Cell-free organic tissue prepared for vitality recovery and methods for preparing it

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is described is a method for preparing a cell-free organic tissue of a human or animal origin for the vitality recovery, particularly for introducing living cells, involving a stage of making a number of holes (4; 14) in the cell-free organic tissue (2; 12) through its surface (8; 18) and setting in the tissue (2; 12); wherein the said number of holes (4; 14) is formed using a needle or a kit of needles. The holes (4; 14) are partially intersected thereby forming partially connected holes (4; 14).

EFFECT: invention also refers to a respective cell-free organic tissue (2; 12) of the human or animal origin.

17 cl, 3 dwg

 

The technical FIELD TO WHICH the INVENTION RELATES

The invention relates to a method of preparation of acellular organic tissue of human or animal origin for transplantation, in particular for the introduction of living cells containing the stage at which the surface of the acellular organic tissue is supplied with a set of apertures passing inside fabric, in which the specified number of holes made through one or more needles.

PRIOR art

As you know, in medicine, in particular in the field of surgery, it is extremely important to be able to use tissue that can be implanted in living beings, in order to meet the growing need for replacement of parts of the body or whole organs.

Production of biological substitutes that are prepared in the laboratory and then implanted donor, whether it be animal or human, relates to medical technology and is known as tissue engineering.

According to known technique, the preparation of tissue for transplants are done in the laboratory by injecting the cells into the matrix consisting of inorganic bases, usually referred to as "frame".

The frame is inserted, in order to replace the damaged organ to be treated, promotes three-dimensional organization of glue is OK, until the tissue is completely formed.

Obviously, this frame must go through a process of destruction, until it completely disappears and it is replaced by regenerated tissue, this process is carried out by cells transplanted on the frame.

Grafts obtained with this system can be obtained as with artificial frames, and natural (from the "donor"), which can be obtained from humans and animals, for example the wall of the esophagus.

About artificial fabrics there are many publications, among them we can mention the following: Tiaw for K.S. et al. in "Laser surface modification of poly(epsilon-caprolactone) (PCL) membrane for tissue engineering applications (Biomaterials 26 (2005) 763-769); Tejas S. Karande et al. in "Diffusion in Musculoskeletal Tissue Engineering Scaffolds: Design Issues Related to Porosity, Permeability, Architecture, and Nutrient Mixing" (Annals of Biomedical Engineering, Vol. 32, no. 12, December 2004, p. 1728-1743); Tejas S. Karande and With Mauli Agrawal in "Functions and Requirements of Synthetic Scaffolds in Tissue Engineering" ("Nanotechnology and Tissue Engineering: The Scaffolds", 2008 CRC Press, Taylor & Francis Group, 6000 Broken Sound Parkway NW, Suite 300, BOCA RATON, FL 33487-2742 USA, p. 53-86); Curtis D. Chin et al. in "A microfabricated porous collagen-based scaffold as prototype for skin substitutes" (Biomed Microdevices (2008) 10:459-467).

Described synthetic fabrics have structural porosity obtained artificially, which can be done in a certain way, to provide sufficient migration within tissue.

Only in recent publications mentioned property, to the m cylindrical pores (taken in porous fabric) contribute significantly to improving the penetration of cells.

The skeleton of a human or animal already has a natural porosity of the organic material which has a homogeneous structure, reminiscent of the pores of the sponge.

In order to be able to use the frame received from the donor, and then transplant to a person, it is necessary to pre-treat the fabric in such a way as to completely delete all cells that are between the fibers of the connective tissue, and sequentially enter human cells belonging to the recipient, to avoid rejection.

Methods of manufacture of the frame, that is acellular matrix, starting with capture from a donor tissue, known and therefore not described in detail because they largely consist in immersing the fabric, which must be processed in a liquid containing the enzyme substance, able to digest and destroy the living cells contained in the tissue, at the same time keeping the fibers of the connective tissue intact.

As soon as acellular tissue of human or animal origin, ready to receive cells taken from the recipient is received, the fabric or frame is placed in the so-called "Petri dish", a small container used in each biological laboratory, at the bottom of which is placed the tissue for transplantation, or in the same condition the device.

Grafting occurs by injecting stem cells of the recipient, grown in a culture medium in which cells eat, live, breed and spread out.

Basically, stem cells, which initially lie on the surface of the tissue, penetrate through the natural pores of this tissue, occupying the spaces that were previously occupied by the donor cells.

