2 / 3 hierarchical composite puncture self-healing artificial blood vessel and preparation method thereof

Abstract

The invention discloses a 2 / 3-level composite puncture self-healing artificial blood vessel and a preparation method thereof. The preparation method comprises the following steps: preparing a blood vessel inner layer, wrapping two ends of the blood vessel inner layer with covering layers, dissolving a self-healing polymer in a solvent to form a spinning solution, wrapping the self-healing polymer through an electrostatic spinning method, and removing the covering layers to obtain a self-healing blood vessel middle layer; and electrospinning a blood vessel outer layer on the blood vessel inner layer and the self-healing blood vessel middle layer to obtain the self-healing artificial blood vessel. The self-healing polymer material is subjected to secondary dissolution and then is prepared into the tubular membrane through the electrostatic spinning method, and the problems of tubular forming nonuniformity of the self-healing material and self-healing of the artificial blood vessel are solved; a 2 / 3 hierarchical composite structure is adopted, a self-healing blood vessel middle layer is only formed in the middle section of the artificial blood vessel, and excellent self-healing and compliance effects are achieved; the anti-bending performance of the artificial blood vessel is improved through the spiral supporting ring; magnetic particles are added to the inner layer of the blood vessel, and the antithrombotic performance is improved through the magnetocaloric effect.

Description

Technical Field

[0001] The present invention relates to the technical field of artificial blood vessels, and in particular to a 2 / 3-layer composite puncture self-healing artificial blood vessel and a preparation method thereof. Background Art

[0002] Patients with end-stage renal disease and chronic renal failure need to rely on hemodialysis to maintain their lives. Using artificial blood vessels to establish arteriovenous fistulas and then forming a circulation pathway with an extracorporeal dialysis machine through puncture is one of the common methods of dialysis treatment. At present, although the expanded polytetrafluoroethylene (ePTFE) artificial blood vessels widely used in establishing arteriovenous fistulas have good mechanical properties, they do not have self-healing properties. Frequent punctures can easily damage the tube wall, leading to vascular bleeding, and gradually evolving into serious lesions such as encapsulated hematomas and vascular pseudoaneurysms, threatening the patient's life safety. In addition, the compliance of ePTFE artificial blood vessels is quite different from that of human blood vessels, and the anastomosis is prone to intimal hyperplasia and thrombosis, leading to stenosis of the lumen. Therefore, it is urgent to develop artificial blood vessels with self-healing properties and high compliance for the establishment of arteriovenous fistulas for dialysis.

[0003] Patent CN111991616A discloses an active artificial blood vessel that can be punctured multiple times and its preparation method. The artificial blood vessel includes a tubular polymer fiber scaffold as a support layer and a puncture-resistant layer interlocked with the support layer. The support layer is made of a degradable polymer material, and the puncture-resistant layer interlocked with the support layer is made of a hydrogel material. Active factors that promote cell proliferation and secretion of extracellular matrix are added to the hydrogel of the puncture-resistant layer. The vascular skeleton is implanted into an animal or human body, and the vascular skeleton is sutured in parallel with the animal or human blood vessel. After 7-62 days, it is removed to obtain an autologous endothelialized tissue-engineered blood vessel that can be punctured multiple times. Patent CN113476661A discloses a three-layer composite self-healing artificial blood vessel and its preparation method. The artificial blood vessel consists of a zwitterionic hydrogel anticoagulant layer, a self-healing polyurethane elastomer layer, and a zwitterionic hydrogel anti-inflammatory layer. The zwitterionic hydrogel in the inner layer of the tube body has super hydrophilicity and super lubricity, which gives the artificial blood vessel good blood compatibility. The dense self-healing polyurethane elastomer in the middle layer of the tube body can not only provide the mechanical properties required for artificial blood vessels; due to its self-healing properties, it can quickly self-heal after suturing and puncture, avoiding blood leakage and blood vessel damage. The zwitterionic hydrogel in the outer layer of the tube body has excellent biocompatibility, which can reduce the stimulation of rejection reactions at the implantation site, and is beneficial to ensure the long-term stability and patency of artificial blood vessels in the body. Patent CN114053479A discloses a method for preparing bionic artificial blood vessels based on self-healing hydrogels. First, dynamic covalent bonds are formed in the hydrogel to prepare a self-healing hydrogel material; then, the self-healing hydrogel material is prepared into a bionic artificial blood vessel preform; finally, the bionic artificial blood vessel preform is cured to obtain a bionic artificial blood vessel.

