Tissue engineering on nanostructured matrices. Tissue engineering - a window into modern medicine Modern possibilities of tissue engineering

Tissue engineering was once classified as a subfield of biological materials, but has grown in scope and importance it can be considered a subfield in its own right. Fabrics require certain mechanical and structural properties to function properly. The term "tissue engineering" also refers to the modification of specific biochemical functions using cells in an artificially created support system (for example, an artificial pancreas, or an artificial liver). The term "regenerative medicine" is often used synonymously with tissue engineering, although regenerative medicine places more emphasis on the use of stem cells to produce tissue.

Typically, tissue engineering, as stated by Langer and Vacanti, is viewed as “an interdisciplinary field that applies the principles of engineering and biology to develop biological substitutes that restore, maintain, or improve the function of tissue or an entire organ.” Tissue engineering has also been defined as "the understanding of the principles of tissue growth, and their application to the production of functional tissue substitutes for clinical use." In more detailed description states that "the basic assumption of tissue engineering is that the use of natural biological systems will allow you to achieve greater success in development therapeutic methods aimed at replacing, repairing, maintaining, and/or expanding the function of tissue."

Cells can be obtained from liquid tissues, such as blood, in a variety of ways, usually by centrifugation. Cells are more difficult to obtain from hard tissues. Typically, the tissue is minced and then digested with trypsin or collagenase enzymes to remove the extracellular matrix that contains the cells. After this, the cells are allowed to float freely and are extracted as if from liquid tissue. The rate of reaction with trypsin is very dependent on temperature, and high temperatures cause great damage to cells. Collagenase requires low temperatures, and therefore there is less cell loss, but the reaction takes longer, and collagenase itself is an expensive reagent. Cells are often implanted into artificial structures that can support the formation of three-dimensional tissue. These structures are called scaffolding.

To achieve the goal of tissue reconstruction, scaffolding must meet some specific requirements. High porosity and defined pore size, which are necessary to promote cell seeding and diffusion throughout the structure, both cells and nutrients. Biodegradability is often a significant factor, as woods are absorbed into surrounding tissues unnecessarily surgical removal. The rate at which decomposition occurs should coincide as closely as possible with the rate of tissue formation: this means that while the manufactured cells have created their own natural matrix structure around themselves, they are already able to provide structural integrity in the body, and ultimately As a result, the scaffolding will be broken, leaving a newly formed tissue that will take on the mechanical load.

A variety of scaffolding materials (natural and synthetic, biodegradable and permanent) have been researched. Most of these materials were known in the medical field even before the emergence of tissue engineering as a research topic, and were already used, for example, in surgery for suturing. In order to develop scaffolding with ideal properties (biocompatibility, non-immunogenicity, transparency, etc.), new materials have been designed for it.

Scaffolds can also be constructed from natural materials: in particular, various extracellular matrix derivatives and their ability to support cell growth have been studied. Protein materials such as collagen or fibrin and polysaccharides such as chitosan or glycosaminoglycan (GAG) are suitable in terms of compatibility, but some questions still remain open. Scaffold functional groups may be useful in delivering small molecules (drugs) to specific tissues.

Carbon nanotubes

Carbon nanotubes are extended cylindrical structures with a diameter from one to several tens of nanometers and a length of up to several centimeters, consisting of one or several hexagonal graphite planes rolled into a tube and usually ending in a hemispherical head, which can be considered as half a fullerene molecule.

As is known, fullerene (C60) was discovered by the group of Smalley, Kroto and Curl in 1985, for which in 1996 these researchers were awarded Nobel Prize in chemistry. Concerning carbon nanotubes, then it is impossible to name the exact date of their opening. Although it is well known that Iijima observed the structure of multi-walled nanotubes in 1991, there is earlier evidence of the discovery of carbon nanotubes. So, for example, in 1974 - 1975. Endo et al. have published a number of papers describing thin tubes with a diameter of less than 100 nm prepared by vapor condensation, but a more detailed study of the structure has not been carried out.

In 1977, a group of scientists from the Institute of Catalysis of the Siberian Branch of the USSR Academy of Sciences, while studying the carbonization of iron-chromium dehydrogenation catalysts under a microscope, recorded the formation of “hollow carbon dendrites”; a mechanism of formation was proposed and the structure of the walls was described. In 1992, an article was published in Nature, which stated that nanotubes were observed in 1953. A year earlier, in 1952, an article by Soviet scientists Radushkevich and Lukyanovich reported electron microscopic observation of fibers with a diameter of about 100 nm, obtained from the thermal decomposition of the oxide carbon on an iron catalyst. These studies were also not continued.

There are many theoretical works to predict this allotropic form of carbon. In his work, chemist Jones (Dedalus) was thinking about coiled tubes of graphite. In the work of L.A. Chernozatonsky and others, published in the same year as the work of Iijima, carbon nanotubes were obtained and described, and M. Yu. Kornilov not only predicted the existence of single-walled carbon nanotubes in 1986, but also suggested their great elasticity.

Nanotube structure

An ideal nanotube is a graphite plane rolled into a cylinder, that is, a surface lined with regular hexagons with carbon atoms at the vertices. The result of such an operation depends on the angle of orientation of the graphite plane relative to the axis of the nanotube. The orientation angle, in turn, determines the chirality of the nanotube, which determines, in particular, its electrical characteristics.

Fig.1. Rolling up a graphite plane to produce an (n, m) nanotube

To obtain a nanotube of chirality (n, m), the graphite plane must be cut along the directions of the dotted lines and rolled along the direction of the vector R

An ordered pair (n, m) indicating the coordinates of a hexagon, which, as a result of folding the plane, must coincide with the hexagon located at the origin of coordinates is called the chirality of the nanotube and is designated. Another way to indicate chirality is to indicate the angle α between the direction of folding of the nanotube and the direction in which adjacent hexagons share a common side. However, in this case for full description The geometry of the nanotube must indicate its diameter. The chirality indices of a single-walled nanotube (m, n) uniquely determine its diameter D. The indicated relationship has the following form:

where d 0 = 0.142 nm is the distance between neighboring carbon atoms in the graphite plane.

The relationship between chirality indices (m, n) and angle α is given by the relation:

Among the various possible directions of folding of nanotubes, those for which alignment of the hexagon (n, m) with the origin of coordinates does not require distortion of its structure are distinguished. These directions correspond, in particular, to the angles α = 0 (armchair configuration) and α = 30° (zigzag configuration). The indicated configurations correspond to chiralities (n, 0) and (2m, m), respectively.