After a certain period of time during which regulates the temperature, and the presence in the culture medium nutrient living cells move into the interstitium fabric that is ready for implantation in the body of the recipient.

It may be noted that usually the cells used to restore the frame are stem that will differentiate or already differentiated and will assume a specific function of the organ that is transplanted recovered tissue.

The success or failure of the transplant tissue prepared as described above, depends on the capillary diffusion of cells within a tissue.

If the diffusion is hindered or surface and does not penetrate into the thickness of the transplanted tissue cannot be restored and often leads to necrosis, which means that the transplant will fail.

The above clearly shows that a necessary and important condition that has to be done is but from which you cannot retreat, is an in-depth restoration of the viability of tissue in all its parts, and first more...)

Currently, even if the preparation and restoration of viability is carried out for a sufficiently long period of time, certain results, guaranteeing the success of transplantation, can be obtained.

This is due to a lack of deep penetration of living cells that must be placed on the frame. In fact, this drawback severely limits the possibilities of the prepared tissue suitable for transplantation, and too thick fabrics, the thickness of which is impossible to penetrate, after transplantation do not restore the vitality completely. It is therefore evident that the described method is suitable for grafting with a very limited thickness, such as not greater than about 0.1 mm

In order to eliminate this drawback, in WO 2008/146106 A2 in the name of the present applicant, describes the way in which acellular organic tissue with openings to facilitate the distribution of cells throughout the tissue. In the US 5112354 described perforating the bone part, designed to increase the surface exposed to demineralized funds, which contributes to the interaction with mesenchymal cells entered for osteoinductive. In the US 2007/0248638 A1 describes SPO is about making biocartis of natural tissues by oxidation of cell-free tissue to increase the current day.

According to the mentioned documents despite a significant improvement compared with the traditional methods of simple perforation of the fabric to prepare it for injection of cells, achieving uniform penetration of cells is still quite time consuming, particularly if the fabric is very thick or stretched.

Therefore, the natural porosity of the fabric of human or animal origin together with the holes made by the method described in WO 2008/146106 A2, is not optimal from the point of view of the migration of cells within a tissue.

Description of the INVENTION

The present invention is to provide a method of preparing acellular organic tissue of human or animal origin, ready to move in living cells and capable of overcoming the disadvantages mentioned above.

In particular, the object of the invention is to provide a method for preparation of acellular organic tissue so that when the fabric is restored by using stem cells, compared with the existing prior art cells are easier and penetrate into each internode grid formed by connective tissue fibers.

Also the object of research is getting more important and significant reduction in processing time required for the formation of cell-free frame, when you enter live cells, designed to prepare tissue for transplantation.

Thus, one object of the invention is to develop a method of obtaining ready acellular organic tissue in an improved form for uniform and rapid introduction of the recovered cells.

The objective of the invention is achieved by the method described initially, in which the holes passing from the outer surface of tissue inside overlap at least partially, forming openings, which at least partially communicated with each other.

In other words, the fabric, which can be obtained by the method described in the invention, equipped with a variety of holes and each reported along the entire length with one or more other hole, thus forming a mesh structure. Mesh communicating hole greatly increases the speed with which they can be filled in reducing the viability of the cells. In addition, the mesh structure promotes uniform distribution of cells.

In the simplest case, these communicating holes, mostly straight, do needle through the outer surface of the specified fabric so that the holes overlap. The use of curved needles may also be taken into account.

None of the documents ashestoashes the prior art does not disclose communicating with each other holes added to the holes that are related to the structural porosity of the fabric. On the contrary, in the documents relating to artificial tissues, is considered the structural porosity (and only in one case, article Curtis D. Chin, the use of an additional cylindrical holes that are isolated from each other), which is satisfactory from the point of view attainable degree of penetration of the cells.

In accordance with the present invention, holes are made so that their depth is at least partially extends in the thickness of the fabric, but preferably almost the entire thickness of the tissue or, in special cases, the entire thickness of the fabric.

On the side opposite the perforated surface, it is desirable to leave a thin non-perforated layer to prevent leakage of the introduced cells.

Mostly holes evenly distributed throughout the tissue and along all its sides.

