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WO2003034945A1 - Vaisseau artificiel et procede de realisation - Google Patents

Vaisseau artificiel et procede de realisation Download PDF

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Publication number
WO2003034945A1
WO2003034945A1 PCT/JP2002/010986 JP0210986W WO03034945A1 WO 2003034945 A1 WO2003034945 A1 WO 2003034945A1 JP 0210986 W JP0210986 W JP 0210986W WO 03034945 A1 WO03034945 A1 WO 03034945A1
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WO
WIPO (PCT)
Prior art keywords
blood vessel
artificial blood
solution
cell
porous
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Ceased
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PCT/JP2002/010986
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English (en)
Japanese (ja)
Inventor
Katsuko Sakai
Takashi Ushida
Tetsuya Tateishi
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Individual
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Publication of WO2003034945A1 publication Critical patent/WO2003034945A1/fr
Anticipated expiration legal-status Critical
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/64—Animal cells

Definitions

  • the present invention relates to a vascular prosthesis for use in the treatment of various vascular diseases of the human body, including heart and brain diseases, and peripheral blood vessels of the extremities, and more particularly, to a porous vascular prosthesis substrate and gel.
  • the present invention relates to an artificial blood vessel in which a living body and a bioactive substance are combined.
  • Artificial blood vessels with large diameters are used in the treatment of vascular diseases such as congenital diseases and arteriosclerosis.
  • vascular diseases such as congenital diseases and arteriosclerosis.
  • human blood vessels made of materials such as polyester fibers and extensible fluorine tetrachloride compounds are used clinically.
  • Large-diameter artificial blood vessels have achieved sufficient clinical results because they have a sufficient blood flow velocity even if made of such materials.
  • Artificial blood vessels of small diameter are used for the treatment of vascular diseases such as arteriosclerosis, vasospasm, damage to peripheral blood vessels, aneurysm formation, and tumor invasion. Demand is very high.
  • vascular diseases such as arteriosclerosis, vasospasm, damage to peripheral blood vessels, aneurysm formation, and tumor invasion.
  • Demand is very high.
  • the above-mentioned materials are non-biodegradable materials, have poor biocompatibility, and have a problem that foreign matter remains in the body even after forceful implantation.
  • a culture solution containing smooth muscle cells is directly inoculated into a biodegradable or non-biodegradable tubular structure, whereby the endothelial cells are cultured until the lumen surface is smoothed.
  • a model for seeding has also been proposed (Niklason et al. Science, 1999, 284, p489-493, JP-A-2001-78750). According to these models, they have excellent mechanical strength and can withstand arterial vascular prostheses.
  • a biodegradable or non-biodegradable tubular structure has a strong hydrophobicity and remarkably poor cell adhesion and proliferation.
  • an artificial blood vessel which is excellent in biocompatibility, mechanical strength, antithrombotic property, etc., does not leak blood, and is easy to manufacture is desired.
  • a cylindrical porous artificial blood vessel base material formed of a fiber-like or sponge-like material having an appropriate mechanical strength is converted into a cell-mixed solution. After impregnating under normal pressure or negative pressure conditions, allowing the cell-containing solution to be taken into the pores, and then gelling the solution, the cells can be densified in a short period of time to the fine details of the porous artificial blood vessel substrate.
  • a cell-mixed solution After impregnating under normal pressure or negative pressure conditions, allowing the cell-containing solution to be taken into the pores, and then gelling the solution, the cells can be densified in a short period of time to the fine details of the porous artificial blood vessel substrate.
  • the present inventors have found that not only cells but also bioactive substances synthesized in vivo, genes encoding those bioactive substances, and pharmaceuticals synthesized or obtained in vitro can be obtained by the same method as described above.
  • Pharmaceutical active ingredients such as E.C. compounds can be incorporated into porous artificial blood vessel substrates, and can be used as artificial blood vessels for various uses, including drug delivery systems and artificial organs other than artificial blood vessels. And found that the present invention was completed.
  • an artificial blood vessel having a tubular porous artificial blood vessel base material, wherein the pores of the porous artificial blood vessel base material are impregnated with a gel solution containing a biologically active substance.
  • the method corresponds to any one of a temperature change, a pH change, a salt concentration change, and an enzyme reaction change.
