Puncture-resistant and bending-resistant artificial blood vessel and preparation method thereof

Abstract

The invention relates to the field of artificial blood vessels, in particular to a puncture-resistant and bending-resistant artificial blood vessel and a preparation method thereof. The puncture-resistant and bending-resistant artificial blood vessel is composed of the inner-layer fiber membrane, the bending-resistant ring and the compact layer and is prepared through low-temperature processes such as electrostatic spinning, 3D printing and ultrasonic atomization spraying, and the problems of thermal damage and poor interface bonding caused by a traditional hot-melt extrusion process are solved. By optimizing the ring distance of the anti-bending ring and the thickness of the compact layer, good balance between the anti-bending performance and the puncture performance is achieved, the number of puncture times can reach 2000 or above, the leakage pressure threshold value is larger than or equal to 120 mmHg, the puncture force is smaller than or equal to 2.0 N, the artificial blood vessel meets the clinical requirement of high-frequency puncture, the service life of the artificial blood vessel is remarkably prolonged, and the safety of the artificial blood vessel is remarkably improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of artificial blood vessels, in particular, to a puncture-resistant and bending-resistant artificial blood vessel and a preparation method thereof. BACKGROUND

[0002] As a blood vessel substitute, artificial blood vessels are widely used in hemodialysis access, peripheral vascular reconstruction and cardiovascular surgery. An ideal artificial blood vessel for hemodialysis should have good biocompatibility, excellent puncture-resistant and bending-resistant performance, stable structural integrity and good hemocompatibility. However, the artificial blood vessels in the prior art still have many deficiencies in structure and performance, especially in the balance of puncture-resistant and bending-resistant performance, long-term stability and biological safety.

[0003] Chinese patent CN112472361B discloses an anti-bending artificial blood vessel and a preparation method thereof. The artificial blood vessel adopts a rigid polymer to form a spiral ring through heat extrusion to enhance the anti-bending performance. However, this structure has certain defects. The rigid ring occupies the puncture area, resulting in an effective puncture area of only 65%-75%, and the needle tip is easy to deviate during puncture. The heat extrusion process has a temperature as high as 200-400℃, which is much higher than the melting point of the inner layer material such as polyurethane, and is easy to cause thermal damage. The ring body and the tube body are physically embedded, and the interface bonding strength is low, which is easy to delaminate and loosen during long-term use, resulting in leakage. Similarly, the wire-wound reinforcing structure in the artificial blood vessel commercially available from NICAST company interferes with puncture, has poor biocompatibility and is easy to loosen in the long term. Chinese patent application CN110548187A discloses an instant puncture dialysis type nanofiber artificial blood vessel, which mainly uses electrospun nanofiber as a support layer to improve flexibility. However, this structure has insufficient anti-bending performance, puncture positioning is difficult, and the number of puncture resistances is limited, which is difficult to meet the high-frequency puncture demand. Chinese patent CN119033501B discloses an anti-bending and arbitrarily puncturable artificial blood vessel. The artificial blood vessel adopts a structure design of a fiber layer, a dense layer and an enhancement layer to balance various performances of the product. However, there are problems such as poor interface bonding of multiple layers, easy delamination during long-term use, and obvious attenuation of anti-bending performance after multiple punctures, poor structural stability.

[0004] The prior art has not solved the core problem of "balancing puncture-resistant and bending-resistant performance, unifying long-term stability and biocompatibility", so there is an urgent need to develop a puncture-resistant and bending-resistant artificial blood vessel to meet the application in different clinical application environments. SUMMARY

[0005] To solve the above technical problems, the first aspect of the present application provides a preparation method of a puncture-resistant and bending-resistant artificial blood vessel, comprising:

[0006] S1, the first high polymer is dissolved and stirred using a first solvent to prepare a spinning solution; the spinning solution is deposited on the surface of a mold through an electrospinning process to obtain an artificial blood vessel inner layer fiber membrane;

[0007] S2, the second high polymer is printed on the surface of the artificial blood vessel inner layer fiber membrane in a spiral trajectory according to the three-dimensional model of the anti-bending ring by 3D printing to obtain an artificial blood vessel body with an anti-bending ring.

[0008] S3, configure an ultrasonic spraying liquid or an immersion liquid, then ultrasonic atomize the ultrasonic spraying liquid on the surface of the artificial blood vessel body with the anti-bending ring, or soak the artificial blood vessel body with the anti-bending ring in the immersion liquid, slightly dissolve the surface of the artificial blood vessel inner layer fiber membrane, at the same time, completely wrap the anti-bending ring in the dense layer, form a dense layer with a thickness of 100-200μm, and then dry treatment, to obtain a puncture-resistant and anti-bending artificial blood vessel.

[0009] As an implementable case, the first high polymer at least includes at least one of PCL (polycaprolactone), PU (polyurethane) or PLA (polylactic acid).

[0010] Further, the weight average molecular weight of the first high polymer is 100-350 thousand.

[0011] Further, the weight average molecular weight of the first high polymer is 250-350 thousand.

[0012] Further, the first solvent includes one or more of HFIP (hexafluoroisopropanol), DMSO (dimethyl sulfoxide), THF (tetrahydrofuran), TFA (trifluoroacetic acid), DCM (dichloromethane) or DMF (N,N-dimethylformamide).

[0013] Further, the mass concentration of the spinning solution is 14-20%.

[0014] As an implementable case, in the electrospinning process, the spinning receiving distance is set to 10-20cm, the spinning environment temperature is controlled to 25-40℃, the relative humidity is 20-30%, the positive and negative electrode voltages of the spinning are adjusted to +10~+12kV and -10~-5kV respectively, the flow rate of the feeding device is set to 0.5-2.0mL / h, the receiving mold rotation speed is controlled to 50-200rad / min, and the spinning platform moving speed is 40-100mm / s.

[0015] Further, the processing time of the electrospinning process is 8-12h, and the thickness of the artificial blood vessel inner layer fiber membrane is 1000-1200μm.

[0016] As an implementable case, the second high molecular polymer includes one or more of TPU (thermoplastic polyurethane elastomer), PLGA (poly-lactic-co-glycolic acid) or PET (polyethylene terephthalate).

[0017] As an implementable case, in the 3D printing process, the ring body height of the anti-bending ring three-dimensional model is set to 1-3mm, the width is 1-2mm, and the ring spacing is 1.7-2.5mm.

