Fiber-based biomimetic polyurethane artificial blood vessels and their preparation methods

Abstract

This invention provides a fiber-based biomimetic polyurethane artificial blood vessel and its preparation method. The method involves using wet spinning technology to obtain filaments, which are then drawn and wound onto the surface of a metal tube to form a polyurethane fiber inner layer. A fabric middle layer is woven onto the surface of the polyurethane fiber inner layer. An organic solvent is sprayed onto the surface of the fabric middle layer, and an outer polyurethane fiber layer is prepared on the fabric surface using electrospinning technology. Finally, after curing and demolding, the fiber-based biomimetic polyurethane artificial blood vessel is obtained. This invention combines wet spinning, weaving, and electrospinning technologies to achieve integrated preparation of polyurethane artificial blood vessels. The resulting artificial blood vessel is of high quality, with a tightly bonded three-layer fiber-based structure that maximally mimics the three-layer structure of natural blood vessels. The inner layer provides excellent compliance, the fabric layer increases the blood vessel's impermeability and sutureability, and the outer layer effectively prevents vascular delamination and promotes endothelialization. Furthermore, the preparation method is environmentally friendly and pollution-free, with a short process flow, making it suitable for continuous industrial production.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and in particular to a fiber-based biomimetic polyurethane artificial blood vessel and its preparation method. Background Technology

[0002] The global morbidity and mortality rates of cardiovascular disease (CVD) are very high. Nearly one-third of patients are unable to use their own blood vessels due to vascular aging, disease, injury, or other reasons. Furthermore, the length and number of autologous transplanted vessels are very limited. In such cases, artificial blood vessels become a good option. Artificial blood vessels can replace and reshape damaged natural blood vessels, used for vascular replacement, bypass surgery, and fistula creation. Currently, two types of polymer blood vessels used clinically are polyester (PET) vessels and polytetrafluoroethylene (ePTFE) vessels, which can be used as large-diameter (inner diameter greater than 6mm) vascular stents for aortic aneurysm repair and aortic coarctation. However, because polymer material vascular stents are much harder than natural blood vessels, have a rough surface, and are highly hydrophobic, they are prone to poor interaction with vascular cells after implantation, activating the coagulation reaction to form thrombi and cause vascular blockage. Although polyester (PET) and polytetrafluoroethylene (ePTFE) blood vessels have good mechanical properties, they do not match the mechanical properties of natural blood vessels, which can easily cause blood flow disturbances at the anastomosis site and weaken the endothelialization effect. At the same time, polyester (PET) and polytetrafluoroethylene (ePTFE) blood vessels have poor elasticity and poor ability to imitate the stress and strain characteristics of natural blood vessels, resulting in low compliance.

[0003] To address the aforementioned issues, an invention patent (application number CN 20161113399.X) discloses a three-layer artificial vascular stent mimicking natural blood vessels and its preparation method. Using a biocompatible polymer material as a precursor, electrospinning is employed to create the inner and outer layers of the three-layer artificial vascular stent, providing good biocompatibility. A fibrous membrane with good mechanical properties is prepared using electrospinning, serving as the intermediate mechanical support layer of the three-layer artificial vascular stent. The prepared three-layer artificial vascular stent exhibits good biocompatibility, and the three-layer structure improves the stent's mechanical properties to some extent. However, the poor bonding strength of all three layers, achieved through electrospinning, results in poor deformation resistance and durability of the artificial vascular stent. Furthermore, the use of electrospinning technology leads to poor elasticity in the stent, making it difficult for the nanofiber membrane to contract and expand with the pressure in the lumen under complex blood pressure conditions. This reduces vascular compliance and increases the risk of thrombosis and blockage.

[0004] Currently, polyurethane has become a popular research subject in various fields. Its high elasticity and wear resistance, resulting from its soft and hard segment structure, make it widely used in the preparation of high-elasticity clothing and wear-resistant coatings. However, its high elasticity limits its application in the field of engineered vascular stents. This is because its high elasticity results in a low recovery rate, making it difficult for polyurethane vascular stents to contract and expand under complex blood pressure conditions. At the same time, polyurethane also faces problems such as poor endothelialization, poor sutureability, and low strength.

[0005] In view of this, it is necessary to design an improved fiber-based biomimetic polyurethane artificial blood vessel and its preparation method to solve the above problems. Summary of the Invention

[0006] The purpose of this invention is to provide a fiber-based biomimetic polyurethane artificial blood vessel and its preparation method. By combining wet spinning, weaving and electrospinning technologies, the polyurethane artificial blood vessel can be prepared in an integrated manner, so that the three-layer structure of the artificial blood vessel is tightly combined, which can imitate the structural characteristics of natural blood vessels to the greatest extent. Moreover, the preparation method is environmentally friendly and pollution-free, with a short process flow, and is suitable for continuous industrial production.

