CN109966548A - A kind of bilayer polymer Material cladding blood vessel - Google Patents

A kind of bilayer polymer Material cladding blood vessel Download PDF

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Publication number
CN109966548A
CN109966548A CN201910163174.2A CN201910163174A CN109966548A CN 109966548 A CN109966548 A CN 109966548A CN 201910163174 A CN201910163174 A CN 201910163174A CN 109966548 A CN109966548 A CN 109966548A
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blood vessel
polymer material
material cladding
acid
close high
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赵一麟
周媛媛
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Sun Rainforest (xiamen) Biomedical Co Ltd
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Sun Rainforest (xiamen) Biomedical Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/16Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/18Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/20Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/22Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/222Gelatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56Porous materials, e.g. foams or sponges
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/42Anti-thrombotic agents, anticoagulants, anti-platelet agents

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Dermatology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Transplantation (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Vascular Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Dispersion Chemistry (AREA)
  • Materials For Medical Uses (AREA)

Abstract

The invention discloses a kind of bilayer polymer Material cladding blood vessels, are made of smooth fine and close high polymer nanometer fiber layer and the porous support layer surrounded except the smooth fine and close high polymer nanometer fiber layer;The size of the hole of the porous support layer allows cell to grow into, and mutually passes to the extracellular matrix generated after permission cell is grown between the hole and be connected with each other.The present invention has good histocompatbility, while can provide and match good compliance with autologous vein, meets mechanical property required for blood vessel graft, and the histocyte of human normal can be grown into wherein, without forming scar in previous anastomotic region.

Description

A kind of bilayer polymer Material cladding blood vessel
Technical field
The invention belongs to technical field of bioengineering, and in particular to a kind of bilayer polymer Material cladding blood vessel.
Background technique
Current clinically widely used artificial blood vessel's major defect has polytetrafluoroethylene (PTFE) blood vessel and autologous vein to mismatch, The compliance of artificial blood vessel is poor, do not have the flexibility of human body artery completely with elasticity, this defect with small-bore artery Just showed when identical clearly, this be also thrombus easily stoma site formation the main reason for, cause thrombosis and Endometrial hyperplasia, long-term patency rate are extremely low.The result of artificial blood vessel and blood interaction depends on the property such as form on its surface Structure, charge, affinity and surface chemical property with water, this can cause different coagulation pathways.Artificial blood vessel after transplanting Surface meeting adsorbing fiber proteinogen, activates blood platelet, its aggregation is made to generate thrombus.
Summary of the invention
It is an object of the invention to overcome prior art defect, a kind of bilayer polymer Material cladding blood vessel is provided.
Technical scheme is as follows:
A kind of bilayer polymer Material cladding blood vessel, by having the function of anticoagulant, antiplatelet, in promotion, membranization is smooth Fine and close high polymer nanometer fiber layer and the porous support layer surrounded except the smooth fine and close high polymer nanometer fiber layer form;It should The size of the hole of porous support layer allows cell to grow into, and the cell generated after permission cell is grown into is mutually passed between the hole Epimatrix is connected with each other.
In a preferred embodiment of the invention, the smooth fine and close high polymer nanometer fiber layer with a thickness of 100nm-200 μm, the diameter of hole is 10nm-20 μm, fibre diameter 10-5000nm.
In a preferred embodiment of the invention, the porous support layer with a thickness of 20-500 μm, porous support The aperture of layer is 10 μm -300 μm.
In a preferred embodiment of the invention, the smooth fine and close high polymer nanometer fiber layer by electrostatic spinning or 3D printing is prepared.
In a preferred embodiment of the invention, the porous support layer is rapidly frozen molding or 3D printing by foaming It is prepared.
In a preferred embodiment of the invention, the smooth fine and close high polymer nanometer fiber inner membrance, passes through grafting Inert material keeps its smooth.
In a preferred embodiment of the invention, the smooth fine and close high polymer nanometer fiber inner membrance is anti-by load Solidifying drug and there is anticoagulating activity, there is antiplatelet function by load antiplatelet drug, by with promoting inner membrance The method of change is processed and has the function of promoting vessel endothelialisation.