  • Preparing a biologically active substance-containing solution by impregnating the biologically active substance with the solution to be gelled; and preparing the biologically active substance-containing solution in the pores of the porous artificial vascular base under normal pressure or negative pressure conditions. And a step of gelling the bioactive substance-containing solution taken into the pores of the porous artificial blood vessel base material.
  • the porous artificial blood vessel substrate is composed of a biodegradable material or a non-biodegradable material.
  • the biodegradable material include polylactic acid, polyglycolic acid, copolymers of lactic acid and glycolic acid, polymalic acid, poly one ⁇ - force caprolactone, epsilon - copolymers of force caprolactone and lactic acid, ⁇ -Co-prolatatatone and glycolic acid, ⁇ - Co-polymer of lactic prolactatone, lactic acid and dalicholic acid, poly-3-hydroxybutyrate, poly_4-hydroxybutyrate, and ⁇ 3-hydroxybutyrate It is preferably at least one material selected from the group consisting of a copolymer of methacrylate and 4-hydroxybutylate.
  • the non-biodegradable material includes polyethylene resin, polypropylene resin, polybutadiene resin, polystyrene resin, polychlorinated vinyl resin, polyacrylic resin, polymethacrylic resin, and polysulfone resin. And at least one material selected from the group consisting of polytetrafluoroethylene resins.
  • the biologically active substance is preferably a cell and Z or a pharmaceutically active ingredient.
  • the cells are preferably one or more cells selected from the group consisting of smooth muscle cells, fibroblasts, undifferentiated cells, hepatocytes, knee cells, and hematopoietic stem cells.
  • the bioactive substance-containing gel solution is at least one selected from the group consisting of a collagen gel solution, a fibrin gel solution, an acrylamide gel solution, an agarose gel solution, and an alginate gel solution. It is preferable that the gel solution contains a bioactive substance.
  • the solution to be gelled may be at least one solution selected from the group consisting of a collagen solution, a fibrin solution, an acrylamide solution, an agarose solution, and an alginic acid solution. preferable.
  • an endothelial cell layer may be formed on a lumen surface of the porous artificial blood vessel base material.
  • the porous artificial blood vessel base material may be formed by gelling the biologically active substance-containing solution taken into the pores of the porous artificial blood vessel base material.
  • the method may further include the step of forming an endothelial cell layer.
  • the porous artificial blood vessel base material may be strengthened by a reinforcing member made of a biodegradable material or a non-biodegradable material.
  • FIG. 1 is a scanning electron microscope observation image of the inner cavity surface of the artificial blood vessel prepared in Example 1.
  • FIG. 2 is a scanning electron microscope observation image of the inner cavity surface of the artificial blood vessel prepared in Comparative Example 1.
  • FIG. 3 is a scanning electron microscope observation image of the lumen surface of the PLLA substrate prepared in Reference Example.
  • FIG. 4 is a cross-sectional image of the artificial blood vessel prepared in Example 1 by a fluorescence microscope.
  • FIG. 5 is a cross-sectional image of the artificial blood vessel prepared in Comparative Example 1 by a fluorescence microscope.
  • FIG. 6 is a cross-sectional image of the artificial blood vessel prepared in Example 2 observed by a transmission microscope.
  • FIG. 7 is a fluorescent microscope cross-sectional image of the artificial blood vessel prepared in Example 2.
  • the artificial blood vessel according to the present invention has a cylindrical porous artificial blood vessel base material, and contains a bioactive substance-containing gel solution in its pores.
  • the porous artificial blood vessel base material used in the present invention is porous and preferably has an open pore structure in which the pores are connected from the viewpoint of facilitating the incorporation of a bioactive substance into the pores.
  • the percentage of pores is preferably from 70% to 99% of the base material, and more preferably from 80% to 95%.
  • the porous artificial blood vessel substrate used in the present invention has a cylindrical shape.
  • the inner diameter is preferably 1 mm to 7 mm, and 1 mm to 5 mm. More preferably, it is still more preferably 1 mm to 4 mm.
  • the inner diameter is preferably from 5 mm to 70 mm, more preferably from 5 mm to 50 mm.
  • Examples of the material of the porous artificial blood vessel base material used in the present invention include a biodegradable material and a non-biodegradable material.
  • a biodegradable material is preferable from the viewpoint of providing an artificial blood vessel in which components that are not derived from the living body are not dissolved after transplantation in consideration of foreign body reaction, immune reaction, and carcinogenicity in the living body.
