CN116983472B - Mixed spinning polymer heart valve and preparation method thereof - Google Patents
Mixed spinning polymer heart valve and preparation method thereof Download PDFInfo
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- CN116983472B CN116983472B CN202311247026.1A CN202311247026A CN116983472B CN 116983472 B CN116983472 B CN 116983472B CN 202311247026 A CN202311247026 A CN 202311247026A CN 116983472 B CN116983472 B CN 116983472B
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- 210000003709 heart valve Anatomy 0.000 title claims abstract description 83
- 229920000642 polymer Polymers 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 229920000747 poly(lactic acid) Polymers 0.000 claims abstract description 84
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 claims abstract description 69
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- 239000004814 polyurethane Substances 0.000 claims abstract description 63
- 229920000669 heparin Polymers 0.000 claims abstract description 59
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims abstract description 40
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- SXGZJKUKBWWHRA-UHFFFAOYSA-N 2-(N-morpholiniumyl)ethanesulfonate Chemical compound [O-]S(=O)(=O)CC[NH+]1CCOCC1 SXGZJKUKBWWHRA-UHFFFAOYSA-N 0.000 claims description 19
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Classifications
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- 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
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
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- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/06—Use of macromolecular materials
- A61L33/08—Polysaccharides
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- 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
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- D01D5/0015—Electro-spinning characterised by the initial state of the material
- D01D5/003—Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion
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- D—TEXTILES; PAPER
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- D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
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- 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
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- 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
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- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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Landscapes
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- Medicinal Chemistry (AREA)
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- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Artificial Filaments (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention belongs to the field of medical appliances, and discloses a hybrid spinning polymer heart valve and a preparation method thereof, wherein the method comprises the following steps: a near-term degradation material, a long-term degradation material, heparin; the recently degraded material is polylactide caprolactone, the long-term degraded material is polyurethane, and the recently degraded material and the long-term degraded material are laminated and staggered and have good biocompatibility, excellent durability, thrombus prevention, degradability, reproducibility and growth ability.
Description
Technical Field
The invention belongs to the field of medical appliances, and relates to a hybrid spinning polymer heart valve and a preparation method thereof.
Background
Valvular heart disease is a common cause of mortality and morbidity worldwide and is also a considerable burden on the global health care system. In 2017, non-rheumatic heart valve disease (mainly calcified aortic valve disease and degenerative mitral valve disease) accounts for about 2970 and 14.5 ten thousand deaths worldwide. In pediatric populations, heart valve disease is mainly caused by congenital or rheumatic heart disease, the incidence of which is 1.54% worldwide, and the incidence of which is as high as 0.7% in developing countries. Surgical replacement is a standard for treating severely dysfunctional or diseased valves, with up to 30 ten thousand valve replacements being performed annually worldwide.
Over the past decade, many studies have reported implantation of prosthetic heart valves in animal models using natural heart valves (e.g., collagen, silk, and fibrin) and synthetic polymeric heart valves. The main objectives of these studies are to utilize rapid manufacturing processes, reduce costs, control degradation rates, and provide sufficient strength to withstand in vivo conditions; among them, mechanical valve mechanical properties are ideal, tissue compatibility is poor, but durability is excellent, and valve replacement is preferred for surgical implantation. Biological valves are free of hemolysis, low in thrombus incidence, free of lifelong anticoagulation, but prone to calcification; the polymer heart valve has the characteristics of good hemodynamic performance, no need of long-term anticoagulation, high durability and the like, is still in a research stage at present, and a satisfactory and practical heart valve has not been constructed yet.
Tissue engineering heart valves are considered as a potential solution, and these valve replacement techniques exhibit remodeling capabilities in acute and chronic large animal models. In order to promote tissue remodeling and self-repair, tissue engineering heart valve research has focused mainly on the fabrication of scaffolds that mimic the extracellular matrix, a micro-nanofiber protein network that provides structure to tissue. Cell-based methods, however, including both cellularized and decellularized matrices, typically require several weeks to months to develop, which makes them costly and largely prohibitive.
Hydrogel heart valve molding techniques provide a customizable and repeatable method and are easy to operate; but cannot reproduce the micro-nano scale features of the extracellular matrix; the 3D printing method provides highly customizable and reproducible valve geometries, but fails to replicate the micro-and nano-scale features of the valve carriage due to insufficient printing resolution and low productivity.
Publication number CN 116568877A the present invention provides a heart valve with reinforcing leaflets, which has the advantage that the aligned and/or non-aligned fibers are bioabsorbable polymer fibers and can be replaced with newly formed tissue over time, which has the disadvantage of thrombosis, paravalvular leakage.
The invention provides an endothelialization-promoting biological material and a preparation method thereof, which are disclosed in publication No. CN 202180075228; the endothelialization-promoting biological material comprises biological material and endothelialization-promoting growth factors loaded on the surface of the biological material, and can capture endothelial progenitor cells, so that the endothelial progenitor cells are attached, grown and differentiated on the surface of the biological material; the method has the advantages of promoting the formation of an endothelial cell layer on the surface of the biological material, and has the defects that thrombus can be caused after the implantation of the valve, the biological material can be calcified, and the perivalvular leakage phenomenon exists.
While current valve replacement procedures, including mechanical valves, biological valves, can improve survival and quality of life for many patients, ideal prosthetic heart valves remain to be developed, which have a wide variety of usability, immune compatibility, ability to grow, self-repair, and lifelong immune performance.
Disclosure of Invention
Based on the technical problems in the background technology, the invention provides a hybrid spinning polymer heart valve, which has the characteristics of good biocompatibility, anticoagulation, calcification resistance, growth and the like.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
the preparation method of the hybrid spinning polymer heart valve is characterized by comprising the following steps of:
in order to better realize the invention, the chemical reagent is one or more of hexafluoroisopropanol, N-dimethylformamide, tetrahydrofuran, a mixed solution of N, N-dimethylformamide and tetrahydrofuran, wherein the mixed solution of N, N-dimethylformamide and tetrahydrofuran is preferably mixed with 95 percent of tetrahydrofuran and 5 percent of N, N-dimethylformamide; in order to better realize the invention, the mass concentration of polyurethane in the spinning solution A is 8% -20%.
