CN114668896B - Preparation method of compliance-matched multilayer small-caliber artificial blood vessel and artificial blood vessel - Google Patents

Preparation method of compliance-matched multilayer small-caliber artificial blood vessel and artificial blood vessel Download PDF

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CN114668896B
CN114668896B CN202111564198.2A CN202111564198A CN114668896B CN 114668896 B CN114668896 B CN 114668896B CN 202111564198 A CN202111564198 A CN 202111564198A CN 114668896 B CN114668896 B CN 114668896B
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layer
dip
blood vessel
electrostatic spinning
coating
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CN114668896A (en
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孟凯
管立桦
赵荟菁
张克勤
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Suzhou University
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Suzhou University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06—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
    • A61L27/02—Inorganic materials
    • A61L27/04—Metals or alloys
    • A61L27/042—Iron or iron alloys
    • 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
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • 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
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/0007—Electro-spinning
    • D01D5/0061—Electro-spinning characterised by the electro-spinning apparatus
    • D01D5/0069—Electro-spinning characterised by the electro-spinning apparatus characterised by the spinning section, e.g. capillary tube, protrusion or pin
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/0007—Electro-spinning
    • D01D5/0061—Electro-spinning characterised by the electro-spinning apparatus
    • D01D5/0076—Electro-spinning characterised by the electro-spinning apparatus characterised by the collecting device, e.g. drum, wheel, endless belt, plate or grid
    • D01D5/0084—Coating by electro-spinning, i.e. the electro-spun fibres are not removed from the collecting device but remain integral with it, e.g. coating of prostheses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2240/001—Designing or manufacturing processes

Abstract

The invention provides a preparation method of a compliance-matched multilayer small-caliber artificial blood vessel, which comprises the following steps: the invention discloses a preparation method of an artificial blood vessel, which comprises the steps of dip coating liquid preparation and PVA solution preparation, wherein a PVA layer is formed by dip coating, a complete dip coating layer is formed by dip coating liquid, electrostatic spinning is carried out on the complete dip coating layer to form an electrostatic spinning layer, an artificial blood vessel is formed by demolding, the dip coating layer and the electrostatic spinning layer are simultaneously arranged in the artificial blood vessel formed by the method, the dip coating layer can achieve controllable single-layer thickness (modulus) and flexible multi-layer compounding, the electrostatic spinning layer can play a role in improving the blood vessel blasting pressure and suturing and retaining strength, and compliance matching preparation of the artificial blood vessel is achieved by respectively controlling the thicknesses of the dip coating layer and the electrostatic spinning layer and flexibly combining different thicknesses of two structural layers, so that blood flow disorder and abnormal mechanical factors caused by mismatch of compliance of the artificial blood vessel are reduced, and thrombus and intimal hyperplasia after artificial blood vessel transplantation are reduced.

Description

Preparation method of compliance-matched multilayer small-caliber artificial blood vessel and artificial blood vessel
Technical Field
The application relates to a compliance-matched multilayer small-caliber artificial blood vessel and a preparation method thereof.
Background
The artificial blood vessel is a substitute for a plurality of severely narrowed or occluded blood vessels, the blood flow dynamics at the anastomotic site after the transplantation can be influenced due to mismatching of the compliance of the artificial blood vessel and the compliance of the host blood vessel, the blood flow can be disturbed or the blood vessel wall can be subjected to abnormal wall shear stress due to overhigh or overlow compliance, the blood vessel is easy to form thrombus or intimal hyperplasia to cause blood vessel restenosis, the influence on the small-caliber artificial blood vessel with the diameter of less than 6mm is particularly serious, the artificial blood vessel is comprehensively limited by blood vessel materials, structure design and preparation methods, the preparation of the artificial blood vessel with the compliance consistent with that of the natural blood vessel still faces challenges, the compliance of most artificial blood vessels is lower than that of the natural blood vessels at present, although the wall thickness of the artificial blood vessel is sacrificed to have a certain effect on the improvement of the compliance, the adverse effect can be brought on other mechanical properties such as burst pressure, suture fixing strength and the like of the artificial blood vessel. Therefore, on the premise that the wall thickness of the artificial blood vessel is equal to that of the replaced blood vessel, how to prepare the small-caliber artificial blood vessel matched with the compliance of the replaced blood vessel is a difficult problem to be solved at present.
