Canadian startups are perfecting techniques to bioprint human tissues

Manufactured tissues could be used in scientific research and to treat diseases like type 1 diabetes.

Karolina Valente was six years old and living in Rio de Janeiro when her mother was first diagnosed with breast cancer. Two decades later, when the disease returned, Valente was focused on cancer research as a PhD candidate at the University of Victoria. Her work, already informed by her mother’s illness, may have had a new urgency, but she still encountered an old problem. “It was very difficult to get access to actual tissue samples,” Valente says.

Human tissue samples derived from patients are considered a gold standard for scientific researchers lab testing potential new therapies. Compared to studies in animals like mice or rats, samples can better replicate conditions in the human body, potentially leading to more accurate results. But they have a major drawback: human samples are expensive and often beyond the tight budgets of regular academic scientists.

“I realized I had to find an alternative,” says Valente. “So, I became interested in engineering them.”

Accelerating drug development

Valente’s interest led her to found VoxCell BioInnovation in 2020. The Victoria, B.C.–based startup uses 3D bioprinting technology to create human-like tissues for use in drug development and cancer research.

Like the more familiar version of 3D printing, bioprinting uses a computer-generated model to build up an object layer by layer. But, instead of plastic filament, the building material is bio-ink, a mixture of human cells and nutrients infused in a natural polymer, such as collagen or gelatin. The gel-like bio-ink acts as a temporary scaffold, allowing the cells time to adhere and grow into tissue, before it degrades.

Over the past eight years, scientists have used the technology to successfully print tissue for skin, bone and kidneys. However, to engineer larger, more complex tissues — and potentially entire organs in the future — an intricately connected vascular network is needed.

VoxCell has taken up the challenge, developing Canada’s first hi-resolution bioprinter, which is precise enough to print one micron in diameter. Crucially, that’s the same size as a capillary, the smallest blood vessel, allowing it to develop tissue models with more life-like vasculature.

VoxCell — the name is a play on the word voxel, the focal point of a laser, which the company uses in its printing process — has now designed cutting-edge 3D modelling software and 12 bio-inks that can copy the compositions of healthy and cancerous breast, ovary, lung, prostate, brain and liver tissues.

“Our vascularized tissue models are bringing us one step closer to mimicking what happens when oncology drugs are injected into the human body,” Valente says.

Valente’s mother is fully recovered, but that won’t be the case for many others. According to estimates from the Canadian Cancer Society, 28,600 women were diagnosed with breast cancer in 2022. Of that number, 5,500 were expected to die. Valente hopes VoxCell’s models will help researchers more quickly identify which drugs have the most potential to be successful, accelerating the entire development process.

Currently, that process is both lengthy and expensive, requiring, on average, 15 years and U.S.$2 billion. All that time and money are no guarantee of success, Valente says. “Ninety-five percent of drugs in the pipeline fail. Our goal is to help pharmaceutical companies achieve results in the lab that translate more easily to the real world.”

Treating diabetes

Tamer Mohamed, CEO and co-founder of Aspect Biosystems, another company working with bioprinting, says this technology reflects how quickly medicine is advancing. “Our understanding of biology seems to change minute by minute,” he says.

Aspect sprang from a University of British Columbia research lab in 2017, where Mohamed and the company’s three other co-founders were exploring advanced bioprinting techniques. The 80-person company has now developed a platform for creating tissues that can be implanted into the body to replace functions of damaged organs.

Mohamed and the team are currently working on therapeutics for Type 1 diabetes. They have bioprinted pancreatic tissues that contain insulin-releasing islet cells and tested them in several animal models, with encouraging results.

When the company proceeds to human trials, the challenge will be to keep those cells safe as patients’ immune systems could identify them as foreign and reject them. With that in mind, Mohamed says Aspect’s tissue has been designed to protect the islet cells — he likens it to the coating on a stealth fighter that makes it invisible to radar. “Our goal is for these implanted islet cells to function in the body without being detected and destroyed,” he says.

The company has also developed bioprinted liver tissue and is conducting animal studies on its potential to treat liver diseases.

Studying the brain

Axolotl Biosciences, another startup spun out of lab work at University of Victoria in 2020, is pushing bioprinting further up the body, using it to create neural tissue models for research into Alzheimer’s and Parkinson’s.

Named for the Mexican salamander that can regenerate its limbs, gills and nervous system, Axolotl’s bio-ink is based on fibrin (the protein that helps blood clot) and can be mixed with cells to replicate neural tissue.

Co-founder Stephanie Willerth says one of the difficulties of tissue engineering is that human cells don’t always endure the printing process. Axolotl collaborates with several bioprinting companies that use the latest printing technologies. “Cells are very delicate. But these bioprinters are very high-end. They’re very gentle on them.”

So far, Willerth and her team have printed neural tissue one centimetre in diameter and half-a-centimetre high. They are now studying this mini-brain, made from cells from Alzheimer’s patients, for signs of the disease. Early results are promising, showing increased levels of amyloid beta and tau, the two proteins associated with neurodegenerative illness.

Not only is Axolotl getting a foot in the door of the U.S.$4 billion Alzheimer’s therapeutic market, the industry itself is taking ethical steps to reduce the need for animal testing. “Our human-like tissue is potentially a more accurate model than an animal, and at one-tenth of the cost,” says Willerth.

Government green light

Researchers have seen the benefits of bioprinting for the past decade and the regulatory bodies are now beginning to share that vision. Last December, the U.S. Food and Drug Administration modernized its criteria, approving bioprinted tissue as a test platform.

“This is very exciting news,” says Valente. “The drug development process has had a very high failure rate. What we have now is the potential to change how we treat disease.”

 
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Photo courtesy of Karolina Valente, CEO of VoxCell BioInnovation