24 August 2020

Gastroscope with bioprinter

Bioprinter-endoscope printed with live cells on the wall of the stomach model

Grigory Kopiev, N+1

Chinese scientists have created a prototype of a bioprinter that can treat stomach wall defects by printing "patches" on it from the inside with hydrogels containing cells of the corresponding tissues. It is delivered into the stomach through the esophagus like an endoscope, and then opens the folded parts and begins to apply layers of hydrogels. The authors of the development showed the work of a bioprinter on a stomach model by printing layers of epithelial cells and smooth muscles on its inner surface. The article was published in the journal Biofabrication.

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Polymer model of the human stomach and bioprinter. Here and further pictures from the article in Biofabrication.

Bioprinters are devices that can create three–dimensional structures from materials containing living cells of humans or other animals, so that they later turn into full-fledged fragments of tissue. So far, however, this technology is far from printing full–fledged organs – its ultimate goal. One of the problems that prevents the creation of artificial organs or their fragments is that invasive surgery is necessary to treat defects in internal organs.

Recently, a group of scientists from Belgium, China and the USA found an original solution to this problem. They have developed a method that allows you to inject a liquid billet under the skin, and then cure it using infrared radiation. The method has previously shown good results, but it can only be used on tissues located shallow under the skin.

Wenxiang Zhao (Wenxiang Zhao) and Tao Xu (Tao Xu) from Tsinghua University has created a 3D bioprinter that can be used even in the gastrointestinal tract without surgical tissue incisions. According to the principle of operation, it is similar to an endoscope, but with a much wider tube with a diameter of three centimeters. This is larger than the endoscopes used today, but the diameter is limited only at the end where the printer itself is located, and in the other parts, where only a few cables and a tube are located, it can be made much smaller.

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Printing scheme.

The printer at the end of the tube has a delta robot design: it consists of three parts connected at the end, between which there is a tube for supplying hydrogel. The principle of operation of the delta robot is that each of the three sections is controlled by one simple motor at the base, but together they can move the end in any direction. The printer has a nozzle for printing at the end of the delta mechanism. During printing, the sections of the mechanism partially extend beyond the diameter of the tube, but during the insertion of the device into the esophagus, they can fold.

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Bioprinter during operation.

The hydrogel for printing consists of an aqueous solution of gelatin and sodium alginate, as well as cells of the desired type added to it. The authors created two types of "ink" for printing: with gastric epithelial cells or with gastric smooth muscle cells in a concentration of 1.5×10-6 cells per milliliter.

The researchers tested the printer on a model of a human stomach made of a polymer created on the basis of CT scans of the stomach. The printer printed a lattice structure of two layers, repeating the location of tissues in the stomach. The lower layer was printed with a gel with muscle cells, and the upper layer with epithelial cells. After that, the printer fed calcium chloride through the nozzle, acting as a binding agent.

After printing, the researchers tested the survival of the cells immediately after application, as well as after three, seven and ten days. They used two substances for this, one of which absorbs living cells and forms a substance with green fluorescence, and the second penetrates through the membranes of dead cells, binds to their DNA and fluoresces red.

The analysis of printed tissues showed that in the first days the survival rate was about 94 percent, and only after ten days it decreased slightly, while still remaining at a level above 90 percent. In addition, the cells actively divided, proliferated and changed their morphology. Thus, when tested on a stomach model, the method proved successful. In the future, scientists will try to repeat the results in real conditions.

Printing with living cells is carried out not only on Earth, but also in space. Recently, Russian scientists summed up the results of an experiment on printing fabric constructs on the ISS, which was conducted at the end of 2018. The results showed that in zero gravity conditions it is possible to create constructs with connected cells and a high survival rate.

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