Easy-to-use 3D bio-printing technology creates realistic fabrics from natural materials

Engineers at the University of California at San Diego have developed a 3D bio printing technique that works with natural materials and is easy to use. It allows researchers from different levels of technical expertise to produce realistic organ tissue models.

To prove the concept, the UC team in San Diego used its method to create networks of blood vessels that could keep a breast cancer tumor alive outside the body. They also created a vascularized human gastrointestinal tract model. The work was published recently in Advanced health materials.

The researchers said that the goal was not to make artificial organs that can be implanted in the body, but to create models of human organs that are easy to grow, that can be studied outside the body. body or used for screening drugs.

"We want to help everyday scientists, who may not have the specialization required for other 3D printing techniques, to create 3D models of all the human tissues studied," he said. the first author, Michael Hu, a specialist in bioengineering. Ph.D. student at the School of Engineering at the University of San Diego Jacobs. "The models would be more advanced than standard 2-D or 3-D cell cultures and more relevant to humans when it comes to testing new drugs, which is currently being done on animal models. "

"You do not need anything complicated to adopt this in your lab," said Prashant Mali, professor of bioengineering at the Faculty of Engineering at the University of San Diego Jacobs, lead author of the # 39; study. "We hope that several labs will be able to work with and experiment with it, the more it will be adopted, the more impact it will have."

The method is simple. To create a network of live blood vessels, for example, the researchers first digitally designed a scaffold with the help of Autodesk. With the help of a commercial 3D printer, researchers print scaffolding from a water-soluble material called polyvinyl alcohol. They then spread a thick layer (made of natural materials) on the scaffold, leave them harden and solidify, and then flush out the material of the scaffolding inside to create hollow channels for the blood vessels. Then they cover the interior of the channels with endothelial cells, which are the cells that line the inside of the blood vessels. The final step is to pass a cell culture medium through the vessels to keep the cells alive and growing.

Vessels are made from natural materials found in the body, such as fibrinogen, a compound found in blood clots, and Matrigel, a commercially available form of mammalian extracellular matrix.

Finding the right material has been one of the biggest challenges, said Xin Yi (Linda) Lei, an undergraduate student in bioengineering, co-author of the study. "We wanted to use natural rather than synthetic materials to be able to create something as close as possible to what's in the body, they also had to be able to work with our method of doing things. 3D printing. "

"We can use these biologically derived materials on a daily basis to manufacture ex vivo tissues that are vascularized, "said Mali. And that's an important aspect if we want to make tissues that can be held for very long periods outside the body. "

Stay alive

In a series of experiments, researchers used printed blood vessels to keep breast cancer tumor tissues alive on the outside of the body. They extracted fragments of mouse tumors and then incorporated some into the networks of printed blood vessels. The other pieces were kept in a standard 3D cell culture. After three weeks, the tumor tissue encapsulated in the blood vessel impressions remained alive. Meanwhile, those in the standard 3D cell culture were mostly dead.

"Our hope is that we can use our system to create tumor models that can be used to test anti-cancer drugs outside the body," said Hu, who is particularly interested in studying cancer models. breast cancer tumors. "Breast cancer is one of the most common cancers. It is one of the largest research projects dedicated to it and one of the largest pharmaceutical groups developed to combat it. So any model we could make would be useful to more people. "

In another series of experiments, the researchers created a vascularized intestinal model. The structure was composed of two channels. One was a rectilinear tube lined with intestinal epithelial cells to mimic the intestine. The other was a blood vessel canal (lined with endothelial cells) that spiraled around the intestinal canal. The goal was to recreate an intestine surrounded by a network of blood vessels. Each channel was then powered with media optimized for its cells. In the space of two weeks, the chains began to adopt more realistic morphologies. For example, the intestinal canal had begun to sprout villi, which are tiny, finger-like projections lining the inside of the intestinal wall.

"With this type of strategy, we can begin to create complex and sustainable systems ex vivo setting. In the future, this could perhaps supplant the use of animals to manufacture these systems, and this is what is happening now, "said Mali.

"It was proof of concept that we could grow different types of cells together, which is important if we want to model multi-organ interactions in the body, and in one impression we can create two distinct local environments, each keeping a different environment, living cell type and placed close enough to interact, "Hu said.

In the future, the team is working to extend and perfect this technique. Future work will focus on optimizing printed blood vessels and developing models of vascularized tumors that more closely mimic those of the body.

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University of California – San Diego