The European Union is funding a five-year project to build living tissue from printed cell capsules as researchers and regulators work out which rules could govern materials that combine living cells with genetically modified microorganisms. The PRISM-LT project will run until 2027. Its work ranges from bone marrow research to cultivated meat, but real-world applications remain distant.
The institutional frame
The project is developing engineered living materials, or ELMs: composite materials made wholly or partly from living cells, including microorganisms such as bacteria or fungi. Unlike static materials, ELMs can grow, respond and adapt to their surroundings. They can also self-organize and self-repair. “Engineered living materials can have additional, dynamic features that we simply cannot replicate with traditional static materials,” said Massimo Vassalli, scientific coordinator and chair of bioengineering at the University of Glasgow.
Researchers make tissue from tiny capsules containing living cells and a gel-like support called bioink. “Instead of printing a continuous stream of bioink, we work with modular living components that are encapsulated,” said Laura Martinelli, PRISM-LT project coordinator and executive director of In Society, a research organization based in Udine, Italy. A robotic arm can position the capsules, or researchers can print them layer by layer.
Each capsule contains a scaffold and artificial microorganisms that help guide cell development. The team genetically modified the microorganisms to detect when stem cells begin to differentiate, then release growth factors that direct them toward a desired tissue type. Manufacturing takes from a few minutes to an hour. Maturation takes about three weeks.
A small print, a large ambition
The team can currently produce roughly one square centimeter of thin tissue and is working toward a one-cubic-centimeter block. The scientists are trying to bring together living components that aren't naturally suited to coexist. “We have to create a symbiotic relationship between two systems not designed to live together, like yeast and stem cells,” Vassalli said. He described finding suitable conditions for both the microorganisms and differentiating stem cells as the main challenge.
The researchers are developing two tissue types: the interface between bone and adipose tissue found in bone marrow, for biomedical research; and muscle-and-fat structures that reproduce the marbling linked to meat’s texture and flavor. The platform could also make miniature tissue models that mimic human organs, potentially for drug testing and personalized medicine. “The project aims to create a platform that allows the design of different tissues for very different purposes, but using the same principles,” Martinelli said.
For health care, the team aims to make three-dimensional bone marrow models to study drugs that treat diseases such as leukemia. For food, Martinelli said the distribution of adipose tissue matters for consumer acceptance. “Thanks to our bioprinting technology, we can achieve the right texture in alternative meats, which gives us the opportunity to commercialize them,” she said. The researchers chose yeast rather than bacteria for cultivated meat because, Martinelli said, “It would be hard to explain to consumers that meat was made using bacteria.”
Who gets to authorize living material?
ELMs combine living cells and, in some cases, genetically modified microorganisms. The article says they don't fit neatly into frameworks designed for conventional medicines or standard food products. Working with the European Innovation Council, the team is in contact with regulatory authorities, including the European Medicines Agency, to examine future rules and authorizations. The institutions are part of the project’s path toward any application: a laboratory result alone doesn't settle how such products may be used.
“We have to adopt a new attitude toward this technology,” Martinelli said. “This collaboration helps us pave the way for the use of ELMs.” The European Union funds the project, and the European Innovation Council provided part of its funding. Its article appeared in Horizon, the EU’s research and innovation magazine.
Vassalli said the researchers asked whether the technology was viable and scalable. “Now we can say it is viable,” he said. Scaling up remains the next challenge. Martinelli cautioned that “we are still far from real-world applications,” saying the team focuses on principles and mechanisms to see what is viable while considering future challenges.