S2, dissolving the poly-lactide caprolactone in hexafluoroisopropanol to obtain a poly-lactide caprolactone solution, dissolving collagen in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to obtain a collagen solution, and mixing the collagen solution and the collagen solution according to a certain volume ratio to obtain a spinning solution B; in order to better realize the invention, further, the polylactide caprolactone is preferably polylactic acid: polycaprolactone has a molecular weight of 4000:2000; in order to better implement the present invention, further, the collagen is silk fibroin or fibrin; in order to better realize the invention, the mass concentration of the polylactide caprolactone in the polylactide caprolactone solution is 7% -12%, the mass concentration of the collagen in the collagen solution is 80% -150 mg/ml, and the endothelial growth promoting factor is one or more of CD34, CD133 and VEGF, and the concentration of the endothelial growth promoting factor is 0.1-1 mug/ml.
In order to better realize the invention, the volume ratio of the polylactide caprolactone solution to the collagen solution is 5:1-1:1.
S3, fixing the spinning solution A on the injector A, fixing the spinning solution B on the injector B, and carrying out coaxial symmetrical spinning on a heart valve model by adjusting voltage, rotating speed, pushing flow and distance parameters to obtain a mixed spinning polymer valve; in order to better realize the invention, the pushing assisting flow of the injector A is 0.6-1.2 ml/min, the voltage is 10-20 kv, and the distance is 10-20 cm; the pushing assisting flow of the injector B is 1-2 ml/min, the voltage is 15-24 kv, and the distance is 12-18 cm; the diameters of the spray heads of the injector A and the injector B are 0.8-0.9mm, and the rotating speed of the receiving mandrel is 1000-10000 r/min.
S4, the polymer valve and the bracket are sewn to prepare the heart valve.
And S5, sequentially adding heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide into 2-morpholinoethanesulfonic acid, stirring uniformly in an ice bath, then adding the valve and the stent in S4 into the solution, reacting for several hours at room temperature, and vibrating and cleaning for several times by using a phosphate buffer solution to obtain the heparinized crosslinked heart valve.
To better practice the invention, further, the mass ratio of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide to N-hydroxysuccinimide: 1: 1-2: and 1, uniformly stirring in an ice bath for 1-3 hours.
The invention has the beneficial effects that:
1. the polylactic acid caprolactone and polyurethane are coaxially and symmetrically spun to form a laminated and staggered nano-scale and micron-scale fiber network interpenetrating structure, which is more similar to the collagen network tissue structure of a natural valve, and the structure provides a firmly attached porous bracket for cells, so that the cells can rapidly permeate, infiltrate, expand and remodel tissues, and gradually replaced by formed new tissues along with the time, and finally replace the biological valve.
2. The temporary filler is made of polylactide caprolactone (recently degradable material), the skeleton is made of polyurethane (long-term degradable material), after the valve is inoculated with cells, interstitial cells are uniformly covered on the valve (nano-and micron-sized fiber network interpenetrating structure), and the polylactide caprolactone is completely degraded for about 6-12 months; after the polylactide caprolactone is degraded, the polyurethane fiber can still maintain a network interpenetrating structure, can still maintain larger porosity, and the hollow structure formed at the moment can still provide attachment points for cells, so that the cells can quickly permeate, infiltrate, expand and remodel tissues; the polyurethane is slowly degraded, structural support can be continuously provided after the polylactide caprolactone is completely degraded, the endogenous cell infiltration capacity is continuously maintained, heparin in polyurethane fibers can also prevent thrombosis, meanwhile, the polyurethane grid structure also has a certain stretching and traction effect, so that tissues grow along the polyurethane grid, and the combination mode of the recent degradation and long-term degradation of the degradable high polymer material can continuously provide mechanical properties for a long time, so that a heart valve which can grow and coexist with the heart valve is established.
3. The biocompatibility is good, heart cells are cultured on the valve, firstly, the polylactide caprolactone fiber induces anisotropic growth of the heart cells, the introduction of collagen improves cell adhesion, and anisotropic diffusion of the cells is induced; the deposition of actin, neogenin, fibrin proteins outside the valve was observed, the infiltration of erythrocytes and leukocytes into the porous scaffold, and good infiltration of cells into the scaffold was observed without side effects, thrombosis or any other problems.
4. The addition of trace zinc nitrate can improve blood compatibility and enhance the proliferation rate of fiber cells.
5. The nano fibers with different diameters and different porosities can be prepared by adjusting the production process, and the proportion of materials is adjusted to realize the matching with the biological functionalization of the biological valve.
6. The polylactic acid caprolactone fiber releases the endothelialization-promoting growth factor in the degradation process, and the endothelialization-promoting growth factor can promote endothelialization of the newly generated tissue surface to form cell membranes, so that contact with blood is reduced, and calcium ion deposition is reduced; after endothelialization, the tissue can be combined with surrounding tissues to prevent perivalvular leakage and pannus tissue proliferation.
7. Good hydrophilicity: the valve has a small water contact angle, and forms a water film after being released from blood, so that calcification, hardening and deformation of the valve are prevented, the valve is not closed completely in the later period, and the valve is prevented from being mechanically pulled by calcification, so that the valve orifice is narrow.
Drawings
Fig. 1 is a schematic view of an electrospinning apparatus.
In the figure, 1, a syringe A; 2. a syringe B; 3. spinning solution A; 4. spinning solution B; 5. a heart valve model mandrel is received.
Fig. 2 is a scanning electron micrograph of the surface of the spin valve.
Detailed Description
Other advantages and effects of the present invention will become apparent to those skilled in the art from the following disclosure, which describes the embodiments of the present invention with reference to specific examples. The invention may be practiced or carried out in other embodiments that depart from the specific details, and the details of the present description may be modified or varied from the spirit and scope of the present invention. It should be noted that the following embodiments and features in the embodiments may be combined with each other without conflict.
Example 1
Preparing polyurethane spinning solution: adding polyurethane, zinc nitrate, polydimethylsiloxane and polyethylene glycol into N, N-dimethylformamide according to the mass ratio of 7:4:3:0.15, uniformly stirring, and adding 50mg heparin to finally obtain the spinning solution A with the mass concentration of 8% of polyurethane.