[0004] However, the above existing technologies generally use hydrogels as materials to prepare self-healing artificial blood vessels, which have disadvantages such as poor long-term stability, harsh storage conditions, and easy water loss or swelling and deformation. At the same time, the existing technologies generally use a mold curling method to prepare self-healing artificial blood vessels, which can easily lead to uneven thickness of the blood vessel wall, especially the weak points formed at the port contact self-healing point, causing leakage or rupture. The prepared artificial blood vessels must be single-layer or three-layer structures with a simple structure. Since the thinner the blood vessel wall, the higher the compliance, the single-layer structure has good compliance but insufficient performance, and the three-layer structure meets the requirements but has poor compliance.

[0005] Therefore, it is of great significance to research and develop an artificial blood vessel with excellent self-healing and compliance. Summary of the Invention

[0006] In response to the deficiencies in the prior art, the present invention provides a 2 / 3-layer composite puncture self-healing artificial blood vessel and a preparation method thereof. The self-healing polymer material is dissolved a second time and then prepared into a tubular membrane by electrospinning, thereby solving the problems of uneven tubular forming of the self-healing material and self-healing of the artificial blood vessel. A 2 / 3-layer composite structure is adopted, with the middle section of the artificial blood vessel being a three-layer structure including a self-healing layer as the puncture site, and the two ends being a two-layer structure without a self-healing layer, thereby ensuring the compliance of the blood vessel.

[0007] In order to solve the above technical problems, the present invention provides a method for preparing a 2 / 3-layer composite puncture self-healing artificial blood vessel, comprising the following steps:

[0008] S1. Prepare the vascular lining;

[0009] S2, wrapping both ends of the vascular inner layer with a covering layer, dissolving the self-healing polymer in a solvent to form a spinning solution, coating the self-healing polymer by electrospinning, removing the covering layer, and obtaining a self-healing vascular middle layer;

[0010] Among them, the length of the covering layer at both ends independently accounts for 10%-25% of the total length of the blood vessel;

[0011] S3. Electrospinning the outer layer of the blood vessel on the surface of the inner layer of the blood vessel and the middle layer of the self-healing blood vessel to obtain the self-healing artificial blood vessel.

[0012] The present invention dissolves the self-healing polymer material a second time and then prepares it into a tubular membrane through an electrostatic spinning method, thereby solving the problems of uneven tubular forming of the self-healing material and self-healing of the artificial blood vessel; a 2 / 3-layer composite structure is adopted, and both ends of the artificial blood vessel are covered during electrostatic spinning of the self-healing polymer, which is removed after spinning, leaving only a self-healing blood vessel middle layer in the middle section of the artificial blood vessel. The middle section of the artificial blood vessel is a three-layer structure including a self-healing layer as the puncture site, and the two ends are a two-layer structure without a self-healing layer, thereby ensuring the compliance of the blood vessel and achieving both excellent self-healing and compliance effects.

[0013] Furthermore, between S1 and S2, it further includes: using PET solution as spinning solution and a 19-22G electrospinning needle to electrospin a spiral support ring in the middle of the inner layer of the blood vessel;

[0014] The length of the spiral support ring accounts for 50%-80% of the total length of the blood vessel and is less than or equal to the length of the self-healing blood vessel middle layer, which covers the spiral support ring. Preferably, the mass volume percentage of the PET solution is 5-30%.

