JP4483545B2 - Artificial blood vessel and manufacturing method thereof - Google Patents

Description

The present invention relates to an artificial blood vessel composed of a tissue body formed so as to cover an artificial object when it is embedded in a living body, and more particularly to an artificial blood vessel that can be easily sutured with a blood vessel and a method for manufacturing the same .

  Conventionally, as an artificial blood vessel, a tube made of a mesh made of polyester resin or PTFE resin has been put into practical use for a long time, and researches are being conducted on issues such as reducing the diameter and improving the patency rate. The technologies that have been studied so far mainly include the use of segmented polyurethane tubes that have a proven track record as antithrombotic materials, and artificial blood vessel materials in which antithrombotic substances such as heparin are immobilized on the surface using graft chains. and so on.

The present applicant has proposed an artificial blood vessel made of a tissue body formed so as to cover an artificial object when it is embedded in a living body in Japanese Patent Application Laid-Open No. 2004-261260. Since the tissue body contains fiber, it has excellent physical strength and excellent tissue compatibility and blood compatibility.
JP 2004-261260 A

An artificial blood vessel using a tissue body formed so as to cover the periphery of an artificial object embedded in a living body described in JP-A-2004-261260 does not have its own shape-retaining property. It tends to be flat and crushed. Therefore, this artificial blood vessel is difficult to suture with a blood vessel in the living body.

  In general, the suture of a blood vessel using a needle and a thread largely depends on the skill of the operator. Especially when a small-diameter blood vessel having a caliber of 3 mm or less is sutured, it is necessary to use a non-free environment under a microscope. Suturing with very small needles and thin threads is necessary, and the operator requires special skills that are well-trained, and it takes a considerable amount of time to acquire such techniques. If the artificial blood vessel does not have shape retention, the difficulty of suturing with the blood vessel is further increased.

The present invention comprises a tissue body that is formed so as to cover an artificial object embedded in a living body excellent in tissue compatibility and blood compatibility, and can be sutured easily with a blood vessel. An object of the present invention is to provide an improved artificial blood vessel and a method for producing the same.

The artificial blood vessel of the present invention is an artificial blood vessel formed of a tubular tissue body formed around an artificial object implanted in a living body, and an annular shape-retaining member is provided inside the end portion of the artificial blood vessel. a that artificial blood vessels,-holding-shaped member is made of a thermoplastic resin of the porous three-dimensional network structure with a communicability, the organization enters the pores of the thermoplastic resin, the thermoplastic resin At least a part of the pores is filled with the tissue body .

The shape-retaining member is preferably made of a thermoplastic resin having a porous three-dimensional network structure having an average pore diameter of 100 to 650 μm and an apparent density of 0.01 to 0.5 g / cm ³ .

The method for producing an artificial blood vessel according to the present invention is a method for producing an artificial blood vessel comprising a tubular tissue body formed around an artificial object implanted in a living body, and has an annular shape inside the end of the artificial blood vessel. An artificial blood vessel provided with a shape-retaining member, wherein the shape-retaining member is made of a thermoplastic resin having a porous, three-dimensional network structure, and the tissue enters the pores of the thermoplastic resin. A method for producing an artificial blood vessel in which at least a part of pores of the thermoplastic resin is embedded in the tissue body , wherein an artificial object equipped with a shape-retaining member made of the thermoplastic resin is a living body (excluding a human body) ) were implanted into, along with adhering the tissue body to the outer surface of the-holding-shaped member and artifacts, a first step of filling at least a portion of the pores of the thermoplastic resin in the organization, the first step after, a second step of taking out the artifacts from the living body,-holding-shaped member及From the tissue body attached to the outer surface of the artefact, it is characterized in that it has a third step of pulling out only the artifacts, the.

  Since the artificial blood vessel of the present invention is composed of a tissue body formed so as to cover an artificial object when it is embedded in a living body, it is excellent in biocompatibility and blood compatibility. Since this artificial blood vessel is provided with a shape-retaining member at its end, it is very easy to suture with the blood vessel.

