As public expectations for regenerative medicine mount, scientists are turning to the vast potential of 3-D printing technologies in their quest to re-create skin, blood vessels, cartilage and other complex human tissue.
Technological hurdles still abound in efforts to copy life-size organs, including the liver and kidneys, but the regenerative medicine industry is expected to grow dramatically in the coming decades. And the Japanese government is eager to promote its expansion.
“Using Japan’s advanced technology to create 3-D tissues with cells, we aim to (put) innovative products for regenerative medicine . . . into practical use ahead of other countries. This will strengthen our international competitiveness,” the New Energy and Industrial Technology Development Organization (NEDO), a Kanagawa-based semi-public body, said in a statement in November.
NEDO, which promotes new energy and industrial technologies, was announcing that it will spend ¥2.5 billion to support projects in five different categories related to regenerating human tissue, using technologies like iPS cells and 3-D printers, over a five-year period.
The five categories include generating micro-caliber blood vessels through 3-D printers and growing cardiac muscles with stem cell sheets.
Takeshi Sakamoto, director of the biotechnology and medical technology department at NEDO, said the need for creating tissue like blood vessels, cartilage and cardiac muscles is huge, and leading this field will open up enormous business opportunities.
The government estimates that the domestic market for regenerative medicine will grow to ¥1 trillion in 2030 from just ¥9 billion in 2012.
Sakamoto said making human tissue via 3-D printing will contribute to creating new drugs and finding treatments for diseases now considered incurable, because the printed tissues would be effective for testing new drugs, as they are based on human cells.
“Criticism against animal tests is getting stronger, especially in Europe . . . also, finding that new drugs safely work with animals doesn’t mean that they will be safe and effective for humans,” he said.
Tsuyoshi Takato, a professor of tissue engineering at the University of Tokyo’s School of Medicine, is trying to produce skin, cartilage and bones. His project has been financially supported by NEDO.
Takato said that if cartilage can be created via a 3-D printer, for instance, many people would benefit greatly.
Treating children with congenital deformities such as microtia, for example, requires transplanting cartilage, but children often don’t have enough available as a transplant source, he said. This often means young patients have to wait until they are adults, when they have more cartilage built up, to undergo surgery.
If cartilage becomes available more easily through 3-D printing, “it can be implanted without hurting people’s bodies. This will be more useful for children,” Takato said. “It’s a big deal.”
Takato’s team has been working to create cartilage and other tissue by printing biomaterials called recombinant peptides (RCP), a synthetic protein developed by Fujifilm Co.
The researchers input 3-D data on human body parts into a computer and print the parts that look exactly like those of humans with RCP and various growth factors, including fibroblast growth factors. Human cells collected from patients and proliferated are then injected into the printed parts. Those made of RCP absorb the cells and eventually acquire the function of human tissue.
“The two keys for this project are a bio 3-D printer and RCP,” said Takato.
He has been trying to create tissue using atelocollagen, which is made of collagen extracted from cows and pigs. But animal-derived collagen carries the risk of animal infections, Takato said, and RCP can eliminate such hazards.
He said his team aims to eventually regenerate human tissue by directly printing biomaterial made from a mixture of human cells, RCP and growth factors.
But when cells are stacked by the printers, it is hard to keep the ones in the middle alive, since oxygen and nutrients don’t really reach them.
Still, 3-D printers can create complex human tissue quickly, so Takato plans to challenge that approach, he said.
His team aims to bring this technology to a practical stage in the next five years.
Although regenerative medicine has huge potential and people have high hopes that human organs will be re-created with 3-D printers, Takato said there’s a long way to go before the dream becomes reality.
“Organs like the liver have a very complex system, so it may not be realistic to make them (via 3-D printers),” Takato said.
Cyfuse Biomedical K.K., a Tokyo-based startup, is also trying to create human tissue, focusing at present on blood vessels.
“Various human tissue and organs will be regenerated and such technologies will be put to practical use in the future, but all organs need blood vessels. So we think technologies to create blood vessels will be vital,” said Koji Kuchiishi, CEO of Cyfuse.
Cyfuse’s 3-D printer, called Regenova, features a super-thin nozzle that picks up lumps of cells collected from a patient or donor and molded into a cluster of spheroids. One spheroid, which measures about 0.5 mm in diameter, consists of tens of thousands of cells.
The spheroids are then stacked on a needle array and turned into the shape of a human tissue using pre-programmed 3-D data on the patient. The cultured cells merge and acquire the functions and firmness of human tissue within a few weeks.
Kuchiishi said Koichi Nakayama, a research adviser to Cyfuse who came up with the method of stacking spheroids on needle arrays, used to place the minuscule spheroids manually. The 3-D printer can dramatically speed up the process, he said.
Kuchiishi said that when cells are made into a form of spheroid, they will not need much oxygen and nutrients, meaning they won’t easily die even if they are stacked.
Cyfuse aims to start clinical research on 3-D printed blood vessels in five years, Kuchiishi said.
He also said Cyfuse aims to make a small replica of a liver. “The ultimate goal may be (creating a life-size organ), but our target is to make functional mini-livers at this point.”
Organs don’t have to be exactly the same size to be useful in clinical applications, he added.
Plus, if small organs that function like a human liver are created, they can be used for testing new drugs to see how a liver reacts to them, Kuchiishi said.
Cyfuse sells the Regenova 3-D printer to other research institutions. Kuchiishi said the company has seen an increasing number of inquiries from around the world.
This section, usually appearing on the second Monday of each month, features technologies that are still under research and development but expected to hit the market in coming years.
IN FIVE EASY PIECES WITH TAKE 5