There have been studies and attempts by some researchers, such as:
the invention patent with publication number CN109498209A discloses a preparation method of a compliance-adjustable multilayer composite artificial blood vessel, which comprises the steps of firstly preparing a single-layer artificial blood vessel by blending and foaming PCL, PLA and TPU, then nesting the single-layer artificial blood vessel into three layers, and filling gel or protein between adjacent composite foaming material pipes. According to the method, the single-layer blood vessels with different moduli are formed by mixing three materials in different proportions, so that the compliance of the prepared blood vessels with three-layer structures is different, but the compliance is influenced by the complexity of a foaming process, the modulus value of the single-layer blood vessel is not well controlled accurately, the uncertainty of the compliance is increased by filling gel and protein between layers, and the matching preparation of the artificial blood vessel is difficult to perform according to the compliance value;
the invention patent with publication number CN109106468A discloses an artificial blood vessel structure capable of improving compliance, the method adopts a weaving method to prepare a polyester artificial blood vessel, the inner layer and the outer layer of the blood vessel are satin structures, and warp yarns adopt PET textured yarns; the middle layer of the blood vessel is plain weave, and the warp adopts PET filament; the weft yarns in each layer of the blood vessel adopt composite yarns consisting of textured yarns or elastic yarns and non-elastic yarns. The method increases the elasticity of weft yarns, so that the radial diameter of blood vessels can adapt to the requirements of a human body, and the compliance of the blood vessels can be improved by 3-5%. But the method is difficult to perform compliance regulation according to different target values;
the invention patent with publication number CN105031735A discloses a three-layer composite structure small-caliber artificial blood vessel and a preparation method thereof, the three-layer composite structure small-caliber artificial blood vessel comprises a woven inner layer, an electrostatic spinning middle layer is arranged on the outer side of the woven inner layer, a polyurethane outer layer is arranged on the outer side of the electrostatic spinning middle layer, the woven inner layer comprises a first woven support tube and a second woven support tube arranged on the outer side of the first woven support tube, and the second woven support tube is a woven support tube with axial yarns. Although the compliance of the blood vessel can be improved by using the material with good elasticity to prepare the multilayer artificial blood vessel, the weaving method and the knitting method are more suitable for preparing the artificial blood vessel with large and medium caliber;
the invention patent with publication number CN 111265721A discloses a preparation method of an electrostatic spinning double-layer artificial blood vessel with different diameters, which is characterized in that a nanofiber membrane obtained by a mixed solution of PCL and RHC through an electrostatic spinning technology is used as an inner layer, then the PCL solution and a PEO solution are co-spun through a coaxial electrostatic spinning technology, PEO fibers in the PCL solution and the PEO solution are dissolved, and an outer layer with a uniform porous structure and appropriate porosity is prepared. Although the method can prepare the artificial blood vessel with a double-layer structure, the method does not relate to the problem of compliance of the blood vessel.
Disclosure of Invention
The invention prepares the multilayer composite small-caliber artificial blood vessel by combining the dip coating method and the electrostatic spinning method, the dip coating layer can achieve controllable monolayer thickness (modulus) and flexible multilayer compounding, the electrostatic spinning layer can play the roles of improving the blood vessel bursting pressure and suturing retention strength, and the combination of the two realizes the preparation of the small-caliber artificial blood vessel with the matching compliance.