In the case where the shape retaining member is made of a thermoplastic resin having a porous three-dimensional network structure having an average pore diameter of 100 to 650 μm and an apparent density of 0.01 to 0.5 g / cm ³ , It becomes easy to uniformly impregnate an extracellular matrix such as collagen into the pores of the porous three-dimensional network structure part to the deep part, and it will be advantageous for invasion of cells from the tissue and construction of capillaries. . In addition, even when this shape-retaining member itself is used as an artificial blood vessel, it is possible for vascular endothelial cells to be present on the inner wall of the artificial blood vessel, which makes it difficult to block, and as a result, a small-diameter artificial blood vessel can be realized. Is possible.

  Hereinafter, embodiments of the artificial blood vessel of the present invention will be described in detail.

  FIG. 1 is a schematic cross-sectional view showing a process for manufacturing an artificial blood vessel according to an embodiment.

  In order to manufacture an artificial blood vessel, a rod-shaped artificial object (hereinafter sometimes referred to as a mandrel) 1 is prepared as shown in FIGS. The member 2 is attached. The shape retaining member 2 has a short cylindrical shape and is fitted on the mandrel 1.

  When the mandrel 1 with the shape-retaining member 2 is embedded in the living body, the tissue 3 is eventually attached to the outer surfaces of the mandrel 1 and the shape-retaining member 2 as shown in FIG. The tissue also enters the sponge-shaped shape retaining member 2, and at least a part of the pores of the sponge-shaped shape retaining member 2 is filled with the tissue.

  Therefore, the implant is taken out from the living body and the mandrel 1 is pulled out. Thereby, the artificial blood vessel 4 which consists of a structure | tissue as shown to (d) figure and in which the shape-retaining member 2 was provided in the both ends is obtained.

  Since the artificial blood vessel 4 is composed of a tissue body formed so as to cover the artificial object when it is embedded in the living body, it is excellent in biocompatibility and blood compatibility. Moreover, since the sponge-shaped cylindrical shape-retaining member 2 is provided at both ends and the both ends maintain a cylindrical shape, it can be easily sutured with a blood vessel. Note that the artificial blood vessel in which the tissue body is grown in its own body can be used as the artificial blood vessel in the state shown in FIG. When a tissue body is grown in an animal body, it is decellularized to obtain an artificial blood vessel.

  1 (e), (f), (g), (h), and (i) are respectively the EE line, the FF line, and the GG line in FIGS. It is sectional drawing which follows the HH line and the II line.

  The method for producing an artificial blood vessel of the present invention will be described in further detail.

  This artificial blood vessel is composed of a tubular tissue body formed around an artificial object implanted in a living body. The living body here means an organism classified into the animal kingdom such as human, goat, cow, dog, rabbit, rat, mouse.

  For example, the site where the artificial object is to be implanted is preferably the abdominal cavity having a certain volume for receiving the artificial object, or the subcutaneous part of the site that is not close to an organ such as the extremity, buttocks or back. In addition, it is preferable to perform the implantation by a minimally invasive method and with a dignified spirit of animal welfare and with a minimal incision under sufficient anesthesia.

  The artificial object (mandrel 1) to be implanted has strength (hardness) that does not deform when implanted, has chemical stability, is resistant to loads such as sterilization, Preferably, in the present invention, acrylic resin, olefin resin, styrene resin, polyester resin, polyamide resin, vinyl chloride resin, silicon resin, fluororesin, epoxy resin, glass, titanium , Platinum and SUS as a base material, and methyl methacrylate, styrene, 2,2,2-trifluoroethylene methacrylate, N, N-dimethylacrylamide, methacrylic acid on the surface of the base material Group consisting of sodium acid and (N, N-dimethylaminopropylacrylamide) methiodide Using one or more kinds of monomers selected those graft polymerization.

  By introducing these monomers into the surface of the base material, the properties of the surface of the base material are modified, and a good structure can be formed.