[0007] To achieve the above-mentioned objectives, this invention provides a method for preparing a fiber-based biomimetic polyurethane artificial blood vessel, comprising the following steps:

[0008] S1. Mix polyurethane particles with solvent and degas to obtain spinning solution A and spinning solution B respectively;

[0009] S2. Using a wet spinning device, the spinning solution A from step S1 is extruded in a coagulation bath and drawn and wound onto a metal tube to obtain a polyurethane fiber inner layer; a fabric is then woven on the outer surface of the polyurethane fiber inner layer to obtain a fabric middle layer.

[0010] S3. In step S2, an organic solvent is sprayed onto the surface of the intermediate layer of the fabric, and the spinning solution B in step S1 is electrospinned to prepare a nanofiber membrane on the surface of the intermediate layer of the fabric as the outer layer of polyurethane fiber. After being soaked in deionized water and completely cured, the fiber-based biomimetic polyurethane artificial blood vessel is obtained after separation from the metal tube.

[0011] As a further improvement of the present invention, in step S2, the intermediate layer of the fabric is woven with yarn in a stretched state, and the fineness of the yarn is 360 to 500 denier.

[0012] As a further improvement of the present invention, in step S2, the coagulation bath is a mixed solution of water and ethanol, and the mass of the ethanol accounts for 10% to 20% of the total mass of the coagulation bath.

[0013] As a further improvement of the present invention, in step S1, the polyurethane mass percentage concentration of spinning solution A is 10% to 30%, and the polyurethane mass percentage concentration of spinning solution B is 5% to 15%; both spinning solution A and spinning solution B contain sodium heparin, and the mass percentage concentration of sodium heparin in spinning solution A or spinning solution B is 1% to 2%.

[0014] As a further improvement of the present invention, in step S2, the extrusion speed of the spinning solution A in the coagulation bath is 2-5 mL / min, the drawing and winding speed is 60-110 r / min, and the diameter of the metal tube is 2-10 mm.

[0015] As a further improvement of the present invention, in step S1, the solvent includes one of dimethylformamide, dimethyl sulfoxide, and dimethylacetamide; the solvents of spinning solution A and spinning solution B are of the same type.

[0016] As a further improvement of the present invention, in step S3, the organic solvent includes one of dimethylformamide, dimethyl sulfoxide, and dimethylacetamide; the organic solvent is of the same type as the solvent in spinning solution A and spinning solution B.

[0017] As a further improvement of the present invention, the raw material of the interlayer of the fabric includes one of spandex, polyester, and polytetrafluoroethylene; the weaving includes one of knitting, machine weaving, and braiding.

[0018] As a further improvement of the present invention, in step S3, the electrospinning technical parameters are as follows: extrusion speed is 1.0 to 2.0 mL / h, voltage is +12 to 25 kV, distance between needle and support is 10 to 20 cm, rotation speed is 500 to 1000 rpm, and spinning temperature is room temperature.

[0019] As a further improvement of the present invention

[0020] A fiber-based biomimetic polyurethane artificial blood vessel prepared by any one of the above methods includes a polyurethane fiber inner layer, a fabric middle layer, and a polyurethane fiber outer layer. The fabric middle layer is interwoven with the polyurethane fiber inner layer by weaving, and the polyurethane fiber outer layer is bonded to the fabric middle layer by an organic solvent.

[0021] The beneficial effects of this invention are:

[0022] 1. This invention provides a method for preparing a fiber-based biomimetic polyurethane artificial blood vessel. Highly oriented filaments are obtained using wet spinning technology and drawn and wound onto the surface of a metal tube to prepare a polyurethane fiber inner layer. A fabric intermediate layer is directly woven onto the surface of the polyurethane fiber inner layer using weaving technology. An organic solvent is then sprayed onto the surface of the fabric intermediate layer, and a nanofiber membrane is prepared on the surface of the fabric intermediate layer using electrospinning technology as the polyurethane fiber outer layer. The membrane is then completely cured in deionized water and separated from the metal tube to obtain the fiber-based biomimetic polyurethane artificial blood vessel. This invention combines wet spinning, weaving, and electrospinning technologies to achieve integrated fabrication of polyurethane artificial blood vessels. The resulting artificial blood vessels are of high quality, with each layer being a fiber-based structure and the three layers tightly bonded together, maximally mimicking the three-layer structure of natural blood vessels. The inner layer provides excellent compliance, the middle fabric layer increases the blood vessel's impermeability and sutureability, the outer layer increases the adhesion between the inner and middle layers, and effectively prevents blood vessel delamination. The micropores on the surface further promote endothelialization of cells. Moreover, the fabrication method is environmentally friendly and pollution-free, with a short process flow, making it suitable for continuous industrial production.

[0023] 2. This invention involves wet spinning to form filaments, which are then wound into a polyurethane fiber inner layer. During the wet spinning process, the solvent in the spinning solution exchanges with the water in the coagulation bath. This bidirectional diffusion exchange causes phase separation in the extruded spinning solution, resulting in solidification into filaments. The partially solidified fibers are then drawn and wound onto a metal tube, which facilitates fiber shaping on the tube surface. Furthermore, the drawing process improves both the fiber orientation and crystallinity, giving the drawn filaments strength and toughness, thus enhancing the sutureability of the artificial blood vessel. It also facilitates the direct weaving of the fabric interlayer onto the polyurethane fiber inner layer. Moreover, the polyurethane fiber inner layer obtained by winding the filaments onto the metal tube possesses a certain corrugated structure, which, combined with the excellent elasticity of polyurethane, significantly improves the compliance of the artificial blood vessel.