Single-walled nanotubes

The structure of single-walled nanotubes observed experimentally differs in many respects from the idealized picture presented above. First of all, this concerns the vertices of the nanotube, the shape of which, as follows from observations, is far from an ideal hemisphere. A special place among single-walled nanotubes is occupied by the so-called armchair nanotubes or nanotubes with chirality (10, 10). In nanotubes of this type, two of the C–C bonds included in each six-membered ring are oriented parallel to the longitudinal axis of the tube. Nanotubes with a similar structure should have a purely metallic structure.

Multi-walled nanotubes

Multi-walled nanotubes differ from single-walled nanotubes in a much wider variety of shapes and configurations. The variety of structures is manifested in both longitudinal and transverse directions. The “Russian dolls” type structure is a collection of cylindrical tubes coaxially nested into each other. Another variation of this structure is a collection of coaxial prisms nested within each other. Finally, the last of the above structures resembles a scroll. All structures are characterized by a distance between adjacent graphite layers that is close to the value of 0.34 nm, inherent in the distance between adjacent planes of crystalline graphite.

The implementation of a particular structure of multi-walled nanotubes in a specific experimental situation depends on the synthesis conditions. An analysis of the available experimental data indicates that the most typical structure of multi-walled nanotubes is a structure with sections of the “Russian nesting doll” and “papier-mâché” type alternately located along the length. In this case, smaller “tubes” are sequentially inserted into larger tubes.

Preparation of carbon nanotubes

The development of methods for the synthesis of carbon nanotubes (CNTs) has followed the path of lowering synthesis temperatures. After the creation of the technology for producing fullerenes, it was discovered that during electric arc evaporation of graphite electrodes, along with the formation of fullerenes, extended cylindrical structures are formed. Microscopist Sumio Iijima, using a transmission electron microscope (TEM), was the first to identify these structures as nanotubes. High-temperature methods for producing CNTs include the electric arc method. If you evaporate a graphite rod (anode) in an electric arc, then a hard carbon build-up (deposit) is formed on the opposite electrode (cathode), the soft core of which contains multi-walled CNTs with a diameter of 15-20 nm and a length of more than 1 μm. Formation of CNTs from fullerene soot at high temperature thermal effects Soot was first observed by the Oxford and Swiss groups. The installation for electric arc synthesis is metal-intensive and energy-consuming, but is universal for producing various types of carbon nanomaterials. In this case, a significant problem is the nonequilibrium of the process during arc combustion. The electric arc method at one time replaced the method of laser evaporation (ablation) with a laser beam. The ablation installation is a conventional oven with resistive heating, producing a temperature of 1200C. To obtain higher temperatures in it, it is enough to place a carbon target in the furnace and point it at it. laser ray, alternately scanning the entire surface of the target.

Thus, Smalley's group, using expensive installations with a short-pulse laser, obtained nanotubes in 1995, “significantly simplifying” the technology of their synthesis. However, the yield of CNTs remained low. The introduction of small additions of nickel and cobalt into graphite made it possible to increase the yield of CNTs to 70-90%. From this moment on, a new stage began in understanding the mechanism of nanotube formation. It became obvious that the metal was a catalyst for growth. This is how the first works appeared on the production of nanotubes by a low-temperature method - the method of catalytic pyrolysis of hydrocarbons (CVD), where iron group metal particles were used as a catalyst. One of the installation options for producing nanotubes and nanofibers by the CVD method is a reactor into which an inert carrier gas is supplied, carrying the catalyst and hydrocarbon to a high-temperature zone. In a simplified way, the growth mechanism of CNTs is as follows. The carbon formed during the thermal decomposition of hydrocarbons dissolves in the metal nanoparticle.

When a high concentration of carbon in a particle is reached, an energetically favorable “release” of excess carbon occurs on one of the faces of the catalyst particle in the form of a distorted semifulerene cap. This is how a nanotube is born. The decomposed carbon continues to enter the catalyst particle, and in order to discharge its excess concentration in the melt, it is necessary to constantly get rid of it. A rising hemisphere (semifullerene) from the surface of the melt carries with it dissolved excess carbon, the atoms of which outside the melt form a C–C bond, which is a cylindrical frame-nanotube. The melting temperature of a particle in a nanosized state depends on its radius. The smaller the radius, the lower the melting temperature. Therefore, iron nanoparticles with a size of about 10 nm are in a molten state below 600C. At the moment, low-temperature synthesis of CNTs has been carried out using the catalytic pyrolysis of acetylene in the presence of Fe particles at 550C. Reducing the synthesis temperature also has Negative consequences. At lower temperatures, CNTs with a large diameter (about 100 nm) and a highly defective structure such as “bamboo” or nested nanocones are obtained. The resulting materials are only composed of carbon, but they do not even come close to the extraordinary characteristics (for example, Young's modulus) observed in single-walled carbon nanotubes obtained by laser ablation or electric arc synthesis.

Tissue engineering constructs are used to create biological substitutes to restore or improve tissue function. Cells, as a component of the construct, can be obtained from different sources and be at different stages of differentiation from poorly differentiated cells to highly differentiated specialized cells. The colonization of the prepared matrix by cells is current problem modern biomedicine. In this case, the properties of the matrix surface influence cell colonization, including cell attachment and proliferation throughout the matrix.

Currently known methods for obtaining tissue-engineered constructs use the preparation of a suspension of cells and the physical application of this suspension to a biocompatible material through the step-by-step deposition of a suspension culture to form a monolayer and placing the material in solution for a long time, sufficient for the penetration of cells throughout the entire volume of the material, as well as the use 3D bioprinting. Various methods have been proposed for the formation of tissue-engineered equivalents of hollow internal organs, such as the urethra, bladder, bile duct, and trachea.