[0015] Furthermore, the electrospinning conditions for the spiral support ring are: spinning voltage 4-8 kV, feed rate 5-30 mK / h, spinning distance 8-15 mm, needle movement rate 1-5 mm / s, and collector speed 50-200 rpm. Using near-field electrospinning, the spiral support ring is formed on the inner surface of the blood vessel, improving the artificial blood vessel's resistance to bending.

[0016] Furthermore, in S1, the method for preparing the vascular lining is: mixing TPU (thermoplastic polyurethane elastomer), PEG (polyethylene glycol), magnetic particles, and a solvent to obtain a dipping solution, placing a cylindrical mold in the dipping solution, and preparing the vascular lining by dipping; preferably, the mass ratio of TPU to PEG is (1-10):1, the mass volume percentage of the dipping solution is 10-50%, and the amount of magnetic particles added is 80-120 mg / mL; the dipping parameters are: standing for 2-10 seconds, and a lifting rate of 300-1500 μm / s;

[0017] Alternatively, the vascular lining is prepared by electrospinning using PTFE (polytetrafluoroethylene) solution as the spinning solution.

[0018] Furthermore, the magnetic particles are Fe3O4 or Fe3O4 / SrFe 12 O 19 Composite materials. Adding magnetic particles improves their anti-thrombotic properties through magnetocaloric effect.

[0019] Furthermore, in S2, the self-healing polymer is formed by mixing a synthetic monomer with a photoinitiator and reacting under irradiation with an ultraviolet light source;

[0020] The synthetic monomer is a mixture of ethyl acrylate (EA) and benzyl methacrylate (BMA), or a mixture of butyl acrylate, methyl methacrylate and 1-vinylimidazole.

[0021] Furthermore, the conditions for the ultraviolet light source irradiation are: light power density 100-1000mW / cm 2 , lighting distance 1-20cm, time 2-30min.

[0022] Furthermore, the viscosity of the self-healing polymer spinning solution is 500-1200 mPa·s.

[0023] Furthermore, a release layer is prepared on the mold surface before the vascular lining is formed by dip coating. The release layer is prepared by dip coating using a PVA solution as the dip coating liquid. Preferably, the dip coating liquid has a mass volume percentage of 5-30%, and the solvent is deionized water and ethanol in a volume ratio of 1:1.

[0024] Furthermore, in S3, the electrospinning solution is a TPU solution, and the preferred mass volume ratio of the TPU solution is 8-12%.

[0025] Furthermore, in S3, the demoulding body is: soaking the mold covering the artificial blood vessel in deionized water at 35-40° C. for 3-5 days, and then taking it out and drying it.

[0026] The second aspect of the present invention provides a 2 / 3-layer composite puncture self-healing artificial blood vessel prepared by the preparation method described in the first aspect.

[0027] Beneficial effects of the present invention:

[0028] The present invention dissolves the self-healing polymer material twice and then prepares it into a tubular film through an electrostatic spinning method, thereby solving the problems of uneven tubular forming of the self-healing material and self-healing of artificial blood vessels.

[0029] The present invention adopts a 2 / 3-layer composite structure, forming a self-healing vascular middle layer only in the middle section of the artificial blood vessel. The middle section of the artificial blood vessel is a three-layer structure including a self-healing layer as the puncture site, and the two ends are two-layer structures without a self-healing layer, ensuring the compliance of the blood vessel and having excellent self-healing and compliance effects.

[0030] The present invention prepares a spiral support ring in the middle section of an artificial blood vessel by a near-field electrostatic spinning method, thereby improving the anti-bending performance of the artificial blood vessel.