[0024] 3. This invention uses a woven fabric as the intermediate layer of the artificial blood vessel. On one hand, this greatly improves the mechanical properties and suture quality of the blood vessel; the dense fabric layer can also prevent stent leakage to a certain extent. Furthermore, the weaving technology allows for flexible modification of fabric parameters, including fabric density, porosity, and structure. The intermediate layer can be directly woven onto the surface of the polyurethane fiber inner layer, maximizing the advantages of the yarn and fabric structure, achieving controllable mechanical properties, and improving suture quality. Spraying an organic solvent before preparing the polyurethane fiber outer layer improves the compatibility and adhesion between the outer layer and the intermediate layer. Simultaneously, the organic solvent can penetrate into the inner layer of the polyurethane fiber through the pores between the fabric layers, further enhancing the bond between the inner and intermediate layers. This results in a high degree of integration in the prepared fiber-based biomimetic polyurethane artificial blood vessel, preventing delamination.

[0025] 4. The present invention discloses a fiber-based biomimetic polyurethane artificial blood vessel, wherein the outer layer is a nanoscale polyurethane fiber structure, and the dense nanofiber membrane layers are stacked. The micropores formed on the surface increase the specific surface area of ​​the artificial blood vessel, which can effectively increase cell adhesion. At the same time, the pores can also promote the transmission of information between cells, promote the secretion of extracellular matrix and growth factors, and improve the endothelialization effect. In addition, the pores of the nanomembrane layers are interconnected, and cells can migrate and grow to the middle layer through this channel, further promoting the endothelialization of the artificial blood vessel. Attached Figure Description

[0026] Figure 1 This is a microscopic electron microscope image of the fiber-based biomimetic polyurethane artificial blood vessel prepared in Example 1 of the present invention.

[0027] Figure 2 for Figure 1 A magnified microscopic image of a medium-fiber biomimetic polyurethane artificial blood vessel.

[0028] Figure 3 This is a schematic diagram illustrating the radial tensile strength test of the artificial blood vessel according to the present invention.

[0029] Figure 4 This is a fluorescence staining effect of the artificial blood vessel of Example 1 after 3 days of culture.

[0030] Figure Labels

[0031] 1-Inner layer of polyurethane fiber; 2-Middle layer of fabric; 3-Outer layer of polyurethane fiber. Detailed Implementation

[0032] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be described in detail below with reference to the accompanying drawings and specific embodiments.

[0033] It should also be noted that, in order to avoid obscuring the present invention with unnecessary details, only the structures and / or processing steps closely related to the present invention are shown in the accompanying drawings, while other details that are not closely related to the present invention are omitted.

[0034] Additionally, it should be noted that the terms “comprising,” “including,” or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0035] A method for preparing a fiber-based biomimetic polyurethane artificial blood vessel includes the following steps:

[0036] S1. Polyurethane particles are mixed with solvent and degassed to obtain spinning solution A and spinning solution B respectively; the mass percentage concentration of polyurethane in spinning solution A is 10% to 30%, and the mass percentage concentration of polyurethane in spinning solution B is 5% to 15%.

[0037] The degassing time is 10 to 20 hours. After the polyurethane particles are mixed with the solvent, the particles gradually swell and dissolve in the solution to form a mixed solution with many bubbles. The bubbles in the solution are removed by vacuum pumping. The purpose of degassing is to form a uniform wet spinning solution, minimize bubbles in the later spinning process, and reduce the breakage of the yarn.

[0038] S2. Using a wet spinning device, the spinning solution A from step S1 is extruded in a coagulation bath and drawn and wound onto a metal tube to obtain a polyurethane fiber inner layer; a fabric is then woven onto the outer surface of the polyurethane fiber inner layer to obtain a fabric middle layer; wherein, the extrusion speed of the spinning solution A in the coagulation bath is 2-5 mL / min, the drawing and winding speed is 60-110 r / min, and the diameter of the metal tube is 2-10 mm;

[0039] S3. In step S2, an organic solvent is sprayed onto the surface of the fabric intermediate layer, and the spinning solution B in step S1 is electrospinned to prepare a nanofiber membrane on the surface of the fabric intermediate layer as the outer layer of polyurethane fiber. After being soaked in deionized water and completely cured, the fiber-based biomimetic polyurethane artificial blood vessel is obtained after being separated from the metal tube.

[0040] Spraying organic solvents before preparing the outer layer of polyurethane fibers can improve the compatibility and adhesion between the outer layer of polyurethane fibers and the middle layer of the fabric. At the same time, the organic solvents can penetrate into the inner layer of polyurethane fibers through the pores between the fabrics, further improving the adhesion between the inner layer and the middle layer. This results in a high degree of integration of the prepared fiber-based biomimetic polyurethane artificial blood vessel and prevents delamination.

