Tissue-engineered constructs are used to create biological substitutes to restore or improve the functioning of tissues. Cells, as a component of the structure, can be obtained from various sources and located on different stages differentiation from poorly differentiated cells to highly differentiated specialized cells. Populating the prepared matrix with cells is an urgent problem of modern biomedicine. In this case, the properties of the matrix surface affect the colonization of cells, including the attachment of cells and their proliferation along the matrix.
Currently known methods of obtaining tissue-engineered constructs use the preparation of a cell suspension and the physical application of this suspension onto a biocompatible material by means of the gradual precipitation of the suspension culture with the formation of a monolayer and placing the material in solution for a long time sufficient for the cells to penetrate the entire volume of the material, as well as to use 3D bioprinting. Offered different ways the formation of tissue-engineered equivalents of hollow internal organs, such as the urethra, bladder, bile duct, trachea.
Clinical researches[ | ]
Tissue-engineered constructions based on biocompatible materials were studied in clinical research on patients with urological and dermatological diseases.
see also [ | ]
Notes (edit) [ | ]
- , Fox C. F. Tissue engineering: proceedings of a workshop, held at Granlibakken, Lake Tahoe, California, February 26-29, 1988. - Alan R. Liss, 1988. - T. 107.
- Atala A., Kasper F. K., Mikos A. G. Engineering complex tissues // Science translational medicine. - 2012. - T. 4, No. 160. - S. 160rv12. - ISSN 1946-6234. - DOI: 10.1126 / scitranslmed.3004890.
- Vasyutin I.A., Lyundup A.V., Vinarov A.Z., Butnaru D.V., Kuznetsov S.L. Reconstruction of the urethra using tissue engineering technologies. (rus.) // Bulletin Russian Academy medical sciences... - 2017. - T. 72, No. 1. - S. 17–25. - ISSN 2414-3545. - DOI: 10.15690 / vramn771.
- Baranovskiy D.S., Lundup A.V., Parshin V.D. Obtaining a functional full-fledged ciliated epithelium in vitro for tissue engineering of the trachea (Russian) // Bulletin of the Russian Academy of Medical Sciences. - 2015. - T. 70, No. 5. - S. 561-567. - ISSN 2414-3545. - DOI: 10.15690 / vramn.v70.i5.1442.
- Lawrence B. J., Madihally S. V. Cell colonization in degradable 3D porous matrices // Cell adhesion & migration. - 2008. - T. 2, No. 1. - S. 9-16.
- Mironov V. et al. Organ printing: computer-aided jet-based 3D tissue engineering // TRENDS in Biotechnology. - 2003. - T. 21. - No. 4. - S. 157-161. doi:
) — creation of new tissues and organs for the therapeutic reconstruction of the damaged organ by delivering support structures, molecular and mechanical signals for regeneration to the desired area.
Description
Conventional implants made from inert materials can only eliminate the physical and mechanical deficiencies of damaged tissues. The goal of tissue engineering is to restore biological (metabolic) functions, that is, to regenerate tissue, rather than simply replacing it with synthetic material.
The creation of a tissue-engineered implant (graft) includes several stages:
- selection and cultivation of own or donor cell material;
- development of a special carrier for cells (matrix) based on biocompatible materials;
- application of cell culture to a matrix and cell propagation in a bioreactor with special conditions cultivation;
- direct insertion of the graft into the area of the affected organ or preliminary placement in an area well supplied with blood for maturation and formation of microcirculation inside the graft (prefabrication).
Cellular material can be cells of regenerated tissue or stem cells. Biologically inert synthetic materials, materials based on natural polymers (chitosan, alginate, collagen), as well as biocomposite materials are used to create graft matrices. For example, the equivalents bone tissue obtained by directed differentiation of bone marrow stem cells, cord blood or adipose tissue. Then the resulting osteoblasts (young bone cells responsible for its growth) are applied to various materials that support their division - donor bone, collagen matrices, porous hydroxyapatite, etc. Living skin equivalents containing donor or own skin cells are now widely used in the USA, Russia, Italy. These designs allow for improved healing of extensive burns. The development of grafts is also carried out in cardiology (artificial heart valves, reconstruction of large vessels and capillary networks); to restore the respiratory system (larynx, trachea and bronchi), small intestine, liver, urinary system organs, glands internal secretion and neurons. metals in tissue engineering are used to control cell growth by acting on them magnetic fields different directions. For example, in this way, it was possible to create not only analogs of liver structures, but also such complex structures as elements of the retina. Also, materials created using the electron beam lithography (EBL) method provide nanoscale matrix surfaces for effective formation bone implants. The creation of artificial tissues and organs will make it possible to abandon the transplantation of most donor organs, and will improve the quality of life and survival of patients.