Preparing a polylactide caprolactone spinning solution: polylactic acid is preferred: the method comprises the steps of dissolving polylactic acid caprolactone with the molecular weight of 4000:2000 and CD34 in hexafluoroisopropanol to prepare a polylactic acid caprolactone solution with the concentration of 7%, wherein the concentration of CD34 is 0.1 mug/m, dissolving silk fibroin in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to prepare a silk fibroin solution with the concentration of 80mg/ml, and mixing the two solutions according to the volume ratio of 2:1 to obtain spinning solution B.
Coaxially and symmetrically spinning: fixing the spinning solution A on an injector A, fixing the spinning solution B on an injector B, wherein the pushing assisting flow rate of the injector A is 0.6ml/min, the voltage is 10kv, and the distance is 10cm; the pushing flow rate of the injector B is 1ml/min, the voltage is 15kv, the distance is 12cm, the diameters of the spray heads of the injector A and the injector B are 0.8mm, the rotating speed of the receiving mandrel is 1000r/min, and coaxial symmetrical spinning is carried out on a heart valve model to obtain the mixed spinning polymer valve.
Sewing the valve and the bracket: the heart valve is manufactured by sewing the polymer valve.
Heparin cross-linking treatment valve: 200 mg heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added into 40 ml of 2-morpholinoethanesulfonic acid in sequence according to the mass ratio of 1:1, and the mixture is stirred uniformly in an ice bath for 1 hour. Then adding the valve and the stent into the solution, and reacting for 24 hours at 37 ℃; shaking with phosphate buffer solution for 5 times and 5 minutes each time to obtain heparinized crosslinked heart valve.
Example 2
Preparing polyurethane spinning solution: adding polyurethane, zinc nitrate, polydimethylsiloxane and polyethylene glycol into N, N-dimethylformamide according to the mass ratio of 7:4:3:0.15, uniformly stirring, and adding 50mg heparin to finally obtain spinning solution A with the mass concentration of 10% of polyurethane.
Preparing a polylactide caprolactone spinning solution: polylactic acid is preferred: the method comprises the steps of dissolving polylactic acid caprolactone with the molecular weight of 4000:2000 and CD34 in hexafluoroisopropanol to prepare a polylactic acid caprolactone solution with the concentration of 8%, wherein the concentration of CD34 is 0.6 mug/m, dissolving silk fibroin in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to prepare a silk fibroin solution with the concentration of 100mg/ml, and mixing the two solutions according to the volume ratio of 2:1 to obtain spinning solution B.
Coaxially and symmetrically spinning: fixing the spinning solution A on the injector A, fixing the spinning solution B on the injector B, wherein the pushing assisting flow rate of the injector A is 0.8ml/min, the voltage is 15kv, and the distance is 15cm; the pushing flow rate of the injector B is 1.2ml/min, the voltage is 18kv, the distance is 15cm, the diameters of the spray heads of the injector A and the injector B are 0.8mm, the rotating speed of the receiving core shaft is 3000r/min, and coaxial symmetrical spinning is carried out on a heart valve model to obtain the mixed spinning polymer valve.
Sewing the valve and the bracket: the heart valve is manufactured by sewing the polymer valve.
Heparin cross-linking treatment valve: 200 mg heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added into 40 ml of 2-morpholinoethanesulfonic acid in sequence according to a mass ratio of 2:1, and the mixture is stirred uniformly in an ice bath for 2 hours. Then adding the valve and the stent into the solution, and reacting for 24 hours at 37 ℃; shaking with phosphate buffer solution for 5 times and 5 minutes each time to obtain heparinized crosslinked heart valve.
Example 3
Preparing polyurethane spinning solution: adding polyurethane, zinc nitrate, polydimethylsiloxane and polyethylene glycol into N, N-dimethylformamide according to the mass ratio of 7:4:3:0.15, uniformly stirring, and adding 50mg heparin to finally obtain the spinning solution A with the mass concentration of polyurethane being 12%.
Preparing a polylactide caprolactone spinning solution: polylactic acid is preferred: the method comprises the steps of dissolving polylactic acid caprolactone with the molecular weight of 4000:2000 and CD34 in hexafluoroisopropanol to prepare a polylactic acid caprolactone solution with the concentration of 10%, wherein the concentration of CD34 is 1 mug/m, dissolving silk fibroin in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to prepare a silk fibroin solution with the concentration of 120mg/ml, and mixing the two solutions according to the volume ratio of 2:1 to obtain spinning solution B.
Coaxially and symmetrically spinning: fixing the spinning solution A on the injector A, fixing the spinning solution B on the injector B, wherein the pushing assisting flow rate of the injector A is 1.0ml/min, the voltage is 12kv, and the distance is 13cm; the pushing flow rate of the injector B is 1.5ml/min, the voltage is 20kv, the distance is 16cm, the diameters of the spray heads of the injector A and the injector B are 0.9mm, the rotating speed of the receiving mandrel is 2000r/min, and coaxial symmetrical spinning is carried out on a heart valve model to obtain the mixed spinning polymer valve.
Sewing the valve and the bracket: the heart valve is manufactured by sewing the polymer valve.
Heparin cross-linking treatment valve: 200 mg heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added into 40 ml of 2-morpholinoethanesulfonic acid in sequence according to the mass ratio of 1:1, and the mixture is stirred uniformly in an ice bath for 3 hours. Then adding the valve and the stent into the solution, and reacting for 24 hours at 37 ℃; shaking with phosphate buffer solution for 5 times and 5 minutes each time to obtain heparinized crosslinked heart valve.
Example 4
Preparing polyurethane spinning solution: adding polyurethane, zinc nitrate, polydimethylsiloxane and polyethylene glycol into N, N-dimethylformamide according to the mass ratio of 7:4:3:0.15, uniformly stirring, and adding 50mg heparin to finally obtain the spinning solution A with the mass concentration of polyurethane being 15%.
Preparing a polylactide caprolactone spinning solution: polylactic acid is preferred: the method comprises the steps of dissolving CD34 in hexafluoroisopropanol in the polylactic acid caprolactone with the molecular weight of 4000:2000 to prepare a 12% polylactic acid caprolactone solution, dissolving the CD34 in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to prepare a 150mg/ml silk fibroin solution, and mixing the two solutions according to a volume ratio of 2:1 to obtain spinning solution B.