[0041] This preparation method combines wet spinning, weaving, and electrospinning techniques to achieve integrated fabrication of polyurethane artificial blood vessels. The resulting artificial blood vessels are of high quality, with each layer being a fiber-based structure and the three layers tightly bonded together, maximally mimicking the three-layer structure of natural blood vessels. The inner layer of the artificial blood vessel provides excellent compliance, the middle fabric layer increases the blood vessel's impermeability and sutureability, the outer layer increases the adhesion between the inner and middle layers, and effectively prevents blood vessel delamination. The micropores on the surface further promote endothelialization of cells. Moreover, the preparation method is environmentally friendly and pollution-free, with a short process flow, making it suitable for continuous industrial production.

[0042] Specifically, in step S2, during the weaving of the interlayer fabric, the yarn is woven under tension, and the yarn fineness is 360–500 denier (D). The raw material for the interlayer fabric includes one of spandex, polyester, and polytetrafluoroethylene; the weaving includes one of knitting, machine weaving, and braiding; preferably, the raw material is spandex, the weaving is knitting, and the yarn fineness is 300–400 denier. Thus, using spandex and other fibers with a woven structure to form the interlayer fabric of the artificial blood vessel can greatly improve the mechanical properties and suture quality of the blood vessel, and the dense fabric layer can also prevent stent leakage to a certain extent. Furthermore, the weaving technology allows for flexible modification of fabric parameters, including fabric density, porosity, and structure, and the interlayer fabric can be directly woven onto the surface of the polyurethane fiber inner layer, maximizing the advantages of the yarn and fabric structure, achieving controllable mechanical properties, and improving suture quality.

[0043] In the wet spinning process, the solvent in the spinning solution exchanges with the water in the coagulation bath. This bidirectional diffusion exchange causes phase separation in the extruded spinning solution, thus solidifying it into filaments. The incompletely solidified fibers are then drawn and wound onto a metal tube, which facilitates fiber shaping on the tube surface. Furthermore, the drawing process improves both the fiber orientation and crystallinity, resulting in filaments with sufficient strength and toughness. This enhances the sutureability of artificial blood vessels and facilitates the direct weaving of the intermediate layer onto the polyurethane fiber inner layer. The polyurethane fiber inner layer, obtained by winding the filaments onto the metal tube, also possesses a corrugated structure, which, combined with the excellent elasticity of polyurethane, significantly improves the compliance of the artificial blood vessel.

[0044] Specifically, in step S2, the coagulation bath is a mixed solution of water and ethanol, with the ethanol accounting for 10% to 20% of the total mass of the coagulation bath, preferably 15% to 20%. Adding ethanol to the coagulation bath can regulate the ion exchange rate between the solvent in the spinning solution and the coagulation bath, slowing down the solidification rate of the filament. This allows the drawn filament to remain viscoelastic after leaving the coagulation bath. After being wound onto the steel tube, the coils can be tightly bonded together through the uncured solution, forming a dense inner layer structure.

[0045] In step S1, both spinning solution A and spinning solution B contain sodium heparin, and the mass percentage concentration of sodium heparin in spinning solution A or spinning solution B is 1% to 2%, preferably 1%. Mixing sodium heparin with the solvent in a one-step process can achieve long-term effective anticoagulation of blood vessels. Adding sodium heparin to spinning solution A and spinning solution B can effectively improve the antithrombotic properties of polyurethane materials. Sodium heparin can bind with prothrombin in the blood to form a complex, inhibiting thrombin formation, thereby interrupting the thrombin-linked reaction and reducing the probability of vascular blockage.

[0046] Specifically, in step S1, the solvent includes one of dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and dimethylacetamide (DMAC); the solvents in spinning solution A and spinning solution B are the same. In step S3, the organic solvent includes one of dimethylformamide, dimethyl sulfoxide, and dimethylacetamide; and the organic solvent sprayed on the intermediate layer of the fabric is the same as the solvents in spinning solution A and spinning solution B. This improves the compatibility between the layers of the artificial blood vessel, ensuring that the nanofibers ejected from the needle adhere tightly to the intermediate layer of the fabric, effectively increasing the adhesion and connection between the outer and middle layers, and preventing delamination of the artificial blood vessel in the later stages.

[0047] Preferably, in step S1, the polyurethane mass percentage concentration of spinning solution A is 18%–20%, and the polyurethane mass percentage concentration of spinning solution B is 12%–14%; the degassing time is preferably 12–15 hours. In step S2, the extrusion speed is 3–4 mL / min, the winding speed is 90–100 r / min, and the diameter of the metal tube is 3–6 mm. In step S3, the spraying speed is 3–20 mL / min, preferably 3–5 mL / min; the curing time is 2–8 hours, preferably 4–8 hours.

[0048] In step S3, the electrospinning technical parameters are as follows: extrusion speed of 1.0–2.0 mL / h, voltage of +12–25 kV, distance between needle and support of 10–20 cm, rotation speed of 500–1000 rpm, and spinning temperature of room temperature. Preferably, the extrusion speed is 1.5–2.0 mL / h, voltage of +15–20 kV, distance between needle and support of 15–17 cm, and rotation speed of 500–800 rpm.