  • non-biodegradable materials are preferred from the viewpoint of maintaining mechanical strength because they do not dissolve after transplantation, and providing stable products at the current stage and at the current technological development level. . 02 10986
  • the biodegradable material is not particularly limited, but includes polydalicholic acid, polylactic acid, a copolymer of lactate and glycolic acid, polymalic acid, poly-coprolataton, and ⁇ coprolataton and lactic acid.
  • Polymers, copolymers of e-proprotatanone and glyco- / reic acid, copolymers of ⁇ -proprotatanone, lactic acid and glycolic acid, poly-3-hydroxybutyrate, poly-1-hydroxybutyrate, Copolymers of 3-hydroxybutyrate and 4-hydroxybutyrate can be mentioned. From the viewpoint of the approval of the Ministry of Health, Labor and Welfare and the FDA (United States Drug Administration), polylactic acid, polyglycolic acid, and lactic acid And a copolymer of glycolic acid and glycolic acid.
  • the non-biodegradable material is not particularly limited, but is a polyethylene resin, a polypropylene resin, a polybutadiene resin, a polystyrene resin, a polyvinyl chloride resin, a polyacryl resin, a polymethacryl resin, a polysulfone resin. And polytetrafluoroethylene-based resin. From the viewpoint of approval by the Ministry of Health, Labor and Welfare and the FDA, polyethylene resin and polytetrafluoroethylene-based resin are preferable.
  • a foaming agent such as sodium chloride, ammonium hydrogencarbonate, or the like is mixed with a solution of the above-described material and molded into a tubular shape.
  • a method of foaming to make it porous can be mentioned.
  • Such a method includes, for example, the method described in Nam et al. J. Biomed. Master Res. 2000, 53, pi-7.
  • bioactive substance-containing gel solution contained in the pores of the porous artificial blood vessel substrate will be described.
  • the gel solution containing a biologically active substance used in the present invention is a gel solution containing a biologically active substance, and it is preferable that the biologically active substance is uniformly mixed.
  • Examples of the biologically active substance contained in the gel solution include cells, pharmaceutically active ingredients, and the like, and one or more of these may be used. Such a biologically active substance can be appropriately determined according to the use of the artificial blood vessel.
  • a pharmaceutically active ingredient refers to a component that exhibits one or more pharmacological activities in a living body, such as a physiologically active substance synthesized in a living body, and a physiologically active substance thereof.
  • Cells used as biologically active substances include, for example, undivided cells such as stem cells and ES cells, smooth muscle cells, fibroblasts, hepatocytes, victory cells, and hematopoietic stem cells. it can.
  • physiologically active substance used as a biologically active substance examples include proteins synthesized in vivo, such as insulin, anti-prion antibody, and anti-AIDS virus antibody.
  • an artificial blood vessel containing such a physiologically active substance as a biologically active substance there is an application such as an artificial blood vessel that also treats diseases such as diabetes and infectious disease.
  • Examples of the gene used as a biologically active substance include a gene encoding the above-mentioned physiologically active substance, such as a gene encoding adenosine deaminase, a gene encoding an eighth blood coagulation factor, 9 Genes encoding blood coagulation factors, and the like.
  • a gene encoding the above-mentioned physiologically active substance such as a gene encoding adenosine deaminase, a gene encoding an eighth blood coagulation factor, 9 Genes encoding blood coagulation factors, and the like.
  • an artificial blood vessel containing a gene as a bioactive substance there is an application as an artificial blood vessel that also serves to treat diseases such as adenosine deaminase deficiency and hemophilia.
  • a pharmaceutical compound synthesized or obtained in vitro can be used as a biologically active substance.
  • examples of such pharmaceutical compounds include organic compounds, antibiotics produced by microorganisms existing in nature, and the like. Specific examples include penicillin, cyclophosphamide, actinomycin D, and 5-f / leuroushi / And pleomycin.
  • An artificial blood vessel containing such a pharmaceutical compound as a biologically active substance has a use as an artificial blood vessel which also serves as an infectious disease, an anticancer treatment and the like.
  • the gel solution contains at least smooth muscle cells and blast cells from the viewpoint of securing the mechanical strength after the artificial blood vessel transplantation.
  • undifferentiated cells are included.
