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- Printing with intelligence: bioprinter created to combat non-healing wounds
Printing with intelligence: bioprinter created to combat non-healing wounds
Russian scientists from Sechenov University have developed a bioprinter to print the equivalent of skin, which could be used to treat poorly healing wounds, such as trophic ulcers in diabetes. The device uses bioinks made from hydrogel and the patient's own cells. The technology may be promising for eliminating wound defects and burns, but further testing is needed, according to experts interviewed by Izvestia. In the near future, the development is planned to be tested on mini-pigs.
Why print skin on a printer
In the Clinic of Skin and Venereal Diseases named after V.A. Rakhmanov. V.A. Rakhmanov Clinic of Skin and Venereal Diseases, Institute of Regenerative Medicine and Design Center of Flexible Bioelectronics of Sechenov University have developed a portable bioprinter "Biogan" for bioprinting tissue equivalent of skin, which will be effective for the treatment of non-healing or poorly healing ulcers, including diabetic nature. To test the system, the scientists plan to conduct an experiment on minipigs at the Laboratory of Regenerative Veterinary Medicine at Sechenov University.
- The goal of the project is to create an approach to the restoration of complexly organized tissue complexes. This is a complex task, for the solution of which our team has developed combined bioinks, portable bioprinter "Biogan" and photobiomodulator for exposure of tissues to low-intensity radiation in the red and near-infrared range to accelerate the regeneration process, - said "Izvestia" head of the laboratory of applied microfluidics of Sechenov University, project leader Anastasia Shpichka.
To create combined bioinks use hydrogel with spheroids - aggregates of cells, which are used as building blocks, as well as extracellular vesicles, which have a pronounced pro-regenerative and anti-inflammatory potential. As part of such ink, cells exchange various signaling molecules and develop as in natural tissue.
Due to the special properties of the hydrogel and extracellular vesicles, the spheroids effectively fill the wound surface.
This should also help people with gangrenous pyoderma, said a project participant, an assistant at the V.A. Rakhmanov Department of Skin and Venereal Diseases. Ekaterina Grekova of the Rakhmanov Department of Skin and Venereal Diseases.
- Sechenov University has already developed its own method of treating this disease, which is based on immunosuppression and uses corticosteroid drugs, but this will be a new step in helping such patients," she said.
How bioinks work
Dmitry Larionov, an associate researcher at the Design Center for Flexible Bioelectronics, explained that the device created will be a hardware complex that is used to transport, apply and irradiate the bioinks.
The bioinks themselves consist of two main components that are stored in separate cartridges. The first contains a hydrogel created from gelatin. Added to the hydrogel are the patient's own cells, as well as extracellular vesicles that promote healing. Such "dyes" are made immediately before surgery. In the second - cross-linking agents that accelerate the process of solidification of the hydrogel.
- The principle of action of biochernyl resembles the work of a two-component adhesive. When mixing the components of biochernyl, a chemical reaction takes place, as a result of which the molecules of the components combine to form a strong gel-like structure, - said Dmitry Larionov.
However, certain environmental conditions are still required for cell delivery - so that they do not degrade during transportation, it is necessary to maintain a constant temperature.
- Now we are developing a system of climate control, which will allow, on the one hand, to maintain the right temperature biohernils during transportation, and on the other - to cool them immediately before applying to the affected area of the skin to achieve optimal physical and mechanical properties of hydrogel, so that it was not too liquid or, conversely, thick - explained the scientist.
Also, for optimal operation of biohernyl, aimed at tissue regeneration, it is necessary to ensure an even distribution of the constituents of the two components in the final volume of the mixture, so that there were no areas where the cells are outside the nutrient medium.
The scientists developed a prototype of a handheld bioprinter. To feed the components, they created a high-precision independent bioink feeding system that resembles medical injectors. And to mix the components, they made mixers that allow the components to be evenly mixed before application to the wound. Once applied, the hydrogel is irradiated with ultraviolet light so that it hardens and doesn't run off the wound. Infrared radiation is then used to stimulate cell growth. For this purpose, the team of scientists plans to develop an optical radiation system that will provide precise and efficient photobiomodulation of the cells.
Promising bioprinting
To test the hydrogel, the scientists plan to conduct an experiment on minipigs in a regenerative veterinary laboratory.
3D bioprinting is a frontier area of tissue engineering and regenerative medicine that has been actively developing over the past few years. New, improved models of bioprinters, innovative materials for bioprinting - hydrogels and bioinks used to create tissues and organs - are appearing, said Denis Alekseev, leading researcher of the STI Center "Bionic Engineering in Medicine" on the basis of SamSMU.
- Closure of wound defects, the more extensive ones, against the background of concomitant diseases such as diabetes mellitus or gangrenous pyoderma, may become a new and effective point of application of bioprinting. The use of this technology in burn patients is already being actively studied. The skin is created from biomaterials in hydrogel form and the patient's own living cells. In this case, the former provide the function of a carrier of cells and an optimal environment for them, and the latter regenerate the tissue, promoting healing of the defect. This approach is used to create bioinks at leading centers involved in bioprinting and regenerative medicine," he said.
In general, work on bioprinting of skin and skin equivalents is extremely relevant - many centers in the world are engaged in this, said Albert Rizvanov, head of the Center of Excellence "Personalized Medicine" of Kazan (Volga Region) Federal University, corresponding member of the Academy of Sciences of the Republic of Tatarstan. Therefore, scientists from Sechenov University in many ways need to closely follow the developments of leaders in this direction in the world.
The research is supported by a grant from the Russian Science Foundation. Now there is already a prototype bioprinter, and soon the final product will be presented, added the director of the Clinic of Skin and Venereal Diseases named after V.A. Rakhmanov. V.A. Rakhmanov Clinic of Skin and Venereal Diseases, corresponding member of the Russian Academy of Sciences Olga Olisova.
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