[0049] In some specific embodiments, in step S1, the polyurethane particles are mixed with the solvent by stirring for 10 to 15 hours at room temperature; the stirring speed is 100 to 300 r / min, preferably for 12 to 14 hours at 200 to 250 r / min.

[0050] In some specific embodiments, in step S1, the polyurethane particles can be one of TPU AC-4075A, PC-3575A, and PC-3572D, preferably TPU AC-4075A, and the spinning solution is prepared in combination with dimethylformamide as a solvent.

[0051] Please see Figures 1-2As shown, a fiber-based biomimetic polyurethane artificial blood vessel comprises a polyurethane fiber inner layer 1, a fabric intermediate layer 2, and a polyurethane fiber outer layer 3. The fabric intermediate layer 2 is interwoven with the polyurethane fiber inner layer 1 by a weaving process, and the polyurethane fiber outer layer 3 is bonded to the fabric intermediate layer 2 by an organic solvent. This fiber-based biomimetic polyurethane artificial blood vessel of the present invention features an outer layer of nanoscale polyurethane fiber structure. The dense nanofiber membrane layers are stacked, and the micropores formed on the surface increase the specific surface area of ​​the artificial blood vessel, effectively increasing cell adhesion. Simultaneously, the pores can promote cell-to-cell communication, promote the secretion of extracellular matrix and growth factors, and improve endothelialization. Furthermore, the interconnected pore sizes of the nanomembrane layers allow cells to migrate and grow into the intermediate layer through these channels, further promoting endothelialization of the artificial blood vessel.

[0052] Example 1

[0053] This embodiment provides a fiber-based biomimetic polyurethane artificial blood vessel and its preparation method, including the following steps:

[0054] S1. Dissolve 18g of TPU AC-4075A polyurethane particles and 1g of heparin sodium in 81g of dimethylacetamide solution, stir at room temperature for 12h at a speed of 200r / min, and then degas under vacuum for 12h to obtain a uniform spinning solution A; Dissolve 12g of TPUAC-4075A polyurethane particles and 1g of heparin sodium in 87g of dimethylacetamide solution, stir at room temperature for 12h at a speed of 200r / min, and then degas under vacuum for 12h to obtain a uniform spinning solution B;

[0055] S2. Mix 100 mL of ethanol and 400 mL of deionized water to obtain a coagulation bath solution. Use a wet spinning device to extrude the spinning solution A from step S1 into the coagulation bath at an extrusion speed of 3 mL / min. Then, draw and wind the solution onto a metal tube with a diameter of 6 mm at a drawing and winding speed of 90 r / min to obtain a polyurethane fiber inner layer. Knit a fabric on the outer surface of the wound polyurethane fiber inner layer with 300 denier spandex yarn, and weave the spandex yarn under tension to obtain a fabric middle layer.

[0056] S3. Dimethylacetamide is sprayed onto the surface of the fabric intermediate layer in step S2 at a spraying speed of 3 mL / min. The spinning solution B from step S1 is used to prepare a nanofiber membrane as the outer layer of polyurethane fibers on the surface of the fabric intermediate layer at room temperature using electrospinning technology. The extrusion speed is 1.5 mL / h, the voltage is +15 kV, the distance between the needle and the support is 15 cm, and the rotation speed is 500 rpm. Finally, the membrane is soaked in deionized water for 4 h to cure. After separation from the metal tube, the fiber-based biomimetic polyurethane artificial blood vessel is obtained.

[0057] Please see Figures 1-2The image shown is a microscopic electron microscope image of the fiber-based biomimetic polyurethane artificial blood vessel prepared in Example 1. As can be seen from the image, this example successfully fabricated an artificial blood vessel with a three-layered, tightly packed structure. The pores in the inner polyurethane fiber layer 1 are due to the exchange of water and solvent within the fiber during extrusion and stretching in the coagulation bath. This bidirectional permeation causes a phase change in the fiber, forming pores of varying diameters within the fiber. The intermediate fabric layer 2 also contains pores due to the specific weaving process. These fabric pores allow for a tight bond between the outer and inner polyurethane fiber layers, improving the overall integrity of the artificial blood vessel structure.

[0058] The radial tensile strength, puncture resistance, and adhesion ability of the fiber-based biomimetic polyurethane artificial blood vessel prepared in Example 1 were tested. The specific testing methods are as follows:

[0059] (1) Radial tensile strength

[0060] First, the artificial blood vessel is cut into samples of a fixed size according to certain standards to facilitate subsequent experimental operations. Second, the artificial blood vessel sample is fitted onto one or more clamps, and the clamps are fixed to a tensile testing instrument. Finally, a universal testing machine is used to test the tensile strength of the sample at a speed of 60 mm / min (e.g., Figure 3 As shown in the figure, record the force values ​​experienced by each sample at fracture. Calculate the radial tensile strength of each sample at fracture using the following formula:

[0061]

[0062] In the above formula, F represents radial tensile strength, which is the maximum radial force that the artificial blood vessel can withstand when it breaks, and its unit is N / mm; T represents maximum tensile strength, which is the maximum axial force applied to the artificial blood vessel, and its unit is N; L represents the length of the test sample, and its unit is mm.