  • the density of the bioactive substance to be mixed with the gel solution is preferably 1 ⁇ 10 4 eell Zml to l ⁇ 10 9 cel 1 Zm1, and 1 ⁇ 10 0 and still more preferably 6 a ce 1 1 / m 1 ⁇ 1 X 1 0 7 ce 1 1 Zm 1.
  • the gel solution is a solution obtained by gelling a solution that gels due to changes in temperature, H, salt concentration, enzymatic reaction, etc., and is not particularly limited as long as it has no toxicity or carcinogenicity. it can.
  • the gelling agent corresponding to the temperature change include collagen, acrylamide resin, and agarose.
  • collagen that can be gelled in response to a pH change can be exemplified.
  • Alginic acid or the like can be used as a gel that responds to changes in salt concentration.
  • fibrin and the like can be mentioned as those that gel in response to the enzymatic reaction, and fibrinogen and the like can be mentioned as the enzyme to be gelled.
  • a gel solution containing a biologically active substance is taken into the pores of the porous artificial blood vessel base material.
  • the bioactive substance-containing gel solution preferably occupies 50% or more of all pores of the porous artificial vascular base material, and 90%, from the viewpoint of preventing blood leakage and securing a scaffold for vascular endothelial cells. It is more preferable to account for the above.
  • an endothelial cell layer may be formed on the lumen surface of the porous artificial blood vessel base material from the viewpoint of improving antithrombotic properties.
  • the porous artificial blood vessel base material is strengthened by a strengthening member made of a biodegradable material or a non-biodegradable material. You may.
  • the reinforcing member may be formed on the outer peripheral surface and / or the inner peripheral surface of the porous artificial blood vessel base material, or may be incorporated inside the porous artificial blood vessel base material.
  • the reinforcing member formed on the outer peripheral surface of the porous artificial blood vessel base material has a substantially same inner diameter as the outer diameter of the porous artificial blood vessel base material, and has a cross section concentric with the base material.
  • a coated tubular member can be mentioned.
  • the capturing member formed on the inner peripheral surface of the porous artificial blood vessel base material has an outer diameter substantially equal to the inner diameter of the porous artificial blood vessel base material, and has a cross section concentric with the base material. And a cylindrical member covered with a base material.
  • a material formed by weaving a fibrous biodegradable material or a non-biodegradable material into a mesh shape can be used.
  • the capturing member can also be incorporated into the porous artificial blood vessel base material.
  • the biodegradation Examples of the porous material and the non-biodegradable material include those described above as the material for the porous artificial blood vessel base material.
  • a biologically active substance is mixed with a solution that gels in response to any of a temperature change, a pH change, a salt concentration change, and an enzyme reaction change to prepare a biologically active substance-containing solution.
  • the biologically active substance to be mixed can be appropriately determined according to the use of the artificial blood vessel, and includes the substances described above.
  • the density of the biological agent to be mixed in the solution to gel, if the biological agent is a cell is a 1 X 1 0 4 ce 1 l Zm l ⁇ 1 X 1 0 9 ce 1 1 Zm 1 It is more preferably 1 ⁇ 10 6 ce 1 l / ml to 1 ⁇ 10 7 ce 11 Zm 1.
  • the porous artificial vascular base material prepared in advance is impregnated with the solution containing the biologically active substance prepared as described above, and the biologically active substance is introduced into the pores of the substrate under normal pressure conditions, preferably under negative pressure conditions. Allow the containing solution to be incorporated.
  • porous artificial blood vessel base material The material and manufacturing method of the porous artificial blood vessel base material are as described above. Further, the porous artificial blood vessel base material may be captured by a capturing member. The reinforcing member and the reinforcing method are as described above.
  • the method for impregnating the porous artificial vascular base material into the biologically active substance-containing solution is as follows. There are several methods. In order to incorporate the biologically active substance into the substrate, the biologically active substance is impregnated until the biologically active substance is sufficiently incorporated into the pores of the porous artificial blood vessel substrate. For example, it is preferable that the bioactive substance-containing solution is impregnated with the porous artificial blood vessel substrate, and is left standing for 10 to 60 minutes, more preferably 30 to 60 minutes.
  • the pressure at the time of addition may be normal pressure, but from the viewpoint of efficiently incorporating the bioactive substance into the pores of the substrate, a pressure lower than the atmospheric pressure is preferable. This pressure is appropriately determined in consideration of the materials to be used, the pressure resistance of the equipment, the possibility of retaining the activity of the biologically active substance to be used, and the like.