[0018] In the present application, the parameters of the anti-bending ring three-dimensional model need to be strictly limited, especially the ring spacing of the anti-bending ring three-dimensional model is limited to 1.7-2.5mm, which can achieve the optimal balance between anti-bending performance, puncture performance, structural stability and clinical applicability, and avoid the two-pole problem of "strong anti-bending but difficult to puncture" or "easy to puncture but easy to bend" in the prior art. Specifically, when the ring spacing is greater than 2.5mm, the support between the anti-bending rings is weakened, and the bending stress cannot be effectively dispersed, resulting in that the blood vessel is easy to kink or collapse when bending, affecting the smooth blood flow, and in actual clinical puncture, the needle tip is easy to pass through the unsupported area, resulting in unstable puncture path, increasing the risk of puncture deviation, and affecting the puncture precision; when the ring spacing is less than 1.7mm, the anti-bending rings are too dense to form a continuous rigid structure, although the anti-bending performance is improved, but the compliance of the blood vessel is significantly reduced, making it rigid and difficult to adapt to the dynamic blood flow and limb movement, and when the anti-bending rings are too dense, they will also hinder the entry path of the puncture needle, increase the puncture resistance, and even cause puncture failure or damage to the blood vessel structure. When the ring spacing is 1.7-2.5mm, the artificial blood vessel prepared thereby achieves the best balance between anti-bending performance and puncture performance, thereby ensuring its safety, operability and durability in clinical application.

[0019] Further, the raw materials of the impregnation solution include one or more of HFIP, DMSO, THF, TFA, DCM or DMF.

[0020] Further, the raw materials of the ultrasonic spraying liquid include one or more of HFIP, DMSO, THF, TFA, DCM, DMF or the first high molecular polymer.

[0021] As an implementable case, in the ultrasonic atomization spraying, the feeding speed of the ultrasonic atomization spraying is set to 0.5-1mL / h, the receiving distance is 1-5cm, the receiving rod rotation speed is kept at 50-200rad / min, the environmental temperature is controlled at 25-30℃, the relative humidity is 30-35%, the ultrasonic spraying gas flow pressure is 0.1-0.2MPa, the operating power is 1-2W, and the ultrasonic atomization spraying time is 5-10h.

[0022] In the conventional artificial blood vessel preparation process, the spiral hot melt extrusion method is usually used, and the processing temperature range is 200-400℃. However, the molecular structure of the polyurethane nanofiber tube will change significantly under this temperature condition. It is found by scanning electron microscopy (SEM) observation that the surface roughness (Ra) of the tube increases significantly with the increase of the hot extrusion temperature: at 200℃, the surface roughness Ra is about 50-80nm; at 400℃, Ra can be increased to 150-200nm. The increase of surface roughness will lead to the formation of more micro defects on the surface of the tube, which are easy to become stress concentration points during puncture, thereby reducing the puncture resistance of the artificial blood vessel. At the same time, the interface bonding strength between the bending resistance ring and the tube of the artificial blood vessel prepared by the spiral hot melt extrusion process is low. By tensile test with electronic universal testing machine, the average bonding strength is only 15N / mm 2 , while the ideal artificial blood vessel structure requires a bonding strength of at least 30N / mm 2 , to ensure that it can withstand the impact of human motion and blood flow during long-term use without delamination. In addition, X-ray tomography analysis shows that there are areas with high porosity at the interface, with an average porosity of about 12%, which significantly reduces the effective contact area of the interface, weakens the bonding force, and increases the risk of interface separation.

[0023] In the simulation of clinical puncture experiment, the artificial blood vessel prepared by the traditional process began to appear fiber fracture in the ring area when the puncture times reached about 850 times; when the puncture times increased to 1000 times, the leakage rate was as high as 15%. In the pressure test, when the pressure rose to 90mmHg, the ring area appeared obvious blood leakage, while the normal human arterial blood pressure is 120-140mmHg, indicating that the artificial blood vessel cannot guarantee the sealing performance after puncture under physiological pressure. In addition, the average puncture force in the puncture process is 3.5N, which is significantly higher than that of the artificial blood vessel with good performance (usually ≤2.0N), which not only increases the difficulty of clinical puncture operation, but also may cause additional damage to the blood vessel and surrounding tissues.

[0024] Therefore, the present application adopts an ultrasonic atomization spraying process or an immersion method to replace a traditional spiral hot melt extrusion preparation process, so as to solve key problems such as thermal damage, weak interface bonding and poor puncture performance in the traditional preparation process. The ultrasonic atomization spraying adopts solvent dissolution and atomization spraying, and the process temperature is much lower than that of hot melt extrusion, so that damage of high temperature to the inner fiber membrane is avoided, the structural integrity and mechanical properties of the tube body are maintained, meanwhile, the solvent of ultrasonic atomization spraying can dissolve part of the nanofiber to form a polymer interpenetrating network, so that the interface bonding strength between the dense layer and the inner fiber membrane of the artificial blood vessel is significantly improved, the porosity is reduced to <10%, by forming a 20-40 mu dense non-porous membrane, the anti-bending ring and the tube body are firmly combined, the risk of delamination under the impact of blood flow is reduced, the puncture performance and the leakage pressure threshold are significantly improved, the needle hole is quickly closed after puncture, and the risk of blood leakage is reduced.

[0025] The present application provides a puncture-resistant and anti-bending artificial blood vessel prepared by the preparation method of the puncture-resistant and anti-bending artificial blood vessel.

[0026] Advantages

[0027] (I) The present application adopts a 3D printing and ultrasonic atomization spraying process to replace a traditional high-temperature hot melt extrusion process of 200-400 DEG C, so as to effectively prevent the molecular structure of the polyurethane nanofiber tube body from being damaged and the surface roughness from being increased due to high temperature, and ensure the mechanical properties and puncture resistance of the inner fiber membrane.

[0028] (II) The present application forms a polymer interpenetrating network structure through solvent ultrasonic atomization spraying, so that the bonding strength between the anti-bending ring and the tube body is improved, the interface porosity is reduced to <10%, and the risk of delamination in long-term use is avoided.

[0029] (III) In the present application, the dense layer is formed by ultrasonic atomization spraying, so that the puncture-resistant times of the artificial blood vessel are ≥2000 times, the leakage pressure threshold is ≥120 mmHg, and the clinical high-frequency puncture demand is met.

[0030] (IV) The present application precisely controls the anti-bending ring spacing to be 1.7-2.5 mm and the dense layer thickness to be 100-200 mu through 3D printing, so that the ring body elastically slips away from the needle tip when puncturing, the anti-bending ability and the effective utilization rate of the puncture area are considered, and the problem that the rigid ring body hinders puncture in the traditional technology is solved.

[0031] (V) The puncture force of the artificial blood vessel prepared by the present application is controlled to be ≤2.0 N, the risk of puncture needle deviation is reduced, the damage to the blood vessel and the surrounding tissue is reduced, the clinical operation fluency and safety are improved; meanwhile, the low-temperature process reduces the solvent residue; the molecular-level bonding mode ensures that each layer of material is uniform and stable, and the service life is prolonged. BRIEF DESCRIPTION OF DRAWINGS

[0032] Figure 1Schematic diagram of the artificial blood vessel structure prepared for Example 1, wherein: 1 - inner layer fiber membrane of the artificial blood vessel, 2 - anti-bending ring, 3 - dense layer.

