to achieve this goal, involves a precise layer-by-layer build-up of biological materials, such as cells, growth factors, and biomaterials, to create three-dimensional structures that mimic natural tissues and organs.
Many things that don’t require living tissue have already been printed this way. Bones and dental implants, for instance, are used in surgery, while 3D printers provide custom-made prosthetics to replace limbs.
Brands like L’Oreal have also made considerable strides in the 3D printing of thin tissue structures such as skin, which the beauty giant has actively invested in since 2015.
Through the firm’s partnership with the University of Oregon, it has produced a skin model that, it claims, can quickly and precisely create structures like natural skin — potentially eradicating the use of animal testing in this area and leading to more effective treatments.
Larger tissues and the complex vascular systems that support organs such as kidneys, lungs, and hearts are harder to duplicate with 3D printing, however.
“Tissue printing with skin is slightly easier because it’s thin,” adds Šakalys.
“You can print 5mm of thickness of the skin; you can print one or two types of cells and provide nutrition and oxygen for both skin cells. That skin is even being used for cosmetic purposes.
“But when it comes to larger tissues, one of the biggest challenges is the ability to print a vascular system to feed the cells inside the large tissue,” he adds.
“It’s a challenge because capillaries are very small, and in large quantities, to be able to feed them, you need to create a complex vasculature network.”
Manufacturing a working vascular system is considered such an achievement that in 2016, NASA offered a $500,000 prize for the first research team to do this.
That challenge was met five years later in 2021, when two teams of scientists from the Wake Forest Institute of Regenerative Medicine (WFIRM) in Winston-Salem, North Carolina, won first and second place.
Wake Forest, which has been printing mini organs in its labs for years, is one of a small handful of research universities making huge strides in bio-printed organs.
Dr Anthony Atala at Boston Children’s Hospital (and Wake Forest University) used a modified 3D inkjet printer to produce a bladder for a young patient who would otherwise have spent years on dialysis machines.
While hollow non-tubular organs have also proved possible to print, larger solid structures that fully mimic organ function are the outstanding challenge.
Vital3D hopes to solve this problem by focusing on developing a 3D bioprinting system that is both fast and precise.
In 3D bioprinting, the process begins by generating the cells that researchers want to bio-print, which are then instructed to become organ-specific cell types.
The cells are then rendered into a printable living ink, or bio-ink, that involves mixing them with materials like gelatine or alginate to give them a toothpaste-like consistency. Some firms, such as Swedish start-up Cellink, have chosen to specialise in this part of the process, creating standardised bioinks from organic materials.
The bio-ink is loaded into syringes and squeezed out of a nozzle. It typically involves laying down different cell types, each loaded into a different nozzle.
Once finished, the tissue is sometimes connected to a pump that drives oxygen and nutrients through it. Given time, the tissue develops independently and increases in both maturity and function.
The two main methods of 3D bioprinting are via inkjet or laser printers. Inkjet bioprinting is said to offer advantages in terms of speed and versatility. At the same time, the laser method excels in the precision and control needed for the cell deposition involved in complex tissue architectures.
For context, a mini heart, produced for research purposes (not surgery), takes about four hours to print.
Vital3D claims to offer a 3D bioprinter that is fast and precise by dynamically changing the size of the laser while printing.
Šakalys explains: “Our outlook is, ‘OK, for most of the wall, you don’t need a pencil to colour it; you need a brush. It will be much faster anyway. Most of the wall will be single colours. It’s the same with tissues; there are a lot of single colours.’
“So, what we do is start with a wide brush, then we find the flower in the wall and switch back to using a pencil to paint the flower and finish the wall with the brush,
“It’s only the start of what we’re developing, but we believe this will be a precise and fast way to print the vascular systems needed for organ tissue feeding,” he adds.
According to Šakalys, rapid developments in AI may speed up the technology’s progress by using printing models, which suggest when the printer should switch from brush beam to pencil. “Eventually, AI will be able to help calculate the fastest printing strategy,” he adds.
The CEO, a computer engineer who does not have a medical background, says that he first came up with the idea of using lasers in 3D bioprinting while running an earlier venture that involved using lasers in precision manufacturing. He was inspired, he says, by a colleague who lost his life to bladder cancer.
“At the end of that journey, we discussed why and how lasers could be used in medical research. How can we help people fight disease? Maybe we could use a laser to create a kidney? A laser would be a good tool to do that… “
In terms of meeting market needs, 3D organ printing could solve the global organ shortage and stamp out black market practices such as organ trafficking.
Most people in need of a kidney wait three to five years for a kidney from the national transplant waiting list in the US (longer in some states), while in the UK, it takes 2 to 3 years on average to wait for a deceased donor kidney while a living donor takes 3-6months.
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Scientists believe that a 3D printing process that uses the patient’s own cells to grow organs would not only potentially curb that waiting list but dramatically reduce the chances of organ rejection and likely eliminate the need for harmful life-long immunosuppressive medication.
Yet most experts also agree that printing a functional 3D kidney for transplant is about ten or fifteen years away. Šakalys is hopeful that the first bio-printed kidney available for printing may be a decade away. But meanwhile, firms like Vital3D still must generate income.
According to Šakalys, while he could make a business out of selling the hardware, for now, the firm is pushing the printer-as-a-service model.
The lab is currently printing small-scale, simplistic but functional replicas of naturally occurring body parts called organoids for drug development testing.
Another key component of engineered tissues is the scaffold, which provides the structural support for cell attachment and subsequent tissue development. Vital hopes to offer a 3D bioprinting service for potential partners requiring bespoke organ scaffolds and release its own organoid scaffold product later this year.
Ultimately, Šakalys says he would like to get to the point where the firm provides a service from its lab and sends the bio-printed organoid structures, and later live cells, to different customers.
Further away lies the vision of the service printing tissues and organs directly to hospitals and delivering them for surgical operations.
Carrying out trials and supplying organoids and scaffolds to labs requires certification, Šakalys adds, which, although necessary, can “also slow things down”.
“We can also earn money from the research,” he adds, although he admits, “It’s not enough. We’re still using our investors’ money. We will still need to raise a further €5m this year.”
So far, the 3D bioprinting firm has received backing from private angel investors in Lithuania and is now looking for a strategic partner that can open doors and share knowledge “not just money”.
Meanwhile, he adds, waiting times for kidney transplants are so long that the start-up is receiving letters from desperate patients willing to receive a 3D-printed kidney right now.
Clearly, the firm can’t do this now, but are the ethics something the company is exploring? “We are still too early for that, but it is something to ponder in a year or so. We have to be careful,” he says.
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