18 December 2013

Bioprinting: another achievement

The retina of the eye was printed on a printer

Kirill Stasevich, Compulenta

Although the technology of three-dimensional printing did not appear at all yesterday, interest in it does not weaken, and many news with the word "3D printer" is still perceived as a miracle. But what's surprising about that? The technology has not yet revealed its potential, and 3D-printer publications, although they pour like peas out of a bag, are very diverse: for example, recently it was possible to print a lithium microaccumulator and even a hybrid car, and last year a sculpture of an ancient mollusk was obtained using the same technology – biologists just needed to see its appearance in more detail...

At the same time, on the one hand, three-dimensional printing continues to develop and be modified (for example, the Microfactory system based on a 3D printer can not only create objects from several materials at once, but also process them), and on the other hand, the method has already "gone to the people": many have probably heard about "printing" firearms at home. The precedent was created in the United States last year and so frightened the authorities that in Philadelphia there was even a law prohibiting the manufacture of weapons in this way.

But now we are not interested in the entire limitless field of possibilities of three-dimensional printing, but only in that area of it that is related to biology and medicine. Biologists quickly saw in a 3D printer a device that in the future will be able to quickly and easily assemble whole organs from cells. The experiments were not long in coming: a couple of years ago, with the help of three-dimensional printing, it was possible to create an ear and a kidney model (the kidney was in the form of a shell, that is, without internal tissue and vascular system). The bioprinter operates not only with cells, but at the same time it creates connective tissue collagen support, thanks to which it is possible to form a stable three-dimensional cellular structure.

The prospects for bioprinting are very wide: scientists are already discussing not only the creation of human tissue samples for biomedical tests, but also the transplantation of such "printed" tissues, and even printing in situ, that is, directly in the body. The latter, of course, looks super-effective: any wound can be healed by placing yourself under a printing device or by sticking an arm or leg into it. However, do not think that bioprinting has no difficulties. After all, the ultimate goal is to create not just an absolutely accurate sculpture of a kidney or other organ, but a working organ. And then biologists had to resort to stem cells again.


One of the varieties of bioprinters (photo Patrik_D).

They have been trying to get something more than a film of differentiated cells from stem cells for a long time, but all attempts encounter difficulties with a three-dimensional structure: you need to somehow force stem cells to form into a three-dimensional organ, but how to do this in laboratory culture (although there is some progress here)?.. It is clear why stem cell and regenerative medicine specialists have seized on bioprinters: with their help, you can create a working organ, you just need to make sure that stem cells can undergo such a procedure.

This year, scientists managed to pass human embryonic stem cells through a bioprinter: 89% of the cells remained alive three days after the procedure, without losing their pluripotency, that is, the ability to transform into cells of any other type.

On the one hand, the use of stem cells simplifies the task: organs usually consist of several types of cells, and, instead of juggling several types, it is enough for us to "mold" an organ from the same type of stem cells, and then give them appropriate instructions – where, to whom and what to turn into. However, this simplification turns into a problem: the resulting "organ" needs to be brought to mind somehow, it is necessary to direct the development of cells and make sure that it goes as it should. And where is the guarantee that, once in an already formed 3D structure, stem cells will not become capricious and will not start to get out of control?

Therefore, many researchers continued to work on the creation of "printed" biostructures from adult, differentiated cells. And here is a major success: Barbara Lorber and her colleagues from Cambridge (UK) managed to create a fragment of the retina using a piezoelectric bioprinter – from fully mature cells.

It should be said right away that the researchers manipulated only two types of cells, whereas there are much more of them in the real retina. That is, during the experiment, not all of its ten layers were recreated at all, so our title (they say, we managed to print the retina) is in some sense an exaggeration. The scientists worked with rat retinal ganglion cells, which receive visual signals from other cells and transmit them to the brain, as well as with glial cells, whose role is to provide support and protection of ganglion neurons.


Mouse retina; orange colored bodies of ganglion neurons,
red – optic nerve fibers, green – glial cells.
(Photo by Visuals Unlimited / Corbis.)

The printing speed was 100 cells per second, and despite the shear forces acting on the cells, the latter remained quite viable. In the journal Biofabrication (Lorber et al., Adult rat retinal ganglion cells and glia can be printed by piezoelectric inkjet printing, in the public domain), the authors report that the cells that underwent printing felt the same as those that did not pass through the printer. Importantly, ganglion cells could even form appendages for connections with neighbors. However, the researchers immediately note that at the exit of the printer, the cells turned out to be less than expected – probably due to the fact that some remained in the printhead.


Ganglion cell in the solution coming out of the printer (photo of the authors of the work).

There is no need to explain the practical significance of the results. A printed retina could be a real salvation for people who have lost their eyesight due to retinal dystrophy and other diseases associated with it. However, it is too early to talk about such an application: first of all, it is necessary to check how functional the cells that have passed through the printer are, whether they are able to conduct a signal, whether other types of cells can be added to them in the same way – for example, photoreceptors. Considering how complex the retina is, we can only hope for a bioprinter: with the help of this device, you can lay out an arbitrarily complex cellular pattern, as long as the cells themselves remain alive at the same time.

It may, of course, give the impression that there is nothing to talk about yet, but we will once again recall the main thing: scientists for the first time managed to mix with the help of a bioprinter as many as two types of mature, differentiated cells, making it so that the cells remained alive after all this.

Prepared based on the materials of LiveScience: Eye Cells Inkjet-Printed for the First Time.

Portal "Eternal youth" http://vechnayamolodost.ru18.12.2013

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