[0033] Figure 2 Schematic diagram of the artificial blood vessel prepared for Comparative Example 1.

[0034] Figure 3 Schematic diagram of the artificial blood vessel prepared for Comparative Example 3. DETAILED DESCRIPTION

[0035] Example 1

[0036] The first aspect of the example provides a method for preparing a puncture-resistant and anti-bending artificial blood vessel, specifically:

[0037] S1, PU with a weight average molecular weight of 320,000 was added to HFIP, and a spinning solution with a mass concentration of 15wt% was prepared by continuously stirring in a constant temperature water bath environment at 37°C for 24h; the spinning receiving distance was set to 17cm, the spinning environment temperature was controlled to 35°C, the relative humidity was 30%, the positive and negative voltages of the spinning were adjusted to +12kV and -10kV respectively, the flow rate of the feeding device was set to 1.0mL / h, the receiving mold rotation speed was controlled to 100rad / min, and the spinning platform moving speed was 50mm / s; the spinning solution was electrospun by electrospinning process for 8h to deposit on the surface of a metal receiving rod mold with an outer diameter of 5.5mm, to obtain an inner layer fiber membrane (1) of the artificial blood vessel with a thickness of about 1200μm;

[0038] S2, TPU with a molecular weight of 100,000 and a melt index of 10g / 10min was first dried at 80°C for 6h to fully remove the water in the raw material; after drying, the TPU particles were loaded into the FDM (fused deposition modeling) equipment and fixed on the clamp in the cabin of the 3D printing equipment; the nozzle temperature was set to 220°C, and the printing platform was preheated to 50°C to reduce the risk of warping deformation of the material during printing; a nozzle with a diameter of 0.3mm was selected. Using the 3D printing method, the slicing software was used to convert the anti-bending ring three-dimensional model into a printing path according to the anti-bending ring three-dimensional model; the anti-bending ring three-dimensional model was set to a ring body height of 2mm, a width of 1.5mm, and a ring spacing of 2mm; a continuous winding structure was used; the layer height was set to 0.1mm, the printing speed was 60mm / s, and the filling rate was 40%; the anti-bending ring was embedded on the surface of the inner layer fiber membrane of the artificial blood vessel in a spiral trajectory; during the printing process, the environmental temperature was maintained at 25°C and the relative humidity was less than 50%; after printing, the printed product was naturally cooled to room temperature of 25°C, to obtain an artificial blood vessel tube with an anti-bending ring (2);

[0039] S3, the PU with a weight average molecular weight of 320,000 is added into the HFIP, and the mixture is magnetically stirred at 25°C for 12 h to prepare a 1 wt% ultrasonic spraying solution (or the spinning solution is directly diluted with THF); the feeding speed of ultrasonic atomization spraying is set to 0.5 mL / h, the receiving distance is 5 cm, the receiving rod rotation speed is kept at 100 rad / min, the environmental temperature is controlled at 30°C, the relative humidity is 35%, the ultrasonic spraying airflow pressure is 0.15 MPa, the running power is 1.2 W, and the ultrasonic atomization spraying time is 6 h; the ultrasonic atomization spraying solution is sprayed on the surface of the artificial blood vessel tube body with the anti-bending ring, the THF solvent droplets (particle size about 30-40 μm) formed by atomization of the ultrasonic atomization spraying solution fully interact with the fibers in the inner layer fiber membrane of the artificial blood vessel, slightly dissolve the surface of the inner layer fiber membrane of the artificial blood vessel, and fuse with the ultrasonic atomization spraying solution to form a colorless and transparent dense layer (3) with a thickness of about 150 μm on the surface of the tube body; the dense layer completely wraps the anti-bending ring in the dense layer; in this process, the inner layer fibers are dissolved and fused due to the solvent, and the thickness is reduced from the initial 1200 μm to about 800 μm; the final overall puncture-resistant and anti-bending artificial blood vessel has a thickness of about 950 μm; then the prepared artificial blood vessel is placed in a 37°C vacuum drying oven and dried overnight to obtain the puncture-resistant and anti-bending artificial blood vessel.

[0040] The second aspect of the present example provides a puncture-resistant and anti-bending artificial blood vessel prepared by the preparation method of the puncture-resistant and anti-bending artificial blood vessel. Figure 1

[0041] Example 2

[0042] The first aspect of the present example provides a preparation method of a puncture-resistant and anti-bending artificial blood vessel, specifically:

[0043] S1, the PU with a weight average molecular weight of 320,000 and the PCL with a weight average molecular weight of 280,000 are mixed in a mass ratio of 3:2, and then added into a mixed solvent of HFIP and DMSO in a volume ratio of 4:1; the mixture is mechanically stirred at a rotation speed of 300 rad / min in a constant-temperature water bath environment at 42°C for 36 h to prepare a 14 wt% spinning solution; the spinning receiving distance is set to 15 cm, the spinning environmental temperature is controlled at 32°C, the relative humidity is 28%, the positive and negative voltages of the spinning are adjusted to +10 kV and -8 kV respectively, the feeding device flow rate is set to 0.8 mL / h, the receiving mold rotation speed is controlled at 80 rad / min, and the spinning platform moving speed is 40 mm / s; the spinning solution is electrospun by an electrospinning process for 10 h to be deposited on the surface of a ceramic receiving rod mold with an outer diameter of 6 mm to obtain an inner layer fiber membrane of an artificial blood vessel with a thickness of about 1000 μm;

[0044] ​S2, select the PLGA with a molecular weight of 120,000 and a melt index of 8 g / 10 min, first dry it at 75℃ for 8h, fully remove the water in the raw material; after drying, the PLGA particles are loaded into the FDM equipment and fixed on the clamp in the cabin of the 3D printing equipment, the nozzle temperature is set to 210℃, the printing platform is preheated to 45℃ to reduce the risk of warping deformation of the material during printing; select a nozzle with a diameter of 0.4mm. Using 3D printing, using slicing software to convert the anti-bending ring three-dimensional model into a printing path according to the anti-bending ring three-dimensional model, the anti-bending ring three-dimensional model is set to a ring body height of 1.8mm, a width of 1.2mm, and a ring spacing of 2mm, a continuous winding structure is used, the layer height is set to 0.1mm, the printing speed is 60mm / s, and the filling rate is 40%, the anti-bending ring is embedded in the spiral track, and the anti-bending ring is printed on the surface of the artificial blood vessel inner layer fiber membrane. During printing, the ambient temperature is maintained at 25℃ and the relative humidity is less than 50%, and after printing, the temperature is naturally cooled to room temperature 25℃, and the artificial blood vessel tube with anti-bending ring is obtained;