  In particular, when methyl methacrylate is graft-polymerized on the surface of the substrate, this surface may be further coated with a dithiocarbonate polymer. That is, the surface of the acrylic resin grafted with methyl methacrylate is hydrophobic with a contact angle of about 70 °. However, the surface of the acrylic resin has a slightly strong contact angle of about 80 °. It becomes possible to make fine adjustments.

  Depending on the type of monomer that is graft-polymerized on the surface, the properties of the resulting tissue will change, so what kind of monomer is used for the acrylic resin that is used depends on the compliance β value of the biological blood vessel that grafts an artificial blood vessel Thus, it can be appropriately selected by those skilled in the art.

  Graft polymerization of these monomers onto the substrate surface is, for example, a thin coating of a polystyrene derivative having a photopolymerization initiator in the side chain on the surface of an acrylic resin substrate, and photoinitiation by dipping in the monomer solution to be grafted. It can be carried out by graft polymerization.

  Examples of the method of coating the surface of the acrylic resin graft-polymerized with methyl methacrylate with a dithiocarbonate polymer include a method of spraying a dithiocarbonate polymer solution and a method of dipping.

The graft ratio can be determined by measuring the elemental fraction by X-ray photoelectron spectroscopy. For example, when grafting polymethylmethacrylate, the O / C ratio is 0.30 to 0.50, especially 0. For example, when it is further coated with a dithiocarbonate polymer, the N / C ratio is 0.022 to 0.032, particularly about 0.027, and the S / C ratio is 0.040 to 0.060, particularly It is preferably about 0.054. When polystyrene is grafted, the O / C ratio is 0.01 to 0.05, particularly about 0.03. When poly (2,2,2-trifluoroethylene methacrylate) is grafted, O / C When the graft introduction of poly (N, N-dimethylacrylamide) is 0.30 to 0.40, especially about 0.35, and the F / C ratio is 0.35 to 0.55, especially about 0.43 N / C ratio of 0.10 to 0.30, especially about 0.20, O / C ratio of 0.10 to 0.30, especially about 0.18, and when sodium polymethacrylate is grafted, O / C ratio of 0.40 to 0.60, especially about 0.49, Na / C ratio of about 0.10 to 0.30, especially about 0.16, poly (N, N-dimethylaminopropylacrylamide) methiodide N / C when graft is introduced 0.05 to 0.25, especially about 0.14, O / C ratio 0.05 to 0.20, especially about 0.13, N / I ratio 0.8 to 1.5, especially 1. About 2 is preferable, and the polymerization time and the monomer concentration of these monomers may be appropriately adjusted by those skilled in the art as parameters to bring the physical properties of the obtained tissue body closer to the body of a biological blood vessel to be transplanted.

  Further, in the present invention, the surface of an artificial object to be implanted into a living body can be fixed by covering the surface with a physiologically active substance as a growth factor. By fixing the growth factor, it is possible to promote the formation of a tissue body, thereby shortening the period for embedding an artifact for the formation of the tissue body. In addition, capillaries can be induced in the tissue body to be formed, and physical properties such as density and flexibility after decellularization can be adjusted to values more preferable as artificial blood vessels.

As such a physiologically active substance, vascular endothelial growth factor, insulin-like growth factor, insulin-like growth factor binding protein and fibroblast growth factor can be used. Induction and endothelialization can be promoted. When fibroblast growth factor is fixed, formation of a tissue body is promoted, and a tissue body useful as an artificial blood vessel can be formed by short-term implantation. In addition, when an insulin-like growth factor or an insulin-like growth factor binding protein is fixed, muscle fibers can be induced in the tissue. Physiologically active substances either as a fixed amount of the physiologically active substances 0.1~1.0μg / cm ^2, is suitable in particular 0.5 [mu] g / cm ² before and after, to thereby physical properties and form required for the artificial blood vessel It may be appropriately increased or decreased by those skilled in the art in consideration of the period.

