Artificial blood vessel with degradable coating and preparation method

Abstract

The invention belongs to the technical field of artificial blood vessel preparation, and particularly relates to a degradable coating artificial blood vessel and a preparation method. The artificial blood vessel provided by the embodiment of the invention consists of three layers, namely a polyhydroxyalkanoate-heparin cross-linked inner layer: polyhydroxyalkanoate (PHA) is spun into a tubular membrane by utilizing an electrostatic spinning technology, and the biocompatibility and the anticoagulation performance are improved through heparin cross-linking. And the compact middle layer is formed by weaving polyester monofilaments (polyester fibers) and provides structural strength and stability. And the physical properties and degradation rate of the middle layer can be further optimized by using the polyester monofilaments with different diameters. The polyurethane-heparin cross-linked outer layer is characterized in that polyurethane is spun into the outer layer through the electrostatic spinning technology, the surface performance is improved through heparin cross-linking, and cell attachment and growth are promoted.

Description

Technical Field

[0001] The invention belongs to the technical field of artificial blood vessel preparation, and in particular relates to an artificial blood vessel with a degradable coating and a preparation method thereof. Background Art

[0002] Cardiovascular disease is the leading cause of morbidity and mortality worldwide. According to the World Health Organization (WHO), cardiovascular and cerebrovascular deaths account for 30.3% of the total number of deaths in the world. In China alone, the "China Cardiovascular Health and Disease Report 2023" shows that there are approximately 330 million cardiovascular disease patients, and the number is increasing year by year.

[0003] Currently, the most effective treatment for cardiovascular diseases is vascular transplantation. However, the availability of high-quality autologous vascular grafts is limited, and allogeneic grafts have immunogenicity issues. Therefore, artificial vascular grafts are often used for treatment. Large-caliber artificial blood vessels made from materials such as ePTFE and PET have been successfully used in clinical practice; however, small-caliber artificial blood vessels still face problems such as insufficient endothelialization, vascular embolism, and low long-term patency in clinical applications. Summary of the invention

[0004] The purpose of the present invention is to provide a biodegradable coated artificial blood vessel and a preparation method thereof, so as to solve the problems of insufficient endothelialization ability, vascular embolism and low long-term patency rate faced by small-caliber artificial blood vessels in the prior art in clinical applications.

[0005] In order to achieve the above object, the present invention adopts the following technical solution: In a first aspect, the present invention provides a biodegradable coated artificial blood vessel, comprising a polyhydroxyalkanoate-heparin cross-linked inner layer, a dense middle layer and a polyurethane-heparin cross-linked outer layer.

[0006] In a second aspect, the present invention provides a method for preparing an artificial blood vessel with a degradable coating, comprising the following steps: Step 1, spinning a pre-configured electrospinning solution A to obtain a tubular electrospun membrane as the inner layer of the blood vessel; wherein the electrospinning solution A is a polyhydroxyalkanoate solution; Step 2, using the pre-prepared polyester monofilament to weave on the inner layer of the blood vessel to obtain a dense middle layer; Step 3, spinning on the dense middle layer with a pre-configured electrospinning solution B to obtain a blood vessel outer layer; wherein the electrospinning solution B is a polyurethane solution; Step 4: After the outer layer of the blood vessel is prepared on the dense middle layer, it is dried; then the entire blood vessel is placed in a pre-configured heparin cross-linking liquid for cross-linking. After the cross-linking is completed, a degradable coated artificial blood vessel with a polyhydroxyalkanoate-heparin cross-linked inner layer, a dense middle layer and a polyurethane-heparin cross-linked outer layer is obtained.

[0007] Further, in step 1, the electrospinning solution A is prepared according to the following steps: The washed and dried polyhydroxyalkanoate was dissolved in a dichloromethane solution to obtain an electrospinning solution A.

[0008] Furthermore, in step 2, the polyester monofilament includes a polyester monofilament of a first diameter and a polyester monofilament of a second diameter; wherein the first diameter is greater than the second diameter.

[0009] Furthermore, in step 2, the preparation method of the polyester monofilament is as follows: melt-extruding polyester into raw polyester monofilaments; The original polyester monofilament is solid-state drawn into a polyester monofilament with a first diameter and a polyester monofilament with a second diameter; wherein the first diameter is greater than the second diameter.

