27 May 2019

Organ bioprinting: new successes

American researchers working under the guidance of Associate Professor Jordan Miller from Rice University managed to solve a complex problem that hindered progress in the field of bioprinting organs for replacement transplantation. The technology developed by them makes it possible to create exceptionally complex intertwining vascular networks that reproduce natural systems that ensure the movement of air, as well as blood, lymph and other biological fluids through the body.

According to Miller, a complex vascular system is needed to supply nutrients to densely populated tissue cells. Moreover, some organs have two independent vascular systems, such as systems of airways and blood vessels in the lungs or bile ducts and blood vessels in the liver. The correct structure of these systems is the key to their effective functioning.

Of greatest interest is the liver, which performs about 500 functions. Due to the complexity of this organ, to date, specialists have not been able to develop a replacement therapy method that could replace it in case of illness. Perhaps, over time, this niche will be filled by organs obtained with the help of bioprinting.

To solve this problem, the authors have developed a new open technology of bioprinting, called SLATE (stereolithography apparatus for tissue engineering, stereolithographic apparatus for tissue engineering). This system uses additive technology for layer-by-layer printing of hydrogel matrix.

The layers are printed from a liquid solution that hardens under the influence of blue color. A digital projector located at the bottom forms light patterns with a pixel size from 10 to 50 micrometers and sequentially projects them onto two-dimensional layers of hydrogel. After the next layer solidifies, the mechanism lifts the growing hydrogel structure just enough so that the new light image from the projector gets to the next layer. The key point proposed by the authors was the addition of blue light absorbing food dyes to the hydrogel. These photo-absorbing compounds allow you to limit the curing zones to very thin layers. All this allows the system to produce soft biocompatible hydrogel structures with an exceptionally complex internal architecture in just a few minutes.

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Experiments with the hydrogel organoid of the lung obtained using the new method have demonstrated that the structure is strong enough and does not collapse under the influence of blood flow, as well as "breathing" – rhythmic intake and exit of air simulating the pressure and frequency of human respiration. In addition, it was shown that red blood cells successfully absorb oxygen when passing through the "vessels" of such a "lung" surrounding the "alveolus". In other words, the hydrogel organoid provides gas exchange, usually occurring in the alveoli of the lungs.

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As part of experiments with therapeutic implants for the treatment of liver diseases, researchers created three-dimensional hydrogel structures and populated them with liver cells. The resulting implants, having independent compartments for blood vessels and liver cells, were implanted in mice with simulated chronic liver damage. Studies conducted after 14 days demonstrated the safety of implanted liver cells.

The authors claim that the bioprinting system they created also makes it possible to reproduce intravascular elements, such as double-leaf valves that provide fluid flow in one direction. In humans, such valves are present in the heart, leg veins and lymphatic ducts.

Currently, the authors are engaged in further complication and improvement of bioprinting technologies, which will make it possible to produce even more complex structures. According to Miller, today they are at the earliest stage of the way of recreating the internal architecture of human organs and further work in this direction will require a lot of effort.

Article by Bagrat Grigoryan et al. Multivascular networks and functional intravascular topologies within biocompatible hydrogels are published in the journal Science.

Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Rice University: Organ bioprinting gets a breath of fresh air.

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