[0031] The present invention adds magnetic particles to the inner layer of the blood vessel to improve the anti-thrombotic performance through the magnetothermal effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the technical solution of the present invention, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are merely embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0033] Figure 1 Figures ac in the middle are macroscopic images of the artificial blood vessel obtained in Example 1;

[0034] Figure 2This is a macroscopic picture of the artificial blood vessel obtained in Comparative Example 1;

[0035] Figure 3 Figures ab are macroscopic images of the artificial blood vessel obtained in Example 3;

[0036] Figure 4 This is the macroscopic morphology of the inner layer of the artificial blood vessel obtained in Example 4;

[0037] Figure 5 This is a comparison chart of the compliance test of the artificial blood vessels obtained in Example 1 and Comparative Example 1;

[0038] Figure 6 a and b are comparison diagrams of the anti-bending effects of the artificial blood vessels obtained in Example 3 and Example 1, respectively;

[0039] Figure 7 These are infrared thermal images of the artificial blood vessels obtained in Example 1, Example 3, and Example 4 under an alternating magnetic field;

[0040] Figure 8 This is a comparison chart of the thrombolysis rates of the artificial blood vessels obtained in Example 1, Example 3, and Example 4;

[0041] Figure 9 a and b are pictures of the artificial blood vessel before and after the pinhole puncture healing in Example 1, respectively;

[0042] Figure 10 Figures a and bc are pictures before and after the artificial blood vessel needle hole puncture healing in Example 5. DETAILED DESCRIPTION

[0043] The following will provide a clear and complete description of the technical solutions of the present invention in conjunction with specific embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention.

[0044] Example 1

[0045] This embodiment relates to a method for preparing a 2 / 3-layer composite puncture self-healing artificial blood vessel, comprising the following steps:

[0046] (1) Preparation of release layer

[0047] A 15% w / v PVA solution (the solvent is deionized water and anhydrous ethanol in a volume ratio of 1:1) was prepared, a stainless steel cylindrical mold with a diameter of 7 mm was fixed on a dip coater, and immersed in the PVA solution at a speed of 5000 μm / s. After dipping for 10 seconds, it was taken out of the solution at a speed of 1000 μm / s, hung for 5 minutes, and then placed in a 60°C oven for 30 minutes to form a release layer.

[0048] (2) Preparation of vascular lining

[0049] TPU and PEG were mixed in a mass ratio of 4:1, hexafluoroisopropanol solvent was added to prepare a 20% w / v mixed solution, and mechanical oscillation was performed to mix evenly to obtain a dipping solution; a mold with a release layer was fixed on a dipping machine and immersed in the dipping solution at a speed of 5000 μm / s. After dipping for 8 seconds, it was withdrawn at a speed of 300 μm / s, suspended and allowed to stand for 12 hours to form the vascular endolayer.

[0050] (3) Preparation of self-healing vascular middle layer

[0051] Benzyl methacrylate (BMA) and ethyl acrylate (EA) were mixed at a molar ratio of 1:5, and 80 μL of photoinitiator 1173 was added. The mixture was evenly mixed and coated on the mold surface. A 365 nm ultraviolet light source (light power density: 300 mW / cm 2 ) was vertically irradiated for 20 minutes, the distance between the light source and the sample was fixed at 10 cm, and the ambient temperature was controlled at 25°C to prepare a P(BMA-EA) polymer; P(BMA-EA) was dissolved in hexafluoroisopropanol (HFIP) and stirred at 25°C and 400 rpm for 6 hours to obtain a homogeneous self-healing polymer solution with a w / v of 40%; the two ends of the cylindrical mold with the inner layer of the blood vessel were wrapped with aluminum foil (each end accounted for 20% of the total length of the blood vessel), and then fixed on the rotating collection device of the electrospinning machine, the self-healing polymer solution was injected into the injection pump of the electrospinning machine, and the electrospinning machine was turned on. , the temperature is 35℃, the humidity is 15%, and the temperature and humidity control device and exhaust device of the electrospinning machine are turned on, the electrospinning parameters are set, the injection pump pushing speed is 1mL / h, the voltage is controlled at 5kV, the receiving distance is 15cm, and the collector speed is 500rpm; the needle movement swing is set to 40mm, and the spinning is carried out within 66.67% of the length of the middle of the blood vessel; after spinning for 30 minutes, the electrospinning machine is turned off, the collecting rod is removed from the collecting device, placed in a 37℃ vacuum drying oven and dried for 6 hours, then taken out, and the tin foil wrapped at both ends is removed to form a self-healing middle layer of the artificial blood vessel.