It is further preferred that the anticoagulant includes between direct thrombin inhibitor/factor IIa inhibitor, fibrin ferment Connect inhibitor, vitamin K antagon and selective Xa factor inhibitor/FXa inhibitor.
Still more preferably, the direct thrombin inhibitor/factor IIa inhibitor includes dabigatran etcxilate, than cutting down Lu Ding, argatroban, lepirudin 023 ludon (lepirudin);The fibrin ferment indirect inhibitor includes heparin (preferably heparin sodium, liver Plain calcium) and low molecular weight heparin (preferably Dalteparin Sodium, Enoxaparin Sodium, nadroparin calcium);The vitamin K antagon (VKA) Including warfarin, the selectivity Xa factor inhibitor/FXa inhibitor includes that the direct inhibitor of selective Xa factor is (preferably sharp Cut down husky class, Eliquis and Yi Dushaban) and selective Xa factor indirect inhibitor (preferably yellow up to liver certain herbaceous plants with big flowers sodium).
It is further preferred that the antiplatelet drug includes COX-1 inhibitor, adp receptor antagonist, human platelet glycoprotein egg White 1I b/IIIa receptor antagonist and phosphodiesterase inhibitors.
Still more preferably, the COX-1 inhibitor includes aspirin, and the adp receptor antagonist includes thiophene chlorine Fixed, clopidogrel, prasugrel and ticagrelor, the platelet glycoprotein 1I b/IIIa receptor antagonist includes Ah former times Monoclonal antibody, tirofiban and eptifibatide, the phosphodiesterase inhibitors include Dipyridamole and Cilostazol.
It is further preferred that in the promotion membranization method include coating vascular endothelial growth factor, smooth muscle protein, Human growth hormone recombinant, CD34 antibody, hyaluronic acid, adhesiveness albumen, Atorvastatin, biologically active polypeptide, biomolecule Modify endangium or the endothelial cell in the smooth fine and close high polymer nanometer fiber layer plantation people.
Still more preferably, the human endothelial cells include Human umbilical vein endothelial cells and endothelial progenitor cells.
It is further preferred that the material of the smooth fine and close high polymer nanometer fiber layer include polyurethane, polytetrafluoroethylene (PTFE), Expanded polytetrafluoroethylsealing, fibroin (fibroin), polycaprolactone (PCL), polylactic acid (PLA), polyethylene terephthalate Ester, polyethylene, polyvinyl chloride, polyglycolic acid (PGA), polymethylacrylic acid, organic silicon rubber, polyglycolic-polylactic acid (PLGA), carboxymethyl starch, acetic starch, chitin, chitosan (Chitosan), carboxymethyl chitosan, alginic acid/alginic acid Salt, carboxymethyl cellulose, gelatin, collagen (I, II, III, IV), hyaluronic acid (HA), polyvinyl alcohol (PVA), polyacrylamide (PAM), at least one of polyacrylic acid and polyvinylpyrrolidone (PVP).
It is further preferred that the material of the porous support layer includes polyurethane, polytetrafluoroethylene (PTFE), extruding polytetrafluoroethyl-ne Alkene, fibroin (fibroin), it is polycaprolactone (PCL), polylactic acid (PLA), polyethylene terephthalate, polyethylene, poly- Vinyl chloride, polyglycolic acid (PGA), polymethylacrylic acid, organic silicon rubber, polyglycolic-polylactic acid (PLGA), carboxymethyl Starch, acetic starch, chitin, chitosan (Chitosan), carboxymethyl chitosan, alginic acid/alginate, carboxymethyl cellulose Element, gelatin, collagen (I, II, III, IV), hyaluronic acid (HA), polyvinyl alcohol (PVA), polyacrylamide (PAM), polyacrylic acid At least one of with polyvinylpyrrolidone (PVP).
The high polymer nanometer fiber inner membrance can keep its inner membrance smooth by being grafted inert material.
The beneficial effects of the present invention are: the present invention has good histocompatbility, while can provide and autologous vein With good compliance, meet mechanical property required for blood vessel graft, and the histocyte of human normal can be grown into wherein, Without forming scar in previous anastomotic region.