Coaxially and symmetrically spinning: fixing the spinning solution A on an injector A, fixing the spinning solution B on an injector B, wherein the pushing assisting flow rate of the injector A is 1.2ml/min, the voltage is 20kv, and the distance is 20cm; the pushing flow rate of the injector B is 1.8ml/min, the voltage is 22kv, the distance is 18cm, the rotating speed is 5000r/min, the diameters of the spray heads of the injector A and the injector B are 0.8-0.9mm, and coaxial symmetrical spinning is carried out on a heart valve model to obtain the mixed spinning polymer valve.
Sewing the valve and the bracket: the heart valve is manufactured by sewing the polymer valve.
Heparin cross-linking treatment valve: 200 mg heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added into 40 ml of 2-morpholinoethanesulfonic acid in sequence according to a mass ratio of 2:1, and the mixture is stirred uniformly in an ice bath for 2 hours. Then adding the valve and the stent into the solution, and reacting for 24 hours at 37 ℃; shaking with phosphate buffer solution for 5 times and 5 minutes each time to obtain heparinized crosslinked heart valve.
Example 5
Preparing polyurethane spinning solution: adding polyurethane, zinc nitrate, polydimethylsiloxane and polyethylene glycol into N, N-dimethylformamide according to the mass ratio of 7:4:3:0.15, uniformly stirring, and adding 50mg heparin to finally obtain the spinning solution A with the mass concentration of 20% of polyurethane.
Preparing a polylactide caprolactone spinning solution: polylactic acid is preferred: the method comprises the steps of dissolving polylactic acid caprolactone with the molecular weight of 4000:2000 and CD34 in hexafluoroisopropanol to prepare a 12% polylactic acid caprolactone solution, wherein the concentration of CD34 is 0.8 mug/m, dissolving silk fibroin in a mixed solution of hexafluoroisopropanol and a high sugar culture medium solution to prepare a silk fibroin solution with the concentration of 150mg/ml, and mixing the two solutions according to the volume ratio of 2:1 to obtain spinning solution B.
Coaxially and symmetrically spinning: fixing the spinning solution A on an injector A, fixing the spinning solution B on an injector B, wherein the pushing assisting flow rate of the injector A is 1.2ml/min, the voltage is 20kv, and the distance is 20cm; the pushing flow of the injector B is 2ml/min, the voltage is 24kv, the distance is 18cm, the diameters of the spray heads of the injector A and the injector B are 0.9mm, the rotation speed of the receiving mandrel is 10000r/min, and coaxial symmetrical spinning is carried out on a heart valve model to obtain the mixed spinning polymer valve.
Sewing the valve and the bracket: the heart valve is manufactured by sewing the polymer valve.
Heparin cross-linking treatment valve: 200 mg heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added into 40 ml of 2-morpholinoethanesulfonic acid in sequence according to the mass ratio of 1:1, and the mixture is stirred uniformly in an ice bath for 3 hours. Then adding the valve and the stent into the solution, and reacting for 24 hours at 37 ℃; shaking with phosphate buffer solution for 5 times and 5 minutes each time to obtain heparinized crosslinked heart valve.
Example 6
Preparing polyurethane spinning solution: adding polyurethane, zinc nitrate, polydimethylsiloxane and polyethylene glycol into N, N-dimethylformamide according to the mass ratio of 7:4:3:0.15, uniformly stirring, and adding 50mg heparin to finally obtain spinning solution A with the mass concentration of 10% of polyurethane.
Preparing a polylactide caprolactone spinning solution: polylactic acid is preferred: the method comprises the steps of dissolving polylactic acid caprolactone with the molecular weight of 4000:2000 and CD34 in hexafluoroisopropanol to prepare a polylactic acid caprolactone solution with the concentration of 8%, wherein the concentration of CD34 is 0.6 mug/m, dissolving silk fibroin in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to prepare a silk fibroin solution with the concentration of 100mg/ml, and mixing the two solutions according to the volume ratio of 5:1 to obtain spinning solution B.
Coaxially and symmetrically spinning: fixing the spinning solution A on the injector A, fixing the spinning solution B on the injector B, wherein the pushing assisting flow rate of the injector A is 0.8ml/min, the voltage is 15kv, and the distance is 15cm; the pushing flow rate of the injector B is 1.2ml/min, the voltage is 18kv, the distance is 15cm, the diameters of the spray heads of the injector A and the injector B are 0.8mm, the rotating speed of the receiving mandrel is 6000r/min, and coaxial symmetrical spinning is carried out on a heart valve model to obtain the mixed spinning polymer valve.
Sewing the valve and the bracket: the heart valve is manufactured by sewing the polymer valve.
Heparin cross-linking treatment valve: 200 mg heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added into 40 ml of 2-morpholinoethanesulfonic acid in sequence according to a mass ratio of 2:1, and the mixture is stirred uniformly in an ice bath for 2 hours. Then adding the valve and the stent into the solution, and reacting for 24 hours at 37 ℃; shaking with phosphate buffer solution for 5 times and 5 minutes each time to obtain heparinized crosslinked heart valve.
Example 7
Preparing polyurethane spinning solution: adding polyurethane, zinc nitrate, polydimethylsiloxane and polyethylene glycol into N, N-dimethylformamide according to the mass ratio of 7:4:3:0.15, uniformly stirring, and adding 50mg heparin to finally obtain spinning solution A with the mass concentration of 10% of polyurethane.
Preparing a polylactide caprolactone spinning solution: polylactic acid is preferred: the method comprises the steps of dissolving polylactic acid caprolactone with the molecular weight of 4000:2000 and CD34 in hexafluoroisopropanol to prepare a polylactic acid caprolactone solution with the concentration of 8%, wherein the concentration of CD34 is 0.6 mug/m, dissolving silk fibroin in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to prepare a silk fibroin solution with the concentration of 100mg/ml, and mixing the two solutions according to the volume ratio of 4:1 to obtain spinning solution B.
Coaxially and symmetrically spinning: fixing the spinning solution A on the injector A, fixing the spinning solution B on the injector B, wherein the pushing assisting flow rate of the injector A is 0.8ml/min, the voltage is 15kv, and the distance is 15cm; the pushing flow rate of the injector B is 1.2ml/min, the voltage is 18kv, the distance is 15cm, the diameters of the spray heads of the injector A and the injector B are 0.8mm, the rotating speed of the receiving mandrel is 8000r/min, and coaxial symmetrical spinning is carried out on a heart valve model to obtain the mixed spinning polymer valve.