Holes can be made in the thickness of the fabric using a needle and a variety of ways, provided that the execution of these holes will not result in deterioration or changes (rupture, necrosis, decrease or increase thickness, changing the composition of the liquid, coagulation) of the connective tissue around the hole and, in any case, the frame as a whole.

According to a particularly preferred variant of the invention the fabric is also equipped with Palast the mi tanks, communicating at least part of the above mentioned holes. Oral tanks can be seen as deepening, i.e. the storage of reserves of the cells for introduction into the tissue, comparable warehouse stocks of cells in the body (for example, storage of epithelial cells in the intestine).

If the cells for introduction into the tissue is not simply distributed on the surface of the fabric, and placed in the cavity of the tank, made in fabrics that are communicated to at least part of the holes, it is possible to further improve the uniformity of cell distribution and further accelerating the penetration of cells throughout the tissue.

The formation of cavities tanks connected to at least part of the above mentioned holes, increases for cells belonging to the cloth (and placed in the cavity of the reservoir), the number of access points to the mesh hole.

Mainly oral tanks are located on the surface of the fabric to facilitate the filling of the cells, that is, to provide easy access to them. Preferably the cavity of the tank evenly distributed.

The resulting diameter of the holes in any case should be sufficient for easy ingress cells in these holes and restore the surrounding tissue.

Relative to the size of the cells, their size should be at least 50 microns.

the selection of the diameter should also be carried out depending on the need to preserve the structural integrity of the tissue, whilst the rapid penetration and complete filling of the holes.

Oral tanks can be prepared before or after the formation of holes.

Preferably the channels are introduced after the creation of cavities tanks, to ensure the durability of the fabric.

Oral tanks basically cylindrical, with a diameter of approximately 1 mm For this problem is especially suitable cavity tanks with a diameter of 700 μm to 1 mm, an essentially cylindrical cavity of the tanks can be easily created as holes, made of a suitable needle, having a corresponding diameter. Obviously, the diameter of the cavities tanks must not be such as to weaken the structure of the tissue. The diameter of the cavities of the tanks should be greater than the diameter of the channels, communicating with them, so that the cavity of the tanks could serve as reserves of cells, and that the channels do not become an additional cavity tanks that will weaken the structure of the fabric itself. The depth of the cavities of the tanks depends on the characteristics of the fabric and can easily be optimized by the person skilled in the art in accordance with the needs.

The same applies to the distance between the channels and cavities of the tanks.

Can be provided by the same distance of about 200 μm between the individual cavities tanks, and more than on the other or short distances.

You must choose the ideal distance in accordance with the needs from the point of view of speed of penetration and stability of the fabric.

In another preferred embodiment of the invention the holes are different from each other in diameter. The same applies to the cavities of the tanks, which may even have a different inside diameter tissue. The choice of the distribution of diameters should be determined by the tradeoff between the increase in the rate of penetration, which, of course, increases with increasing diameter, and the need to avoid excessive weakening of the strength of the fabric in the result of excessive perforation. The ability to change the diameters of the holes on the inside fabric creates greater flexibility in regulating the balance between accelerated penetration and strength of the fabric.

Preferably, in order to effectively prevent problems necrosis in the formation of holes and/or cavities tanks specified set of apertures and/or cavities tanks made by one or more metal needle, connected to a power source, calling on the tip of each needle passing an electric current of such intensity and waveform to provide an amount of energy sufficient to break links that connect molecules organic t the Ani in the immediate vicinity of the tip of the specified needle, as described, for example, in the already mentioned WO 2008/146106 A2.

In this case, each hole is such that the specified tip of the needle penetrates into the space left free by breaking the specified molecular bonds, and forms these holes. It should be understood that the holes and/or cavities tanks can also be made by another method, for example mechanically.

The best results from the point of view of quality holes/cavities tanks made in the tissue, is achieved by applying a voltage of high frequency at the tip of each needle, typically 4 MHz, creating an electrical current that is weak, but enough to break the nexus between the molecules of connective tissue, so that a hole without destruction of the molecules. Preferably the holes and/or cavities tanks made with a needle, which is energized with a frequency of 4 MHz, above.

Preferably the voltage is 200-230 Century Mainly applied sinusoidal voltage is distorted sine wave with harmonics at least first, second and third order.

Available at the tip of each needle current is preferably adjusted to have a value of from 2 to 2.5 mA.