[0052] (4) Preparation of the outer layer of blood vessels

[0053] TPU was added to hexafluoroisopropanol to prepare a 10% w / v TPU solution; the mold with the inner layer and middle layer of the blood vessel was fixed on the collecting device of the electrospinning machine, the polyurethane solution was injected into the injection pump of the electrospinning machine, the electrospinning machine was turned on, the temperature was in the range of 30-35°C, the humidity was in the range of 15-30%, the temperature and humidity control device and exhaust device of the electrospinning machine were turned on, the electrospinning parameters were set, the injection pump pushing speed was 0.75mL / h, the voltage was controlled at 13kV, the receiving distance was 18cm, and the collector speed range was 500rpm; the spinning length completely covered the length of the blood vessel, and after spinning for 120 minutes, the electrospinning machine was turned off; the collecting rod was removed from the collecting device, placed in a 37°C vacuum drying oven and dried for 3 hours, and then taken out to form the outer layer of the blood vessel.

[0054] (5) Demolding

[0055] Pour an appropriate amount of deionized water into a beaker and heat it to 37°C. Immerse the cylindrical mold for preparing the artificial blood vessel in 37°C deionized water for 5 days. Take out and remove the self-healing artificial blood vessel from the mold using tweezers, and place it in a 37°C oven for drying to obtain the 2 / 3-layer composite puncture self-healing artificial blood vessel.

[0056] Example 2

[0057] The difference between this embodiment and embodiment 1 is that in step (3), during the preparation of the middle layer of the self-healing blood vessel, each end of the tinfoil accounts for 10% of the total length of the blood vessel, and the other steps and parameters remain unchanged.

[0058] Example 3

[0059] The difference between this embodiment and embodiment 1 is that in step (2), SrFe 12 O 19 / Fe3O4, the concentration of the dipping solution is 100 mg / mL; at the same time, a spiral support ring preparation step is added between step (2) and step (3):

[0060] Add PET to hexafluoroisopropanol to prepare a PET solution with a w / v of 18%. Fix the cylindrical mold with the inner layer of the blood vessel on the collecting device of the electrospinning machine. Inject the PET solution into the injection pump of the electrospinning machine. Turn on the electrospinning machine. Set the temperature and humidity in the electrospinning machine to within the range of 30-35°C and the humidity to within the range of 15%-25%. Turn on the temperature and humidity control device and exhaust device of the electrospinning machine. Set the electrospinning parameters to a rate of 25 mL / h for the injection pump, a voltage of 5 kV, a receiving distance of 10 mm, a collector speed of 150 rpm, a needle movement speed of 3 mm / s, and a needle movement amplitude of 40 mm. Spin within 60% of the length of the middle of the blood vessel. Remove the collecting rod from the collecting device, place it in a vacuum drying oven at 37°C and dry it for 3 hours before taking it out to form a spiral support ring.

[0061] Example 4

[0062] The difference between this embodiment and embodiment 3 is that the magnetic particles are replaced with Fe3O4, and the other steps and parameters remain unchanged.

[0063] Example 5

[0064] This embodiment relates to a method for preparing a 2 / 3-layer composite puncture self-healing artificial blood vessel, comprising the following steps:

[0065] (1) Preparation of vascular lining

[0066] A 60wt% PTFE aqueous dispersion and a 4wt% PEO aqueous solution were mixed in a mass ratio of 97:3, and deionized water was added as a solvent to prepare a spinning solution with an overall mass fraction of 35%. An elastic metal bracket with a length of 15cm and a diameter of 4mm was placed on a 4mm thick stainless steel round rod as a receiving device, and the stainless steel metal rod drove the elastic bracket to rotate at a speed of 400rpm. The air flow was controlled by a homemade EBS electric blowing device, and the polymer solidification solvent evaporated to obtain a PTFE / PEO composite nanofiber membrane deposited on the collector. The fiber membrane was transferred to a muffle furnace, and the temperature was increased from room temperature to 330℃ at a rate of 5℃ / min, maintained for 15 minutes, and then cooled to room temperature. The sintered fiber membrane was removed and plasma treated in an air atmosphere with a processing power of 300W and a processing time of 30s.