[0010] Furthermore, in step 2, the pre-prepared polyester monofilament is used to weave on the inner layer of the blood vessel, and the specific steps are as follows: fixing the starting point of the polyester monofilament of the first diameter to the first end of the inner layer of the blood vessel; Starting from the first end of the blood vessel inner layer, a polyester monofilament of a first diameter is woven on the blood vessel inner layer along a first spiral direction; when the polyester monofilament of the first diameter is woven to the second end of the blood vessel inner layer, an end point of the polyester monofilament of the first diameter is fixed to the second end of the blood vessel inner layer; fixing the starting point of the polyester monofilament of the second diameter to the first end or the second end of the inner layer of the blood vessel; Starting from any end of the blood vessel inner layer, a polyester monofilament of a second diameter is woven on the blood vessel inner layer along a second spiral direction; when the polyester monofilament of the second diameter is woven to the other end of the blood vessel inner layer, an end point of the polyester monofilament of the second diameter is fixed to a corresponding end of the blood vessel inner layer; wherein the first spiral direction intersects with the second spiral direction; After the second diameter polyester monofilament is braided, the blood vessel is annealed at a set temperature to obtain a dense middle layer.

[0011] Further, in step 3, the electrospinning solution B is prepared as follows: The washed and dried polyurethane is dissolved in a mixed solution of N,N-dimethylformamide and tetrahydrofuran to obtain an electrospinning solution B.

[0012] Furthermore, in step 4, the heparin cross-linking liquid includes 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC), N-hydroxysuccinimide (NHS) and (-N-morpholino)ethanesulfonic acid (MES) in a molar mass ratio of (1.5-2.5):(1.5-2.5):(4.5-5.5).

[0013] Furthermore, in step 4, the entire blood vessel is placed in a pre-configured heparin cross-linking liquid for cross-linking, specifically: The dried blood vessel is immersed in the heparin cross-linking liquid and placed in a constant temperature shaker at a preset temperature for a preset time.

[0014] Furthermore, in step 1 and step 3, double-needle electrospinning technology is used for spinning.

[0015] Compared with the prior art, the beneficial effects of the present invention are as follows: The artificial blood vessel provided by the embodiment of the present invention is composed of three layers: a polyhydroxyalkanoate-heparin cross-linked inner layer: polyhydroxyalkanoate (PHA) is spun into a tubular membrane using electrospinning technology, and heparin cross-linking is used to improve biocompatibility and anti-coagulation performance. A dense middle layer: woven with polyester monofilament (polyester fiber) to provide structural strength and stability. The use of polyester monofilaments of different diameters can further optimize the physical properties and degradation rate of the middle layer. A polyurethane-heparin cross-linked outer layer: polyurethane is also spun into the outer layer using electrospinning technology, and heparin cross-linking is used to improve surface properties and promote cell attachment and growth. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The drawings constituting a part of the present application are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings: Figure 1 This is a schematic diagram of a dense middle layer structure in an embodiment of the present invention; Figure 2 This is a schematic diagram of the structure of an artificial blood vessel with a degradable coating according to an embodiment of the present invention; Figure 3 This is a schematic flow chart of a method for preparing an artificial blood vessel with a degradable coating according to an embodiment of the present invention; Figure 4 This is a schematic diagram of the principle of a method for preparing an artificial blood vessel with a degradable coating according to an embodiment of the present invention; Among them: 1. Polyhydroxyalkanoate-heparin cross-linked inner layer; 2. Dense middle layer; 3. Polyurethane-heparin cross-linked outer layer. DETAILED DESCRIPTION

[0017] The present invention will be described in detail below with reference to the accompanying drawings and in combination with embodiments. It should be noted that the embodiments and features in the embodiments of the present application can be combined with each other without conflict.

[0018] The following detailed description is an exemplary description, which is intended to provide further detailed description of the present invention. Unless otherwise specified, all technical terms used in the present invention have the same meaning as those generally understood by those skilled in the art to which the present application belongs. The terms used in the present invention are only for describing specific embodiments, and are not intended to limit exemplary embodiments according to the present invention.