It is logical and obvious that the formation of several perniciosi the Xia hole means creating new ways for transplantation of cells in the deep layers of tissue, it ensures complete restoration of the viability of the tissue.

Preparation of acellular organic tissue for transplantation may include the steps of applying various materials, for example, leaching solutions, nutrient solutions, different cell types (e.g., autologous cells, cells from another donor or other type of cells, which must be differentiated or already differentiated) and so on. Mainly the introduction of these materials into the holes occurs with suction system, which contains the actuator, suitable to facilitate the ingress of material into the holes.

The suction system may include a peristaltic pump. Cloth, prepared for the revitalisation according to the present invention, similar to permeable sponge for liquids, but also for cells along the holes. In the case when the fabric is supplied through the holes and, therefore, does not have a non-perforated layer on the side opposite the perforated surface, the fabric is on biodegradable membrane with micropores permeable to liquid, but not cells, thereby preventing the leakage of the cells during the suction phase.

Mostly the holes drilled in the tissue with a needle or set of needles are moved and tilted with the accordance with the command of the control system, which works according to the algorithm, which ensures that the holes are formed so as to overlap with a predetermined density, i.e. forming a certain number of points where they cross each other.

The method described above can be used for all types of organic tissue.

Acellular tissue, provided with connecting holes, can be recovered by using all types of cells suitable for further use of the fabric.

The fabric of the present invention creates virtually no restrictions on the thickness of tissue for transplantation, since the communicating holes that can be made through the entire thickness of the fabric and across its surface, ensures full recovery. This is due to the fact that living cells are again placed in a cell-free frame and, preferably, in the cavity of the tank, can reach every part of the fabric.

The method according to the present invention allows to obtain an acellular organic tissue of human or animal origin, prepared to restore viability, in particular for the introduction of living cells that contains holes that are made by the puncture needle and pass from the surface of the fabric inside it where the holes overlap, at least partially, the investigator is about, at least partially communicated with each other.

In accordance with the variants of the method described above, the fabric may also contain cavities tanks. Holes and/or cavities tanks in tissue prepared according to the invention, have the features of, in particular diameters, depths and distances described above.

Variants of design of the present invention are subject to additional claims. Additional features and details of the invention will be disclosed in more detail in the description of the preferred variants of the invention are presented as examples that do not have restrictive.

BRIEF DESCRIPTION of DRAWINGS

Further, the invention is illustrated with the help of the attached drawings, on which:

Figure 1 - schematic cross-section of acellular organic tissue, prepared for the revitalisation and provided with connecting holes;

Figure 2 is a top view of acellular organic tissue, prepared for the revitalisation and provided with cavities tanks and holes;

Figure 3 is a section along the line III-III of the fabric of figure 2.

DESCRIPTION EXAMPLES

As shown in figure 1, the fabric, indicated generally by the number 2, is equipped with a number of holes 4, which intersect at the points 6 ruggedness, demand of the Oia and therefore, communicated with each other.

In the above example, all holes 4 are tilted with respect to the surface 3 fabric 2.

Obviously, penetration/perforation should be repeated over the entire surface 8 of the frame 2 to obtain a uniform distribution of holes 4 through the entire thickness and the entire useful area of the fabric 2 for transplantation.

Figure 2 shows a top view of an additional variant of the invention, in which acellular organic tissue 12 is equipped with not only the holes (to simplify the holes shown only in cross section in figure 2, that is, figure 3), but the cavities of the tank 20.

The drawing shows a lot of cavities tanks 20 in the form of large circular holes on the surface 18 of the fabric 12.

Finally, figure 3 shows in cross section along the line III-III in figure 2 as holes 14 are communicated with each other and the cavities of the tank 20.

Since the number of holes 4, 14 (and, if necessary, cavities tanks 20) performed in cell-free tissue 2, 12, as described above, it is clear that the specified fabric without cells can be placed in a Petri dish or similar device, which entered the living cells, usually stem type, the future recipient.

These stem cells are receiving proper nutrition in the media for cultivation, can easily and quickly get all available holes 4, 14, thus guarantee the associated full and effective restoration of the viability of the entire tissue for transplantation.

Standard process has the following stages: organic fabric 2, 12, no cells and pre-processed, called frame, is placed on a flat surface and distribute it. The needle serves electric current thereby to apply for molecules fabric to handle this amount of energy, which is enough to break the bonds between molecules, in which the current flows, while the surrounding area is not affected tearing or damaging effect, not subject to necrosis, increase or decrease the thickness or changing the composition of the liquid, coagulation or other degenerative effects.