A method for preparing a compliance-matched multilayer small-caliber artificial blood vessel, which is characterized by comprising the following steps:
s1: preparing dip-coating liquid and preparing PVA solution:
adding a polymer material into an organic solvent to prepare dip-coating liquid, wherein the polymer material is polylactide caprolactone or polyurethane, and the organic solvent is hexafluoroisopropanol, trichloromethane or tetrahydrofuran;
weighing polyvinyl alcohol (PVA), dissolving in a mixed solvent of alcohol and deionized water, and preparing into a PVA solution;
s2: dip coating to form a PVA layer:
fixing a stainless steel bar on a dip-coating machine, immersing the stainless steel bar into PVA solution, staying, withdrawing the stainless steel bar, fixing the stainless steel bar on a homogenizing motor, and rotationally drying to form a PVA layer on the stainless steel bar;
s3: dip coating the dip coating solution to form a complete dip coating:
fixing the stainless steel bar dipped with the PVA layer on a dip-coating machine again, dipping the stainless steel bar into the prepared dip-coating solution, staying, withdrawing the stainless steel bar, standing, and performing reverse dip-coating, wherein the two dip-coatings are used as a complete dip-coating layer;
s4: and (3) performing electrostatic spinning on the complete dip-coating layer to form an electrostatic spinning layer:
mounting a stainless steel bar with a complete dip coating on a receiving device of an electrostatic spinning machine as a receiving bar; preparing a solution with a certain concentration suitable for electrostatic spinning: the raw materials are the same as the dip coating solution; and performing electrostatic spinning on the complete dip-coating layer to form an electrostatic spinning layer.
S5: and demolding to form the artificial blood vessel.
Further, in the above-mentioned case,
in the step S2, dipping and coating to form a PVA layer, dipping the PVA layer into a PVA solution at the speed of 1000-5000 um/S, staying for 10S, withdrawing the stainless steel rod at the withdrawal speed of 500-5000 um/S, fixing the stainless steel rod on a homogenizing motor, rotating for 5-10 minutes at the speed of 200-500 r/min, placing the stainless steel rod in a 60 ℃ baking oven for 30min, inversely fixing the stainless steel rod on a dip-coating machine, and repeating the dipping and coating once, wherein the two times of dipping and coating are used as a complete PVA layer.
In a further aspect of the present invention,
in the step S3, the dip-coating solution is dipped into the prepared dip-coating solution at the speed of 1000-5000 um/S to form a complete dip-coating layer, the prepared dip-coating solution is stayed for 10S, the stainless steel bar is withdrawn at the speed of 500-5000 um/S, and the stainless steel bar is kept stand for 5-10 minutes.
Further, in the above-mentioned case,
in step S4, the electrostatic spinning process parameters are as follows: the extrusion speed range is 0.5-1 ml/h, the voltage range is 10-15 kv, the collection distance range is 15-20 cm, the rotation speed of the collection rod is 500-800 r/min, and meanwhile, the thickness of the electrostatic spinning layer is controlled by controlling the electrostatic spinning time.
Further, in the above-mentioned case,
in step S4, the process parameters of electrostatic spinning are: the extrusion speed range is 0.5-1 ml/h, the voltage range is 10-15 kv, the collection distance range is 15-20 cm, the rotation speed of the collection rod is 500-800 r/min, and meanwhile, the thickness of the electrostatic spinning layer is controlled by controlling the electrostatic spinning time.
Further, a pore-forming agent is added into the formed dip coating liquid or when the dip coating liquid is formed, wherein the pore-forming agent is polyethylene glycol (PEG).
Further, the alcohol and deionized water in the mixed solvent are 50 (W/W), and the concentration of the PVA solution is 13-16%.
Further, the polymer material is polylactide caprolactone, the organic solvent is hexafluoroisopropanol, and the content of polyethylene glycol (PEG) in the dip-coating solution is 0.5-0.7%, and the content of polylactide caprolactone (PLCL) is 12-15%.
Further, the method also comprises the step of repeating the step S3 at least twice to form at least two complete dip-coating layers before the step S4.