Clinical researches[ | ]

Tissue-engineered structures based on biocompatible materials have been studied in clinical studies on patients with urological and dermatological diseases.

see also [ | ]

Notes [ | ]

1. , 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.
2. 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.
3. Vasyutin I.A., Lyndup A.V., Vinarov A.Z., Butnaru D.V., Kuznetsov S.L. Reconstruction of the urethra using tissue engineering technologies. (Russian) // Bulletin of the Russian Academy medical sciences. - 2017. - T. 72, No. 1. - pp. 17–25. - ISSN 2414-3545. - DOI:10.15690/vramn771.
4. Baranovsky D.S., Lyndup A.V., Parshin V.D. Obtaining functionally complete ciliated epithelium in vitro for tissue engineering of the trachea (Russian) // Bulletin of the Russian Academy of Medical Sciences. - 2015. - T. 70, No. 5. - pp. 561–567. - ISSN 2414-3545. - DOI:10.15690/vramn.v70.i5.1442.
5. Lawrence B. J., Madihally S. V. Cell colonization in degradable 3D porous matrices // Cell adhesion & migration. - 2008. - T. 2, No. 1. - pp. 9-16.
6. Mironov V. et al. Organ printing: computer-aided jet-based 3D tissue engineering //TRENDS in Biotechnology. – 2003. – T. 21. – No. 4. – pp. 157-161. doi:

IN Lately All over the world there is an alarming pattern, which consists in an increase in the number of diseases and disability of people of working age, which urgently requires the development and introduction into clinical practice of new, more effective and accessible methods rehabilitation treatment sick.

One of these methods, along with implantation and transplantation, is tissue engineering. Cell and tissue engineering is the latest advance in the field of molecular and cellular biology. This approach has opened up broad prospects for the creation of effective biomedical technologies, with the help of which it becomes possible to restore damaged tissues and organs and treat a number of severe human metabolic diseases.

The goal of tissue engineering is the design and cultivation of living, functional tissues or organs outside the human body for subsequent transplantation to a patient in order to replace or stimulate the regeneration of a damaged organ or tissue. In other words, the three-dimensional structure of the tissue must be restored at the site of the defect.

Conventional implants made of inert materials can only eliminate the physical and mechanical deficiencies of damaged tissues, in contrast to engineered tissues, which restore, among other things, biological (metabolic) functions. That is, tissue regeneration occurs, and not its simple replacement with synthetic material.

However, to develop and improve methods of reconstructive medicine based on tissue engineering, it is necessary to develop new highly functional materials. These materials used to create bioimplants should impart characteristics to tissue-engineered structures that are characteristic of living tissues. Among these characteristics:

• 1) ability to self-heal;
• 2) the ability to maintain blood supply;
• 3) the ability to change structure and properties in response to factors environment, including mechanical load.

The most important element for success is the presence of the required number of functionally active cells capable of differentiating, maintaining the appropriate 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 of various origins can be used, including primary and stem cells. Primary cells are mature cells of a specific tissue that can be taken directly from a donor organism (ex vivo) by surgery. If primary cells are taken from a specific donor organism, and subsequently it is necessary to implant these cells into it as a recipient, then the likelihood of rejection of the implanted tissue is eliminated, since the maximum possible immunological compatibility of the primary cells and the recipient is present. 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), dedifferentiation, that is, loss of specific, individual properties, is possible for some types of cells. For example, chondrocytes cultured outside the body often produce fibrous rather than transparent cartilage.

Since primary cells are unable to divide and may lose their specific properties, there is a need for alternative cell sources for the development of cell engineering technologies. Stem cells became such an alternative.

Stem cells are undifferentiated cells that have the ability to divide, self-renew, and differentiate into various types of specialized cells when exposed to specific biological stimuli.

Stem cells are divided into “adult” and “embryonic”. Embryonic stem cells are formed from the inner cell mass of early embryonic development, while adult stem cells are formed from adult tissue, the umbilical cord, or even fetal tissue. However, there is an ethical problem associated with the inevitable destruction of the human embryo when obtaining embryonic stem cells. Therefore, it is preferable to “extract” cells from the tissues of an adult organism. For example, in 2007, Shinya Yamanaka from Kyoto University in Japan discovered induced pluripotent stem cells (iPSCs) obtained from human integumentary tissues (mainly skin). iPSCs offer truly unprecedented opportunities for regenerative medicine, although many problems remain to be solved before they seriously enter medical practice.

To guide the organization, maintain the growth and differentiation of cells during the reconstruction of damaged tissue, a special cell carrier is required - a matrix, which is a three-dimensional network similar to a sponge or pumice. 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 bone marrow stem cells, 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.).

Today, one of the tissue engineering strategies is as follows:

• 1) selection and cultivation of own or donor stem cells;
• 2) development of a special carrier for cells (matrix) based on biocompatible materials;
• 3) applying a cell culture to the matrix and cell proliferation in a bioreactor with special cultivation conditions;
• 4) direct introduction of a tissue-engineered construct 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 construct (prefabrication).

Some time after implantation into the host’s body, the matrices completely disappear (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 fabric("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 surrounding tissues. But, unfortunately, ideal matrices that satisfy everyone necessary conditions, have not yet been created.

Promising tissue engineering technologies have opened up the possibility of creating living tissues and organs in the laboratory, but science is still powerless when it comes to creating complex organs. However, relatively recently, scientists led by Dr. Gunter Tovar from the Fraunhofer Society in Germany made a huge breakthrough in the field of tissue engineering - they developed a technology for creating blood vessels. But it seemed that it was impossible to create capillary structures artificially, since they must be flexible, elastic, small form and at the same time interact with natural tissues. Oddly enough, they came to the rescue production technologies- rapid prototyping method (in other words, 3D printing). This means that a complex 3D model (in our case a blood vessel) is printed on a 3D inkjet printer using special “ink”.

The printer deposits the material in layers, and in certain places the layers are chemically bonded. However, we note that for the smallest capillaries, 3D printers are not yet accurate enough. In this regard, the multiphoton polymerization method used in the polymer industry was applied. The short, intense laser pulses that treat the material excite the molecules so strongly that they interact with each other, linking together in long chains. In this way, 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 according to 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 the vessels. At the next stage, endothelial cells (a single-layer layer of flat cells lining the inner surface of blood vessels) are fixed in the system of created “tubules” so that blood components do not stick to the walls of the vascular system, but are freely transported along it.

However, it will still be some time before lab-grown organs with their own blood vessels can actually be implanted.

In the fall of 2008, the head of the clinic of the University of Barcelona (Spain) and the Medical School of Hannover (Germany), Professor Paolo Macchiarini, conducted the first successful operation on transplantation of a bioengineered tracheal equivalent to a patient with 3 cm of stenosis of the left main bronchus.