  The shape of the artificial object to be embedded (mandrel 1) may be any shape as long as it has a rod-shaped portion having a diameter of 0.3 to 15.0 mm. The organization body is obtained. When this artificial object has a branched portion, it is possible to use the same or smaller diameters of the branch portions after the branched portion, thereby obtaining various branch-like structures. Can do.

The shape-retaining member 2 is preferably a continuous, continuous, porous three-dimensional network thermoplastic having an average pore diameter of 100 to 650 μm and an apparent density of 0.01 to 0.5 g / cm ³ . Made of resin.

The average pore diameter of the porous three-dimensional network structure made of this thermoplastic resin is 100 to 650 μm and the apparent density is 0.01 to 0.5 g / cm ³ , but the preferable average pore diameter is 100 to 400 μm, more preferably 100 ˜300 μm. If the apparent density is in the range of 0.01 to 0.5 g / cm ³ , cell engraftment is good, excellent physical strength is maintained, and elastic properties approximate to a living body are obtained. 0.01 to 0.3 g / cm ³ , more preferably 0.01 to 0.2 g / cm ³ .

  In the concept of average pore size, monodispersion is preferable for the pore size distribution, and it is desirable that the contribution ratio of pores having a pore size of 150 to 300 μm, which is an important pore size for cell invasion, is high. When the contribution ratio of pores having a pore diameter of 150 to 300 μm is 10% or more, preferably 20% or more, more preferably 30% or more, still more preferably 40% or more, and particularly preferably 50% or more, cells easily invade, Since invading cells are easy to adhere and grow, it is effective for use as an artificial blood vessel.

  Note that the contribution ratio of pores having a pore diameter of 150 to 300 μm in the average pore diameter of the porous three-dimensional network structure is the number of pores having a pore diameter of 150 to 300 μm with respect to the total number of holes in the method for measuring the average pore diameter in Example 1 described later. Refers to the percentage of

  With such a porous three-dimensional network structure having an average pore size, apparent density, and pore size distribution, cells can easily penetrate into the pores, and the cells can easily adhere to and grow in the porous structure layer.

The thermoplastic resin constituting the shape retaining member 2, it is possible to obtain a segment polyurethane resin excellent artificial blood vessel in terms of antithrombotic and physical properties, preferable.

  The segmented polyurethane resin is synthesized from three components of a polyol, a diisocyanate and a chain extender, and has an elastomeric property due to a block polymer structure having a so-called hard segment portion and soft segment portion in the molecule. The scaffold material and the artificial blood vessel obtained by using the S-S curve that is elastodynamically approximate to a biological blood vessel (high compliance and low elasticity in the low blood pressure region, and lower than the low blood pressure region in the high blood pressure region) It is also possible to form into a tubular structure exhibiting high compliance compliance properties, and excellent antithrombogenicity and physical properties.

  Also, if the thermoplastic resin is hydrolyzable or biodegradable, it is gradually decomposed and absorbed after the transplantation of the artificial blood vessel, and finally the resin base material leaving the engrafted cells. It is also possible to exclude itself from the living body.

  Porous three-dimensional network structures composed of such thermoplastic resins include collagen type I, collagen type II, collagen type III, collagen type IV, atelocollagen, fibronectin, gelatin, hyaluronic acid, heparin, keratan Acid, chondroitin, chondroitin sulfate, chondroitin sulfate B, copolymer of hydroxyethyl methacrylate and dimethylaminoethyl methacrylate, copolymer of hydroxyethyl methacrylate and methacrylic acid, alginic acid, polyacrylamide, polydimethylacrylamide and polyvinylpyrrolidone One or more selected may be retained, and may be fibroblast growth factor, interleukin-1, tumor growth factor β, epidermal growth factor and diploid fibroblast growth factor. 1 type or 2 or more types of cytokines selected from the group which may be hold | maintained from embryonic stem cells, vascular endothelial cells, mesoderm cells, smooth muscle cells, peripheral vascular cells, and mesothelial cells One or two or more cells selected from the group may be adhered. Embryonic stem cells may be differentiated.