The invention also provides an artificial blood vessel which is prepared by the preparation method and comprises at least one complete dipping coating and an electrostatic spinning layer.
Has the advantages that: the invention provides a preparation method of a compliance-matched multilayer small-caliber artificial blood vessel, which comprises the following steps: the invention discloses a preparation method of an artificial blood vessel, which comprises the steps of dip coating liquid preparation and PVA solution preparation, wherein a PVA layer is formed by dip coating, a complete dip coating layer is formed by dip coating liquid, electrostatic spinning is carried out on the complete dip coating layer to form an electrostatic spinning layer, an artificial blood vessel is formed by demolding, the dip coating layer and the electrostatic spinning layer are simultaneously arranged in the artificial blood vessel formed by the method, the dip coating layer can achieve controllable single-layer thickness (modulus) and flexible multi-layer compounding, the electrostatic spinning layer can play the roles of increasing the bursting pressure of the blood vessel and suturing and retaining strength, and the matching preparation of the artificial blood vessel is achieved by respectively controlling the thicknesses of the dip coating layer and the electrostatic spinning layer and flexibly combining different thicknesses of two structural layers, so that blood flow disorder and abnormal mechanical factors caused by mismatching of the compliance of the artificial blood vessel are reduced, and the formation of thrombus and intimal hyperplasia after artificial blood vessel transplantation is reduced.
Detailed Description
The preparation method of the compliance-matched multilayer small-caliber artificial blood vessel comprises the following steps:
s1: preparing a dip coating solution and preparing a PVA solution;
the dip-coating solution can be prepared by selecting polymer materials suitable for dip-coating, such as degradable material polylactide caprolactone (PLCL), non-degradable material Polyurethane (PU) and the like, and selecting corresponding organic solvents, such as hexafluoroisopropanol, trichloromethane, tetrahydrofuran and the like, according to the polymer materials; further, a proper amount of pore-forming agent can be added into the formed dip-coating solution, the proper amount of pore-forming agent can be polyethylene glycol (PEG), and the mixture is uniformly stirred, specifically, for example, a polylactide caprolactone material (PLCL) can be weighed to serve as a substrate, the polyethylene glycol pore-forming agent is added with hexafluoroisopropanol, and a mixed solution containing the PEG and the PLCL is prepared, wherein the mixed solution is a dip-coating layer solution.
Preparing a PVA solution, namely weighing polyvinyl alcohol (PVA), dissolving the PVA in a mixed solvent of alcohol and deionized water to prepare a PVA polymer aqueous solution;
s2: dip coating to form a PVA layer:
fixing a stainless steel bar on a dip-coating machine, immersing the stainless steel bar into PVA solution at the speed of 1000-5000 um/s, staying for 10s, withdrawing the stainless steel bar at the withdrawal speed of 500-5000 um/s, fixing the stainless steel bar on a homogenizing motor, rotating for 5-10 minutes at the speed of 200-500 r/min, placing the stainless steel bar in a 60 ℃ drying oven for 30min, inverting and fixing the stainless steel bar on the dip-coating machine, and repeatedly dip-coating once, wherein the two dip-coating processes are used as a complete PVA layer which is mainly used for subsequent demoulding;
s3: dip coating the dip coating solution to form a complete dip coating:
specifically, the stainless steel bar with the PVA layer being dipped is fixed on the dip coater again, and is dipped into the prepared dip coating solution at the speed of 1000-5000 um/s, and after staying for 10s, the stainless steel bar is withdrawn at the speed of 500-5000 um/s, stands for 5-10 minutes, and is dipped in the reverse direction once again, and the two times of dip coating are used as a complete dip coating layer;
s4: electrostatic spinning on the complete dip coating:
in particular, the method comprises the following steps of,
mounting a stainless steel bar with a complete dip coating on a receiving device of an electrostatic spinning machine as a receiving bar;
preparing a solution with a certain concentration suitable for electrostatic spinning: the raw materials are the same as the dip coating solution;
the electrostatic spinning process parameters are as follows: the extrusion speed range is 0.5-1 ml/h, the voltage range is 10-15 kv, the collection distance range is 15-20 cm, the rotation speed of the collection rod is 500-800 r/min, and the thickness of the electrostatic spinning layer is controlled by controlling the electrostatic spinning time;
s5: demolding to form the artificial blood vessel:
the collecting rod is taken down and soaked in normal-temperature deionized water for 3 days, then one end of the collecting rod is clamped by a pair of tweezers, the vascular wall is clamped by another pair of tweezers, the artificial blood vessel is separated from the stainless steel rod and is naturally dried, and the artificial blood vessel is placed in a sealing bag for constant-temperature preservation.