Detailed description of the invention
Fig. 1 is the photo of the bilayer polymer Material cladding blood vessel in the embodiment of the present invention 3.
Fig. 2 is the scanning electron microscope photograph of the internal layer of the vascular grafts in the embodiment of the present invention 3, outer layer (A: internal layer, B: outer layer) Piece.
Fig. 3 is the photo of the bilayer polymer Material cladding blood vessel in the embodiment of the present invention 2.
Fig. 4 is the scanning electron microscope photograph of the internal layer of the vascular grafts in the embodiment of the present invention 2, outer layer (A: internal layer, B: outer layer) Piece.
Fig. 5 is the vascular grafts cytotoxicity experiment result picture in the embodiment of the present invention 3.
Fig. 6 is 3 medium vessels material mechanical drawing force result picture of the embodiment of the present invention.
Specific embodiment
Technical solution of the present invention is further explained and described below by way of specific embodiment combination attached drawing.
Embodiment 1
A kind of bilayer polymer Material cladding blood vessel, by having the function of anticoagulant, antiplatelet, in promotion, membranization is smooth Fine and close high polymer nanometer fiber layer and the porous support layer surrounded except the smooth fine and close high polymer nanometer fiber layer form, should The size of the hole of porous support layer allows cell to grow into, and the cell generated after permission cell is grown into is mutually passed between the hole Epimatrix is connected with each other.
It is preferred: the smooth fine and close high polymer nanometer fiber layer with a thickness of 100nm-200 μm, the diameter of hole is 10nm-20 μm, fibre diameter 10-5000nm;The porous support layer with a thickness of 20-500 μm, the aperture of porous support layer It is 10 μm -300 μm;The smooth fine and close high polymer nanometer fiber layer is prepared by electrostatic spinning or 3D printing;It is described porous Bracket is rapidly frozen molding by foaming or 3D printing is prepared.
Above-mentioned electrostatic spinning carries out dry spinning using certain density electrostatic spinning raw material solution is prepared.Electrostatic spinning raw material solution It is squeezed out by micro pump, flow velocity 0.1-2mL/h, spout connects high-voltage positive electrode, reception device ground connection, and the revolving speed of receiver is 10- 1000r.p.m, electrostatic spinning voltage 10-30kV, jet opening distance reception device 5-30cm, nozzle diameter 0.1-1mm, environment temperature 10-30 DEG C, ambient humidity 20-80%, collect nanofiber pipe;
Above-mentioned foaming is rapidly frozen molding specifically: prepares certain density expanding foam solution, is frozen into tubulose using a fixed mold Structure obtains individual porous support tube after freeze-drying, the inner membrance prepared with electrostatic spinning is allowed to using certain method The two is combined closely;Or be uniformly applied to expanding foam solution on above-mentioned smooth fine and close high polymer nanometer fiber layer, in certain temperature Lower precooling for a period of time, consecutive low temperature vacuumize a period of time, after in certain temperature be dried in vacuo a period of time,.
The material of the smooth fine and close high polymer nanometer fiber layer and the porous support layer includes polyurethane, polytetrafluoroethyl-ne Alkene, expanded polytetrafluoroethylsealing, fibroin (fibroin), polycaprolactone (PCL), polylactic acid (PLA), poly terephthalic acid second Diol ester, polyethylene, polyvinyl chloride, polyglycolic acid (PGA), polymethylacrylic acid, organic silicon rubber, the poly- hydroxyl of polylactic acid- Acetic acid (PLGA), carboxymethyl starch, acetic starch, chitin, chitosan (Chitosan), carboxymethyl chitosan, alginic acid/sea Alginates, carboxymethyl cellulose, gelatin, collagen (I, II, III, IV), hyaluronic acid (HA), polyvinyl alcohol (PVA), polypropylene At least one of amide (PAM), polyacrylic acid and polyvinylpyrrolidone (PVP).
It is further preferred that above-mentioned smooth fine and close high polymer nanometer fiber inner membrance, keeps its smooth by being grafted inert material.