A 7 cm long segment of cadaveric trachea was taken as the matrix of the future transplant. To obtain a natural matrix, the properties of which are superior to anything that can be made from polymer tubes, the trachea was cleared of the surrounding connective tissue, donor cells and histocompatibility antigens. The cleansing consisted of 25 cycles of devitalization 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 to determine the presence of histocompatibility antigens HLA-ABC, HLA-DR, HLA-DP and HLA-DQ in the tissue. Using a bioreactor of their own design, scientists uniformly applied a cell suspension with a syringe to the surface of a slowly rotating section of the trachea. The graft, half immersed in the culture medium, was then rotated around its axis to alternately expose the cells to the medium and air.

Tissue engineering (TI), as a discipline, began its history in the first half of the 20th century. The foundation for its foundation was theoretical and practical developments in the creation of “artificial” organs and tissues and work on transplantation of cells and biologically active components on carriers to restore damage in various tissues of the body (Langer R., Vacanti J.P., 1993).

Currently, tissue engineering is one of the youngest branches in medicine, based on the principles of molecular biology and genetic engineering. The interdisciplinary approach used in it is aimed primarily at creating new biocomposite materials to restore the lost functions of individual tissues or organs as a whole (Spector M., 1999). The basic principles of this approach are the development and application of carriers made of biodegradable materials, which are used in combination with either donor cells and/or bioactive substances, when implanting into a damaged organ or tissue. For example, when treating wound process- these can be collagen coatings with allofibroblasts, and in vascular surgery - artificial vessels with anticoagulants (Vacanti S.A. et.al., 1993). In addition, one of the serious requirements for such carrier materials is that they must provide reliable supporting, that is, support and/or structure-forming function in the damaged area of ​​the tissue or organ.

Consequently, one of the main tasks of tissue engineering in the treatment of bone pathologies is the creation of artificial biocomposites consisting of allo- and/or xenomaterials in combination with bioactive molecules (bone morphogenetic proteins, growth factors, etc.) and capable of inducing osteogenesis. Moreover, such biomaterials must have a number of necessary bone properties (Yannas I.V. et.al., 1984; Reddi A.H.et.al., 1987; Reddi A.H., 1998).

First, they must scaffold the scope of the defect.

Secondly, it must be osteoidductive, that is, actively induce osteoblasts and possibly other mesenchymal cells to form bone.

And, thirdly, to have good indicators of biointegration and biocompatibility, that is, to be degradable and not cause inflammatory and immune reactions in the recipient. Last quality usually achieved in a biomaterial only by reducing its antigenic characteristics.

The combination of all these properties allows such biomaterials, in parallel with the supporting, mechanical function, to provide biointegration - the ingrowth of cells and blood vessels into the implant structure with the subsequent formation of bone tissue.

It is known that the supporting effect of any biomaterial is ensured, as a rule, by its structural features. For biomaterials, this indicator is usually related to the architecture of the native tissue from which it is obtained. For bone, the main parameters of its structural strength are the hard-elastic characteristics of the bone matrix and the size of the pores in it (Marra P. G. 1998; Thomson R. C. et.al., 1998).

The most common biomaterials with a clearly defined support function include artificial and natural hydroxyapatite (HA), bioceramics, polyglycolic acid, and collagen proteins (Friess W., 1998).

Currently, many are used to replace bone defects in surgical dentistry, orthopedics and traumatology. various forms hydroxyapatite, differing in the shape and size of particles. It is believed that artificially obtained hydroxyapatite is almost identical in chemical composition and crystallographic characteristics to native bone hydroxyapatite (Parsons J., 1988). Many authors have shown both experimentally and clinically that the use of hydroxyapatite has significant advantages over other implantation materials. Thus, its positive characteristics include such indicators as ease of sterilization, long shelf life, high level of biocompatibility and extremely slow resorption in the body (Volozhin A.I. et al., 1993). Hydroxyapatite is a bioinert and highly compatible material with bone (Jarcho M. et.al., 1977), as shown through experimental studies. In the process of replacing a bone defect in the presence of GA under the influence biological fluids and tissue enzymes, hydroxyapatite can be partially or completely resorbed (Klein A.A., 1983). The positive effect of hydroxyapatite after its implantation into the bone cavity is apparently explained not only by the osteoconductive properties of the material, but also by its ability to sorb proteins on its surface that induce osteogenesis (Ripamonti U., Reddi A.H., 1992).

Currently, the bulk of biomaterials for the restoration of bone defects are obtained from cartilage and/or bone tissue of humans or various animals. Often, components of other types of connective tissue - skin, tendons, meninges, etc. - are used to make composite materials. (Vope P.J., 1979; Yannas I.V. et.al., 1982; Chvapel M., 1982; Goldberg V.M. et.al., 1991; Damien C.J., Parsons J.R., 1991).

The most famous of modern biomaterials is collagen. Its widespread use in practical medicine is associated with the development of reconstructive surgery and the search for new materials that perform frame and plastic functions in tissue regeneration. The main advantages of collagen as a plastic biomaterial include its low toxicity and antigenicity, high mechanical strength and resistance to tissue prostheses (Istranov L.P., 1976). Sources of collagen in the manufacture of products for plastic surgery tissues rich in this protein serve - skin, tendons, pericardium and bone. A solution of skin collagen produced by Collagen Corp. is widely used in medical practice. (Palo-Alto USA), under the names "Zyderm" and "Zyplast". Based on this collagen, various medical products have been developed, such as implants, wound coverings, surgical threads for suturing wound surfaces, etc.

In the 70s of the last century, data were first obtained on the effect of collagen grafts on bone tissue repair. It was found that collagen implants promote the proliferation of fibroblasts, vascularization of nearby tissues and, apparently, induce the formation of new bone tissue with its subsequent restructuring (Reddi A.H., 1985). As a rapidly biodegradable material, collagen was also used in the form of a gel for the restoration of bone defects (De Balso A.M., 1976). The results obtained by this author also suggested that collagen-based preparations are capable of stimulating bone tissue regeneration.