It can be understood that, in the above description, for the preparation method of the double-layer composite artificial blood vessel of a complete dip coating layer plus an electrostatic spinning layer, composite artificial blood vessels with different conformability can be formed by controlling the thickness of the dip coating layer and the thickness of the electrostatic spinning layer. Such as: the method comprises the following steps of preparing an artificial blood vessel with a certain structure by using a complete dip coating layer, a complete dip coating layer and an electrostatic spinning layer, and the like, so as to regulate the compliance of the artificial blood vessel or prepare the artificial blood vessel with the corresponding structure according to the given compliance value in a matching way, wherein the compliance is the maximum when the artificial blood vessel is completely dip coated, and the maximum value is different according to the used materials and the wall thickness of the blood vessel.
The present application will be described in further detail with reference to examples.
Example 1
(vessel wall thickness 200um, dip-coating: electrospun layer thickness ratio 1:1)
(1) Weighing 7.5g of polyvinyl alcohol (PVA), dissolving in a mixed solvent of alcohol and deionized water (50);
(2) Weighing 6.39g of polylactide caprolactone material (PLCL) as a matrix, a polyethylene glycol (PEG, molecular weight 600) porogen, adding 45ml of hexafluoroisopropanol, and preparing a mixed solution containing 0.60% PEG and 14.2% PLCL, which is a dip coating solution;
(3) A stainless steel rod with the inner diameter of 4mm and the length of 10cm is fixed on a dip coater, the dipping speed is 5000um/s, the withdrawal speed is 1000um/s, the stainless steel rod is connected to a homogenizer motor after being dipped, the rod is rotated for 5 minutes at the speed of 300 revolutions per minute, and then the stainless steel rod is placed in an oven with the temperature of 60 ℃ for drying for 30 minutes. Inverting the dried stainless steel bar with the PVA coating, and dip-coating for one time according to the same process and parameters to form a PVA layer;
(4) The stainless steel rod coated with the PVA layer was immersed in a mixed solution of PEG and PLCL using a dip coater. The immersion speed was set to 5000um/s, and 1000um/s was selected as the exit rate. And (3) standing for 10min after the stainless steel rod is withdrawn, reversely fixing the stainless steel rod on a dip-coating machine, and repeatedly dip-coating once according to the process to form a complete dip-coating layer. Repeating the above process, and dip-coating 2 complete dip-coating layers;
(5) Weighing 1g of polylactide caprolactone, and preparing a PLCL (polylactic-co-glycolic acid) electrostatic spinning solution with the concentration of 10% by using hexafluoroisopropanol as a solvent;
(6) Assembling a stainless steel bar with a dip coating on a rotating motor, forming the outermost layer of a blood vessel by utilizing an electrostatic spinning technology under the driving of a three-axis moving platform, wherein the voltage is 10KV, the rotating speed is 500 rpm, the receiving distance is 15cm, the time is 2h, the stainless steel bar is placed in a fume hood for one night, and the wall thickness of an electrostatic spinning layer is 100 mu m;
(7) And (3) soaking the stainless rod with the dip coating layer and the electrostatic spinning layer in normal-temperature deionized water for 3 days, clamping one end of the collecting rod by using a pair of tweezers, clamping the vessel wall by using the other pair of tweezers, separating the artificial blood vessel from the stainless rod, and naturally drying.