[0045] S3, select a mixed solvent of DMF and DMSO with a volume ratio of 1:1 as the ultrasonic spraying liquid; set the feeding speed of ultrasonic atomization spraying to 0.6mL / h, the receiving distance to 4cm, the receiving rod rotation speed to 90rad / min, the environmental temperature to 28℃, the relative humidity to 32%, the ultrasonic spraying airflow pressure to 0.12MPa, the running power to 1.0W, and the ultrasonic atomization spraying time to 7h, and at the same time, apply a static voltage of +5kV to assist atomization. The ultrasonic spraying liquid is ultrasonically atomized and sprayed on the surface of the artificial blood vessel tube with anti-bending ring; after 7h of spraying, the ultrasonic spraying liquid slightly dissolves the surface of the artificial blood vessel inner layer fiber membrane, and finally forms a dense layer with a thickness of about 120μm. The thickness of the artificial blood vessel inner layer fiber membrane is reduced from the initial 1000μm to about 700μm, and at this time the overall puncture-resistant and anti-bending artificial blood vessel has a thickness of about 820μm. Then the prepared artificial blood vessel is placed in a 35℃ vacuum drying oven for drying for 12h, and a puncture-resistant and anti-bending artificial blood vessel is obtained.

[0046] The second aspect of the present example provides a puncture-resistant and anti-bending artificial blood vessel prepared by the preparation method of the puncture-resistant and anti-bending artificial blood vessel.

[0047] Example 3

[0048] The first aspect of the present example provides a preparation method of a puncture-resistant and anti-bending artificial blood vessel, specifically:

[0049] S1, PU with a weight average molecular weight of 300,000 and PLA with a weight average molecular weight of 250,000 were mixed in a mass ratio of 3:2, added to a mixed solvent of TFA and DCM in a volume ratio of 5:1, stirred at a constant temperature water bath environment of 45℃ at a speed of 400 rad / min for 40h, and a spinning solution with a mass concentration of 16wt% was prepared; the spinning receiving distance was set to 16cm, the spinning environment temperature was controlled to 33℃, the relative humidity was 25%, the positive and negative electrode voltages of the spinning were adjusted to +11kV and -9kV respectively, the flow rate of the feeding device was set to 0.9mL / h, the receiving mold rotating speed was controlled to 90rad / min, and the spinning platform moving speed was 45mm / s; the spinning solution was electrospun by the electrospinning process for 9h, deposited on the surface of a metal receiving rod mold with an outer diameter of 5.8mm, and an artificial blood vessel inner layer fiber membrane with a thickness of about 1100μm was obtained;

[0050] S2, TPU with a molecular weight of 80,000 and a melt index of 10g / 10min was selected, dried at 85℃ for 5h to remove water in the raw material; after drying, the TPU particles were loaded into the FDM device and fixed on the clamp in the 3D printing device cabin, the nozzle temperature was set to 230℃, the printing platform was preheated to 55℃ to reduce the risk of warping deformation of the material during printing; a nozzle with a diameter of 0.35mm was selected. Using 3D printing, the slicing software was used to convert the anti-bending ring three-dimensional model into a printing path according to the anti-bending ring three-dimensional model; the anti-bending ring three-dimensional model was set to a ring height of 2.2mm, a width of 1.3mm, and a ring spacing of 2.5mm, and a continuous winding structure was used; the layer height was set to 0.09mm, the printing speed was 55mm / s, and the filling rate was 38%; the anti-bending ring was embedded on the surface of the artificial blood vessel inner layer fiber membrane in a spiral trajectory; during the printing process, the environmental temperature was maintained at 24℃ and the relative humidity was less than 48%; after the printing was completed, the device was naturally cooled to room temperature of 25℃, and an artificial blood vessel tube with anti-bending rings was obtained;

[0051] S3, PCL with a weight average molecular weight of 280,000 was added to THF, and a dipping solution (ultrasonic spraying solution) with a mass concentration of 20 wt% was prepared by magnetic stirring at 25°C for 12 h. The artificial blood vessel body with the anti-kinking ring was completely immersed in the dipping solution, and the dipping solution was allowed to fully penetrate into the gaps of the inner layer fiber membrane and the anti-kinking ring for 15 min. Subsequently, the artificial blood vessel was quickly taken out of the dipping solution and placed in a vacuum drying box with a vacuum degree of-0.09 MPa and a temperature of 30°C for rapid drying for 4 h. During the drying process, the THF solvent was rapidly volatilized, the inner layer fiber membrane of the artificial blood vessel was slightly dissolved, PCL was solidified on the surface and inside of the artificial blood vessel, a dense layer with a thickness of about 180 μm was formed, the anti-kinking ring was completely wrapped therein, the thickness of the inner layer fiber membrane was reduced from 1100 μm to about 850 μm due to partial fusion, and finally a puncture-resistant and anti-kinking artificial blood vessel with a total thickness of about 1030 μm and a dense layer was obtained.

[0052] The second aspect of the example provides a puncture-resistant and anti-kinking artificial blood vessel prepared by the preparation method of the puncture-resistant and anti-kinking artificial blood vessel.

[0053] Example 4

[0054] The first aspect of the example provides a preparation method of a puncture-resistant and anti-kinking artificial blood vessel, specifically:

[0055] S1, PU with a weight average molecular weight of 270,000 was added to DMF, and a spinning solution with a mass concentration of 18 wt% was prepared by stirring at a constant temperature of 50°C for 36 h at a rotation speed of 450 rad / min; the spinning receiving distance was set to 18 cm, the spinning environment temperature was controlled to be 35°C, the relative humidity was controlled to be 30%, the positive and negative voltages of the spinning were adjusted to +12 kV and-10 kV respectively, the flow rate of the feeding device was set to 1.0 mL / h, the rotation speed of the receiving mold was controlled to be 100 rad / min, and the moving speed of the spinning platform was 50 mm / s. The spinning solution was electrospun by an electrospinning process for 8 h to deposit on the surface of a metal receiving rod mold with an outer diameter of 6 mm, and an artificial blood vessel inner layer fiber membrane with a thickness of about 1000 μm was obtained.

[0056] S2, first dry the PET particles at 100°C for 6h to remove moisture; after drying, load the PET particles into the FDM device and fix them on the clamp in the 3D printing device cabin, set the nozzle temperature to 250°C, preheat the printing platform to 60°C to reduce the risk of warping deformation of the material during printing; select a nozzle with a diameter of 0.4mm. Using 3D printing, use slicing software to convert the anti-bending ring three-dimensional model into a printing path according to the anti-bending ring three-dimensional model. The anti-bending ring three-dimensional model is set to a ring height of 2.0mm, a width of 1.2mm, and a ring spacing of 2.0mm. A continuous winding structure is used, and the layer height is set to 0.1mm, the printing speed is 60mm / s, and the filling rate is 40%. The anti-bending ring is embedded in the spiral track on the surface of the inner layer of the artificial blood vessel. During printing, the ambient temperature is maintained at 25°C and the relative humidity is less than 50%. After printing, the temperature is naturally cooled to room temperature of 25°C, and the artificial blood vessel with anti-bending ring is obtained.

