Prospects for organ replacement
How do scientists create artificial organs? What is the future of transplantology? Post-science experts talk about the latest discoveries and promising achievements of materials science.
Fedor Senatov: 3D printer
In the 2010s, when commercial 3D printers became available, scientists realized that artificial tissues could be produced using this technology. Companies that print cartilage, bone and joint implants are developing now.
Additive technologies have a great advantage in obtaining artificial organs and tissues – high reproduction accuracy and individualization. They allow you to repeat the geometry of the organ and tissue of a particular patient, and sometimes completely restore the architectural features of the lost organ.
However, such products have a serious disadvantage: they have low mechanical strength. For example, titanium implants printed on a 3D printer and implants cast from metal are different in mechanics. Printed implants have low strength, so they need to be further processed, for example, by temperature firing.
Peter Timashev: Tissue Engineering
Each person is unique, so now all medicine is becoming personalized: medicines and diets are selected for a specific patient. When it comes to large-scale production of organs and tissues, the question arises: how to standardize this process? We won't be able to talk about the industrial scale of artificial organ production for a long time. The future is a clinic for one person, when the doctor sees the patient as a combination of age, genetic and epigenetic factors that affect his health.
The main trend in tissue engineering is not the creation of identical organs or tissues, but an industry around one person. A striking example is three–dimensional bioprinting technologies, where damage is removed using computer or magnetic resonance imaging, and lost tissues are reproduced on a 3D bioprinter.
The key topic of all scientific conferences on tissue engineering is the transmission of developments to the clinic. So in the next 10-20 years, some approaches of tissue engineering will appear in clinical practice. There are already operations for the transplantation of artificial organs and human tissues. However , in Only 10-12 clinical trials have been registered in Russia, of which only one in 2019 (according to data from Clinicaltrials.gov , there have been four clinical trials in tissue engineering over the past 10 years, thirty-eight in general in regenerative medicine, and only one in 2019).
Vladimir Mironov: 3D bioprinting
There are three main directions for obtaining an artificial organ. The first is classical tissue engineering, when a sponge or fibrous scaffold is produced from a biodegradable (dissolvable) polymer. After that, the scientists build up the patient's cells on the scaffold and place the structure in a special bioreactor – a reservoir with a nutrient medium. There, the cells begin to proliferate, synthesize the cell matrix, integrate, and eventually a living tissue is formed.
The second direction is decellularization: cleaning the skeleton of an organ or tissue from a cellular component. All living cells are covered with a lipid membrane, and chemical detergents – acids or enzymes – dissolve it. After that, the skeleton of the organ remains, the extracellular matrix, where the blood vessels are preserved. Next, scientists inject recipient cells into the matrix, for example, liver, hepatocytes, and endothelial cells (cells of the lining of blood vessels) are injected into the remaining vessels, ensuring blood flow without thrombosis. In 2018, in Minnesota and Miami, scientists successfully transplanted pig liver for the first time.
However, decellularization has problems: organ supply and vascular endothelization. If blood is perfused in areas where there is no endothelium, thrombosis will occur, and embolism may develop, which will lead to the death of a person.
The third direction is three–dimensional bioprinting, one of the promising and multidisciplinary directions in modern biomedicine. On the one hand, this is the logical development of tissue engineering, that is, the robotic or automatic biofacturing of three-dimensional human tissues and organs from living cells and biomaterials. But on the other hand, it is a manifestation of a technical revolution based on the use of rapid prototyping or additive manufacturing technologies in biomedicine. Three–dimensional bioprinting is part of the rapidly developing digital economy, since it is impossible to print a human organ without developing a digital model.
Although work on the technology of three-dimensional bioprinting has been underway for two decades, despite the progress made, not a single printed organ has yet been transplanted to a person. However, there is an International Biofacturing Society that organizes regular international conferences, publishes journals, textbooks and monographs on three-dimensional bioprinting technologies. Commercial bioprinters are already produced by several dozen companies. In 2015, our team managed to print a functional organ for the first time – the thyroid gland of a mouse, and in the future we will be able to print a human organ.
Hybrid, in situ and four-dimensional bioprinting are singled out as promising areas in technology. Hybrid bioprinting is based on a combination of two or more biofacturing methods, of which at least one is a three–dimensional bioprinting method. For example, the method of extrusion bioprinting can be combined with inkjet bioprinting or with electroforming (electrospinning), which allows you to obtain a tissue or organ structure of more complex geometry and composition. In situ bioprinting allows you to print tissues in the operating room directly on the patient's body. One of the promising options for in situ bioprinting is the technology of robotic bioprinting of tissue–engineered hair for the treatment of baldness. Four-dimensional bioprinting uses biomaterials with shape memory (so-called shape-memory biomaterials), which allow programming changes in the shape of the printed structure after the end of bioprinting.
Anna Karyagina, Alexander Gromov: Recombinant proteins
The future of medicine lies in the creation of structures with specified properties for a specific person. The task of scientists is to make the implant as close as possible in properties to human tissues. Science allows you to take chemicals as parts for a designer and assemble objects from them with the necessary functions and a certain shape.
Obtaining polymers saturated with biologically active growth factors is a difficult task that can be solved only by the collective efforts of scientists of various specialties. This opens the doors for the development of personalized medicine – the replacement of organs and tissue defects is solved privately. People have different bone shapes and loads on organs, so it is important to choose the shape of implants individually.
At the National Research Center of Epidemiology and Microbiology named after Honorary Academician N. F. We are developing recombinant proteins, in particular bone morphogenetic protein-2 (BMP-2) and erythropoietin, which can induce bone formation and promote better blood supply to newly formed bone. From a composite compound of proteins with polymer materials, implants of various shapes and sizes with different properties can be made – for example, resorbable and non-resorbable implants capable of dense fusion with the maternal bone. The new materials are suitable both for the formation of individual implants in maxillofacial surgery and for the replacement of fragments of large bones in severe fractures. The development is carried out jointly with colleagues from NUST MISIS. We are creating innovative implantable materials that will be widely used in personalized medicine – the medicine of the future.
About the authors:
Fedor Senatov is a candidate of Physical and Mathematical Sciences, an employee of the Research Laboratory of Hybrid Nanostructured Materials, the Research Center for Composite Materials of NUST MISIS.
Vladimir Mironov – MD, PhD, Scientific Director of the Laboratory of Biotechnological Research 3D Bioprinting Solutions.
Peter Timashev – Doctor of Chemical Sciences, Director of the Institute of Regenerative Medicine, Head of the Department of Modern Biomaterials, Sechenov Moscow State Medical University.
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