  • the biologically active substance-containing solution taken into the pores of the porous artificial blood vessel substrate is gelled.
  • the gelling conditions are set appropriately according to the solution to be used. Gelled In this case, from the viewpoint of forming a smooth lumen surface, it is preferable to further allow the mixture to stand for 10 minutes to 120 minutes under gelation conditions, and more preferably to allow the mixture to stand still for 30 minutes to 60 minutes. .
  • an endothelial cell layer can be formed on the luminal surface of the porous artificial blood vessel base material.
  • the endothelial cell layer is easily formed by pouring a culture solution containing endothelial cells into the lumen of a porous artificial blood vessel substrate holding a solution containing a bioactive substance that has undergone genoleration in the pores and rotating the culture. be able to.
  • the number of rotations during the culture of endothelial cells is preferably from 0.5 rpm to 100 rpm, more preferably from 5 rpm to 10 rpm.
  • the culture time is preferably from 10 minutes to 24 hours, and more preferably from 20 minutes to 60 minutes.
  • the bioactive substance is contained at high density in the hole of a cylindrical porous artificial blood vessel base material, blood leakage does not occur, the lumen surface is almost smooth, and the porous artificial blood vessel Since it has a base material, an artificial blood vessel having excellent mechanical properties can be provided. Further, according to the present invention, a biologically active substance can be efficiently and rapidly incorporated into an artificial blood vessel in a short time.
  • a porous artificial blood vessel substrate (hereinafter, referred to as “PLLA substrate”) composed of polylactic acid with a length of about 2 mm and a length of about 2 Omm was prepared.
  • a solution was prepared by mixing human normal aortic vascular smooth muscle cells at a concentration of 5 ⁇ 10 6 cells / ml with a 0.39% collagen solution.
  • the PLLA substrate prepared in the reference example was placed in a glass tube and immersed in 1.4 ml of the above-mentioned collagen solution containing human normal aortic vascular smooth muscle cells, and this was pumped with a hydraulic pump (ULVAC, G The pressure was reduced according to -5), and the mixture was allowed to stand under negative pressure for 30 minutes.
  • the tube is moved to an incubator at 37 ° C and left standing for 60 minutes to gel the collagen solution in the PLLA substrate. Then, an artificial blood vessel was prepared.
  • Human normal aortic vascular smooth muscle cells were mixed with a culture solution (Dulbecco's minimum essential medium (DMEM)) to prepare a cell-containing solution having a concentration of 5 ⁇ 10 6 cells / ml.
  • DMEM Dulbecco's minimum essential medium
  • the PLLA substrate prepared in Reference Example was placed in a glass tube, immersed in 1.4 ml of the above-described culture medium containing human normal aortic vascular smooth muscle cells, and this was immersed in a hydraulic pump ( , G-5) and allowed to stand under negative pressure for 30 minutes.
  • a hydraulic pump , G-5
  • the tube was moved to an incubator at 37 ° C and left standing for 60 minutes to produce an artificial blood vessel.
  • Example 1 The numbers of human normal aortic vascular smooth muscle cells taken into the artificial blood vessels prepared in Example 1 and Comparative Example 1 were compared. For comparison, calculate the ratio (%) of the number of cells in the solution after immersing the PLLA substrate to the number of cells in the human normal aortic vascular smooth muscle cell solution before immersing the PLLA substrate. It was done by doing. The number of cells was determined by calculating the number of nuclei developed with 4,, 6-diamidino 2-phenylindole dihydrochloride (DAP I) using a fluorescence spectrophotometer. Since the immersion time is 30 minutes, smooth muscle cells do not proliferate during this time. Table 1 below shows the percentage of cells taken up. Example 1 Comparative Example 1 Percentage of cells taken up (%) 100% 18%
  • Example 1 takes up cells extremely efficiently as compared to the artificial blood vessel prepared in Comparative Example 1.
  • FIG. Fig. 2 shows an EM photograph
  • Fig. 3 shows an SEM photograph of the state of the lumen surface of the PLLA substrate prepared in Reference Example for reference. From FIGS. 1 and 2, the luminal surface of the artificial blood vessel of Comparative Example 1 is smooth without any holes, while the luminal surface of the artificial blood vessel of Comparative Example 1 is still large. I understand.