[0063] The test results showed that the tensile strength of the fiber-based biomimetic polyurethane artificial blood vessel prepared in Example 1 reached 15.86±1.20 N / mm.

[0064] (2) Puncture resistance

[0065] The artificial blood vessel sample was placed on a clamp and fixed with a tensioning device. Tensioning was then initiated at a constant displacement speed, and data recording began. This method is the same as the radial tensile strength test method, except that different numbers of punctures were performed on the sample: 0, 8, 16, and 24 punctures. The sample was then fitted onto the clamp and fixed to the machine. The clamp position and angle were adjusted, and both ends were tightened to prevent displacement during the test. The sample was stabilized for 1 minute, and then stretched at a constant speed of 60 mm / min until fracture. The maximum tensile force experienced by each sample at fracture was recorded.

[0066] The test results showed that the fiber-based biomimetic polyurethane artificial blood vessel prepared in Example 1 had a tensile strength of 13.82±3.54 N / mm after 24 punctures.

[0067] (3) Adhesion ability to endothelial cells

[0068] Cell viability was detected using the CCK-8 assay, and the absorbance values ​​at 450 nm were statistically analyzed using an ELISA reader. The CCK-8 assay is a commonly used non-radioactive method for detecting cell proliferation and toxicity. Its principle is to use an ELISA reader to measure absorbance to reflect cell number and viability.

[0069] Please see Figure 4 As shown, the artificial blood vessel of Example 1 exhibits cell fluorescence staining effect after 3 days of culture. It can be seen from the figure that there are already a large number of cells on the surface of the artificial blood vessel; and after 5 days of culture, the cell adhesion rate of the artificial blood vessel reaches 70%.

[0070] Example 2

[0071] This embodiment provides a fiber-based biomimetic polyurethane artificial blood vessel and its preparation method, including the following steps:

[0072] S1. Dissolve 19g of TPU PC-3575A polyurethane particles and 1g of sodium heparin in 80g of dimethylacetamide solution, stir at room temperature for 13h at a speed of 300r / min, and then degas under vacuum for 13h to obtain a uniform spinning solution A; Dissolve 13g of TPU PC-3575A polyurethane particles and 1g of sodium heparin in 86g of dimethylacetamide solution, stir at room temperature for 13h at a speed of 300r / min, and then degas under vacuum for 13h to obtain a uniform spinning solution B;

[0073] S2. Mix 100 mL of ethanol and 300 mL of deionized water to obtain a coagulation bath solution. Use a wet spinning device to extrude the spinning solution A from step S1 into the coagulation bath at an extrusion speed of 3.5 mL / min. Then, draw and wind the solution onto a metal tube with a diameter of 5 mm at a drawing and winding speed of 95 r / min to obtain a polyurethane fiber inner layer. Knit a layer of fabric on the outer surface of the wound polyurethane fiber inner layer using 350 denier spandex yarn to obtain a fabric middle layer.

[0074] S3. Dimethylacetamide is sprayed onto the surface of the fabric intermediate layer in step S2 at a spraying speed of 4 mL / min. The spinning solution B from step S1 is used to prepare a nanofiber membrane as the outer layer of polyurethane fiber on the surface of the fabric intermediate layer at room temperature using electrospinning technology. The extrusion speed is 1.6 mL / h, the voltage is +17 kV, the distance between the needle and the support is 16 cm, and the rotation speed is 600 rpm. Finally, the membrane is soaked in deionized water for 5 h to cure. After separation from the metal tube, the fiber-based biomimetic polyurethane artificial blood vessel is obtained.

[0075] Example 3

[0076] This embodiment provides a fiber-based biomimetic polyurethane artificial blood vessel and its preparation method, including the following steps:

[0077] S1. Dissolve 20g of TPU PC-3572D polyurethane particles and 1g of heparin sodium in 79g of dimethylacetamide solution, stir at room temperature for 14h at a speed of 400r / min, and then degas under vacuum for 14h to obtain a uniform spinning solution A; Dissolve 14g of TPU PC-3572D polyurethane particles and 1g of heparin sodium in 85g of dimethylacetamide solution, stir at room temperature for 14h at a speed of 400r / min, and then degas under vacuum for 13h to obtain a uniform spinning solution B;

[0078] S2. Mix 100 mL of ethanol and 350 mL of deionized water to obtain a coagulation bath solution. Use a wet spinning device to extrude the spinning solution A from step S1 into the coagulation bath at an extrusion speed of 4 mL / min. Then, draw and wind the solution onto a metal tube with a diameter of 4 mm at a drawing and winding speed of 100 r / min to obtain a polyurethane fiber inner layer. Knit a layer of fabric on the outer surface of the wound polyurethane fiber inner layer using 400 denier spandex yarn to obtain a fabric middle layer.