[0057] S3, select DMF as the impregnating liquid, immerse the artificial blood vessel with anti-bending ring in the impregnating liquid, and soak for 20min to fully penetrate into the gap between the inner layer of the fiber membrane and the anti-bending ring. Then, quickly take out the artificial blood vessel from the impregnating liquid and place it in a well-ventilated environment for natural drying for 12h. During the drying process, the solvent gradually volatilizes, slightly dissolves the surface of the inner layer of the artificial blood vessel, promotes the formation of a dense structure on the surface of the inner layer of the fiber membrane, forms a dense layer with a thickness of about 150μm, and completely wraps the anti-bending ring. The thickness of the inner layer of the fiber membrane is reduced to about 750μm due to the action of the solvent, and finally the overall thickness of the anti-puncture and anti-bending artificial blood vessel wrapped with PET is about 900μm.

[0058] The second aspect of the example provides an anti-puncture and anti-bending artificial blood vessel prepared by the preparation method of the anti-puncture and anti-bending artificial blood vessel.

[0059] Comparative Example 1

[0060] The specific implementation of the example is the same as that of Example 4, except that:

[0061] The specific implementation of step S2 is: fix the inner layer of the artificial blood vessel and the mold on the hot melt extrusion device, and select PET as the anti-bending ring raw material. Set the barrel temperature of the hot melt extrusion device to 280°C, which is higher than the conventional processing temperature of PET, to speed up the extrusion efficiency. Use a circular die with a diameter of 3mm, and set the extrusion speed to 15mm / s. The extruded PET strip is wound around the surface of the artificial blood vessel to form an anti-bending ring structure with a height of 2.0mm, a width of 1.2mm, and a ring spacing of 2.0mm. Due to the high temperature of the hot melt, the contact area between the inner layer of the fiber membrane and the PET appears to be damaged by fiber melting and carbonization during the extrusion process, and the surface becomes rough and uneven.

[0062] Comparative Example 2

[0063] The first aspect of the example provides a method for preparing a puncture-resistant and kink-resistant artificial blood vessel, specifically:

[0064] S1, PU with a weight average molecular weight of 300,000 and PLA with a weight average molecular weight of 250,000 were mixed in a mass ratio of 3:2 and added to a mixed solvent of TFA and DCM in a volume ratio of 5:1. The spinning solution with a mass concentration of 16wt% was prepared by stirring at a constant temperature of 45°C in a water bath environment at a speed of 400 rad / min for 40h. The spinning receiving distance was set to 16cm, the spinning environment temperature was controlled to 33°C, the relative humidity was 25%, the positive and negative voltages of the spinning were adjusted to +11kV and -9kV respectively, the flow rate of the feeding device was set to 0.9mL / h, the receiving mold speed was controlled at 90rad / min, and the spinning platform moving speed was 45mm / s. The spinning solution was electrospun for 9h by electrospinning process and deposited on the surface of a metal receiving rod mold with an outer diameter of 5.8mm to obtain an artificial blood vessel inner layer fiber membrane with a thickness of about 1100μm;

[0065] S2, TPU with a molecular weight of 80,000 and a melt index of 12g / 10min was first dried at 85°C for 5h to fully remove the water in the raw material. After drying, the TPU particles were loaded into the FDM device and fixed on the clamp in the cabin of the 3D printing device. The nozzle temperature was set to 230°C, and the printing platform was preheated to 55°C to reduce the risk of warping deformation of the material during printing. A nozzle with a diameter of 0.35mm was selected. Using 3D printing, the slicing software was used to convert the anti-kink ring three-dimensional model into a printing path according to the anti-kink ring three-dimensional model. The anti-kink ring three-dimensional model was set to a ring height of 2.2mm, a width of 1.3mm, and a ring spacing of 2mm. The continuous winding structure was used, and the layer height was set to 0.09mm, the printing speed was 55mm / s, and the filling rate was 38%. The anti-kink ring was embedded on the surface of the artificial blood vessel inner layer fiber membrane in a spiral trajectory. During the printing process, the environmental temperature was maintained at 24°C and the relative humidity was less than 48%. After printing, the device was naturally cooled to room temperature of 25°C to obtain an artificial blood vessel with anti-kink rings;

[0066] S3, the spinning solution prepared in S1 is diluted with a mixed solvent of TFA and DCM in a volume ratio of 5:1 to prepare an ultrasonic spraying solution with a mass concentration of 2wt%; the artificial blood vessel body with the anti-kinking ring is fixed on the rotating support of the ultrasonic spraying device, the ultrasonic spraying frequency is set to 40 kHz, the spraying distance is 15 cm, the spraying time is 4 h, and the solution supply speed is 1.05 mL / h. Start the device, and in the process of uniform rotation of the artificial blood vessel, the ultrasonic nozzle atomizes and uniformly sprays the solution on the surface of the tube body. After spraying is completed, the artificial blood vessel is placed in a vacuum drying box with a vacuum degree of -0.09 MPa and a temperature of 30°C for drying for 4 h, so that the solvent volatilizes, and a dense layer with a thickness of about 300 μm is formed on the surface of the artificial blood vessel, while the anti-kinking ring is completely wrapped therein, the thickness of the inner layer of the fiber membrane is reduced to about 800 μm due to partial fusion, and finally a puncture-resistant and anti-kinking artificial blood vessel with a total thickness of about 1100 μm and a dense layer wrapping the anti-kinking ring is obtained.

[0067] The second aspect of the present example provides a puncture-resistant and anti-kinking artificial blood vessel prepared by the preparation method of the puncture-resistant and anti-kinking artificial blood vessel.