[0019] In the description of the present invention, it should be understood that the terms "center", "longitudinal", "lateral", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside" and "outside" etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present invention.

[0020] In addition, the terms "first" and "second" are used for descriptive purposes only and cannot be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, unless otherwise specified, the meaning of "multiple" is two or more. In the description of the present invention, it should be noted that, unless otherwise clearly specified and defined, the terms "installed", "connected" and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be a connection between the two elements. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0021] Glossary Small-caliber artificial blood vessels, in this case, refer to artificial blood vessels with a diameter of less than 6 mm.

[0022] Example 1 like Figure 1 As shown, Example 1 of the present invention provides a biodegradable coated artificial blood vessel, comprising a polyhydroxyalkanoate-heparin cross-linked inner layer, a dense middle layer and a polyurethane-heparin cross-linked outer layer.

[0023] The degradable coated artificial blood vessel provided by the embodiment of the present invention has selective permeability, and the inner layer is prepared by PHA. As a degradable material, PHA has good biocompatibility, has the characteristics of layer-by-layer degradation over time, and no collapse, and the degradation product 3HB can be converted into acetyl coenzyme A through the "ketolysis" path, enters the tricarboxylic acid cycle to produce ATP, and promotes cell and blood vessel repair. The dense middle layer is woven with polyester, which has anti-bleeding and antibacterial capabilities to prevent infection. The outermost layer is spun from polyurethane, has good physical and mechanical properties, can adapt to the blood pressure environment in the body, and maintain the normal morphology of blood vessels.

[0024] At the same time, this scheme also uses heparin to cross-link the inner and outer layers of blood vessels to improve vascular hydrophilicity and cell adhesion, and also has anti-coagulation and anti-platelet aggregation functions. At the same time, PHA can slowly release cross-linked heparin, prolong its release cycle in the body, and increase its effect of promoting endothelial cell adhesion.

[0025] Example 2 Embodiment 2 of the present invention provides a method for preparing an artificial blood vessel with a degradable coating, which is used to prepare the artificial blood vessel with a degradable coating in Embodiment 1. The method comprises the following steps: Step 1, spinning a pre-configured electrospinning solution A to obtain a tubular electrospun membrane as the inner layer of the blood vessel; wherein the electrospinning solution A is a polyhydroxyalkanoate solution; Step 2, using the pre-prepared polyester monofilament to weave on the inner layer of the blood vessel to obtain a dense middle layer; Step 3, spinning on the dense middle layer with a pre-configured electrospinning solution B to obtain a vascular outer layer; wherein the electrospinning solution B is a polyurethane solution; Step 4: After the outer layer of the blood vessel is prepared on the dense middle layer, it is dried; then the entire blood vessel is placed in a pre-configured heparin cross-linking liquid for cross-linking. After the cross-linking is completed, a degradable coated artificial blood vessel with a polyhydroxyalkanoate-heparin cross-linked inner layer, a dense middle layer and a polyurethane-heparin cross-linked outer layer is obtained.

[0026] The embodiment of the present invention provides a method for preparing a degradable coated artificial blood vessel. The method combines electrospinning technology with traditional weaving technology and heparin cross-linking treatment to prepare an artificial blood vessel with excellent biocompatibility, degradability and good mechanical properties.

[0027] As an optional embodiment, in step 1, the electrospinning solution A is prepared according to the following steps: The washed and dried polyhydroxyalkanoate was dissolved in a dichloromethane solution to obtain an electrospinning solution A.

[0028] The microstructure of the electrospun membrane is a mesh, with gaps between the meshes of 40 to 60 microns.

[0029] As an optional embodiment, in step 2, the polyester monofilament includes a polyester monofilament of a first diameter and a polyester monofilament of a second diameter; wherein the first diameter is greater than the second diameter.

[0030] As an optional embodiment, in step 2, the preparation method of the polyester monofilament is as follows: melt-extruding polyester into raw polyester monofilaments; The original polyester monofilament is solid-state drawn into a polyester monofilament with a first diameter and a polyester monofilament with a second diameter; wherein the first diameter is greater than the second diameter.

