AI turns bioprinter into a partner for tissue engineering
With GRACE (Generative, Adaptive, Context-Aware) bioprinting, the printer assists users in creating the correct the design
The team led by Riccardo Levato at UMC Utrecht and Utrecht University is taking an important step toward bioprinting implantable tissues. Using computer vision, a branch of artificial intelligence, they’ve developed a 3D printer that doesn’t just print, it also sees and co-designs printable parts. Their study, published in Nature, tackles one of the biggest challenges in 3D bioprinting: improving both the survival and functionality of cells in printed living tissue. But how exactly does GRACE (Generative, Adaptive, Context-Aware 3D printing) work?
We usually associate 3D printing with building structures layer by layer. But there are other forms, such as volumetric bioprinting. This technique creates a complete structure in a single step, using a light-sensitive gel that solidifies when exposed to cell-friendly laser light. The advantage? It is incredibly fast, taking just seconds, and much gentler on living cells. To produce a high-quality print, it is crucial to understand what’s inside the printing material, so that the printed object is built as optimally as possible. The new technology, called GRACE, makes that possible. It opens up new possibilities for bioprinting functional tissues, and brings us closer to repairing tissues, testing new drugs, and even replacing entire organs.
Why do we need GRACE?
In 3D bioprinting, researchers use living cells to create functional tissues and organs. Instead of printing with plastic, they print with living cells. This comes with great challenges. Cells are fragile and wouldn’t survive a regular 3D printing process. That’s why Riccardo Levato’s team developed a special bio-ink, a mix of living cells and nourishing gels that protect the cells during the printing process.
With the advancements in bio-inks, layer-by-layer 3D bioprinting became possible. But this method is still time-consuming and puts a lot of stress on the cells. Researchers from Utrecht developed a solution: volumetric bioprinting.
Volumetric bioprinting is faster and gentler on cells. Using cell-friendly laser light, a 3D structure is created all at once. “To build a structure, we project a series of light patterns into a spinning tube filled with light-sensitive gel and cells,” Riccardo Levato explains. “Where the light beams converge, the material solidifies. This creates a full 3D object in one go, without having to touch the cells.” To do this, it is crucial to know exactly where the cells are in the gel. GRACE now makes that possible.
Innovating cells with laser light
Sammy Florczak, a PhD student in Riccardo’s lab, worked on the development of GRACE, short for Generative, Adaptive, Context-Aware 3D printing. He built a new device in a specialized lab, using advanced laser technologies. Before entering, a red light signaling “LASER” indicates whether it’s safe to proceed. Laser light plays a crucial role, not just in the printing step, but also in the added imaging step that sets this new technology apart. GRACE combines volumetric bioprinting with this advanced laser-based light-sheet imaging. But what can we do with that?
One of the biggest challenges in 3D bioprinting is creating functional blood vessels. Blood vessels are essential to provide oxygen and nutrients to the cells, and thus printing these blood vessels at the correct place is key to creating viable tissues. Yet, in conventional printing methods, a 3D design is made before knowing where the cells are located in the light-sensitive gel and thus where the blood vessels must be printed. With GRACE, the printer ‘sees’ where the cells are located and, within seconds, designs a network of blood vessels around those cells as effectively as possible. This new printer essentially has its own ‘eyes’ and ‘brain’.
From blueprint to customization
“In the past, printing always depended on the designer’s blueprint. Now, GRACE contributes to the design itself,” Sammy explained. “The printer ‘sees’ what kind of cells are in the material, and where they are. Then, using AI tools, it creates a matching design for the object to be printed. This new printer essentially has its own ‘eyes’ – the laser-based imaging- and ‘brain’ – the new AI software. That level of customization leads to tissues that survive and function better.”
GRACE can do more than create adaptive blood vessel networks. The technology can also automatically align multiple printing steps. Take a piece of printed bone tissue, for example, that later needs a layer of cartilage added. Typically, this is a complex process that requires considerable manual labor. GRACE scans the existing tissue and automatically designs and prints a second layer that fits perfectly on top. At the high printing speed of volumetric bioprinting, objects of cm3 size can be created within seconds.
Automatic correction is just the start
Another challenge in bioprinting is that light can sometimes be blocked, for example, by previously printed parts of the structure. This can create shadows and flaws in the final product. GRACE can solve this, too. By scanning the surface of any obstacles, the system automatically adjusts the light projection. This makes the print more precise and consistent. Moreover, this allows pre-made objects to be inserted into the printing vial. Think, for example, of a stent in which you could print blood vessel cells or objects that can release medicines.
Bioprinting is highly promising, but significant work is still needed to translate this technology to the clinic. Riccardo emphasized that further research is necessary to understand how printed cells can mature to replicate the functionality of native tissues. Even considering the challenges ahead, Riccardo Levato dreams big. “This first work on GRACE is just the beginning. We are currently working on increasing the number of cells that can be printed, so that other tissues, such as the heart and liver, can also be printed. Moreover, we would like to make this technique openly accessible to other labs so that others could apply it to their printing method.”