Authors
- Naroditsky Boris Savelievich
- Nesterenko Lyudmila Nikolaevna
Sources of
- Nanotechnology in tissue engineering // Nanometer. -www.nanometer.ru/2007/10/16/tkanevaa_inzheneria_4860.html
- Stem cell// Wikipedia, the free encyclopedia.www.ru.wikipedia.org / wiki / Stem_cells (date accessed: 10/12/2009).
Article for the competition "bio / mol / text": Peter I dreamed of "opening a window to Europe", and scientists of our time - a window into modern medicine... The combination of "medicine + biotechnology" is reflected in tissue engineering - a technology that opens up the possibility of restoring lost organs without transplantation. The methods and results of tissue engineering are striking: this is the production of living (and not artificial!) Organs and tissues; tissue regeneration; 3D printing of blood vessels; the use of surgical sutures "melting" in the body and much more.
In recent decades, alarming tendencies of an aging population, an increase in the number of diseases and disability of people of working age have become clearly manifested, which urgently requires the development and implementation of clinical practice new, more efficient and available methods rehabilitation treatment sick. Figure 1 shows how the structure of diseases is changing at present.
Today science and technology offers several alternative ways to restore or replace damaged or diseased tissues and organs:
- transplantation;
- implantation;
- tissue engineering.
Within the framework of this article, we will dwell in more detail on the possibilities and prospects of tissue engineering.
Tissue engineering is a modern innovative technology
Fundamentally new approach - cell and tissue engineering- is the latest advancement in the field of molecular and cellular biology. This approach opened up broad prospects for the creation of effective biomedical technologies, with the help of which it becomes possible restoration damaged tissues and organs and treatment of a number of severe metabolic diseases in humans.
The purpose of tissue engineering- designing and growing outside the human body of living, functional tissues or organs for subsequent transplantation to a patient in order to replace or stimulate the regeneration of the damaged organ or tissue. In other words, at the site of the defect must be restored three-dimensional fabric structure.
It is important to note that conventional implants made from inert materials can only eliminate physical and mechanical disadvantages of damaged tissues, - in contrast to tissues obtained by the method of engineering, which restore, including biological(metabolic) functions. That is, tissue regeneration occurs, and not a simple replacement of it with synthetic material.
However, for the development and improvement of methods of reconstructive medicine based on tissue engineering, it is necessary to master new highly functional materials. These materials, used to create bioimplants, should impart to tissue-engineered constructions the characteristics inherent in living tissues:
- the ability to self-heal;
- the ability to maintain blood supply;
- the ability to change structure and properties in response to factors environment including mechanical stress.
Cells and Matrices - the Basics of Tissue Engineering
Most important element success is the presence of the required number of functionally active cells capable of differentiating, maintaining the corresponding phenotype and performing specific biological functions... The source of cells can be body tissues and internal organs... It is possible to use appropriate cells from a patient in need of reconstructive therapy, or from close relative(autogenous cells). Cells can be used of various origins, including primary (Fig. 2) and stem cells (Fig. 3).
Figure 2. Primary human cell.
Library of the Kyokushinkai Federation of Yuzhnouralsk
Primary cells are mature cells of a certain tissue that can be taken directly from a donor organism ( ex vivo) surgically... If the primary cells are taken from a certain donor organism, and subsequently it is necessary to implant these cells in him as a recipient, then the probability of rejection of the implanted tissue is excluded, since there is the maximum possible immunological compatibility of the primary cells and the recipient. However, primary cells, as a rule, are not able to divide - their potential for reproduction and growth is low. When cultivating such cells in vitro(through tissue engineering) for some types of cells dedifferentiation is possible, that is, the loss of specific, individual properties. For example, chondrocytes introduced into culture outside the body often produce fibrous rather than transparent cartilage.
Since primary cells are unable to divide and may lose their specific properties, the need arose for alternative sources of cells for the development of cell engineering technologies. Stem cells have become such an alternative.
