AI turns printer into a partner in tissue engineering
Organ donors can save lives, for example those of patients with kidney failure. Unfortunately, there are too few donors, and the waiting lists are long. 3D bioprinting of (parts of) organs may offer a solution to this shortage in the future. But printing living tissues, bioprinting, is extremely complex and challenging.
The team of at UMC Utrecht and Utrecht 木瓜福利影视 is now taking an important step toward printing implantable tissues. Using computer vision, a branch of artificial intelligence (AI), they鈥檝e developed a 3D printer that doesn鈥檛 just print, it also sees and even co-designs. Their innovation was published today in . With this innovation, they tackle one of the biggest challenges in 3D bioprinting: improving both the survival and functionality of cells in printed living tissue. But how exactly does that work?
We usually associate 3D printing with building structures layer by layer. But there are other forms, such as . 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鈥檚 inside the printing material, so that the printed object is built as optimal 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?
What is 3D-bioprinting?
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鈥檛 survive a regular 3D printing process. That鈥檚 why Riccardo Levato鈥檚 team developed a special a mix of living cells and nourishing gels that protect the cells during the printing process.
Volumetric bioprinting
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 came up with 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. 鈥淭o build a structure, we project a series of light patterns into a spinning tube filled with light-sensitive gel and cells,鈥 Riccardo Levato explains. 鈥淲here the light beams converge, the material solidifies. This creates a full 3D object in one go, without having to touch the cells.鈥 To do this, it is crucial to know exactly where the cells are in the gel. GRACE now makes that possible.
Innovating with laser light
, a PhD student in Riccardo鈥檚 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 鈥淟ASER鈥 shows whether it鈥檚 safe to go in. 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?
Smart blood vessels around living cells
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 鈥榮ees鈥 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 鈥榚yes鈥 and 鈥榖rain鈥
From blueprint to customization
鈥淚n the past, printing always depended on the designer鈥檚 blueprint. Now, GRACE contributes to the design itself,鈥 Sammy explains. 鈥淭he printer 鈥榮ees鈥 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 鈥榚yes鈥 鈥 the laser-based imaging- and 鈥榖rain鈥 鈥 the new AI software. That level of customization leads to tissues that survive and function better.鈥
More than just blood vessels
GRACE can do more than create adaptive blood vessels networks. The technology can also align multiple printing steps automatically. Take a piece of printed bone tissue, for example, that later needs a layer of cartilage added. Normally, that is a complex process with a lot of manual work. GRACE scans the existing tissue and automatically designs and prints a second layer that fits perfectly on top. All at the high printing speed of volumetric bioprinting, creating cm3-sized objects within seconds.
Automatically correcting for obstacles
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.
Just the beginning
Bioprinting is highly promising, but significant work is still needed to translate this technology to the clinic. Riccardo underlines that further research is needed to determine how printed cells can mature to replicate the functionality of native tissues. Even considering the challenges ahead, Riccardo is not afraid to dream big. 鈥淭his first work on GRACE is just the beginning. We are now working on increasing the amount of cells that can be printed, so that other tissues like heart and liver can also be printed. Moreover, we would like to make this technique openly accessible to other labs, so other could apply it to their printing method.鈥