[0079] S3. Dimethylacetamide is sprayed onto the surface of the fabric intermediate layer in step S2 at a spraying speed of 5 mL / min. The spinning solution B from step S1 is used to prepare a nanofiber membrane as the outer layer of polyurethane fibers on the surface of the fabric intermediate layer at room temperature using electrospinning technology. The extrusion speed is 2.0 mL / h, the voltage is +20 kV, the distance between the needle and the support is 17 cm, and the rotation speed is 700 rpm. Finally, the membrane is soaked in deionized water for 6 h to cure. After separation from the metal tube, the fiber-based biomimetic polyurethane artificial blood vessel is obtained.

[0080] Comparative Example 1

[0081] Comparative Example 1 provides a fiber-based biomimetic polyurethane artificial blood vessel and its preparation method. The difference from Example 1 is that the polyurethane fiber inner layer is not prepared by wet spinning technology, but the spandex thread is directly woven onto the surface of the metal tube. The rest is roughly the same as Example 1, and will not be repeated here.

[0082] Comparative Example 2

[0083] Comparative Example 2 provides a fiber-based biomimetic polyurethane artificial blood vessel and its preparation method. The difference from Example 2 is that in step S2, a fabric intermediate layer is not woven on the surface of the inner layer of the polyurethane fiber. The rest is roughly the same as Example 1, and will not be repeated here.

[0084] Comparative Example 3

[0085] Comparative Example 3 provides a fiber-based biomimetic polyurethane artificial blood vessel and its preparation method. Compared with Example 2, the difference is that step S3 was not performed. The rest is roughly the same as Example 1, and will not be repeated here.

[0086] Comparative Example 4

[0087] Comparative Example 4 provides a fiber-based biomimetic polyurethane artificial blood vessel and its preparation method. The difference from Example 2 is that dimethylacetamide was not sprayed on the surface of the fabric intermediate layer in step S3. The rest is roughly the same as Example 1, and will not be described again here.

[0088] Comparative Example 5

[0089] Comparative Example 5 provides a fiber-based biomimetic polyurethane artificial blood vessel and its preparation method. The difference from Example 2 is that the coagulation bath in step S2 does not contain ethanol. The rest is roughly the same as Example 1 and will not be repeated here.

[0090] Comparative Example 6

[0091] Comparative Example 6 provides a fiber-based biomimetic polyurethane artificial blood vessel and its preparation method. The difference from Example 2 is that in step S2, no stretching and winding process is performed. Instead, the fiber is wound onto the metal tube while remaining in a relaxed state. The rest is roughly the same as Example 1 and will not be described again here.

[0092] Comparative Example 7

[0093] Comparative Example 7 provides a fiber-based biomimetic polyurethane artificial blood vessel and its preparation method. The difference from Example 2 is that in step S2, the spandex thread is woven in a relaxed and tension-free state. The rest is roughly the same as Example 1, and will not be repeated here.

[0094] The radial tensile strength, puncture resistance, and adhesion ability of the fiber-based biomimetic polyurethane artificial blood vessels prepared in Comparative Examples 1 to 7 were tested, and the results are shown in the table below.

[0095] Table 1. Performance characterization of artificial blood vessels in Examples 1 and 7 (Comparative Examples 1-7)

[0096] Fracture strength (N / mm) Puncture strength (N / mm) Cell adhesion rate (%) Example 1 15.86±1.20 13.82±3.54 70 Example 2 16.90±1.00 15.72±3.04 75 Example 3 13.76±1.50 12.89±2.98 68 Comparative Example 1 10.02±2.50 10.33±2.68 65 Comparative Example 2 11.10±1.50 10.56±3.98 64 Comparative Example 3 12.66±1.30 9.89±1.98 58 Comparative Example 4 9.70±2.60 10.50±2.76 70 Comparative Example 5 8.98±1.20 10.35±2.05 67 Comparative Example 6 9.55±1.35 8.87±2.08 69 Comparative Example 7 10.01±1.34 9.87±2.88 70

[0097] As shown in Table 1, the artificial blood vessels composed of an inner polyurethane fiber layer, a middle fabric layer, and an outer polyurethane fiber layer exhibit good mechanical properties and cell adhesion properties. However, removing any layer in Comparative Examples 1-3 reduces the mechanical properties and biocompatibility of the artificial blood vessels to some extent. After removing the inner layer, cells find it difficult to adhere and grow on the rough woven layer. In addition, the rough surface greatly increases non-specific adsorption and reduces cell adhesion. Removing the middle fabric layer significantly reduces the mechanical properties of the stent, resulting in decreased stent elasticity and a greatly increased risk of stent bleeding. Removing the outermost layer significantly reduces the bending resistance of the artificial blood vessel, thereby reducing its puncture resistance.

[0098] In addition, the lack of solvent adhesion in Comparative Example 4, the absence of ethanol in the coagulation bath of Comparative Example 5, and the rapid and complete curing of the filaments, the lack of fiber stretching treatment in Comparative Example 6, and the loose fabric structure caused by the slack state of the spandex yarn in Comparative Example 7, all of these factors reduce the mechanical properties of the artificial blood vessel to some extent, thus causing the vascular stent to be unstable.