  • each artificial blood vessel was further cultured for one day, and then a cross-sectional section (8 ⁇ thick) of each artificial blood vessel was prepared.
  • the nucleus of human normal aortic vascular smooth muscle cells was Hoechst ( Hextone earth) (100 ⁇ g / m1).
  • FIG. 4 shows a fluorescence photograph of a cross section of the artificial blood vessel produced in Example 1
  • FIG. 5 shows a fluorescence photograph of a cross section of the artificial blood vessel produced in Comparative Example 1.
  • the dotted line in the figure indicates the lumen surface. 4 and 5 that the artificial blood vessel prepared in Example 1 'incorporates cells at a higher density than the artificial blood vessel prepared in Comparative Example 1. '
  • a culture solution containing normal human umbilical vein vascular endothelial cells at a concentration of 5.0 ⁇ 10 6 cells / ml was prepared in a volume of 1 ml, and poured into the lumen of the artificial blood vessel prepared in Example 1.
  • a rotary culture device Titech, RT-50
  • 5111 to 10 ⁇ An endothelial cell layer was formed by culturing for 60 minutes while rotating at a rotating speed.
  • Fig. 6 shows a transmission micrograph of the cross section of the artificial blood vessel
  • Fig. 7 shows a fluorescence photograph of the same cross section.
  • the arrow in FIG. 7 indicates the endothelial cell layer. 6 and 7 that the endothelial cell layer is continuously formed on the luminal surface of the artificial blood vessel prepared in Example 2.
  • the present invention it is possible to smooth the minimum cavity surface in direct contact with blood, which is indispensable for an artificial blood vessel, in a short period of time, and to efficiently and efficiently produce a bioactive substance in a short time. Incorporation into blood vessels is possible.
  • an artificial blood vessel which does not cause blood leakage, has excellent antithrombotic properties, has a substantially smooth lumen surface, and has excellent mechanical properties.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Vascular Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Prostheses (AREA)
  • Materials For Medical Uses (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

L'invention concerne un vaisseau artificiel, qui offre une biocompatibilité, une résistance mécanique et des propriétés antithrombotiques excellentes (entre autres caractéristiques), qui ne présente aucun risque de fuite de sang, et dont la réalisation est aisée. L'invention concerne également un procédé relatif à la réalisation d'un vaisseau artificiel ne présentant aucun risque de fuite de sang et offrant d'excellentes propriétés antithrombotiques, qui a une surface interne presque lisse et qui possède des propriétés mécaniques favorables. On peut réaliser un tel vaisseau en peu de temps, selon les étapes suivantes: immersion d'une substance biologiquement active dans une solution capable de se gélifier, pour donner une solution renfermant cette substance biologiquement active; incorporation de la solution renfermant la substance biologiquement active en question dans les pores d'un matériau de base poreux en forme de tube, utilisé pour la réalisation du vaisseau artificiel; puis gélification de la solution renfermant ladite substance biologiquement active, précédemment incorporée aux pores du matériau de base susmentionné.
PCT/JP2002/010986 2001-10-24 2002-10-23 Vaisseau artificiel et procede de realisation Ceased WO2003034945A1 (fr)

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JP2001-326426 2001-10-24
JP2001326426A JP2003126125A (ja) 2001-10-24 2001-10-24 人工血管及びその製造方法

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JP2007501676A (ja) * 2003-05-07 2007-02-01 アリーヴァ メディカル インコーポレイテッド 栄養分および老廃物の交換を回復することによる腰痛の治療
CN116808279A (zh) * 2023-08-25 2023-09-29 北京国械堂科技发展有限责任公司 一种亲水性复合胶原蛋白海绵及其制备方法

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JP2005034239A (ja) * 2003-07-16 2005-02-10 Gunze Ltd 人工血管用基材
WO2005077432A2 (fr) * 2004-02-09 2005-08-25 Cook Incorporated Prothese coulee bioremodelable
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JP2007307300A (ja) * 2006-05-22 2007-11-29 Hokkaido Univ 人工血管用材料
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CN116808279A (zh) * 2023-08-25 2023-09-29 北京国械堂科技发展有限责任公司 一种亲水性复合胶原蛋白海绵及其制备方法
CN116808279B (zh) * 2023-08-25 2023-11-21 北京国械堂科技发展有限责任公司 一种亲水性复合胶原蛋白海绵及其制备方法

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