  Fine pores may be provided in the skeleton itself made of the thermoplastic resin for constructing the porous three-dimensional network structure layer. Such micropores make the skeletal surface not a smooth surface but a complex uneven surface, and are also effective in retaining collagen and cell growth factors, and as a result, it is possible to increase cell engraftment. is there. However, the micropores in this case are not introduced into the concept of calculating the average pore diameter of the porous three-dimensional network structure referred to in the present invention.

  The thickness (the difference between the outer diameter (radius) and the inner diameter (radius)) of the shape retaining member 2 is preferably about 0.5 to 1.0 mm.

  If the mandrel 1 in which the tissue body is formed is extracted from the living body if the mandrel 1 is linear, a tubular tissue body can be obtained by removing the mandrel 1 from the body as it is, and a straight artificial blood vessel can be obtained. it can. In addition, the mandrel 1 can be easily extracted in the state immersed in physiological salt water.

  When the artificial object has a branched portion, a tubular tissue body having a branched portion can be easily removed from the tissue body by partially cutting, crushing, or dissolving the artificial object after extraction from the living body. Is obtained. An artificial blood vessel using a tissue having a branch portion is the most preferable example of the present invention. That is, the blood vessel branch site is a site where the blood flow hits the blood vessel wall, and an aneurysm is likely to occur. If such a branch type artificial blood vessel is used, it is used as it is for the treatment of the aneurysm. can do.

  When the artificial blood vessel composed of the tissue body thus obtained is grown in its own body, it can be used as it is. When grown in other animals, the tissue is decellularized. Methods for decellularization include elution of extracellular matrix by enzyme treatment such as collagenase and washing with a water-soluble organic solvent such as alcohol, but aldehyde compounds such as glutaraldehyde and formaldehyde and / or Alternatively, there is a method of treating with a water-soluble organic solvent such as methanol, ethanol or isopropyl alcohol. Specifically, a method in which the aldehyde compound is adjusted so as to have a final concentration of about 1 to 3%, and the tissue body is immersed in a fixative having a volume of about 50 times the volume of the tissue body for 2 hours or more is preferable. As a result, the structure of the tissue can be maintained by crosslinking lysine residues and the like of the protein chain.

  The tissue body after the decellularization treatment can be stably controlled in density and the like by further freeze-drying. It can be stored in water-soluble organic solvents such as alcohol, phosphate buffered saline, and physiological saline without lyophilization after decellularization treatment, but it is also lyophilized to suppress changes in physical properties during storage. It is preferable. Here, as a drying method, there is a possibility that pores are closed and fiber association occurs in the shrinkage phenomenon at the time of drying, and there is a possibility that a tissue body having physical properties useful as an artificial blood vessel cannot be obtained with good reproducibility. Therefore, lyophilization is preferred.

  According to the present invention, various compliance β values can be obtained by adjusting the material of the artifact, the type and amount of the monomer to be introduced, the type and amount of the physiologically active substance immobilized on the surface, the implantation period, and the like. An artificial blood vessel can be formed. Therefore, in the present invention, it is preferable to form an artificial blood vessel having a compliance β value close to the compliance β value of the biological blood vessel to be anastomosed by adjusting these conditions. For example, in the case of a human coronary artery, the compliance β value is about 40, but a tissue body obtained by implanting an artificial product made of acrylic resin grafted with polymethyl methacrylate chain on the surface for one month is decellularized. The compliance β value of the obtained artificial blood vessel is about 40, which is useful as an artificial blood vessel for a coronary artery.

  Hereinafter, the present invention will be described more specifically with reference to examples.