Mainly, this break the molecular bonds is equivalent to the formation of micro-holes 4, 14, which in practice have the same diameter, and each needle, given that in any case the minimum diameter of the needle may not be less than the diameter of restoring the viability of the cells.

Thus, the needle slowly enough so that while moving the tip finds a hole, already prepared with the passage of the current and subsequent rupture of molecular bonds.

Cavity of the tank 20 can be prepared in the same way, selecting a needle of suitable diameter, preferably, but not necessarily, to make hollow tanks to the hole.

The formation of the W grid of holes is very important and useful because the cells are re-introduced, can penetrate deep into the tissue and to settle down in the walls of the hole, to multiply and therefore very quickly to restore the entire organic fabric.

It should be understood that the method and the fabric of the present invention successfully solves all issues of the invention is achieved because the perfect and effective restoration of viability, thus precluding any risk of transplant rejection, which must be replanted.

In addition, the recovery process is even faster and with a more uniform distribution of cells than in the known methods.

In practice, the present invention may be further amended or can be used variants of the method according to the invention, not described in this document.

All these changes or options should be reasonably protected by the present patent, provided that they are included in the scope of protection of the attached claims.

If the technical features mentioned in any claim are referred to the reference positions, these reference positions are added solely to enhance the clarity of the claims and, accordingly, such reference position does not have any limiting effect on the scope of protection of each e is ment, indicated for example by such reference positions.

1. The method of preparation of acellular organic tissue of human or animal origin for the revitalisation containing the stage at which the specified acellular organic tissue (2; 12) perform a variety of openings (4; 14), passing through its surface (8; 18) and included inside fabric (2; 12), with the specified number of holes (4; 14) perform using a single needle or multiple needles, characterized in that the openings (4; 14) overlap at least partially, thus forming a hole (4; 14)that communicate at least partially with each other.

2. The method according to claim 1, characterized in that it also contains the phase in which the tissues (12) create a cavity reservoir (20), who reported at least part of the holes (14).

3. The method according to claim 1, characterized in that the preparation of acellular organic tissue is carried out for the introduction of living cells.

4. The method according to any one of claims 1 to 3, characterized in that the said holes and/or cavities of tanks performed by one or more metal needle, connected to a power source that generates at the end of each needle electric current of such intensity and waveform to apply sufficient energy to break the SV is zi, which is connected molecules of organic tissue near the end of this needle.

5. The method according to claim 4, characterized in that the electric current is determined by the voltage frequency of 4 MHz, while the applied sinusoidal voltage is distorted sine wave and, consequently, with harmonics at least first, second and third order.

6. The method according to any one of claims 1 to 3, characterized in that the openings (4; 14) have a diameter of at least 50 microns.

7. The method according to claim 2, characterized in that the said cavity reservoir (20) is made essentially cylindrical and have a diameter of up to 1 mm.

8. The method according to any one of claims 1 to 3, characterized in that the openings (4; 14) have different diameters.

9. The method according to claim 2, characterized in that the said cavity reservoir (20) have different diameters.

10. The method according to any one of claims 1 to 3, characterized in that it contains the phase in which the openings (4; 14) using suction systems impose different materials, the materials are selected from cleaning solutions, nutrient solutions and/or living cells.

11. The method according to claim 2, characterized in that the holes have a diameter of at least 50 μm, the cavity of the tank (20) is made essentially cylindrical and have a diameter of up to 1 mm.

12. The method according to claim 11, characterized in that it contains the phase in which the openings (4; 14) with what omashu suction systems impose different materials, this material is chosen from cleaning solutions, nutrient solutions and/or living cells.

13. The method according to any of claim 2, 11 or 12, characterized in that the said hole and the said cavity of the tanks are of different diameter.

14. The method according to any of claims 7, 11, or 12, characterized in that the said holes and/or cavities of tanks performed by one or more metal needle, connected to a power source that generates at the end of each needle electric current of such intensity and waveform to apply sufficient energy to break the bonds which connected the molecules of the organic tissue near the end of this needle.

15. The method according to 14, characterized in that the electric current is determined by the voltage frequency of 4 MHz, while the applied sinusoidal voltage is distorted sine wave and, consequently, with harmonics at least first, second and third order.