[0067] (2) Vascular middle layer

[0068] Butyl acrylate (BA), methyl methacrylate (MMA) and 1-vinylimidazole (VIM) were mixed as monomers in a molar ratio of 3:1:1, and 0.5 wt% of photoinitiator Irgacure 1173 was added. The mixture was stirred at 30 °C for 6 h to prepare an oligomer emulsion, which was then coated on the mold surface and illuminated using a 365 nm ultraviolet light source (optical power density: 300 mW / cm 2 ) was vertically irradiated for 10 min, the distance between the light source and the sample was fixed at 10 cm, and the ambient temperature was controlled at 25±1°C to prepare a transparent elastic resin P(BA-MMA-VIM); hexafluoroisopropanol (HFIP) was used to dissolve P(BA-MMA-VIM), and the mixture was stirred at 25°C and 300 rpm for 4 hours to obtain a 15 wt% homogeneous self-healing polymer solution; both ends of the cylindrical mold with the inner layer of the blood vessel were wrapped with aluminum foil (each end accounted for 20% of the total length of the blood vessel), and fixed on the rotating collection device of the electrospinning machine as the negative electrode, and the self-healing polymer solution was injected into the injection pump of the electrospinning machine, and a 27-gauge stainless steel needle was used. head, using the healing polymer solution as the positive electrode; turning on the electrospinning machine, the temperature is 30℃, the humidity is 25%, and the temperature and humidity control device and exhaust device of the electrospinning machine are turned on, and the electrospinning parameters are set, the injection pump pushing speed is 1mL / h, the voltage is controlled at 5.5kV, the receiving distance is 20cm, and the collector speed is 400rpm; the needle movement swing is set to 40mm, and spinning is carried out within the middle 60% length range of the blood vessel; after spinning for 30 minutes, the electrospinning machine is turned off; the collecting rod is removed from the collecting device, placed in a 37℃ vacuum drying oven for drying for 6 hours, and then taken out and the aluminum foil is removed to form a self-healing middle layer of the artificial blood vessel.

[0069] (3) Outer layer of blood vessels

[0070] TPU was added to hexafluoroisopropanol to prepare a 10% w / v TPU solution. A cylindrical mold containing the inner and middle layers of the blood vessel was fixed to the collection device of the electrospinning machine. The polyurethane solution was injected into the syringe pump of the electrospinning machine. The electrospinning machine was turned on, the temperature was maintained between 30-35°C, and the humidity was between 15-30%. The temperature and humidity control and exhaust system of the electrospinning machine were activated. The electrospinning parameters were set to a syringe pump feed rate of 1 mL / h, a voltage of 13 kV, a receiving distance of 18 cm, and a collector speed of 500 rpm. The spinning length completely covered the length of the blood vessel. After spinning for 60 minutes, the electrospinning machine was turned off. The collection rod was removed from the collection device and dried in a 37°C vacuum drying oven for 3 hours before being stored in a ziplock bag at a constant temperature.

[0071] Comparative Example 1

[0072] The difference between this comparative example and Example 1 is that in the preparation process of the self-healing blood vessel middle layer in step (3), the self-healing blood vessel middle layer is not coated with tin foil, and the self-healing blood vessel middle layer completely covers the length of the blood vessel. Other steps and parameters remain unchanged.