[0099] In summary, this invention provides a fiber-based biomimetic polyurethane artificial blood vessel and its preparation method. Highly oriented filaments are obtained using wet spinning technology and drawn and wound onto the surface of a metal tube to prepare a polyurethane fiber inner layer. A fabric intermediate layer is directly woven onto the surface of the polyurethane fiber inner layer using weaving technology. An organic solvent is then sprayed onto the surface of the fabric intermediate layer, and a nanofiber membrane is prepared on the surface of the fabric intermediate layer using electrospinning technology as the polyurethane fiber outer layer. The membrane is then completely cured by soaking in deionized water and separated from the metal tube to obtain the fiber-based biomimetic polyurethane artificial blood vessel. This invention combines wet spinning, weaving, and electrospinning technologies to achieve integrated fabrication of polyurethane artificial blood vessels. The resulting artificial blood vessels are of high quality, with each layer being a fiber-based structure and the three layers tightly bonded together, maximally mimicking the three-layer structure of natural blood vessels. The inner layer provides excellent compliance, the middle fabric layer increases the blood vessel's impermeability and sutureability, the outer layer increases the adhesion between the inner and middle layers, and effectively prevents blood vessel delamination. The micropores on the surface further promote endothelialization of cells. Moreover, the fabrication method is environmentally friendly and pollution-free, with a short process flow, making it suitable for continuous industrial production.

[0100] The above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.

Claims

1. A method for preparing a fiber-based biomimetic polyurethane artificial blood vessel, characterized in that, Includes the following steps: S1. Mix polyurethane particles with solvent and degas to obtain spinning solution A and spinning solution B respectively; S2. Using a wet spinning device, the spinning solution A from step S1 is extruded in a coagulation bath and drawn and wound onto a metal tube to obtain a polyurethane fiber inner layer; a fabric is then woven on the outer surface of the polyurethane fiber inner layer to obtain a fabric middle layer; the coagulation bath is a mixed solution of water and ethanol; during the weaving of the fabric middle layer, the yarn is woven in a stretched state. S3. Spray an organic solvent onto the surface of the fabric intermediate layer in step S2, and use electrospinning technology to prepare a nanofiber membrane on the surface of the fabric intermediate layer as the outer layer of polyurethane fiber. After being soaked in deionized water and completely cured, the fiber-based biomimetic polyurethane artificial blood vessel is obtained after being separated from the metal tube. The organic solvent includes one of dimethylformamide, dimethyl sulfoxide, and dimethylacetamide; the organic solvent is of the same type as the solvent in spinning solution A and spinning solution B; The intermediate layer of the fabric is interwoven with the inner layer of polyurethane fibers by means of weaving, and the outer layer of polyurethane fibers is bonded to the intermediate layer of the fabric by means of organic solvent.

2. The method for preparing the fiber-based biomimetic polyurethane artificial blood vessel according to claim 1, characterized in that, In step S2, the fineness of the yarn is 360~500 denier.

3. The method for preparing the fiber-based biomimetic polyurethane artificial blood vessel according to claim 1, characterized in that, In step S2, the mass of the ethanol accounts for 10% to 20% of the total mass of the coagulation bath.

4. The method for preparing the fiber-based biomimetic polyurethane artificial blood vessel according to claim 1, characterized in that, In step S1, the polyurethane mass percentage concentration of spinning solution A is 10%~30%, and the polyurethane mass percentage concentration of spinning solution B is 5%~15%; both spinning solution A and spinning solution B contain sodium heparin, and the mass percentage concentration of sodium heparin in spinning solution A or spinning solution B is 1%~2%.

5. The method for preparing the fiber-based biomimetic polyurethane artificial blood vessel according to claim 1, characterized in that, In step S2, the extrusion speed of the spinning solution A in the coagulation bath is 2~5 mL / min, the drawing and winding speed is 60~110 r / min, and the diameter of the metal tube is 2~10 mm.

6. The method for preparing the fiber-based biomimetic polyurethane artificial blood vessel according to claim 1, characterized in that, In step S1, the solvent includes one of dimethylformamide, dimethyl sulfoxide, and dimethylacetamide; the spinning solution A and spinning solution B use the same type of solvent.

7. The method for preparing the fiber-based biomimetic polyurethane artificial blood vessel according to claim 2, characterized in that, The raw material of the intermediate layer of the fabric includes one of spandex, polyester, and polytetrafluoroethylene; the weaving includes one of knitting, machine weaving, and braiding.

8. The method for preparing the fiber-based biomimetic polyurethane artificial blood vessel according to claim 1, characterized in that, In step S3, the electrospinning technical parameters are as follows: extrusion speed is 1.0~2.0 mL / h, voltage is +12~25 kV, distance between needle and support is 10~20 cm, rotation speed is 500~1000 rpm, and spinning temperature is room temperature.

9. A fiber-based biomimetic polyurethane artificial blood vessel prepared by the preparation method according to any one of claims 1 to 8, characterized in that, It includes a polyurethane fiber inner layer, a fabric middle layer, and a polyurethane fiber outer layer.

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