16. The method according to claim 10, characterized in that the said holes and/or cavities of tanks performed by one or more metal needle, connected to a power source that generates at the end of each needle electric current of such intensity and waveform to apply sufficient energy to break the bonds which connected moleculargenetic tissue near the end of this needle.

17. The method according to item 16, wherein the electric current is determined by the voltage frequency of 4 MHz, while the applied sinusoidal voltage is distorted sine wave and, consequently, with harmonics at least first, second and third order.



 

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24 cl, 4 dwg

FIELD: medicine.

SUBSTANCE: what is described is a method for applying a chitosan coating on a pericardial surface of a biological heart valve prosthesis by direct chitosan application from a non-immunogenic solvent absolutely biocompatible with a human body and possessing antimicrobial properties, - high-pressure carbonated water, onto the pericardium of the biological heart valve prosthesis pre-processed with 0.625% glutaric aldehyde. The method for chitosan coating from high-pressure carbonated water enables providing higher effectiveness and prolonged functioning of the biological heart valve prosthesis ensured by avoiding formation of deposited calcium on the surface, providing better elasticity, enhancing antimicrobial properties enabled by the chitosan coating on the surface.

EFFECT: making the non-immunogenic calcification resistant biological heart valve prostheses possessing the antimicrobial properties.

12 cl, 1 dwg, 4 tbl, 12 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to surgery, and may be used in reconstructive surgery for performing endoscopic operations. Cadaveric dura mater tissue is prepared. The prepared dura mater is immersed into a preserving solution. Dura mater biografts are de-frozen, and the adequate biografts are cut out. The prepared grafts are packed into plastic bags and lyophilised. The prepared graft is split out to make a dura mater biograft 0.2-0.4 mm thick.

EFFECT: developing the method for making a biocompatible and thinned human dura mater biograft that makes it applicable in endoscopic operations.

4 cl, 1 tbl, 1 ex, 2 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to methods for improving the biocompatibility of valve and vascular grafts ensured by reducing the immunogenicity and preventing the calcification. The method for improving the biocompatibility of valve and vascular grafts consists in pre-incubation of the tissue grafts in normal saline containing 0.9% sodium chloride, EDTA (0.5-2 mM), organic buffer HEPES (5-20 mM) at pH 7.0 for 4-6 hours, incubation in normal saline containing 0.9% sodium chloride, HEPES 5-20 mM (pH 7.8), 1% sodium deoxycholate for 30-48 h; the tissue grafts are washed from sodium deoxycholate in a solution containing 0.9% sodium chloride, HEPES 5-20 mM (pH 7.8) and 20% ethanol for 8 days with the medium replaced for the fresh one every day and washed from ethanol for one day.

EFFECT: method for improving the biocompatibility enables preventing the graft calcification, reducing their cell toxicity and the immune response to the tissue grafts.

3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and pharmacology, and represents a bioengineered collagen construct for reconstruction or replacement of damaged tissue, characterised by the fact that it comprises a layer of a purified collagen tissue matrix taken from the small intestinal submucosa, wherein said purified collagen tissue matrix is processed by a pharmaceutically acceptable antimicrobial agent and has the anti-microbial properties.

EFFECT: invention provides the bioengineered collagen construct with the improved antimicrobial properties.

17 cl, 11 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is described is a sterile dehydrated cell-free implant which when rehydrated by water or body fluids is exposed to anisotropic expansion, and can be used as a substrate for living cell adhesion, migration and growth. Collagen structures of a transplant are at least partially denatured after exposure to heat or organic solvents, such as lower aliphatic alcohols and ketones which are simultaneously preserving and sterilising agents, especially with respect to specific types of viruses. The implant is sterilised by radiation, preferentially by accelerated electrons, practically in the dehydrated condition. The transplant can be produced of various animal tissues, especially of mammalian tissues, such as human or swine tissues. Tissues suitable for the prevent invention can represent, e.g. skin, placenta, pericardium, peritoneum, intestinal wall, tendon, blood vessel, etc.

EFFECT: dehydrated implant is suitable as a temporary coating for a wound or a burn, for recovery, replacement and regeneration of tissues, and also as a substrate for cell cultivation in the laboratory conditions, and easier to flex, and being less fragile.