To direct the organization, support the growth and differentiation of cells during the reconstruction of damaged tissue, a special cell carrier is required - matrix, which is a three-dimensional network similar to a sponge or pumice stone (Fig. 4). To create them, biologically inert synthetic materials, materials based on natural polymers (chitosan, alginate, collagen) and biocomposites are used. For example, bone tissue equivalents are obtained by directed differentiation of stem cells from bone marrow, umbilical cord blood, or adipose tissue into osteoblasts, which are then applied to various materials that support their division (for example, donor bone, collagen matrices, etc.).
"Branded" tissue engineering strategy
Today one of the strategies of tissue engineering is as follows:
- Selection and cultivation of own or donor stem cells.
- Development of a special carrier for cells (matrix) based on biocompatible materials.
- Application of a cell culture to a matrix and cell propagation in a bioreactor with special cultivation conditions.
- Direct insertion of a tissue-engineered structure into the area of the affected organ or preliminary placement in an area well supplied with blood for maturation and formation of microcirculation within the structure (prefabrication).
The scaffolds disappear completely after some time after implantation into the host organism (depending on the rate of tissue growth), and only new tissue will remain at the site of the defect. It is also possible to introduce a matrix with already partially formed new tissue ("biocomposite"). Of course, after implantation, the tissue-engineered structure must retain its structure and functions for a period of time sufficient to restore normally functioning tissue at the site of the defect, and integrate with the surrounding tissues. But, unfortunately, ideal matrices that satisfy all the necessary conditions have not yet been created.
Blood vessels from the printer
Promising tissue engineering technologies have opened up the possibility of laboratory creation of living tissues and organs, but science is still powerless before the creation of complex organs. However, relatively recently, scientists under the leadership of Dr.Gunter Tovar ( Gunter Tovar) from the Fraunhofer Society in Germany made a huge breakthrough in tissue engineering - they developed the technology for creating blood vessels. But it seemed that it was impossible to create capillary structures artificially, since they must be flexible, elastic, small in shape and at the same time interact with natural tissues. Oddly enough, but production technologies came to the rescue - a method of rapid prototyping (in other words, 3D printing). It is understood that a complex 3D model (in our case, a blood vessel) is printed on a 3D inkjet printer using special "ink" (Fig. 5).
The printer applies material in layers, and in certain places the layers are chemically bonded. Note, however, that 3D printers are not yet accurate enough for the smallest capillaries. In this regard, the method of multiphoton polymerization, used in the polymer industry, was applied. Short, intense laser pulses that process the material excite the molecules so strongly that they interact with each other to form long chains. Thus, the material polymerizes and becomes hard, but elastic, like natural materials. These reactions are so controllable that they can be used to create the smallest structures from a three-dimensional "blueprint".
And in order for the created blood vessels to dock with the cells of the body, modified biological structures (for example, heparin) and "anchor" proteins are integrated into them during the manufacture of vessels. At the next stage, endothelial cells (a single layer of flat cells lining inner surface blood vessels) - so that blood components do not stick to the walls vascular system, and were freely transported along it.
However, before you can actually implant lab-grown organs with their own blood vessels, some time will pass.
Come on, Russia, come on ahead!
Without false modesty, we can say that in Russia, too, a scientific basis for practical application biomedical materials of a new generation. An interesting development was suggested by a young scientist from Krasnoyarsk Ekaterina Igorevna Shishatskaya (Fig. 6) - a soluble biocompatible polymer bioplastotane... She explains the essence of her development simply: “Currently, medical practitioners are experiencing a great shortage of materials that can replace segments human body... We managed to synthesize a unique material that is able to replace the elements of human organs and tissues "... The development of Ekaterina Igorevna will find application, first of all, in surgery. “The simplest is, for example, sutures made from our polymer, which dissolve after the wound heals., - says Shishatskaya. - You can also make special inserts into the vessels - stents. These are small, hollow tubes that are used to expand a vessel. Some time after the operation, the vessel is restored, and the polymer substitute dissolves " .
The first experience of tissue-engineered construct transplantation in the clinic
Figure 7. Paolo Macchiarini, whose master class "Cell technologies for tissue engineering and organ growth" was held in Moscow in 2010.
In autumn 2008, the head of the clinic of the University of Barcelona (Spain) and the School of Medicine of Hannover (Germany), Professor Paolo Macchiarini ( Paolo macchiarini; rice. 7) performed the first successful transplantation of a bioengineering equivalent of the trachea to a patient with 3 cm stenosis of the main left bronchus (Fig. 8).