Sewing the valve and the bracket: the heart valve is manufactured by sewing the polymer valve.
Heparin cross-linking treatment valve: 200 mg heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added into 40 ml of 2-morpholinoethanesulfonic acid in sequence according to a mass ratio of 2:1, and the mixture is stirred uniformly in an ice bath for 2 hours. Then adding the valve and the stent into the solution, and reacting for 24 hours at 37 ℃; shaking with phosphate buffer solution for 5 times and 5 minutes each time to obtain heparinized crosslinked heart valve.
Example 8
Preparing polyurethane spinning solution: adding polyurethane, zinc nitrate, polydimethylsiloxane and polyethylene glycol into N, N-dimethylformamide according to the mass ratio of 7:4:3:0.15, uniformly stirring, and adding 50mg heparin to finally obtain spinning solution A with the mass concentration of 10% of polyurethane.
Preparing a polylactide caprolactone spinning solution: polylactic acid is preferred: the method comprises the steps of dissolving polylactic acid caprolactone with the molecular weight of 4000:2000 and CD34 in hexafluoroisopropanol to prepare a polylactic acid caprolactone solution with the concentration of 8%, wherein the concentration of CD34 is 0.6 mug/m, dissolving silk fibroin in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to prepare a silk fibroin solution with the concentration of 100mg/ml, and mixing the two solutions according to the volume ratio of 1:1 to obtain spinning solution B.
Coaxially and symmetrically spinning: fixing the spinning solution A on the injector A, fixing the spinning solution B on the injector B, wherein the pushing assisting flow rate of the injector A is 0.8ml/min, the voltage is 15kv, and the distance is 15cm; the pushing flow rate of the injector B is 1.2ml/min, the voltage is 18kv, the distance is 15cm, the diameters of the spray heads of the injector A and the injector B are 0.8mm, the rotating speed of the receiving core shaft is 3000r/min, and coaxial symmetrical spinning is carried out on a heart valve model to obtain the mixed spinning polymer valve.
Sewing the valve and the bracket: the heart valve is manufactured by sewing the polymer valve.
Heparin cross-linking treatment valve: 200 mg heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added into 40 ml of 2-morpholinoethanesulfonic acid in sequence according to a mass ratio of 2:1, and the mixture is stirred uniformly in an ice bath for 2 hours. Then adding the valve and the stent into the solution, and reacting for 24 hours at 37 ℃; shaking with phosphate buffer solution for 5 times and 5 minutes each time to obtain heparinized crosslinked heart valve.
Example 9
Preparing polyurethane spinning solution: adding polyurethane, zinc nitrate, polydimethylsiloxane and polyethylene glycol into N, N-dimethylformamide according to the mass ratio of 7:5:4:0.3, uniformly stirring, and adding 50mg heparin to finally obtain spinning solution A with the mass concentration of 10% of polyurethane.
Preparing a polylactide caprolactone spinning solution: polylactic acid is preferred: the preparation method comprises the steps of dissolving polylactic acid caprolactone with the molecular weight of 4000:2000 and VEGF in hexafluoroisopropanol to prepare a polylactic acid caprolactone solution with the concentration of 8%, wherein the concentration of VEGF is 0.6 mug/m, dissolving silk fibroin in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to prepare a silk fibroin solution with the concentration of 100mg/ml, and mixing the two solutions according to the volume ratio of 2:1 to obtain spinning solution B.
Coaxially and symmetrically spinning: fixing the spinning solution A on the injector A, fixing the spinning solution B on the injector B, wherein the pushing assisting flow rate of the injector A is 0.8ml/min, the voltage is 15kv, and the distance is 15cm; the pushing flow rate of the injector B is 1.2ml/min, the voltage is 18kv, the distance is 15cm, the diameters of the spray heads of the injector A and the injector B are 0.8mm, the rotating speed of the receiving core shaft is 3000r/min, and coaxial symmetrical spinning is carried out on a heart valve model to obtain the mixed spinning polymer valve.
Sewing the valve and the bracket: the heart valve is manufactured by sewing the polymer valve.
Heparin cross-linking treatment valve: 200 mg heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added into 40 ml of 2-morpholinoethanesulfonic acid in sequence according to a mass ratio of 2:1, and the mixture is stirred uniformly in an ice bath for 2 hours. Then adding the valve and the stent into the solution, and reacting for 24 hours at 37 ℃; shaking with phosphate buffer solution for 5 times and 5 minutes each time to obtain heparinized crosslinked heart valve.
Example 10
Preparing polyurethane spinning solution: adding polyurethane, zinc nitrate, polydimethylsiloxane and polyethylene glycol into N, N-dimethylformamide according to the mass ratio of 7:3:2:0.1, uniformly stirring, and adding 50mg heparin to finally obtain spinning solution A with the mass concentration of 10% of polyurethane.
Preparing a polylactide caprolactone spinning solution: polylactic acid is preferred: the method comprises the steps of dissolving polylactic acid caprolactone with the molecular weight of 4000:2000 and CD133 in hexafluoroisopropanol to prepare a polylactic acid caprolactone solution with the concentration of 8%, wherein the concentration of CD133 is 0.6 mug/m, dissolving silk fibroin in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to prepare a silk fibroin solution with the concentration of 100mg/ml, and mixing the two solutions according to the volume ratio of 2:1 to obtain spinning solution B.
Coaxially and symmetrically spinning: fixing the spinning solution A on the injector A, fixing the spinning solution B on the injector B, wherein the pushing assisting flow rate of the injector A is 0.8ml/min, the voltage is 15kv, and the distance is 15cm; the pushing flow rate of the injector B is 1.2ml/min, the voltage is 18kv, the distance is 15cm, the diameters of the spray heads of the injector A and the injector B are 0.8mm, the rotating speed of the receiving core shaft is 3000r/min, and coaxial symmetrical spinning is carried out on a heart valve model to obtain the mixed spinning polymer valve.
Sewing the valve and the bracket: the heart valve is manufactured by sewing the polymer valve.
Heparin cross-linking treatment valve: 200 mg heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added into 40 ml of 2-morpholinoethanesulfonic acid in sequence according to a mass ratio of 2:1, and the mixture is stirred uniformly in an ice bath for 2 hours. Then adding the valve and the stent into the solution, and reacting for 24 hours at 37 ℃; shaking with phosphate buffer solution for 5 times and 5 minutes each time to obtain heparinized crosslinked heart valve.