Example 2 (vessel wall thickness 200um, dip coating: electrospun layer thickness ratio 3:1)
(1) Weighing 7.5g of polyvinyl alcohol (PVA), dissolving in a mixed solvent of alcohol and deionized water (50);
(2) Weighing 6.39g of polylactide caprolactone material (PLCL) as a matrix, a polyethylene glycol (PEG, molecular weight 600) porogen, adding 45ml hexafluoroisopropanol, formulating a mixed solution containing 0.60% PEG and 14.2% PLCL, the mixed solution being a dip coating solution;
(3) Weighing 1g of polylactide caprolactone, and preparing a PLCL (polylactic-co-glycolic acid) electrostatic spinning solution with the concentration of 10% by using hexafluoroisopropanol as a solvent;
(4) A stainless steel rod with the inner diameter of 4mm and the length of 10cm is fixed on a dip coater, the dipping speed is 5000um/s, the withdrawal speed is 1000um/s, the stainless steel rod is connected to a homogenizer motor after being dipped, the rod is rotated for 5 minutes at the speed of 300 revolutions per minute, and then the stainless steel rod is placed in an oven with the temperature of 60 ℃ for drying for 30 minutes. Inverting the dried stainless steel bar with the PVA coating, and dip-coating for one time according to the same process and parameters to form a PVA layer;
(5) The stainless steel rod coated with the PVA layer was immersed in a mixed solution of PEG and PLCL using a dip coater. Setting the immersion speed to be 5000um/s, selecting 1000um/s as the withdrawal speed, withdrawing the stainless steel bar, standing for 10min, reversely fixing the stainless steel bar on a dip-coating machine, repeatedly performing dip-coating once according to the process to form a complete dip-coating layer, and repeating the process to perform dip-coating of 3 complete dip-coating layers in total;
(6) Assembling a stainless steel bar with a dip coating on a rotating motor, forming the outermost layer of a blood vessel by utilizing an electrostatic spinning technology under the driving of a three-axis moving platform, wherein the voltage is 12KV, the rotating speed is 500 rpm, the receiving distance is 15cm, the time is 1h, the stainless steel bar is placed in a fume hood overnight, and the thickness of an electrostatic spinning layer is 50um;
(7) And (3) soaking the stainless steel rod with the dip coating layer and the electrostatic spinning layer in normal-temperature deionized water for 3 days, clamping one end of the collecting rod by using a pair of tweezers, clamping the vessel wall by using the other pair of tweezers, separating the artificial blood vessel from the stainless steel rod, and naturally drying.
The invention can achieve the matching preparation of the artificial blood vessel by respectively controlling the thickness of the dip coating layer and the electrostatic spinning layer and flexibly combining different thicknesses of the two structural layers, thereby reducing blood flow disorder and abnormal mechanical factors caused by the unmatched compliance of the artificial blood vessel and being beneficial to reducing the formation of thrombus and intimal hyperplasia after the artificial blood vessel is transplanted.
The invention also provides an artificial blood vessel formed by applying the method.
The above description is only an example of the present application and is not intended to limit the scope of the present application, and all modifications of equivalent structures and equivalent processes, which are made by the present specification and directly or indirectly applied to other related technical fields, are also included in the scope of the present application.