At the same time, to replace bone tissue defects, research began on the use of biocomposite materials containing both collagen and hydroxyapatite. Yes, for maxillofacial surgery and surgical dentistry, the compositions “Alveloform” and “Bigraft” were developed, containing purified fibrillar dermal collagen and HA particles (Collagen Corp., Palo Alto, USA). These biomaterials were used to restore the alveolar ridge during the surgical treatment of patients with periodontitis (Krekel G. 1981, Lemons M.M. 1984, Miller E. 1992). Histological and ultrastructural studies have proven that the composition - collagen and HA has a positive effect on the regeneration of the crest bone, but at the same time, this kind of biomaterials perform mainly frame and conductor functions, that is, they exhibit their osteoconductive properties (Mehlisch D.R., 1989). Later, many other researchers came to similar conclusions, and currently this point of view is shared by most scientists (Glimcher M.J., 1987; Friess W., 1992; VaccantiC.A. et.al., 1993).

However, according to another group of researchers, biocomposite materials containing dermal collagen "Ziderm" and synthetic hydroxyapatite have certain ostegenic potencies. Thus, Katthagen et al. (1984), studying the effect of the Kollapat material containing dermal collagen type 1 and highly dispersed hydroxyapatite particles on the restoration of bone defects of the femur in rabbits, found that bone tissue regeneration in experimental animals was 5 times faster than in the control. These experimental results formed the basis for the further use of the Kollapat material in clinical practice.

It is well known that the most suitable for transplantation and subsequent biointegration are undoubtedly autografts, which are prepared from the patient’s own tissues and this completely eliminates the main immunological and most infectious complications during subsequent transplantation (Enneking W.F. et.al., 1980; Summers B.N., Eisenstein S.M., 1989 ; Reddi A.H., 1985; Goldberg V.M. et.al., 1991). However, such materials must be prepared immediately before transplantation, otherwise the clinic must have a bone bank to store such biomaterial, which in reality is only available to very large medical institutions due to the high cost of preparing and storing these materials. In addition, the possibilities of obtaining significant quantities of autologous material are very limited and when it is collected, as a rule, the donor undergoes serious surgical interventions. All this significantly limits the widespread use of autografts (Bos G.D. et.al., 1983; Horowitz M.C. 1991). Consequently, in the field of treatment of bone pathologies, tissue engineering faces a real challenge in creating biocomposite materials, the use of which will provide a solution to many problems both in cell transplantation and stimulation of bone formation in places of damage, and in reducing labor and financial costs when eliminating bone damage in patients. patients of various profiles.

Currently, through the efforts of a number of researchers working in the field of tissue engineering, biocomposite materials have been developed and introduced, which include both native bone marrow cells and stromal osteogenic precursor cells grown in monolayer bone marrow cultures (Gupta D., 1982 ; Bolder S., 1998). These authors found that for successful induction of osteogenesis at the transplantation site it is necessary to create a high initial density of stromal precursors - about 108 cells. However, simply introducing a suspension of such cells did not give good results. In connection with this there arose serious problem searching for carriers for cell transplantation into the recipient's body.

For the first time as such a carrier, Gupta D. et. al. (1982) proposed using xenobone that had previously been defatted and decalcified. It was further found that, depending on the degree of xenobone purification, the percentage of attachment of cellular elements to the carrier increases, and the cells bind much better to its organic part than to natural bone hydroxyapatite (Hofman S., 1999).

Of the synthetic materials, ceramics are currently widely used as carriers for cell transplantation (Burder S. 1998), which is an artificial hydroxyapatite obtained by treating tri-calcium phosphate at high temperatures.

Domestic dental surgeons used solid tissue as a suitable carrier for transplantation of allogeneic fibroblasts. meninges and noted that the use of this graft with allofibroblasts in the treatment of moderate and severe chronic generalized periodontitis has a number of advantages over other treatment methods (Dmitrieva L.A., 2001).

Previously, in a series of works on the construction of “artificial skin,” it was discovered that the success of the restoration of this tissue after its damage depends on the state of the cellular microenvironment in the damaged area. On the other hand, the microenvironment itself is created by an optimal combination of the main components of the intercellular matrix, such as collagens, glycoproteins and proteoglycans (Yannas I. et.al., 1980, 1984; Pruitt B., Levine N., 1984; Madden M. et.al. ., 1994).

Collagen is a typical fibrillar protein. Its individual molecule, tropocollagen, consists of three helical polypeptide chains, called a-chains, which are twisted together into one common helix and stabilized by hydrogen bonds. Each a-chain contains on average about 1000 amino acid residues. There are two main combinations of chains in bone tissue - two λ1 and one λ2 or type 1 collagen and three λ-1 or type III collagen. In addition to the named types, other collagen isoforms were found in the bone in minor quantities (Serov V.P., Shekhter A.B., 1981).

Proteoglycans are complex compounds of polysaccharides and proteins. The polysaccharides that make up proteoglycans are linear polymers built from different disaccharide subunits formed by uronic acids (glucuronic, galacturonic and iduronic), N-acetylhexosamines (IM-acetylglucosamine, N-acetyl-galactosamine) and neutral saccharides (galactose, mannose and xylose). These polysaccharide chains are called glycosaminoglycans. At least one of the Sugars in the disaccharide has a negatively charged carboxyl or sulfate group (Stacy M, Barker S, 1965). Mature bone tissue contains mainly sulfated glycosaminoglycans (sGAGs), such as chondroitin-4- and chondroitin-6-sulfates, dermatan sulfate and keratan sulfate. The biosynthesis of proteoglycans in bone tissue is carried out mainly by activated osteoblasts and, to a small extent, by mature osteocytes (Juliano R., Haskell S., 1993; Wendel M., Sommarin Y., 1998).

The functional significance of sulfated glycosaminoglycans in connective tissue (CT) is great and is primarily associated with the formation of collagen and elastin fibers. Sulfated glycosaminoglycans are involved in almost all metabolic processes of connective tissue and can have a modulating effect on the differentiation of its cellular elements (Panasyuk A.F. et al., 2000). Many indicators of CT regeneration depend on their qualitative and quantitative characteristics in tissues, as well as the specifics of interaction with other components of the intercellular matrix.

Regeneration and restoration of bone tissue are a complex of sequential processes, including both the activation of osteogenic cells (recruitment, proliferation and differentiation) and the direct formation of a specialized matrix - its mineralization and subsequent remodeling of bone tissue. Moreover, these cells are always under the control and influence of a number of biological and mechanical factors.

By modern ideas Tissue engineering (TI) of bone tissue relies on three basic principles to ensure successful replacement of this tissue.