Comparative example 1
Preparing polyurethane spinning solution: adding polyurethane, polydimethylsiloxane and polyethylene glycol into N, N-dimethylformamide according to the mass ratio of 7:3:0.15, uniformly stirring, and adding 50mg heparin to finally obtain spinning solution A with the mass concentration of 10% of polyurethane.
Preparing a polylactide caprolactone spinning solution: polylactic acid is preferred: the method comprises the steps of dissolving polylactic acid caprolactone with the molecular weight of 4000:2000 and CD34 in hexafluoroisopropanol to prepare a polylactic acid caprolactone solution with the concentration of 8%, wherein the concentration of CD34 is 0.6 mug/m, dissolving silk fibroin in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to prepare a silk fibroin solution with the concentration of 100mg/ml, and mixing the two solutions according to the volume ratio of 2:1 to obtain spinning solution B.
Coaxially and symmetrically spinning: fixing the spinning solution A on the injector A, fixing the spinning solution B on the injector B, wherein the pushing assisting flow rate of the injector A is 0.8ml/min, the voltage is 15kv, and the distance is 15cm; the pushing flow rate of the injector B is 1.2ml/min, the voltage is 18kv, the distance is 15cm, the diameters of the spray heads of the injector A and the injector B are 0.8mm, the rotating speed of the receiving core shaft is 3000r/min, and coaxial symmetrical spinning is carried out on a heart valve model to obtain the mixed spinning polymer valve.
Sewing the valve and the bracket: the heart valve is manufactured by sewing the polymer valve.
Heparin cross-linking treatment valve: 200 mg heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added into 40 ml of 2-morpholinoethanesulfonic acid in sequence according to a mass ratio of 2:1, and the mixture is stirred uniformly in an ice bath for 2 hours. Then adding the valve and the stent into the solution, and reacting for 24 hours at 37 ℃; shaking with phosphate buffer solution for 5 times and 5 minutes each time to obtain heparinized crosslinked heart valve.
Comparative example 2
Preparing polyurethane spinning solution: adding polyurethane, zinc nitrate and polyethylene glycol into N, N-dimethylformamide according to the mass ratio of 7:4:0.15, uniformly stirring, and adding 50mg heparin to finally obtain spinning solution A with the mass concentration of 10% of polyurethane.
Preparing a polylactide caprolactone spinning solution: polylactic acid is preferred: the method comprises the steps of dissolving polylactic acid caprolactone with the molecular weight of 4000:2000 and CD34 in hexafluoroisopropanol to prepare a polylactic acid caprolactone solution with the concentration of 8%, wherein the concentration of CD34 is 0.6 mug/m, dissolving silk fibroin in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to prepare a silk fibroin solution with the concentration of 100mg/ml, and mixing the two solutions according to the volume ratio of 2:1 to obtain spinning solution B.
Coaxially and symmetrically spinning: fixing the spinning solution A on the injector A, fixing the spinning solution B on the injector B, wherein the pushing assisting flow rate of the injector A is 0.8ml/min, the voltage is 15kv, and the distance is 15cm; the pushing flow rate of the injector B is 1.2ml/min, the voltage is 18kv, the distance is 15cm, the diameters of the spray heads of the injector A and the injector B are 0.8mm, the rotating speed of the receiving core shaft is 3000r/min, and coaxial symmetrical spinning is carried out on a heart valve model to obtain the mixed spinning polymer valve.
Sewing the valve and the bracket: the heart valve is manufactured by sewing the polymer valve.
Heparin cross-linking treatment valve: 200 mg heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added into 40 ml of 2-morpholinoethanesulfonic acid in sequence according to a mass ratio of 2:1, and the mixture is stirred uniformly in an ice bath for 2 hours. Then adding the valve and the stent into the solution, and reacting for 24 hours at 37 ℃; shaking with phosphate buffer solution for 5 times and 5 minutes each time to obtain heparinized crosslinked heart valve.
Comparative example 3
Preparing polyurethane spinning solution: adding polyurethane, zinc nitrate and polydimethylsiloxane into N, N-dimethylformamide according to the mass ratio of 7:4:3, uniformly stirring, and adding 50mg heparin to finally obtain spinning solution A with the mass concentration of 10% of polyurethane.
Preparing a polylactide caprolactone spinning solution: polylactic acid is preferred: the method comprises the steps of dissolving polylactic acid caprolactone with the molecular weight of 4000:2000 and CD34 in hexafluoroisopropanol to prepare a polylactic acid caprolactone solution with the concentration of 8%, wherein the concentration of CD34 is 0.6 mug/m, dissolving silk fibroin in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to prepare a silk fibroin solution with the concentration of 100mg/ml, and mixing the two solutions according to the volume ratio of 2:1 to obtain spinning solution B.
Coaxially and symmetrically spinning: fixing the spinning solution A on the injector A, fixing the spinning solution B on the injector B, wherein the pushing assisting flow rate of the injector A is 0.8ml/min, the voltage is 15kv, and the distance is 15cm; the pushing flow rate of the injector B is 1.2ml/min, the voltage is 18kv, the distance is 15cm, the diameters of the spray heads of the injector A and the injector B are 0.8mm, the rotating speed of the receiving core shaft is 3000r/min, and coaxial symmetrical spinning is carried out on a heart valve model to obtain the mixed spinning polymer valve.
Sewing the valve and the bracket: the heart valve is manufactured by sewing the polymer valve.
Heparin cross-linking treatment valve: 200 mg heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added into 40 ml of 2-morpholinoethanesulfonic acid in sequence according to a mass ratio of 2:1, and the mixture is stirred uniformly in an ice bath for 2 hours. Then adding the valve and the stent into the solution, and reacting for 24 hours at 37 ℃; shaking with phosphate buffer solution for 5 times and 5 minutes each time to obtain heparinized crosslinked heart valve.
Comparative example 4
Preparing a polylactide caprolactone spinning solution: polylactic acid is preferred: the method comprises the steps of dissolving polylactic acid caprolactone with the molecular weight of 4000:2000 and CD34 in hexafluoroisopropanol to prepare a polylactic acid caprolactone solution with the concentration of 8%, wherein the concentration of CD34 is 0.6 mug/m, dissolving silk fibroin in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to prepare a silk fibroin solution with the concentration of 100mg/ml, and mixing the two solutions according to the volume ratio of 2:1 to obtain spinning solution B.