Claims (10)

1. A method for preparing a compliance-matched multilayer small-caliber artificial blood vessel, which is characterized by comprising the following steps:
s1: preparing a dip coating solution and preparing a PVA solution:
adding a polymer material into an organic solvent to prepare dip-coating liquid, wherein the polymer material is polylactide caprolactone or polyurethane, and the organic solvent is hexafluoroisopropanol, trichloromethane or tetrahydrofuran;
weighing polyvinyl alcohol (PVA), dissolving in a mixed solvent of alcohol and deionized water, and preparing into a PVA solution;
s2: dip coating to form a PVA layer:
fixing a stainless steel bar on a dip-coating machine, immersing the stainless steel bar into a PVA solution, staying, withdrawing the stainless steel bar, fixing the stainless steel bar on a homogenizing motor, and rotationally drying to form a PVA layer on the stainless steel bar;
s3: dip coating the dip coating solution to form a complete dip coating:
fixing the stainless steel bar with the PVA layer on a dip coater again, dipping the stainless steel bar into the prepared dip coating solution, staying, withdrawing the stainless steel bar, standing, and performing reverse dip coating, wherein the two dip coatings are used as a complete dip coating;
s4: and (3) performing electrostatic spinning on the complete dip-coating layer to form an electrostatic spinning layer:
mounting a stainless steel bar with a complete dip coating on a receiving device of an electrostatic spinning machine as a receiving bar; preparing a solution with a certain concentration suitable for electrostatic spinning: the raw materials are the same as the dip-coating solution; carrying out electrostatic spinning on the complete dip-coating layer to form an electrostatic spinning layer;
s5: and demolding to form the artificial blood vessel.
2. The method according to claim 1,
in the step S2, dipping to form a PVA layer, dipping the PVA layer into a PVA solution at the speed of 1000-5000 um/S, staying for 10S, withdrawing the stainless steel rod at the withdrawal speed of 500-5000 um/S, fixing the stainless steel rod on a homogenizing motor, rotating for 5-10 minutes at the speed of 200-500 r/min, placing the stainless steel rod in a 60 ℃ oven for 30min, inverting and fixing the stainless steel rod on a dipping machine, and repeating the dipping and coating once, wherein the two times of dipping and coating are used as a complete PVA layer.
3. The method according to claim 1, wherein the reaction mixture,
in the step S3, dipping the dip-coating solution to form a complete dip-coating layer, dipping the complete dip-coating layer into the prepared dip-coating solution at the speed of 1000-5000 um/S, staying for 10S, withdrawing the stainless steel bar at the speed of 500-5000 um/S, and standing for 5-10 minutes.
4. The method of making a compliant-matchable multi-layer small-caliber prosthesis of claim 1,
in step S4, the electrostatic spinning process parameters are as follows: the extrusion speed range is 0.5-1 ml/h, the voltage range is 10-15 kv, the collection distance range is 15-20 cm, the rotation speed of the collection rod is 500-800 r/min, and meanwhile, the thickness of the electrostatic spinning layer is controlled by controlling the electrostatic spinning time.
5. The method according to claim 1, wherein the reaction mixture,
in step S4, the electrostatic spinning process parameters are as follows: the extrusion speed range is 0.5-1 ml/h, the voltage range is 10-15 kv, the collection distance range is 15-20 cm, the rotation speed of the collection rod is 500-800 r/min, and meanwhile, the thickness of the electrostatic spinning layer is controlled by controlling the electrostatic spinning time.
6. A preparation method according to any one of claims 1 to 5, wherein a pore-forming agent is further added to or during the formation of the dip coating solution, wherein the pore-forming agent is polyethylene glycol (PEG).
7. The method according to claim 6, wherein the alcohol and deionized water in the mixed solvent are 50 (W/W) and the concentration of the PVA solution is 13-16%.
8. The method according to claim 7, wherein the polymer material is poly (lactide-co-caprolactone), the organic solvent is hexafluoroisopropanol, and the dip coating solution contains 0.5-0.7% of polyethylene glycol (PEG) and 12-15% of poly (lactide-co-caprolactone) (PLCL).
9. The method of claim 8, further comprising repeating step S3 at least twice to form at least two full dip-coats before step S4.
10. An artificial blood vessel prepared by the preparation method of claim 1, and comprising at least one entire dip-coating layer and one electrospun layer.
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