Example 1
[Mandrel production]
Light on a round bar made of silicon resin with an outer diameter of 2 mm and a length of 30 mm (the round bar surface is mirror-finished and both ends are hemispherically curved so as not to physically irritate living tissue more than necessary). A polystyrene derivative having a polymerizable initiator in the side chain was applied, immersed in a methyl methacrylate / benzene solution purified by a conventional method, photoinitiated graft polymerization was performed, and a polymethyl methacrylate chain was grafted onto the surface. The graft ratio was confirmed to be 0.4 in O / C ratio by X-ray photoelectron spectroscopy. Cylindrical shape-retaining members having an inner diameter of 2 mm, an outer diameter of 4 mm, and a length of 3 mm were attached to both ends of the mandrel 1 made of this round bar. The mandrel 1 with the shape retaining member 2 was sterilized with ethylene oxide gas by a conventional method.

  This shape-retaining member is manufactured as follows.

[Manufacture of shape-retaining members]
Dissolve a thermoplastic polyurethane resin (Nippon Miractran, Milactolan E980PNAT) in N-methyl-2-pyrrolidinone (Kanto Chemical Co., peptide synthesis reagent, NMP) at room temperature using a dissolver (about 2,000 rpm). A 5.0% solution (weight / weight) was obtained. About 1.0 kg of this NMP solution was weighed into a planetary mixer (Inoue Seisakusho, 2.0 L, PLM-2 type), and methyl cellulose equivalent to the weight of polyurethane resin (Kanto Chemical Co., Reagent, 25 cp grade) ) Was mixed at 40 ° C. for 20 minutes, and then defoamed under reduced pressure to 20 mmHg (2.7 kPa) for 10 minutes with continued stirring to obtain a polymer dope.

  A cylindrical paper tube with an inner diameter of 4 mmφ, an outer diameter of 6 mmφ, and a length of 60 mm made with a filter paper for chemical experiments (manufactured by Toyo Roshi Kaisha, No. 2), a core rod made of SUS440 with a diameter of 2 mmφ, and this core The polymer dope was injected and injected using a 23 gauge needle into a tube forming jig composed of a cylindrical seal plug made of medical polypropylene resin capable of fixing the rod to the center of the paper tube, and then sealed after being sealed. The polyurethane resin was coagulated by throwing it into methanol in a state and continuing to reflux for 72 hours to extract and remove the internal NMP solvent from the paper tube surface. At this time, methanol was replaced with a new solution as needed while maintaining the reflux state. After 72 hours, the tube forming jig is transferred from the refluxed methanol to a methanol bath at room temperature without drying, and the contents are taken out from the tube forming jig in the bath and washed in Japanese Pharmacopoeia purified water for 72 hours. As a result, methylcellulose, methanol and remaining NMP were extracted and removed. Water for washing was supplied with new solution as needed. This was dried under reduced pressure (20 mmHg (2.7 kPa)) at room temperature for 24 hours to produce a tubular porous three-dimensional network structure. This was cut into a predetermined length to obtain a shape retaining member 2.

  About the obtained shape-retaining member, the average pore diameter and the apparent density were measured by the following method. In the measurement of the average pore diameter and the apparent density, the sample was cut at room temperature using a double-edged razor (manufactured by Feather, high stainless steel).

(1) Measurement of average pore diameter Using a photograph taken with a stereomicroscope (VH-6300, manufactured by Keyence Corporation) of the plane (cut surface) of a sample cut with a double-blade razor, individual holes on the same plane are tertiary. Image processing as a figure surrounded by the skeleton of the original network structure (Image processing device is LUZEX of Nireco)
AP was used and the image capturing CCD camera was a Sony LE N50. ) And the area of each figure was measured. This was defined as the perfect circle area, and the diameter of the corresponding circle was determined and used as the hole diameter. As a result of ignoring the fine holes drilled in the skeleton portion of the porous body and measuring only the communicating holes on the same plane, the average pore diameter was measured to be 169 ± 55 μm. At the same time, the contribution ratio of the pore size of 150 to 300 μm in the pore size distribution was measured to be 71.2%, and it was confirmed that the porous body was mainly composed of pores having a size effective for cell adhesion.