[0068] Comparative Example 3

[0069] The specific implementation of the present example is the same as that of Comparative Example 2, except that the specific implementation of S3 is as follows:

[0070] The spinning solution prepared in S1 is diluted with a mixed solvent of TFA and DCM in a volume ratio of 5:1 to prepare an ultrasonic spraying solution with a mass concentration of 2wt%; the artificial blood vessel body with the anti-kinking ring is fixed on the rotating support of the ultrasonic spraying device, the ultrasonic spraying frequency is set to 40 kHz, the spraying distance is 15 cm, the spraying time is 1.5 h (4 h in Comparative Example 2), and the solution supply speed is 1.05 mL / h. Start the device, and in the process of uniform rotation of the artificial blood vessel, the ultrasonic nozzle atomizes and uniformly sprays the solution on the surface of the tube body. After spraying is completed, the artificial blood vessel is placed in a vacuum drying box with a vacuum degree of -0.09 MPa and a temperature of 30°C for drying for 4 h, so that the solvent volatilizes, and a dense layer with a thickness of about 40 μm is formed on the surface of the artificial blood vessel. Due to the short spraying time, the contact time of the solvent with the inner layer of the fiber membrane is limited, and the inner layer of the fiber membrane is less dissolved and fused, with a thickness of about 900 μm. Finally, a puncture-resistant and anti-kinking artificial blood vessel with a total thickness of about 940 μm is obtained.

[0071] The second aspect of the present example provides a puncture-resistant and anti-kinking artificial blood vessel prepared by the preparation method of the puncture-resistant and anti-kinking artificial blood vessel, and a schematic diagram of the product is shown in Figure 3 As can be seen from the figure, due to the thin dense layer, a large amount of liquid will leak out under high pressure of the artificial blood vessel.

[0072] Comparative Example 4

[0073] The specific embodiment of this example is the same as Comparative Example 2, except that:

[0074] 1. The anti-bending ring three-dimensional model is set to a ring body height of 2.2 mm, a width of 1.3 mm, and a ring spacing of 3.5 mm;

[0075] 2. The specific embodiment of S3 is: the spinning solution prepared in S1 is diluted with THF to prepare an ultrasonic spraying solution with a mass concentration of 2wt%; the artificial blood vessel body with anti-bending rings is fixed on the rotating support of the ultrasonic spraying equipment, the ultrasonic spraying frequency is set to 40 kHz, the spraying distance is 15 cm, the spraying time is 10 h, and the solution supply speed is 1.05 mL / h. Start the equipment, and in the process of uniform rotation of the artificial blood vessel, the ultrasonic nozzle atomizes and uniformly sprays the solution on the surface of the tube body. After spraying is completed, the artificial blood vessel is placed in a vacuum drying box with a vacuum degree of -0.09 MPa and a temperature of 30°C for drying for 4 h, so that the solvent volatilizes and the inner layer fiber membrane surface is slightly dissolved, forming a dense layer with a thickness of about 400 μm on the surface of the artificial blood vessel, and the anti-bending ring is completely wrapped therein. The thickness of the inner layer fiber membrane is reduced to 600 μm due to excessive dissolution, and a puncture-resistant anti-bending artificial blood vessel with a thickness of about 1000 μm is obtained.

[0076] In this example, due to the excessive ring spacing and the excessive thickness of the dense layer, the compliance of the artificial blood vessel decreases, and the mechanical properties and puncture sealing cannot be balanced. Excessive ring spacing leads to bending stress concentration, and the kink diameter increases significantly, and the lumen is easily deformed and blocked. Although the excessive thickness of the dense layer does not directly lead to leakage, the anti-bending ring cannot elastically slip away from the needle tip during puncture, the puncture resistance increases, and the needle hole closure is delayed, increasing the risk of blood leakage.

[0077] Comparative Example 5

[0078] The specific embodiment of this example is the same as Example 2, except that:

[0079] 1. The anti-bending ring three-dimensional model is set to a ring body height of 1.5 mm, a width of 1.0 mm, and a ring spacing of 1.0 mm;

[0080] 2. The specific embodiment of S3 is the same as S3 of Comparative Example 3.

[0081] In this example, due to the ring spacing <1.7 mm, the anti-bending rings are too dense to hinder the puncture path, although they can resist bending well, but the too dense rings will cause the tube body to be too rigid, the compliance will decrease significantly, and the dynamic radial compliance is 0.05%. At the same time, due to the excessive thinness of the dense layer, which is less than 100 μm, an effective anti-leakage barrier cannot be formed, the needle hole is not fully closed after puncture, the leakage pressure threshold is not up to standard, and the high-frequency puncture requirement in clinical practice cannot be met.

[0082] The raw material information used in Examples 1-4 and Comparative Examples 1-2 is shown in Table 1, and other component raw materials are ordinary commercially available products unless otherwise specified.

[0083] Table 1

[0084]

[0085]

[0086] Performance test

[0087] 1. Test object: artificial blood vessels prepared from Example 2 and Comparative Examples 2-5

[0088] 2. Test items: dense layer thickness, bending resistance ring spacing, artificial blood vessel dynamic radial compliance, leakage under 16 kPa water pressure, puncture resistance, and experimental results are shown in Table 2.

[0089] Table 2

[0090]

[0091]

[0092] Note: Compliance is an important mechanical property of artificial blood vessels that measures the elastic deformation ability of artificial blood vessels under blood pressure changes. Its core meaning refers to the ability of artificial blood vessels to expand and contract under blood vessel pressure fluctuations, similar to the "elasticity" performance of natural blood vessels. The thicker the dense layer, the lower the compliance, i.e., the weaker the ability to expand and contract under pressure. The test standard for compliance in this application is YY / T 0500-2021.

[0093] Experimental result analysis:

[0094] Regarding Comparative Example 2: A dense layer thickness of more than 200 μm can cause two problems:

[0095] 1. Puncture resistance increases to the clinical critical value, increasing the risk of operation;

[0096] 2. Compliance drops sharply, destroying the mechanical matching of the blood vessel.

[0097] The excessive thickness of the dense layer increases the rigidity of the material, and the bending resistance ring cannot elastically slip to avoid the needle tip during puncture, and the resistance increases from 2.0 N to 3.2 N, close to the upper limit of clinical acceptance (3 N), significantly increasing the difficulty of operation.

[0098] Regarding Comparative Example 3: The product meets the bending resistance performance standard, but the dense layer is too thin, resulting in insufficient interfacial bonding strength, and the bending resistance ring is easily separated from the tube body. In addition, even if the ring spacing is optimized, when the dense layer thickness is <100 pm, molecular-level bonding cannot be achieved through polymer interpenetrating networks, there is a risk of delamination during long-term use, and the blood leakage rate after puncture is significantly increased.

[0099] Regarding Comparative Example 4: The compliance is only 0.02%, which is significantly lower than the 1.8% of Example 2. This is because the dense layer is too thick (400 pm), forming a "rigid shell" that completely restricts the elastic deformation of the blood vessel wall; at the same time, the ring spacing is too large (3.5 mm), causing the bending resistance ring to be unable to evenly disperse stress, further exacerbating the stiffness of the tube body. At the same time, the low compliance of Comparative Example 4 results in poor mechanical matching between the artificial blood vessel and the natural blood vessel, leading to abnormal blood flow dynamics such as turbulence, pressure fluctuations, etc., increasing the risk of thrombosis, and possibly causing vascular access dysfunction during long-term use.