Above-mentioned smooth fine and close high polymer nanometer fiber inner membrance has anticoagulating activity by load anticoagulant, passes through load Antiplatelet drug and there is antiplatelet function, have and being processed with the method for membranization in promoting and promote blood vessel The function of endothelialization.
It is further preferred that the anticoagulant includes between direct thrombin inhibitor/factor IIa inhibitor, fibrin ferment Connect inhibitor, vitamin K antagon and selective Xa factor inhibitor/FXa inhibitor.
Still more preferably, the direct thrombin inhibitor/factor IIa inhibitor includes dabigatran etcxilate, than cutting down Lu Ding, argatroban, lepirudin 023 ludon (lepirudin);The fibrin ferment indirect inhibitor includes heparin (preferably heparin sodium, liver Plain calcium) and low molecular weight heparin (preferably Dalteparin Sodium, Enoxaparin Sodium, nadroparin calcium);The vitamin K antagon (VKA) Including warfarin, the selectivity Xa factor inhibitor/FXa inhibitor includes that the direct inhibitor of selective Xa factor is (preferably sharp Cut down husky class, Eliquis and Yi Dushaban) and selective Xa factor indirect inhibitor (preferably yellow up to liver certain herbaceous plants with big flowers sodium).
It is further preferred that the antiplatelet drug includes COX-1 inhibitor, adp receptor antagonist, human platelet glycoprotein egg White 1I b/IIIa receptor antagonist and phosphodiesterase inhibitors.
Still more preferably, the COX-1 inhibitor includes aspirin, and the adp receptor antagonist includes thiophene chlorine Fixed, clopidogrel, prasugrel and ticagrelor, the platelet glycoprotein 1I b/IIIa receptor antagonist includes Ah former times Monoclonal antibody, tirofiban and eptifibatide, the phosphodiesterase inhibitors include Dipyridamole and Cilostazol.
It is further preferred that in the promotion membranization method include coating vascular endothelial growth factor, smooth muscle protein, Human growth hormone recombinant, CD34 antibody, hyaluronic acid, adhesiveness albumen, Atorvastatin, biologically active polypeptide, biomolecule Modify endangium or the endothelial cell in the smooth fine and close high polymer nanometer fiber layer plantation people.
Still more preferably, the human endothelial cells include Human umbilical vein endothelial cells and endothelial progenitor cells.
Embodiment 2
(1) PVA- carboxymethyl chitosan (9: 1) is dissolved in deionized water, obtains electrostatic spinning raw material solution, it is specific to join Number is as shown in table 1 below:
1 electrostatic spinning solution of table prepares parameter
The design parameter of electrostatic spinning is as shown in table 2 below:
The control of 2 electrospinning parameters of table
(2) above-mentioned electrostatic spinning raw material solution is subjected to electrostatic spinning, obtains smooth fine and close high polymer nanometer fiber layer;This is smooth After fine and close high polymer nanometer fiber layer is crosslinked with sodium trimetaphosphate, hydrophily is good, conducive to the hidden danger for mitigating blood vessel blockage, specifically Shown in water absorbing properties the following table 3:
The test of 3 water imbibition of table
Length (mm) Weight (g) Water absorption (g) Water absorption rate (%)
98.90±0.0315 0.1169±0.0046 0.2089±0.0065 178.70±0.0358
(3) hair prepared is uniformly smeared in the outer surface of the smooth fine and close high polymer nanometer fiber layer made from step (2) Liquid is steeped, carries out freeze setting in liquid nitrogen, vacuumizes 3-6h, for 24 hours, acquisition internal layer is smooth densification PVA- carboxymethyl shell for vacuum drying Glycan layers of nanofibers, the bilayer polymer Material cladding blood vessel of the invention that outer layer is porous support layer, appearance such as Fig. 3 institute Show, the scanning electron microscope (SEM) photograph of internal layer and outer layer is as shown in Figure 4.