(2) Measurement of apparent density Volume is obtained from the dimension obtained by measuring a sample cut with a double-blade razor to a length of about 10 mm with a projector (Nikon, V-12), and the value obtained by dividing the weight by the volume. As a result, it was calculated as 0.077 ± 0.002 g / cm ³ .

[Embedding and extraction]
The epidermis of the back of a rabbit that was locally anesthetized and shaved by a normal procedure was dissected immediately after disinfection with isodine, and a sterilized round bar was embedded under the subcutaneous tissue and sutured. The suture site was disinfected with isodine twice a day, water was freely supplied, and an appropriate amount of ORC4 manufactured by Oriental Yeast Co., Ltd. was fed as feed.

  During the implantation period, there was no evidence of infection in the sutured area, and no antibiotics were required. One month after the implantation, a round bar was extracted in the same manner as at the time of implantation. The extracted mandrel 1 and shape retaining member 2 were uniformly coated with a tissue having a thickness of about 100 microns.

  As a result of observation with an electron microscope, it can be seen that there is no irregular portion in the tissue body, and the porous body is homogeneous in the thickness direction.

  Next, a tissue body was generated in the same manner except that the period of embedding the mandrel 1 was extended from 1 month to 2, 3, 4 months.

[Internal pressure resistance test]
When the internal pressure resistance test is performed with the embedding period of 1 month and 4 months, the inner diameter does not rupture even when the internal pressure is applied up to 200 mmHg (26.6 kPa) by water injection, and the outer diameter is about 10 at this time. %. The pressure load was gradually changed up and down between 0 to 200 mmHg, and the change in the outer diameter with respect to the repeated pressure load was confirmed, but the outer diameter change showed the same behavior regardless of the number of histories, and the artificial blood vessel of the present invention was It was confirmed that it has the flexibility to follow the pulsation of blood vessels.

  Since this artificial blood vessel has a sponge-like shape-retaining member at the end, it was extremely easy to suture with the blood vessel.

It is typical sectional drawing which shows the manufacturing method of the artificial blood vessel of this invention.

1 Mandrel 2 Shape-retaining member 3 Tissue 4 Artificial blood vessel

Claims (5)

In an artificial blood vessel made of a tubular tissue body formed around an artificial object embedded in a living body, an artificial blood vessel in which an annular shape-retaining member is provided inside an end portion of the artificial blood vessel,
The shape-retaining member is made of a thermoplastic resin having a porous three-dimensional network structure having communication,
An artificial blood vessel, wherein the tissue body enters a hole of the thermoplastic resin, and at least a part of the hole of the thermoplastic resin is filled with the tissue body.   2. The artificial blood vessel according to claim 1, wherein the thermoplastic resin is a segmented polyurethane resin. ^{3. The} artificial blood vessel according to claim 1, wherein the porous three-dimensional network structure has an average pore diameter of 100 to 650 μm and an apparent density of 0.01 to 0.5 g / cm ³ .   The artificial blood vessel according to any one of claims 1 to 3, wherein the tissue body is decellularized. In a method for producing an artificial blood vessel composed of a tubular tissue body formed around an artificial object implanted in a living body,
An artificial blood vessel in which an annular shape-retaining member is provided inside the end of the artificial blood vessel,
The shape-retaining member is made of a thermoplastic resin having a porous three-dimensional network structure having communication,
A method for producing an artificial blood vessel in which the tissue body enters the pores of the thermoplastic resin, and at least a part of the pores of the thermoplastic resin is filled with the tissue body ,
An artificial object equipped with a shape-retaining member made of the thermoplastic resin is embedded in a living body (excluding a human body) , and a tissue body is attached to the outer surface of the shape-retaining member and the artificial object. A first step of filling at least a portion of the hole with a tissue;
After the first step, a second step of removing the artifact from the living body,
A third step of extracting only the artificial object from the shape- retaining member and the tissue attached to the outer surface of the artificial object;
A method for producing an artificial blood vessel, comprising:

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