Three-dimensional printing by weight

Artificial organs have learned to "hang" during 3D printing

Oleg Lischuk, N+1

British scientists have developed a universal 3D printing method of complex biological structures with different types of cells (organoids), which allows you to clearly observe their morphology, mechanical and chemical properties. This is achieved by "hanging" the sample during printing in a medium of micrometer gel particles. The results of the work are published in the journal Advanced Materials (Moxon et al., Suspended Manufacture of Biological Structures).

Organoids, or artificial organs from human cells, serve as models for a variety of studies. In many cases, their use leads to more reliable results than animal experiments. As a rule, when creating organoids, hydrogels are used as an extracellular matrix that supports cells and gives shape to the entire structure (in a living organism it consists of connective tissue), which are given the desired structure in various ways.

One of these methods is 3D printing, which allows to form complex structures from cells and hydrogel with high accuracy. The use of this method is limited by the fact that the hydrogel must be sufficiently liquid during printing, which is why the base of the organoid must have a much larger area than the tip so that it does not spread. Such a configuration does not always meet the needs of researchers.

To circumvent this restriction, employees of the Universities of Huddersfield and Birmingham, as well as the Royal Orthopedic Hospital, proposed using micrometer-diameter gel particles as a supporting medium. Such a medium prevents the gel with cells from sinking to the bottom during the printing process and preserves the three-dimensional configuration of the organoid during solidification. At the same time, by changing the viscosity of the medium, you can adjust the print resolution. Gels with cells are injected with an injection needle. Hydrogels with different cell types can be used to fabricate organoids. After solidification of the structure, the supporting medium is removed if necessary.

Experiments have shown that various materials, such as gelatin, gellan gum, collagen, hyaluronic acid, agarose and alginate in any combination, can be used to make supporting microparticles and hydrogel for printing. As a demonstration of the technology's capabilities, scientists printed a helical structure made of gellan gum with colloidal hydroxyapatite in an agarose medium (the latter is needed for analyzing the structure of the structure using computed tomography, since it is opaque to X-rays).

The principle of operation of the technology, a cylindrical sample in a supporting medium extracted from it, and its tomogram (here and below are drawings from an article in Advanced Materials).

After that, the researchers moved on to experiments with living cells. Their goal was to confirm that with the help of the developed technology, it is possible to create a complex tissue structure from different types of cells and with a heterogeneous structure. To do this, they used the femoral condyle with cartilage removed from the patient during knee replacement. With the help of a drill, a cylindrical defect was made in the cartilage and the underlying bone, live cells were extracted from the removed tissue. Then, a 3D model of the defect was built on the basis of a computed tomogram of the sample. It was used for layer-by-layer printing in an agarose supporting medium of a "patch" of gellan gum, hydroxyapatite crystals and cells (osteoblasts and chondrocytes), exactly repeating the anisotropic structure of bone and cartilage.

After four weeks of cultivation in a nutrient medium, the printed tissue retained its structure and cellular composition, and also had satisfactory mechanical properties. In the cartilaginous part of the sample, the synthesis of type II collagen and aggrecan, markers of cartilage formation, was observed. In the direction of the bone part, the ratio of type II and type I collagens gradually changed, as in natural bone-cartilage structures.

The process of creating a bone-cartilage "patch"

"The results obtained indicate that the technique we have developed for creating three–dimensional tissue-like structures is promising for use in regenerative medicine and research of complex tissue structures," the researchers write.

To obtain the necessary three-dimensional structure of artificial organs, scientists have to resort to various tricks. For example, American developers have proposed using a cotton candy machine for this purpose, and researchers from Taiwan have created a universal platform that turns the process of creating complex three-dimensional hydrogel structures into an analogue of tetris.

Recently, an international research team reported on the successful cultivation of full-fledged intestinal tissue from stem cells, which has become one of the most complex artificial tissues to date.

Portal "Eternal youth" http://vechnayamolodost.ru  03.02.2017