The composition and preparation parameter of above-mentioned expanding foam solution are as shown in the following table 4 and table 5:
4 expanding foam solution of table prepares parameter
5 expanding foam solution preparation parameter of table
Embodiment 3
(1) by PCL- Gelatin in hexafluoroisopropanol, electrostatic spinning raw material solution, design parameter such as -6 institute of following table are obtained Show:
6 electrostatic spinning solution of table prepares parameter
The design parameter of electrostatic spinning is as shown in table 7 below:
The control of 7 electrospinning parameters of table
(2) above-mentioned electrostatic spinning raw material solution is subjected to electrostatic spinning, obtains smooth fine and close high molecular nanometer as shown in Figure 2 A Fibrous layer;The smooth fine and close high polymer nanometer fiber layer hydrophily is good, conducive to the hidden danger for mitigating blood vessel blockage, specific water imbibition Shown in energy the following table 8:
The test of 8 water imbibition of table
Length (mm) Weight (g) Water absorption (g) Water absorption rate (%)
99.90±0.0015 0.1052±0.0046 0.2689±0.0065 255.02±0.0315
(3) by the expanding foam solution prepared (polyurethane, polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylsealing, fibroin (fibroin), it is polycaprolactone (PCL), polylactic acid (PLA), polyethylene terephthalate, polyglycolic acid (PGA), poly- Ethylene, polyvinyl chloride, polyglycolic-polylactic acid (PLGA), polymethylacrylic acid, organic silicon rubber, carboxymethyl starch, acetic acid Starch, chitin, chitosan (Chitosan), carboxymethyl chitosan, alginic acid/alginate, carboxymethyl cellulose, gelatin, Collagen (I, II, III, IV), hyaluronic acid (HA), polyvinyl alcohol (PVA), polyacrylamide (PAM), polyacrylic acid, polyethylene At least one of pyrrolidones (PVP)), it is uniformly applied to the tubular die of certain internal diameter, carries out freeze setting, vacuum in low temperature It is dry to obtain flexible porous tubulose bracket for 24 hours, in conjunction with the smooth fine and close high polymer nanometer fiber layer prepared in step (2), The bilayer polymer Material cladding blood vessel of the invention that internal layer is smooth compact nanometer layer, outer layer is porous support layer is obtained, outside Pipe such as Fig. 1, scanning electron microscope (SEM) photograph is as shown in Figure 2.
(4) CCK-8 method is used, cytotoxicity detection is carried out to the patching material of preparation, concrete operations are as follows: cell is hanged Liquid (100 hole μ L/) is seeded in 96 orifice plates, and control group is with normal incubation medium culture cell, and treated group is to impregnate preparation Bilayer polymer Material cladding blood vessel culture medium culture cell for 24 hours.Preculture certain time (the example in moist incubator Such as, at 37 DEG C, under the conditions of 5%CO2).10 μ L CCK-8 solution are added into each hole of plate.It is careful not to introduce gas into hole Bubble, because they can interfere O.D. value to detect.Culture plate is put and is incubated for 1-4 hours in the incubator.It is measured using microplate reader Absorbance at 450nm.Result is obtained as shown in figure 5, no difference of science of statistics, illustrates bilayer polymer Material cladding of the invention Blood vessel is non-toxic.
(5) bilayer polymer Material cladding blood vessel of the invention is cut into growth 20mm, tests material with small power tensilometer Expect drawing force, it is as shown in Figure 6 with the relationship of pulling force to obtain displacement.
The foregoing is only a preferred embodiment of the present invention, the range that the present invention that therefore, it cannot be limited according to is implemented, i.e., Equivalent changes and modifications made in accordance with the scope of the invention and the contents of the specification should still be within the scope of the present invention.

Claims (12)

1. a kind of bilayer polymer Material cladding blood vessel, it is characterised in that: by smooth fine and close high polymer nanometer fiber layer and wrapping Porous support layer composition except the smooth fine and close high polymer nanometer fiber layer;The size of the hole of the porous support layer allows Cell is grown into, and is mutually passed to the extracellular matrix generated after permission cell is grown between the hole and be connected with each other.