Coaxially and symmetrically spinning: and fixing the spinning solution B on an injector B, wherein the pushing assisting flow of the injector B is 1.2ml/min, the voltage is 18kv, the distance is 15cm, the diameter of a nozzle of the injector B is 0.8mm, the rotating speed of a receiving mandrel is 3000r/min, and coaxial and symmetrical spinning is carried out on a heart valve model to obtain the mixed spinning polymer valve.
Sewing the valve and the bracket: the heart valve is manufactured by sewing the polymer valve.
Heparin cross-linking treatment valve: 200 mg heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added into 40 ml of 2-morpholinoethanesulfonic acid in sequence according to a mass ratio of 2:1, and the mixture is stirred uniformly in an ice bath for 2 hours. Then adding the valve and the stent into the solution, and reacting for 24 hours at 37 ℃; shaking with phosphate buffer solution for 5 times and 5 minutes each time to obtain heparinized crosslinked heart valve.
Comparative example 5
Preparing polyurethane spinning solution: adding polyurethane, zinc nitrate, polydimethylsiloxane and polyethylene glycol into N, N-dimethylformamide according to the mass ratio of 7:4:3:0.15, uniformly stirring, and adding 50mg heparin to finally obtain spinning solution A with the mass concentration of 10% of polyurethane.
Coaxially and symmetrically spinning: fixing the spinning solution A on an injector A, wherein the pushing assisting flow of the injector A is 0.8ml/min, the voltage is 15kv, and the distance is 15cm; the diameter of a nozzle of the injector A is 0.8mm, the rotating speed of the receiving mandrel is 3000r/min, and coaxial symmetrical spinning is carried out on a heart valve model to obtain the mixed spinning polymer valve.
Sewing the valve and the bracket: the heart valve is manufactured by sewing the polymer valve.
Heparin cross-linking treatment valve: 200 mg heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added into 40 ml of 2-morpholinoethanesulfonic acid in sequence according to a mass ratio of 2:1, and the mixture is stirred uniformly in an ice bath for 2 hours. Then adding the valve and the stent into the solution, and reacting for 24 hours at 37 ℃; shaking with phosphate buffer solution for 5 times and 5 minutes each time to obtain heparinized crosslinked heart valve.
Comparative example 6
Preparing polyurethane spinning solution: adding polyurethane, zinc nitrate, polydimethylsiloxane and polyethylene glycol into N, N-dimethylformamide according to the mass ratio of 7:4:3:0.15, uniformly stirring, and adding 50mg heparin to finally obtain spinning solution A with the mass concentration of 10% of polyurethane.
Preparing a polylactide caprolactone spinning solution: polylactic acid is preferred: the method comprises the steps of dissolving polylactic acid caprolactone with the molecular weight of 4000:2000 and CD34 in hexafluoroisopropanol to prepare a polylactic acid caprolactone solution with the concentration of 8%, wherein the concentration of CD34 is 0.6 mug/m, dissolving silk fibroin in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to prepare a silk fibroin solution with the concentration of 100mg/ml, and mixing the two solutions according to the volume ratio of 2:1 to obtain spinning solution B.
Coaxially and symmetrically spinning: fixing the spinning solution A on the injector A, fixing the spinning solution B on the injector B, wherein the pushing assisting flow rate of the injector A is 0.8ml/min, the voltage is 15kv, and the distance is 15cm; the pushing flow rate of the injector B is 1.2ml/min, the voltage is 18kv, the distance is 15cm, the diameters of the spray heads of the injector A and the injector B are 0.8mm, the rotating speed of the receiving core shaft is 3000r/min, and coaxial symmetrical spinning is carried out on a heart valve model to obtain the mixed spinning polymer valve.
Sewing the valve and the bracket: the heart valve is manufactured by sewing the polymer valve.
Heparin cross-linking treatment valve: 200 mg heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added into 40 ml of 2-morpholinoethanesulfonic acid in sequence according to the mass ratio of 2:1, and the mixture is stirred in warm water for 2 hours uniformly. Then adding the valve and the stent into the solution, and reacting for 24 hours at 37 ℃; shaking with phosphate buffer solution for 5 times and 5 minutes each time to obtain heparinized crosslinked heart valve.
Comparative example 7
Preparing polyurethane spinning solution: adding polyurethane, zinc nitrate, polydimethylsiloxane and polyethylene glycol into N, N-dimethylformamide according to the mass ratio of 7:2:1:0.1, uniformly stirring, and adding 50mg heparin to obtain spinning solution A with the mass concentration of 10% of polyurethane; the rest of the preparation method is the same as in example 10.
Comparative example 8
Preparing polyurethane spinning solution: adding polyurethane, zinc nitrate, polydimethylsiloxane and polyethylene glycol into N, N-dimethylformamide according to the mass ratio of 7:6:5:0.2, uniformly stirring, and adding 50mg heparin to obtain spinning solution A with the mass concentration of 10% of polyurethane; the rest of the preparation method is the same as in example 10.
Fiber diameter, young's modulus, porosity, total reflux ratio, strain recovery, cell number, cell activity, blood compatibility, water contact angle data measured in the above examples and comparative examples are shown below:
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from the above data, it can be found that the fiber diameter, young's modulus, porosity, total reflux ratio, strain recovery, cell number, cell activity, blood compatibility, and water contact angle data measured in the examples of the present invention obtain excellent performance, and the size length of the valve after animal experiments is increased by more than 5 to 30% compared with that before implantation, but the performance is found to be reduced when the process or formulation is changed, the cell adsorption rate of comparative example 1 is low, the porosity of comparative example 2 is low, the strain recovery effect is reduced, the Young's modulus of comparative example 3 is reduced, the durability of comparative example 4 is poor, and trace amount of thrombus, the cell adsorption of comparative example 5 is poor, and the thrombus rate of comparative example 6 is high, so that the above comparative example cannot meet the relevant requirements.