A 7 cm long segment of a cadaveric trachea was taken as a matrix for the future graft.To obtain a natural matrix, superior in properties to anything that can be made from polymer tubes, the trachea was cleaned of the surrounding connective tissue, donor cells and histocompatibility antigens. Purification consisted of 25 devitalization cycles using 4% sodium deoxycholate and deoxyribonuclease I (the process took 6 weeks). After each cycle of devitalization, a histological examination of the tissue was performed to determine the number of remaining nucleated cells, as well as an immunohistochemical study for the presence of histocompatibility antigens HLA-ABC, HLA-DR, HLA-DP, and HLA-DQ in the tissue. Thanks to a bioreactor of their own design (Fig. 9), scientists evenly applied a cell suspension with a syringe to the surface of a slowly rotating section of the trachea. Then the graft, half submerged in the culture medium, was rotated around its axis in order to alternately contact the cells with the medium and air.
Figure 9. Bioreactor for creating the tissue-engineered equivalent of the trachea. A- diagram of a bioreactor, side view. B- sealing the bioreactor. V- bioreactor with tissue engineering equivalent of the trachea in situ. G- bioreactor after removal of the trachea equivalent. D- view of the trachea equivalent immediately before the operation.
The tracheal equivalent was in the bioreactor for 96 hours; then it was transplanted to the patient. During the operation, the main left bronchus and the part of the trachea, to which it was adjacent, was completely removed. A graft was sutured into the formed gap, and some discrepancy between the diameters of the lumen of the tissue-engineered equivalent and the recipient's bronchus was overcome due to the elasticity of the donor tissue.
Ten days after the operation, the patient was discharged from the clinic without signs respiratory failure and immune response to graft rejection. According to computed tomography, with the help of which the virtual 3D reconstruction was made respiratory tract, the tissue-engineered equivalent was practically indistinguishable from the patient's own bronchi (Fig. 10).
;. DailyMail;Tissue engineering Is the science of designing and manufacturing tissues, including bone and other musculoskeletal tissues. Both tissue engineering and morphogenesis are based on three components - morphogenetic signals, competent stem cells, and scaffold structures. Musculoskeletal tissue restoration generalizes both embryonic development and morphogenesis. Morphogenesis is a developing group of sciences studying the formation of structures, general structure the body on its way to adult functioning.
Therefore, the impulses involved in morphogenesis must be used in bone tissue engineering. Bone morphogenetic proteins have a broadly directed (pleotropic) function in the primary formation of structures, cell differentiation, and restoration of bone and articular cartilage. The ability of the bone to change it (recreational ability) depends on the morphogenetic proteins of the bone in the bone matrix. Bone morphogenetic proteins act through receptors and Smads 1, 5 and 8 to stimulate cartilage and bone cell lines. The homeostasis of tissue-engineered bone and cartilage depends on the maintenance of the extracellular matrix and biomechanics. The use of morphogenetic bone proteins in gene therapy and the release of stem cells in biomimetic extracellular matrix scaffolds leads to bone functionality. In conclusion, it should be noted that our time is a time of exciting discoveries in the field of functional tissue engineering, bone impulses, framework structures and stem cells.
One of the challenges faced by an orthopedic surgeon is the restoration and reconstruction of a large segment of the skeletal bone damaged as a result of removal malignant tumor bones or injuries. Although allogeneic graft for large bone segments has gained increasing acceptance, it has the drawbacks of possible fractures. The problem of bone fractures in patients with postmenopausal osteoporosis, metastases caused by breast cancer or prostate, and metabolic disorders such as diabetes require tissue engineering principles to be applied to bone.
Tissue Engineering is the science of designing and manufacturing new tissues for functional repair damaged organs and replacement of body parts lost due to cancer, various diseases and injuries. Among many tissues of the body, bone has a high ability to repair, and therefore is the benchmark for the principles of tissue engineering in general. In the near future, the accumulation of knowledge in the field of tissue engineering will lead to the creation of bone implants with specified parameters for use in orthopedic surgery.
The three main components of tissue engineering and tissue regeneration are signals, stem cells, and scaffolds. The specificity of signals depends on tissue morphogenesis and inductive stimuli in the developing embryo. They are generally reproduced during regeneration. Bone grafts have been used by surgeons for over a century. Urist did the most important discovery showing that implantation of demineralized, freeze-dried segments of rabbit allogeneic bone caused new bone to form. It has been shown that the stimulation of bone formation is a sequential, step-by-step action, where three key stages - chemotaxis, mitosis and differentiation take place. Chemotaxis is the directed movement of cells under the influence of chemical signals released from the demineralized bone matrix. The movement and subsequent adhesion of bone-forming cells on the collagen matrix is determined by the presence of fibronectin in it.