2. a kind of bilayer polymer Material cladding blood vessel as described in claim 1, it is characterised in that: the smooth fine and close high score Sub- layers of nanofibers with a thickness of 100nm-200 μm, the diameter of hole is 10nm-20 μm, fibre diameter 10-5000nm.
3. a kind of bilayer polymer Material cladding blood vessel as described in claim 1, it is characterised in that: the porous support layer With a thickness of 20-500 μm, the aperture of porous support layer is 10 μm -300 μm.
4. a kind of bilayer polymer Material cladding blood vessel as described in claim 1, it is characterised in that: the smooth fine and close high score Sub- layers of nanofibers is prepared by electrostatic spinning or 3D printing.
5. a kind of bilayer polymer Material cladding blood vessel as described in claim 1, it is characterised in that: the porous support layer by Foaming is rapidly frozen molding or 3D printing is prepared.
6. a kind of bilayer polymer Material cladding blood vessel as described in claim 1, it is characterised in that: the smooth fine and close high score Sub- nanofiber inner membrance keeps its smooth by being grafted inert material.
7. a kind of bilayer polymer Material cladding blood vessel as described in claim 1, it is characterised in that: the smooth fine and close high score Sub- nanofiber inner membrance has anticoagulating activity by load anticoagulant, has anti-blood small by load antiplatelet drug The function of plate has the function of promoting vessel endothelialisation and with promoting the method for interior membranization to be processed.
8. a kind of bilayer polymer Material cladding blood vessel as claimed in claim 7, it is characterised in that: the anticoagulant includes Direct thrombin inhibitor/factor IIa inhibitor, fibrin ferment indirect inhibitor, vitamin K antagon and selective Xa factor suppression Preparation/FXa inhibitor.
9. a kind of bilayer polymer Material cladding blood vessel as claimed in claim 7, it is characterised in that: the antiplatelet drug Inhibit including COX-1 inhibitor, adp receptor antagonist, platelet glycoprotein 1I b/IIIa receptor antagonist and phosphodiesterase Agent.
10. a kind of bilayer polymer Material cladding blood vessel as claimed in claim 7, it is characterised in that: membranization in the promotion Method include coating vascular endothelial growth factor, it is smooth muscle protein, human growth hormone recombinant, CD34 antibody, hyaluronic acid, viscous Attached property albumen, Atorvastatin, biologically active polypeptide, biomolecule are modified endangium or are received in the smooth fine and close macromolecule The endothelial cell of rice fibrous layer plantation people.
11. a kind of bilayer polymer Material cladding blood vessel as described in any claim in claims 1 to 10, feature exist In: the material of the smooth fine and close high polymer nanometer fiber layer includes polyurethane, polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylsealing, silkworm Silk-fibroin, polycaprolactone, polylactic acid, polyethylene terephthalate, polyethylene, polyvinyl chloride, polyglycolic acid, poly- methyl Acrylic acid, organic silicon rubber, polyglycolic-polylactic acid, carboxymethyl starch, acetic starch, chitin, chitosan, carboxymethyl Chitosan, carboxymethyl cellulose, gelatin, collagen, hyaluronic acid, polyvinyl alcohol, polyacrylamide, gathers alginic acid/alginate At least one of acrylic acid and polyvinylpyrrolidone.
12. a kind of bilayer polymer Material cladding blood vessel as described in any claim in claims 1 to 10, feature exist In: the material of the porous support layer includes polyurethane, polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylsealing, fibroin, gathers in oneself Ester, polylactic acid, polyethylene terephthalate, polyethylene, polyvinyl chloride, polyglycolic acid, polyglycolic-polylactic acid, Polymethylacrylic acid, organic silicon rubber, carboxymethyl starch, acetic starch, chitin, chitosan, carboxymethyl chitosan, seaweed Acid/alginate, carboxymethyl cellulose, gelatin, collagen, hyaluronic acid, polyvinyl alcohol, polyacrylamide, polyacrylic acid and poly- At least one of vinylpyrrolidone.
CN201910163174.2A 2019-03-05 2019-03-05 A kind of bilayer polymer Material cladding blood vessel Pending CN109966548A (en)

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