The research finds that: when the diameter of the spray head is smaller than 0.8mm, the fiber diameter is easy to break and can not form filaments, and when the diameter of the spray head is larger than 0.9mm, the fiber diameter is thick, and although the mechanical property is improved, cells are not easy to attach and grow; when the concentration of the solution is not in the test range, the electrostatic force can not overcome the surface tension of the solution and can not form fibers when the concentration of the solution is too large, and the phenomena of fiber discontinuity, yarn breakage and the like are caused when the concentration of the solution is too low; when the voltage is too large, the jet flow of the spinning solution is unstable, and before the jet flow reaches a receiving device, the solution is not completely exerted, so that the uniformity of fibers is poor, and fibers are adhered; increasing the receiving distance, reducing the electric field intensity, reducing the tensile electric field force applied to the jet flow and increasing the fiber diameter; when the ice bath time of heparin crosslinking is not in the experimental range, the ice bath time can be reduced, the heparin crosslinking rate is low, the application requirements cannot be met, the ice bath time is long, the mechanical property is reduced, and the crosslinking effect is reduced.
The above description is only of specific embodiments of the present invention, and is not intended to limit the invention in any way, and any simple modification, equivalent variations and modifications of the above embodiments by those skilled in the art will fall within the scope of the present invention.
Claims (6)
1. A hybrid spun polymeric heart valve, the polymeric heart valve comprising: a recently degraded polymer, namely polylactide caprolactone, a long-term degraded polymer, namely polyurethane and heparin; the preparation method comprises the following steps:
s1, adding polyurethane, zinc nitrate, heparin, polyethylene glycol and polydimethylsiloxane into a chemical reagent to obtain spinning solution A; the mass ratio of the polyurethane to the zinc nitrate to the polyethylene glycol to the polydimethylsiloxane is (7:3:2:0.1) - (7:5:4:0.3); the chemical reagent is one or more of hexafluoroisopropanol, N-dimethylformamide, tetrahydrofuran, and a mixed solution of N, N-dimethylformamide and tetrahydrofuran;
s2, polylactic acid: the method comprises the steps of dissolving polylactic acid caprolactone and endothelial growth promoting factor with the molecular weight of 4000:2000 in hexafluoroisopropanol to obtain a polylactic acid caprolactone solution, dissolving collagen in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to obtain a collagen solution, and mixing the polylactic acid caprolactone solution and the collagen solution according to a certain volume ratio to obtain a spinning solution B;
s3, fixing the spinning solution A on the injector A, fixing the spinning solution B on the injector B, and carrying out coaxial symmetrical spinning on a heart valve model by adjusting voltage, receiving mandrel rotating speed, pushing flow and distance parameters to obtain a mixed spinning polymer valve; the pushing assisting flow of the injector A is 0.6-1.2 ml/min, the voltage is 10-20 kv, and the distance is 10-20 cm; the pushing assisting flow of the injector B is 1-2 ml/min, the voltage is 15-24 kv, and the distance is 12-18 cm; the rotating speed of the receiving mandrel is 1000-10000 r/min;
s4, the polymer valve and the bracket are sewn to prepare the heart valve;
s5, sequentially adding heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide into 2-morpholinoethanesulfonic acid, stirring uniformly in an ice bath, then adding the valve and a bracket in S4 into the solution, reacting for several hours at room temperature, and vibrating and cleaning for several times by using a phosphate buffer solution to obtain the heparinized crosslinked heart valve.
2. A method of making a hybrid spun polymeric heart valve of claim 1, comprising the steps of:
s1, adding polyurethane, zinc nitrate, heparin, polyethylene glycol and polydimethylsiloxane into a chemical reagent to obtain spinning solution A;
s2, dissolving the polylactide caprolactone and the endothelial growth promoting factor in hexafluoroisopropanol to obtain a polylactide caprolactone solution, dissolving collagen in a mixed solution of hexafluoroisopropanol and a high-sugar culture medium solution to obtain a collagen solution, and mixing the polylactide caprolactone solution and the collagen solution according to a certain volume ratio to obtain a spinning solution B;
s3, fixing the spinning solution A on the injector A, fixing the spinning solution B on the injector B, and carrying out coaxial symmetrical spinning on a heart valve model by adjusting voltage, receiving mandrel rotating speed, pushing flow and distance parameters to obtain a mixed spinning polymer valve;
s4, the polymer valve and the bracket are sewn to prepare the heart valve;
s5, sequentially adding heparin sodium, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide into 2-morpholinoethanesulfonic acid, stirring uniformly in an ice bath, then adding the valve and a bracket in S4 into the solution, reacting for several hours at room temperature, and vibrating and cleaning for several times by using a phosphate buffer solution to obtain the heparinized crosslinked heart valve.
3. The method for preparing the hybrid spinning polymer heart valve according to claim 2, wherein the mass concentration of polyurethane in the spinning solution A is 8% -20%.
4. The method for preparing a hybrid spun polymeric heart valve of claim 2, wherein S2 the collagen is silk fibroin or fibrin; the mass concentration of the polylactide caprolactone in the polylactide caprolactone solution is 7% -12%, the mass concentration of the collagen in the collagen solution is 80-150 mg/ml, and the volume ratio of the polylactide caprolactone solution to the collagen solution is 5:1-1:1; the endothelial growth factor is one or more of CD34, CD133 and VEGF, and its concentration is 0.1-1 μg/ml.
5. The method for preparing a hybrid spinning polymer heart valve according to claim 2, wherein the nozzle diameter of the injector a and the injector B of S3 is 0.8-0.9mm.
6. The method for preparing a hybrid spun polymeric heart valve of claim 2, wherein the mass ratio of S5 of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide to N-hydroxysuccinimide is 1: 1-2: 1, stirring uniformly in ice bath for 1-3 h.
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CN111850818A (en) * | 2019-04-30 | 2020-10-30 | 深圳市罗湖区人民医院 | Preparation method and product of conjugate electrospun nanofiber artificial small-caliber intravascular stent |
CN113304320A (en) * | 2021-05-27 | 2021-08-27 | 武汉纺织大学 | Drug-loaded induction cell-network-type growth acellular heart valve stent and preparation method thereof |
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CN111850818A (en) * | 2019-04-30 | 2020-10-30 | 深圳市罗湖区人民医院 | Preparation method and product of conjugate electrospun nanofiber artificial small-caliber intravascular stent |
CN113304320A (en) * | 2021-05-27 | 2021-08-27 | 武汉纺织大学 | Drug-loaded induction cell-network-type growth acellular heart valve stent and preparation method thereof |
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