Firstly, the most important principle when creating biomaterials and structures for implantation is to reproduce the basic characteristics of the natural bone matrix, because it is the unique structure of bone tissue that has the most pronounced effect on regeneration processes. It is known that these characteristics of the matrix depend on its three-dimensional structure and chemical composition, as well as on its mechanical properties and ability to influence the cellular forms of connective tissue (CT).

The architecture of the matrix includes such parameters as the surface-to-volume ratio, the presence of a pore system, and, most importantly, its functional and mechanical properties. Through these properties, the matrix appears to be able to regulate vascular ingrowth, provide chemotactic stimuli to endogenous cells, modulate cell attachment, and stimulate division, differentiation, and subsequent mineralization. It is believed that the three-dimensional structure of the matrix can influence not only the induction processes, but also the regeneration rate itself.

Therefore, a biomaterial or structure constructed using tissue engineering must have properties that, under in vivo conditions, can provide both conductive and inductive properties of the natural matrix. The first include such indicators as the ability to fill and maintain volume, mechanical integration, and ensuring permeability to cells and blood vessels. The second - provide a direct or indirect effect on cellular forms, stimulating them to form cartilage and/or bone tissue.

The next important principle for the success of targeted bone tissue engineering is the use of exogenous and/or activation of endogenous cells that are directly involved in the processes of creation of this tissue. In this case, the source of such cells can be either one’s own or a donor’s body. For example, the use of specific cell types, from pluripotent bone marrow stromal cells to committed osteoblast-like cells, has been successfully used both in animal experiments and in the clinic.

As a rule, upon retransplantation into the body, stromal progenitor cells are able to differentiate into mature forms, synthesize a matrix, and trigger a cascade of endogenous bone tissue repair reactions. At the same time, an alternative view on the use of composite biomaterials involves their direct impact on endogenous bone and other connective tissue cells, their recruitment (attraction) to the implantation zone, stimulation of their proliferation and increase in their biosynthetic activity, forcing these cells to actively form bone tissue. In addition, such materials can be good cell carriers on which it is possible to grow stem cells before transplantation. The final key to the success of bone tissue engineering is the use of bioactive molecules, including growth factors, cytokines, hormones and other bioactive substances.

For the induction of bone formation, the most well-known factors are bone morphogenetic proteins, transforming growth factor - TGF-β, insulin-like growth factor IGF and vascular endothelial growth factor VEGF. Therefore, the biocomposite material can be saturated and/or contain these bioactive molecules in its structure, which allows it to be used during implantation as a depot for such substances. The gradual release of these factors can actively influence the processes bone restoration. In addition to these substances, composite materials may include micro- and macroelements, as well as other molecules (sugars, peptides, lipids, etc.) that can stimulate and maintain increased physiological activity of cells in recovering bone tissue.

Currently, there are a large number of different bioplastic materials that have osteoconductive and/or osteoinductive properties. Thus, materials containing almost pure hydroxyapatite (HA), such as Osteogaf, Bio-Oss, Osteomin, Ostim, exhibit mainly conductive properties, although they are capable of exerting a weak osteoinductive effect. Another group of materials consists of completely or partially demineralized bone tissue, as well as combinations of these materials with biologically active substances, such as bone morphogenetic proteins and/or growth factors [Panasyuk A.F. et al, 2004].

The most important requirements for bioplastic materials remain such parameters as their antigenic and inductive properties. In addition, various types of operations often require materials that, along with the above indicators, have good plastic or strength characteristics to create and maintain the necessary shapes and configurations when filling cavities and tissue defects.

Taking into account all of the above, the company "Conectbiopharm" LLC has developed a technology for producing bone collagen and bone sulfated glycosaminoglycans (sGAG) and based on them, biocomposite osteoplastic materials of the "Biomatrix" and "Osteomatrix" series have been manufactured. The main difference between these groups of biomaterials is that “Biomatrix” contains bone collagen and bone sulfated glycosaminoglycans, and “Osteomatrix”, having the same two main components of bone tissue, also contains hydroxyapatite in its natural form [Panasyuk A. F. et al, 2004]. The source of these biomaterials are spongy and cortical bones of various animals, as well as humans. The bone collagen obtained using this technology does not contain other proteins and, under in vitro conditions, is practically insoluble in sufficiently concentrated solutions of alkalis and organic acids.

This property allows biomaterials to be not only inert in relation to immune system body, but also be resistant to biodegradation for a long time after their implantation. Currently, to accelerate the growth of bone and soft tissue, the method of stimulating cells with platelet-rich plasma (PRP) is actively used. This new biotechnology of targeted tissue engineering and cell therapy is, according to some authors, a real breakthrough in surgical practice. However, to obtain such plasma, certain technical equipment is required, and in some cases, specially trained employees. The use of the Biomatrix material for these purposes completely solves the real problem with minimal costs because there is no need to isolate platelets from the patient's blood. In a series of experiments, we established that the Biomatrix material is capable of specifically large quantities bind peripheral blood platelets (Table 1).

Table 1. Binding of blood platelets by bone collagen.

* - 6 ml of blood was incubated with 1 gram of bone collagen (1 gram of dry bone collagen occupies a volume of 2 to 7 cm³ depending on its porosity). The data in the table are presented as the content of platelets in 1 ml of blood after passing it through 1 cm³ of bone collagen.

Thus, 1 cm³ of Biomatrix biomaterial is capable of binding almost all platelets (more than 90%) from 1 ml of blood, that is, from 226 to 304 million platelets. In this case, the binding of platelets by bone collagen occurs quickly and is completed within a few minutes (graph 1).

Graph 1. Rate of binding of blood platelets to bone collagen.

It was also found that if the Biomatrix biomaterial was used without covering with anticoagulants, then the formation of a clot occurred almost instantly. It has now been proven that the working concentration for platelet-rich plasma begins with 1 million platelets per μl. Therefore, to obtain platelet-rich plasma, blood platelets must be concentrated on average 5 times, but such isolation requires both significant financial costs and certain professional experience. In addition, to activate platelets and release 7 growth factors: 3 types PDGF-aa, -bb, -ab, two transforming growth factors - TGF-β1 and β2, vascular endothelial growth factor VEGF and epithelial growth factor EGF - rich Plasma must be coagulated with platelets before use. Compared with known methods, the biomaterial "Biomatrix" can significantly increase the concentration of platelets. At the same time, collagen is precisely the protein that can activate the Hageman factor (XII blood coagulation factor) and the complement system.