[0073] Test Case

[0074] (1) Macromorphology

[0075] Figure 1 Middle ac is the macroscopic picture of the artificial blood vessel obtained in Example 1, and the thickness of the 2 / 3 layer is about 75 μm ( Figure 1 b) and 100μm ( Figure 1 c middle three-layer area). Figure 2 This is a macroscopic picture of the artificial blood vessel obtained in Comparative Example 1. The blood vessel has a three-layer structure as a whole and a thickness of about 100 μm. Figure 3 Figures a and b are macroscopic images of the artificial blood vessel obtained in Example 3. The thickness of the middle three layers is about 150 μm. Figure 3 Middle b. Figure 4 This is the macroscopic morphology of the inner layer of the artificial blood vessel obtained in Example 4, showing that the magnetic particles Fe3O4 are evenly dispersed.

[0076] (2) Compliance test analysis

[0077] The compliance of the blood vessels obtained in Example 1 and the comparative example was tested according to the test method provided in ISO 7198 standard. The compliance of Example 1 and the comparative example 1 in the pressure range of 80 mmHg-120 mmHg was as follows: Figure 5 As shown, the compliance of Example 1 containing a 2 / 3 layer composite structure is significantly higher than that of Comparative Example 1 containing a three-layer composite structure, and is closer to the compliance of human arteries of about 8%.

[0078] (3) Anti-bending effect test analysis

[0079] Figure 6 Figures a and b are comparative diagrams of the anti-bending effects of the artificial blood vessels obtained in Example 3 and Example 1, respectively. Example 1 is a 2 / 3-layer tubular structure without a spiral structure, while Example 3 adopts a spiral support structure. When the bending diameter of Example 3 reaches 60°, the lumen cross-sectional area retention rate is still greater than 90%, and no plastic deformation or structural delamination is observed; while when the bending angle of Example 1 reaches 80°, the cross-sectional area collapse rate exceeds 60%. It can be seen that the anti-bending performance of Example 3 containing a spiral support ring is significantly enhanced.

[0080] (4) Antithrombotic performance test

[0081] When the inner layers of the three artificial blood vessels of Example 1, Example 3 and Example 4 were placed in an alternating magnetic field with a frequency of 100 kHz for 45 minutes, the surface temperature changes of each sample were recorded using an infrared thermal imager. Figure 7 As shown, it can be observed that the surface temperature of the artificial blood vessel of Example 4 containing Fe3O4 magnetic particles reaches 41.8°C. It can be seen that when the artificial blood vessel is loaded with pure Fe3O4, it has the best magnetocaloric performance.

[0082] 1 mL of 0.2 mol / L calcium chloride solution was injected into 2 mL of anticoagulated rabbit blood and allowed to stand at room temperature for 24 hours to prepare a thrombus clot. The thrombus clot of the same mass was placed inside Example 1, Example 3 and Example 4 and exposed to a 100 kHz alternating magnetic field for 60 minutes. The artificial blood vessel and the thrombus clot were then placed in a glass bottle containing 3 mL of normal saline and incubated at 37°C for 30 minutes. The dissolution of the thrombus was observed and the mass of the thrombus incubated for 30 minutes was weighed. The thrombus dissolution rate of each example was calculated as follows: Figure 8 Compared to Example 1, Examples 3 and 4 showed improved hemolysis rates, particularly Example 4, which effectively promoted thrombus dissolution through the magnetothermal effect generated under an alternating magnetic field. The thrombolysis rate reflects a material's ability to dissolve thrombi, typically expressed as the percentage of dissolved thrombus mass to the initial thrombus mass. A higher thrombolysis rate indicates a material's greater thrombus dissolving ability.

[0083] (5) Pinhole puncture healing test

[0084] For Example 1 and Example 5, after puncturing the blood vessel with a 17G dialysis needle and flattening the blood vessel, the microscopic morphology of the puncture hole on the surface of the artificial blood vessel is as follows: Figure 9 middle ab and Figure 10 As shown in the middle ac, after pressing and rubbing with the palm for 10 minutes, the process of rubbing the blood vessel to make it heal after puncture of the artificial blood vessel is simulated, and the puncture hole heals itself. The healing situation is as follows Figure 9 From Figures 10b and 10bc, it can be seen that the artificial blood vessels obtained in Example 1 and Example 5 can both self-heal.