31 cl, 8 dwg, 6 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine. The group of inventions consists of two objects: a method of processing and a biological tissue. The method is characterised by taking the biological tissue stabilised by glutaric dialdehyde and presented by both animal and human biological tissue, e.g. swine or bovine pericardium or human cadaver mitral valves wherein physical plasma processing, particularly of collagen tissue is performed.

EFFECT: group of inventions provides higher biocompatibility of biological tissue, cell colonisation and prolonged service life.

9 cl

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine, and can be used for production of transplantable tissues. A method for cell-free organic tissue preparation for living cell reimplantation involves cell-free tissue preparation on a substantially flat surface and creation of a number of holes on the surface, spaced along the whole surface mentioned above and arranged so that they penetrate deep down at least a portion of thickness of said tissue with the holes designed for keeping the reimplanted living cells. Said number of the holes is created by means of one or more metal needles connected to a power supply which on each needle point induces current flow of such intensity and of such waveform to provide adequate energy for destruction of molecular couplings comprising organic tissue near to the needle point mentioned above. Each hole is formed by current flow and is great enough that the needle point mentioned above could penetrate into a space formed by opening of the molecular couplings. The group of inventions also refers to cell-free organic tissue for living cell reimplantation produced by said method.

EFFECT: group of inventions enables reducing time of producing transplantation tissue and provides living cell penetration along the whole thickness of cell-free tissue.

24 cl, 4 dwg

FIELD: medicine.

SUBSTANCE: acellular transplant is described comprising (i) a connected skeletal matrix with openness of pores of biologically and pharmaceutically usable material and (ii) human serum. In accordance with a particularly preferred embodiment, the matrix also contains a gel. Also the method of manufacturing such acellular transplant is described when the matrix and the gel contact with human blood serum. If necessary, the transplant and the serum can be dried. Alternatively, the matrix and the gel can be presented in a dry form prior to contacting. Use of acellular transplant for regeneration of tissues and in particular for regeneration of cartilage and/or bones is also described.

EFFECT: transplant is easy to manufacture, long stored and easy to use.

16 cl, 2 dwg, 2 ex

FIELD: medicine.

SUBSTANCE: there is offered method for chemical treatment of xenopericardium that involves chemical stabilisation of xenopericardium with 0.625% glutardialdehyde and following processing with 1% sodium dodecyl sulphate; chemically stabilised xenopericardium is additionally processed with 0.05÷0.25% aqueous solution of chitosan or metal-containing chitosan with deacetylation degree 50÷98% and molecular weight 4÷140·103 at pH 3÷5; upon termination of processing, xenopericardium is fixed in 70% aqueous solution of ethanol; then modified xenopericardium is kept in 0.10÷0.50% aqueous solution of chitosan N-sulphosuccinate with molecular weight 10÷166·103 or chitosan 3,6-O-disulphate with molecular weight 7÷180·103 at pH 4÷8 during 20÷60 mines at temperature 20÷30°C with following fixation in absolute ethanol.

EFFECT: improved durability and biocompatibility of bioprostheses.

3 ex, 7 tbl, 3 dwg

FIELD: medicine.

SUBSTANCE: method involves chemical stabilisation of biotissue with 0.625 % aqueous solution of glutaraldehyde, pH 7.4, followed with preparation with a surface-active substance and quadruple change of a working solution. Immediately ahead of implantation, bioprostheses are thoroughly washed with sterile physiologic saline sixfold changed, at 500 ml of the solution for 100 g of biotissue. Then it is processed with 0.05-0.5% aqueous solution of chitosan N-sulphosuccinate of molecular weight 50-150 kDa in intensive stirring during 0.5-2 h with pH within 5 to 8, and to temperature 22±2°C. Further, it is fixed in sterile absolute ethanol and put in sterile physiologic saline, and stored at temperature 6-8°C before implantation.

EFFECT: improved durability of bioprostheses.

5 ex, 4 tbl

FIELD: medicine.

SUBSTANCE: bone-and-mineral product contains porous bone mineral particles produced from natural bone and having crystalline structure practically corresponding to natural bone structure and practically containing no endogenous organic material. The particles have fibers of physiologically compatible type II resorbable collagen at least on their surface. Mass proportion of type II collagen fibers and porous bone mineral is at least equal to approximately 1:40.

EFFECT: enhanced effectiveness in recovering combined injuries of cartilage and bone tissue in articulations having defects.

8 cl, 6 dwg

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