The peak of cell proliferation under the influence of growth stimulants released from the insoluble demineralized matrix is observed on the third day. Cartilage formation reaches its maximum on days 7-8, followed by vascular invasion and, starting from day 9, osteogenesis is observed. Bone formation peaks at 10-12 days, as indicated by alkaline phosphatase activity. This is followed by an increase in osteocalcin, bone protein-containing γ-carboxyglutamic acid (BGP). Newly formed immature bone fills with red bone marrow by day 21. Demineralized bone due to the release of bone morphogenetic proteins that determine the initial impulses for bone morphogenesis, as well as the formation of many organs other than bone, such as the brain, heart, kidneys, lungs, skin and teeth. Therefore, it is possible to treat morphogenetic proteins of the bone as morphogenetic proteins of the body.
J.P. Fisher and A.H. Reddi, Functional Tissue Engineering of Bone: Signals and Scaffolds
Translation by Borisova Marina
Tissue engineering- a young and developing direction of medicine, which opens up new opportunities for humanity. The profession is suitable for those who are interested in chemistry and biology (see choosing a profession based on interest in school subjects).
In this article, we will tell you about the profession of tissue engineer - one of the professions of the future in this direction.
What is tissue engineering?
This is a science that originated on the border between cell biology, embryology, biotechnology, transplantation and medical materials science.
She specializes in the development of biological analogs of organs and tissues created from living cells and designed to restore or replace their functions.
Who is a Fabric Engineer?
This is a specialty that will be in demand in the near future. This professional is responsible for developing and controlling production process, selection of materials and formation necessary conditions for the creation of tissue-engineered implants (grafts) and their further transplantation. According to some reports, this profession will begin to spread after 2020.
The development and implementation of a graft includes a number of stages:
- first, it is necessary to select and cultivate cells;
- then a cell carrier (matrix) is created using biocompatible materials;
- after that, the cells are placed on the matrix and they multiply in the bioreactor;
- finally, the implant is placed in the area of the non-functioning organ. If necessary, before this, the graft is inserted into an area with good blood supply for its maturation (this process is called prefabrication).
The starting material can be tissue cells that need to be regenerated, or stem cells. In the production of matrices, various types of materials can be used (biocomposite, synthetic biologically inert, natural polymer).
Where are grafts used?
- Creation of artificial analogs of the skin to aid in regeneration skin with extensive burns.
- Tissue-engineered implants also have great potential in the field of cardiology (biological analogs of heart valves, reconstruction of arteries, veins and capillaries).
- In addition, they are applied when recreating respiratory system, digestive organs, urinary system, glands of external and internal secretion.
Where to study to be a tissue engineer
V this moment in our country no educational programs teaching in this specialty, there are only a number of laboratories at research institutes specializing in tissue engineering. Professionals wishing to develop in this area can get a basic medical education... You should also consider the possibility of studying abroad: in the USA and Europe, master's degrees in this specialty are actively developing.
Professionally important qualities:
- systematic thinking;
- interest in working in an interdisciplinary field;
- readiness to work in conditions of uncertainty;
- research interest;
- Responsibility for teamwork.
Major disciplines:
- biology;
- chemistry;
- physics;
- maths;
- computer science.
Advances in modern tissue engineering
Nipple analogs have been created and successfully applied female breast, tissue engineering bladder and ureters. Research is underway on the creation of the liver, trachea and intestinal elements.
Leading research laboratories are working to recreate another hard-to-restore human organ- a tooth. The difficulty lies in the fact that tooth cells develop from several tissues, the combination of which could not be reproduced. Currently, only the early stages of tooth formation are not fully recreated. artificial eye is currently at the initial stage, but it has already turned out to develop analogs of its individual membranes - the cornea, sclera, iris.
At the same time, the question of how to integrate them into a single whole remains open.
A group of German scientists from the University of Kiel was able to successfully restore lower jaw the patient, almost entirely removed due to the tumor.
The patient's stem cells, along with bone growth factors, were placed in a titanium mesh replica of his jaw. Then, for the incubation period, this construct was placed in his muscle under right shoulder blade from where it was then transplanted to the patient.
It is too early to talk about how effectively such a jaw will function. However, this is the first reliable case of a bone transplant literally grown inside the human body.
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