It is known that activated Hageman factor triggers a cascade of reactions in the blood coagulation system and leads to the formation of a fibrin clot. This factor or its fragments can also initiate the kallikrein-kinin system of the blood. Thus, bone collagen in the composition of the Biomatrix and Osteomatrix materials is capable of activating the main blood plasma proteolysis systems, which are responsible for maintaining hemodynamic balance and ensuring the regenerative reactions of the body. Unlike platelet-rich plasma, which itself does not have an osteoinductive effect, that is, cannot initiate bone formation without the presence of bone cells, the Biomatrix and Osteomatrix materials have such a potential.

Thus, with intramuscular implantation of biomaterials “Biomatrix” and, especially, “Osteomatrix”, ectopic bone tissue is formed, which directly proves the osteoinductive activity of these materials [Ivanov S.Yu. et al., 2000]. The combined use of platelet-rich plasma with recombinant bone morphogenetic protein, which can stimulate connective tissue cells to form bone tissue, solves this problem, but this leads to a significant increase in the cost of the technique. It should also be noted that the materials of the "Osteomatrix" series contain natural bone hydroxyapatite, which is capable of affinity accumulating on its surface bone morphogenetic proteins synthesized by osteoblasts, and thus additionally stimulating osteogenesis ("induced osteoinduction").

At the same time, the objection about the possibility of tumor development due to the use of recombinant proteins is completely removed because in the case of a similar use of the Biomatrix and Osteomatrix materials, only natural proteins are present in the implantation zone natural origin. Materials of the "Biomatrix" and "Osteomatrix" series also have another unique quality - they are able to bind sulfated glycosaminoglycans with affinity [Panasyuk A.F., Savashchuk D.A., 2007]. This binding, under conditions similar to platelet binding, occurs in a short period of time and the amount of bound sulfated glycosaminoglycans significantly exceeds physiological parameters (Table 2).

Table 2. Binding of sulfated glycosaminoglycans by bone collagen.

It is now well known that, when used separately, both collagen and hydroxyapatite have mainly osteoconductive properties, that is, they can only play the role of a “facilitating” material for the creation of new bone. However, these molecules can also have a weak osteoinductive effect on osteoblastic cells due to some of their biological properties.

This osteoinductive effect is enhanced by the combined use of these two types of molecules. On the other hand, if, along with collagen and hydroxyapatite, sulfated glycosaminoglycans are also present in biomaterials, then such a complex will be closer in structure to the natural bone matrix and, therefore, have its functional characteristics to a fuller extent. Thus, it is known that sulfated glycosaminoglycans affect many indicators of connective tissue metabolism.

They are able to reduce the activity of proteolytic enzymes, suppress the synergistic effect of these enzymes and oxygen radicals on the intercellular matrix, block the synthesis of inflammatory mediators by masking antigenic determinants and canceling chemotaxis, prevent cell apoptosis induced by damaging factors, as well as reduce lipid synthesis and thereby prevent degradation processes. In addition, these compounds are directly involved in the construction of the collagen fibers themselves and the intercellular matrix as a whole.

In the early stages of connective tissue damage, they act as initiators of the creation of a temporary matrix and make it possible to stop the disintegration of connective tissue and the formation of a rough scar, and subsequently ensure its faster replacement with connective tissue usual for a given organ [Panasyuk A.F. et al, 2000]. Unfortunately, the role of sulfated glycosaminoglycans in the regulation of osteogenesis has not been sufficiently studied, however, it has been shown that the main candidate for the role of inducer of ectopic osteogenesis in the model system is proteoglycan secreted by bladder epithelial cells [Fridenshtein A.Ya., Lalykina K.S., 1972] .

Other authors share a similar opinion, believing that proteoglycans are one of the factors of the stromal microenvironment that regulates hematopoiesis and other histogenesis of mesenchymal derivatives. In addition, it has been shown that under in vitro and in vivo conditions, chondroitin sulfates have a pronounced effect on bone mineralization. Thus, we have found that when the Osteomatrix material is exposed to a culture of human chondrocytes, their chondrogenic properties are induced. Under the influence of the material, human chondrocytes formed histotypic structures in culture, in which phosphate deposition and mineralization of the bone matrix occurred during its ossification.

Further, it was found that after implantation of biomaterials “Biomatrix”, “Allomatrix-implant” and “Osteomatrix” into rabbits, ectopic bone is formed and subsequently populated with bone marrow. In addition, these materials were successfully used as carriers for transplantation of stromal progenitor stem cells [Ivanov S.Yu. et al., 2000]. To date, these materials have gained recognition in both dental and orthopedic practice [Ivanov S.Yu. et al., 2000, Lekishvili M.V. et al., 2002, Grudyanov A.I. et al., 2003, Asnina S.A. et al., 2004, Vasiliev M. G. et al., 2006]. They have been used with high efficiency in cases of osteogenesis imperfecta, hand restoration, surgical treatment of periodontal diseases and elimination of jaw bone defects. These biomaterials, thanks to the developed technology for their production, are so far the only materials in the world that almost completely preserve the collagen and mineral structure of natural bone, but at the same time these materials are completely devoid of antigenicity.

The great advantage of these biomaterials is that they contain bone sulfated glycosaminoglycans, affinity bound to collagen and hydroxyapatite, which significantly distinguishes them from analogues available in the world and significantly enhances their osteogenic potency. Thus, the presented experimental and clinical data really prove that, based on modern principles of tissue engineering, domestic biocomposite materials based on bone collagen, sulfated glycosaminoglycans and hydroxyapatite have been developed and introduced into clinical practice. These modern, effective and safe new generation biomaterials open up broad prospects for solving many problems of bone tissue restoration in traumatology and orthopedics, as well as in many other areas of surgical practice.

The electronogram (Fig. 1) shows that bone collagen preparations are a network of ordered bundles and fibers. At the same time, the fibers themselves are tightly packed into second-order bundles, without breaks or defects. In appearance, the material has a classic porous-cellular structure, which fully corresponds to the architectonics of native cancellous bone and is free from blood vessels, proteins, mechanical and other inclusions. The pore size ranges from 220 to 700 microns.