[0100] The overall water permeability, puncture resistance, initial strength, and residual strength after repeated puncture of the artificial blood vessels of Comparative Example 4 and Comparative Example 1 were compared. The experimental results are shown in Table 3.

[0101] Table 3

[0102]

[0103] The experimental results are analyzed as follows:

[0104] 1. In the overall water permeability test, the artificial blood vessels prepared in Example 4 and Comparative Example 1 were tested under a pressure of 16 kPa according to the YY0500-2021 standard. The artificial blood vessel prepared in Example 4 showed excellent water tightness during the entire test. When placed in the test device and subjected to a pressure of 16 kPa, the surface of the artificial blood vessel remained dry at all times, with no signs of water leakage. Through precise measurement instruments, the water permeation amount was 0 mL / min. This is mainly due to the reasonable structural design and excellent material properties of the artificial blood vessel: the inner layer composite fiber membrane structure of Example 4 is dense, with fibers tightly interwoven; the 3D-printed bending resistance ring is well combined with the inner layer fiber membrane and the dense layer, with seamless connection between the layers, effectively blocking the permeation of water, preventing blood leakage and other problems during clinical use, and ensuring the safety and reliability of the artificial blood vessel.

[0105] On the other hand, the artificial blood vessel of Comparative Example 1 behaved quite differently under the same test conditions. When the pressure reached 16 kPa, a large number of water spouts appeared on the surface of the artificial blood vessel, and water continuously seeped out from the contact position between the bending resistance ring and the inner layer blood vessel, as well as the damaged fiber membrane. The specific situation is shown in Figure 2. Figure 2The water permeation amount continued to increase over time, and eventually a water permeation amount of up to 8.2 mL / min was measured. Due to the damage to the inner layer fiber membrane caused by the hot melt extrusion process, interface defects existed at the position where the anti-kinking ring contacted the inner layer blood vessel, and the dense layer could not effectively cover these weak areas, forming a large number of water permeation channels. Water quickly permeated through these gaps and holes, not only seriously affecting the sealing performance of the artificial blood vessel, but also possibly causing a series of clinical complications such as infection and thrombosis, making it difficult for the artificial blood vessel to meet the actual use requirements.

[0106] 2. In the test of the artificial blood vessel prepared in Example 4, there was no obvious jamming phenomenon when the puncture needle contacted the surface of the blood vessel. Due to the complete and uniform structure of the inner layer composite fiber membrane, as well as the tight and stable combination of the 3D printed anti-kinking ring with each layer of material, the puncture needle could penetrate the artificial blood vessel relatively smoothly. The entire puncture process was smooth, and the resistance change of the puncture needle during the process was stable. According to the records and calculations of the test equipment, the average puncture resistance finally obtained was only 2.0 N, which was within the clinically acceptable range (not more than 3 N). This indicates that the artificial blood vessel of Example 4 performs well in terms of puncture performance, and can meet the requirements of smoothness and safety in clinical operation.

[0107] In contrast, the artificial blood vessel of Comparative Example 1 performed quite differently during the puncture test. When the puncture needle contacted the surface of the artificial blood vessel, it immediately felt a significant resistance, and it was difficult for the puncture needle to penetrate smoothly. Due to the melting and carbonization damage to the inner layer fiber membrane caused by the hot melt extrusion process, the surface became rough and uneven, and there were serious interface defects at the position where the anti-kinking ring contacted the inner layer blood vessel, and the dense layer could not effectively cover them. During the puncture process, these structural defects caused the resistance of the puncture needle to increase irregularly and significantly, and the puncture needle showed obvious jamming and deviation phenomena, and the operator had to exert more force to push the puncture needle forward. Finally, the average puncture resistance recorded by the test equipment was as high as 4.5 N, far exceeding the clinically acceptable range, which made the artificial blood vessel increase the difficulty of operation and increase the risk of surgery, seriously affecting its use performance.

[0108] Example 4 used 3D printing to prepare the anti-kinking ring, with precise control of process parameters, without causing damage to the inner layer fiber membrane of the artificial blood vessel, and the combination of the layers of material was tight, which could disperse external force during puncture and effectively reduce the puncture resistance. The hot melt extrusion process of Comparative Example 1 caused damage to the structure of the inner layer fiber membrane due to the high temperature, and the interface between the anti-kinking ring and the inner layer blood vessel was poorly combined, so that the artificial blood vessel could not form a stable support structure during the puncture process, and a large amount of resistance was concentrated in the contact area between the puncture needle and the blood vessel, resulting in a significant increase in the puncture resistance.

[0109] 3. After completing the basic performance test, further develop the strength determination experiment after repeated puncture. Select the flat area of the middle part of the artificial blood vessel prosthesis, and mark a test range of 1 square centimeter. Use the clinically common 18G puncture needle, and according to the requirement that the puncture process should be limited within 1 / 3 of the periphery of the vascular prosthesis, 24 puncture operations are performed on the area, and the puncture speed is kept at 10mm / min.

[0110] During the repeated puncture process, the artificial blood vessel prepared by Example 4 showed strong anti-puncture damage ability due to good structural stability and material performance. After each puncture, only a small pinhole appeared on the surface of the artificial blood vessel, and there was no large-area tearing of the fiber membrane, no displacement of the anti-bending ring, etc. After 24 punctures, according to the YY0500-2021 standard, the strength test was performed, and the strength was measured to be 13.8N, compared with the initial strength of 15N, the strength retention rate was 92%. This shows that the artificial blood vessel can still maintain a high structural strength after repeated puncture, meeting the requirements of clinical use for durability.

[0111] The artificial blood vessel of Comparative Example 1 had a problem of too much puncture resistance due to structural defects caused by the hot melt extrusion process at the first puncture. During the repeated puncture process, the damaged fiber membrane and the interface defect of the anti-bending ring were further deteriorated. With the increase of the number of punctures, the fiber membrane around the pinhole began to crack and peel off, and the gap between the anti-bending ring and the fiber membrane expanded. When the strength test was performed after 24 punctures, the strength was measured to be only 6.75N, compared with the initial strength of 15N, the strength retention rate was only 45%. This result shows that the structure of the artificial blood vessel is severely damaged after repeated puncture, the strength decreases sharply, and it is difficult to withstand various mechanical actions in subsequent clinical use, which cannot guarantee the safety of use.

[0112] Through the strength determination experiment after repeated puncture, it is more directly reflected that the process of Example 4 has advantages in preparing high-performance artificial blood vessels, and the hot melt extrusion process in Comparative Example 1 causes structural damage, which seriously affects the durability and reliability of the artificial blood vessel.

