Shrinking makes material smaller and resolution higher

Minuscule 3D printed material due to new shrinkage technique

Utrecht scientists have shrunk 3D printed hydrogels for the first time, significantly increasing the resolution with which these materials can be printed. Hydrogels are being used as scaffolds to culture cells in or to replace damaged tissues. By shrinking the material, the researchers succeeded in making the hydrogels smaller by a factor of 10. This brings applications for ultra-thin tissues such as blood vessels and kidney tubes one step closer. The Utrecht scientists, together with colleagues from Harvard Medical School, are publishing their findings in 9 March Nature Communications.

Shrinking reduces the size of the hydrogel significantly within 24 hours.
Shrinking reduces the size of the hydrogel significantly within 24 hours.

"Hydrogels look like gelatine pudding", says shared last author Tina Vermonden, associate professor of biomaterials, tissue engineering and drug delivery. "It's a very soft material, which consists of more than 80 percent water. Long polymer chains based for instance on amino acids or sugars form the network in the hydrogels and hold the material together."

Hydrogels have wide applications, in the medical world, but also for example as contact lenses. They correspond well with tissues in the human body because they contain a lot of water and are made on the basis of endogenous substances. This makes them suitable for culturing cells and tissues in the lab, and for replacing tissues in the body. They have the potential to regenerate tissues such as blood vessels and kidney tubes.

However, making such small and thin structures is a big challenge when using hydrogels. "Hydrogel structures are made using a 3D printer that creates the structure in a layer by layer fashion. It is very difficult to print small diameter tubes", says shared first author Carl Schuurmans. "Smaller than 100 to 200 micrometers cannot be printed with conventional techniques."

First they print the hydrogel with a 3D-printer and then shrink it
The researchers developed a new technique in which they first print the hydrogel with a 3D-printer and then shrink it, to make it even smaller.

Shrink

As a result, the researchers came up with the idea of shrinking the 3D printed materials. By adding a liquid with positively charged polymers to the negatively charged polymer network, water disappears from the hydrogel. The result is that the material shrinks and the print resolution increases. Researchers in Utrecht developed the materials and optimized the shrinking process; scientists at Harvard used advanced techniques to print the hydrogels.

"In this publication we show that you can shrink 3D printed hydrogels. Our focus was how small you can make the materials”, says Vermonden. With the shrink technique, the researchers succeeded in making tubular hydrogels a factor of 10 smaller. They also show that liquids can still flow through those tiny tubes. "The fact that the hydrogels can become so small is amazing", says Vermonden. "It's a technical feat, in which cooperation was essential."

Publication

Complexation-induced resolution enhancement of 3D printed hydrogel constructs. Nature Communications, 9 March 2020. Jiaxing Gong, Carl C.L. Schuurmans*, Anne Metje van Genderen*, Xia Cao, Wanlu Li, Feng Cheng, Jacqueline Jialu He, Arturo López, Valentin Huerta, Jennifer Manríquez, Ruiquan Li, Hongbin Li, Clément Delavaux, Shikha Sebastian, Pamela E. Capendale*, Huiming Wang, Jingwei Xie, Mengfei Yu, Rosalinde Masereeuw*, Tina Vermonden*& Yu Shrike Zhang

*Authors affiliated with Utrecht University.

This research is co-funded by the Future Medicines Program (UIPS/NWO), the Dutch Kidney Foundation and a travel grant for Carl Schuurmans and Anne-Metje van Genderen by Materials-Driven Regeneration Gravity Program.

Micrographs of 3D printed hydrogel tubes before (left) and after (right) 24 hours of shrinkage
Micrographs of 3D printed hydrogel tubes before (left) and after (right) 24 hours of shrinkage