[0085] The present invention has been described in detail above with reference to specific embodiments and exemplary examples. However, these descriptions should not be construed as limiting the present invention. Those skilled in the art will appreciate that various equivalent substitutions, modifications, or improvements may be made to the technical solutions and implementations of the present invention without departing from the spirit and scope of the present invention, all of which fall within the scope of the present invention. The scope of protection of the present invention shall be determined by the appended claims.

Claims

1. A method for preparing a 2 / 3-layer composite puncture self-healing artificial blood vessel, characterized in that: The steps include: S1. Prepare the vascular lining; S2, wrapping both ends of the vascular inner layer with a covering layer, dissolving the self-healing polymer in a solvent to form a spinning solution, coating the self-healing polymer by electrospinning, removing the covering layer, and obtaining a self-healing vascular middle layer; Among them, the length of the covering layer at both ends independently accounts for 10%-25% of the total length of the blood vessel; S3. Electrospinning the outer layer of the blood vessel on the surface of the inner layer of the blood vessel and the middle layer of the self-healing blood vessel to obtain the self-healing artificial blood vessel.

2. The method for preparing the 2 / 3-layer composite puncture self-healing artificial blood vessel according to claim 1, characterized in that: Between S1 and S2, it also includes: using PET solution as the spinning solution and a 19-22G electrospinning needle to electrospin a spiral support ring in the middle of the inner layer of the blood vessel; The length of the spiral support ring accounts for 50%-80% of the total length of the blood vessel and is less than or equal to the length of the middle layer of the self-healing blood vessel.

3. The method for preparing the 2 / 3-layer composite puncture self-healing artificial blood vessel according to claim 2, characterized in that: The conditions of the electrospinning spiral support ring are: spinning voltage 4-8kV, pushing rate 5-30mK / h, spinning distance 8-15mm, needle moving rate 1-5mm / s, collector speed 50-200rpm.

4. The method for preparing a 2 / 3-layer composite puncture self-healing artificial blood vessel according to claim 1, characterized in that: In S1, the method for preparing the vascular lining comprises: mixing TPU, PEG, magnetic particles, and a solvent to obtain a dipping solution, placing a cylindrical mold in the dipping solution, and preparing the vascular lining by a dipping method; Alternatively, the vascular lining is prepared by electrospinning using PTFE solution as the spinning solution.

5. The method for preparing the 2 / 3-layer composite puncture self-healing artificial blood vessel according to claim 4, characterized in that: The magnetic particles are Fe3O4 or Fe3O4 / SrFe 12 O 19 Composite materials.

6. The method for preparing a 2 / 3-layer composite puncture self-healing artificial blood vessel according to claim 1, characterized in that: In S2, the self-healing polymer is formed by mixing a synthetic monomer with a photoinitiator and reacting under irradiation of an ultraviolet light source; The synthetic monomer is a mixture of ethyl acrylate and benzyl methacrylate, or a mixture of butyl acrylate, methyl methacrylate and 1-vinylimidazole.

7. The method for preparing a 2 / 3-layer composite puncture self-healing artificial blood vessel according to claim 6, characterized in that: The conditions for the ultraviolet light source irradiation are: light power density 100-1000mW / cm 2 , lighting distance 1-20cm, time 2-30min.

8. The method for preparing a 2 / 3-layer composite puncture self-healing artificial blood vessel according to claim 4, characterized in that: Before preparing the inner layer of the blood vessel by the dip coating method, a release layer is prepared on the surface of the mold. The preparation method is: using PVA solution as the dip coating liquid, and preparing the release layer by the dip coating method.

9. The method for preparing a 2 / 3-layer composite puncture self-healing artificial blood vessel according to claim 1, characterized in that: In S3, the spinning solution for electrospinning is a TPU solution.

10. A 2 / 3-layer composite puncture self-healing artificial blood vessel prepared by the preparation method according to any one of claims 1 to 9.

Images