[0113] In the preparation of the puncture-resistant and anti-bending artificial blood vessel described in the present application, ultrasonic spraying (Examples 1-2) and solution immersion (Examples 3-4) are two core methods for preparing a dense layer. Both can achieve the wrapping of the anti-bending ring and the formation of the dense layer, but there are significant differences in process controllability, structural precision and performance stability. Among them, the ultrasonic spraying process shows higher precision and advancement. The specific comparison is as follows:

[0114] I. Process control precision

[0115] Ultrasonic spraying converts the spraying liquid into tiny droplets through ultrasonic atomization technology, combined with precisely controlled parameters such as feeding speed, receiving distance, receiving rod speed, air flow pressure, and environmental temperature and humidity, which can realize the uniform deposition of droplets on the surface of the pipe body. The coordinated control of the atomization process and deposition trajectory can accurately match the spiral structure of the anti-bending ring, ensuring the sufficient filling of the dense layer in the gap between the ring body and the inner layer of the fiber membrane, and avoiding local over-thickness or over-thin.

[0116] Solution immersion, on the other hand, relies on the soaking time of the pipe body in the immersion liquid and the drying rate, and realizes the surface dissolution of the fiber membrane and the formation of the dense layer through natural solvent penetration. This process is greatly affected by liquid convection and surface tension differences, which can easily lead to uneven thickness of the dense layer, especially in the contact interface between the anti-bending ring and the inner layer of the fiber membrane, which may not be fully covered, making it difficult to achieve precise control at the microscale.

[0117] II. Dense layer structure and interface bonding

[0118] In ultrasonic spraying, atomized droplets can uniformly penetrate into the pores of the inner layer of the fiber membrane and the gaps of the anti-bending ring, and after local dissolution of the solvent and the surface of the fiber membrane, a molecular-level interpenetrating network is formed with the polymers in the spraying liquid, reducing the interfacial porosity of the dense layer and the inner layer of the fiber membrane to below 10%, significantly improving the bonding strength. At the same time, its controllable deposition rate can ensure the stable thickness of the dense layer, forming a continuous and non-porous barrier structure.

[0119] Although solution immersion can form a dense layer by dissolving the surface of the fiber membrane with a solvent, the concentration of the solvent decreases over time during the soaking process, which can easily lead to differences in the degree of dissolution between the outer layer and the inner layer, resulting in a gradient structure of the dense layer with "dense outside and sparse inside", and the interface bonding strength is lower than that of the ultrasonic spraying process. In addition, the control of the thickness of the dense layer by immersion method depends on the soaking time, if the time is too short, the thickness will be insufficient, and if the time is too long, the inner layer of the fiber membrane may be excessively dissolved, damaging the structural integrity of the pipe body.

Claims

1. A method for producing a puncture-resistant and kink-resistant artificial blood vessel, characterized by comprising the steps of: The application relates to a puncture-resistant and bend-resistant artificial blood vessel and a preparation method thereof. ​ S1, a first high polymer is dissolved and stirred by using a first solvent to prepare a spinning solution; The spinning solution is deposited on the surface of a mold by an electrostatic spinning process to obtain an inner-layer fiber membrane of the artificial blood vessel; S2, a second high polymer is printed on the surface of the inner-layer fiber membrane of the artificial blood vessel in a spiral track according to a three-dimensional model of the bend-resistant ring by a 3D printing mode to obtain the artificial blood vessel body with the bend-resistant ring; S3, an ultrasonic spraying liquid or an immersion liquid is configured, then the ultrasonic spraying liquid is ultrasonic atomized and sprayed on the surface of the artificial blood vessel body with the bend-resistant ring, or the artificial blood vessel body with the bend-resistant ring is soaked in the immersion liquid, the surface of the inner-layer fiber membrane of the artificial blood vessel is slightly dissolved, meanwhile, the bend-resistant ring is completely wrapped in a dense layer, a dense layer with a thickness of 100-200 mu m is formed, and then drying treatment is carried out, so that the puncture-resistant and bend-resistant artificial blood vessel is obtained.

2. The method of producing a puncture-resistant and kink-resistant artificial blood vessel according to claim 1, characterized by, The first high polymer comprises at least one of polycaprolactone, polyurethane or polylactic acid.

3. The method of producing a puncture-resistant and kink-resistant vascular prosthesis according to claim 2, characterized by, The weight average molecular weight of the first high polymer is 100-350 thousand.

4. The method of producing a puncture-resistant and kink-resistant vascular prosthesis according to any one of claims 1 to 3, characterized in that, The first solvent comprises one or more of hexafluoroisopropanol, dimethyl sulfoxide, tetrahydrofuran, trifluoroacetic acid, dichloromethane or N, N-dimethylformamide.

5. The method for preparing the puncture-resistant and bend-resistant artificial blood vessel according to claim 1, characterized in that, In the electrostatic spinning process, the spinning receiving distance is set to 10-20 cm, the spinning environment temperature is controlled to be 25-40 DEG C, the relative humidity is 20-30%, the positive and negative electrode voltages of the spinning are respectively adjusted to +10 to +12 kV and -10 to -5 kV, the flow rate of the feeding device is set to 0.5-2.0 mL / h, the receiving mold rotating speed is 50-200 rad / min, and the spinning platform moving speed is 40-100 mm / s.

6. The method of claim 1, wherein the puncture-resistant, kink-resistant vascular graft is prepared by the steps of: The second high polymer comprises one or more of thermoplastic polyurethane elastomer, polylactic acid-hydroxyacetic acid copolymer or polyethylene terephthalate.

7. The method of claim 1, wherein the puncture-resistant, kink-resistant vascular graft is prepared by the steps of: In the 3D printing process, the ring body height of the three-dimensional model of the bend-resistant ring is set to 1-3 mm, the width is 1-2 mm, and the ring spacing is 1.7-2.5 mm.

8. The method of claim 1, wherein the puncture-resistant, kink-resistant vascular graft is prepared by the steps of: The raw material of the immersion liquid comprises one or more of hexafluoroisopropanol, dimethyl sulfoxide, tetrahydrofuran, trifluoroacetic acid, dichloromethane, N, N-dimethylformamide.

9. The method of claim 1, wherein the puncture-resistant, kink-resistant vascular graft is prepared by the steps of: In the ultrasonic atomized spraying, the feeding speed of the ultrasonic atomized spraying is set to 0.5-1 mL / h, the receiving distance is 1-5 cm, the receiving rod rotating speed is 50-200 rad / min, the environment temperature is controlled to be 25-30 DEG C, the relative humidity is 30-35%, the ultrasonic spraying airflow pressure is 0.1-0.2 MPa, the operation power is 1-2 W, and the ultrasonic atomized spraying time is 5-10 h.

10. A puncture-resistant and bend-resistant artificial blood vessel prepared by the preparation method of the puncture-resistant and bend-resistant artificial blood vessel according to any one of claims 1-9.

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