We assessed the biocompatibility of bone collagen using standard tests when they were implanted under the skin of Wistar rats. Using histo-morphological analysis and scanning electron microscopy, it was found that bone collagen, after a month and a half stay in the recipient’s body, is practically not destroyed and retains its structure.

Fig 1. Fig 2.

As can be seen in Fig. 2, the pores, trabeculae and cells of the implanted bone collagen are partially filled with loose fibrous CT, the fibers of which are weakly fused to the implant. It is clearly visible that a slight fibrous layer is formed around it, and in the implant itself the presence of a small number of cellular elements is noted, the main of which are fibroblasts. It is characteristic that the implant is not fused with the surrounding dermal tissue throughout almost its entire length. These results clearly indicate the high resistance of this material to biodegradation and the complete bioinertness of the surrounding connective tissue in relation to it.

We conducted studies on the effect of biomaterials “Biomatrix”, “Allomatrix-implant” and “Osteomatrix” on osteoreparation on a model of segmental osteotomy using generally accepted methods (Katthagen B.D., Mittelmeeir H., 1984; Schwarz N. et.al., 1991). The experiment used Chinchilla rabbits weighing 1.5-2.0 kg, which underwent segmental osteotomy of the radius under intravenous anesthesia.

Two months after the operation, the formation of new bone tissue was noted in the implantation area. In Fig. 3 is the result of a histomorphological study of the Allomatrix-implant material after 2 months. after operation. In the proximal zone of the defect, well-developed young bone tissue is visible. Osteoblasts are adjacent to bone beams in large numbers.

In the interstitial substance, ostecytes are found in the lacunae. Densely packed collagen fibers are formed in the new bone substance. The interstitial substance with active cells is well developed. The implant area (top and left) is actively being rebuilt.

In general, there is accelerated maturation of bone tissue around the implant area.

In addition, it turned out that the porous-cellular structure of bone collagen provides not only the maintenance of volume in the defect due to its elastic properties, but also the optimal opportunity for the ingrowth of connective tissue cells into it, the development of blood vessels and bone formation when replacing this defect.

Definition One of the areas of biotechnology that deals with the creation of biological substitutes for tissues and organs. Description The creation of biological tissue substitutes (grafts) includes several stages: 1) selection and cultivation of one’s own or donor cellular material; 2) development of a special carrier for cells (matrix) based on biocompatible materials; 3) applying a cell culture to the matrix and cell proliferation in a bioreactor with special cultivation conditions; 4) direct introduction 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). The cellular material can be represented by cells of the regenerated tissue or stem cells. To create graft matrices, biologically inert synthetic materials, materials based on natural polymers (chitosan, alginate, collagen), as well as biocomposite materials are used. For example, bone tissue equivalents are obtained by directed differentiation of stem cells from bone marrow, umbilical cord blood or adipose tissue. Then the resulting osteoblasts 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 currently widely used in the USA, Russia, and Italy. These designs can improve the healing of extensive burn surfaces. 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. The use of stem cells is widely used in the field of tissue engineering, but has limitations both ethical (embryonic stem cells) and genetic (in some cases, malignant division of stem cells occurs). Research recent years showed that with the help of genetic engineering manipulations it is possible to obtain so-called pluripotent stem cells (iPSc) from skin fibroblasts, similar in their properties and potential to embryonic stem cells. Metal nanoparticles in tissue engineering are used to control cell growth by influencing them magnetic fields different directions. For example, in this way it was possible to create not only analogues of liver structures, but also such complex structures as elements of the retina. Nanocomposite materials also provide nanoscale surface roughness of matrices for the effective formation of bone implants using electron beam lithography (EBL). The creation of artificial tissues and organs will eliminate the need for transplantation of most donor organs and will improve the quality of life and survival of patients. Authors

• Naroditsky Boris Savelievich, Doctor of Biological Sciences
• Nesterenko Lyudmila Nikolaevna, Ph.D.

1. Nanotechnology in tissue engineering / Nanometer. - URL: http://www.nanometer.ru/2007/10/16/tkanevaa_inzheneria_4860.html (access date 10/12/2009)
2. Stem cell / Wikipedia - the free encyclopedia. URL: ttp://ru.wikipedia.org/wiki/Stem cells (access date 10/12/2009)

encyclopedic Dictionary nanotechnology. - Rusnano. 2010 .

See what “tissue engineering” is in other dictionaries:

tissue engineering- Methods for controlling body cells in order to form new tissues or express biologically active substances Biotechnology topics EN tissue engineering ... Technical Translator's Guide

The term bioengineering The term in English bioengineering Synonyms biomedical engineering Abbreviations Related terms biodegradable polymers, biomedical microelectromechanical systems, biomimetics, biomimetic nanomaterials, ... ...

The term biomimetic nanomaterials The term in English biomimetic nanomaterials Synonyms of biomimetics, biomimetics Abbreviations Related terms proteins, biodegradable polymers, bioengineering, biomimetics, biocompatibility, biocompatible... ... Encyclopedic Dictionary of Nanotechnology

Vadim Sergeevich Repin Date of birth: July 31, 1936 (1936 07 31) (76 years old) Place of birth: USSR Country ... Wikipedia

- (Latin placenta, “cake”) an embryonic organ in all female placental mammals, some marsupials, hammerhead fish and other viviparous cartilaginous fish, as well as viviparous onychophorans and a number of other groups of animals, allowing ... ... Wikipedia

Contains some of the most outstanding current events, achievements and innovations in various fields modern technology. New technologies are those technical innovations that represent progressive changes within the field... ... Wikipedia

Articlesamphiphilicbiodegradable polymersbiological membranebiological motorsbiologicalatingsbisl... Encyclopedic Dictionary of Nanotechnology

Articles"two-faced" particlesactuamotorsbiological nanomaterialsbiosensbased on nanomaterialshydrogen bond... Encyclopedic Dictionary of Nanotechnology

Articles "soft" chemistrybiological membranebiomimeticsbiomimetic nancoatingsbilayer engineeringhybrid materialsDNADNA microchipgene deliverycap... Encyclopedic Dictionary of Nanotechnology

This is a service list of articles created to coordinate work on the development of the topic. This warning does not apply... Wikipedia

Books

• Tissue engineering, Creative team of the show “Breathe Deeper”. Fundamentally new approach– cell and tissue engineering – is the latest achievement in the field of molecular and cellular biology. This approach opened up broad prospects for creating... audiobook