[0031] As an optional embodiment, in step 2, the pre-prepared polyester monofilament is used to weave on the inner layer of the blood vessel, and the specific steps are as follows: fixing the starting point of the polyester monofilament of the first diameter to the first end of the inner layer of the blood vessel; Starting from the first end of the blood vessel inner layer, a polyester monofilament of a first diameter is woven on the blood vessel inner layer along a first spiral direction; when the polyester monofilament of the first diameter is woven to the second end of the blood vessel inner layer, an end point of the polyester monofilament of the first diameter is fixed to the second end of the blood vessel inner layer; fixing the starting point of the polyester monofilament of the second diameter to the first end or the second end of the inner layer of the blood vessel; Starting from any end of the blood vessel inner layer, a polyester monofilament of a second diameter is woven on the blood vessel inner layer along a second spiral direction; when the polyester monofilament of the second diameter is woven to the other end of the blood vessel inner layer, an end point of the polyester monofilament of the second diameter is fixed to a corresponding end of the blood vessel inner layer; wherein the first spiral direction intersects with the second spiral direction; After the second diameter polyester monofilament is braided, the blood vessel is annealed at a set temperature to obtain a dense middle layer.

[0032] As an optional embodiment, in step 3, the electrospinning solution B is prepared as follows: The washed and dried polyurethane is dissolved in a mixed solution of N,N-dimethylformamide and tetrahydrofuran to obtain an electrospinning solution B.

[0033] As an optional embodiment, in step 4, the heparin cross-linking liquid includes 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC), N-hydroxysuccinimide (NHS) and (-N-morpholino)ethanesulfonic acid (MES) in a molar mass ratio of (1.5-2.5): (1.5-2.5): (4.5-5.5). Preferably, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC), N-hydroxysuccinimide (NHS) and (-N-morpholino)ethanesulfonic acid (MES) are added to a 1600U / ml heparin solution in a molar mass ratio of 2:2:5 to prepare the heparin cross-linking liquid.

[0034] In an optional embodiment, each 5 ml of the cross-linking liquid contains 20 mM 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC), 20 mM N-hydroxysuccinimide (NHS), 50 mM (-N-morpholino)ethanesulfonic acid (MES) and 8000 U heparin sulfate, and the pH of the heparin cross-linking liquid is 6.5.

[0035] As an optional embodiment, in step 4, the entire blood vessel is placed in a pre-configured heparin cross-linking liquid for cross-linking, specifically: The dried blood vessel is immersed in the heparin cross-linking liquid and placed in a constant temperature shaker at a preset temperature for a preset time.

[0036] As an optional embodiment, in both step 1 and step 3, double-needle electrospinning technology is used for spinning.

[0037] The above scheme constructs a multi-layer structure with good biocompatibility and degradability as well as excellent mechanical properties through the inner layer of PHA, the middle layer of dense polyester braided layer and the outer layer of PU. The heparin cross-linking treatment is used to improve the biological activity and anticoagulant properties of the artificial blood vessel, extend its service life and reduce the risk of postoperative complications.

[0038] This solution can also prepare biodegradable coated artificial blood vessels with different performance requirements by adjusting the diameter of the polyester monofilament, the weaving method, and the composition and concentration of the spinning solution.

[0039] Example 3 Step 1: Clean the polyhydroxyalkanoate and polyurethane with sterile PBS solution, dry them in a vacuum drying oven at 60°C to constant weight, dissolve the polyhydroxyalkanoate in a dichloromethane solution with a mass fraction of 3% to obtain electrospinning solution A; dissolve the polyurethane in a mixed solution of N,N-dimethylformamide (DMF) and tetrahydrofuran (THF) (v:v, 1:1) with a mass fraction of 15% to obtain electrospinning solution B.

[0040] Step 2: Spinning the electrospinning solution A using double-needle electrospinning technology to obtain an electrospun membrane as the inner layer of the blood vessel, the electrospinning receiver used has a diameter of 5 mm, a distance of 16 cm, a voltage of 16 kV, and a flow rate of 1.5 ml / h; the collection core shaft has a diameter of 2 mm and a rotation speed of 100 rpm; Step 3: At a melt temperature of 260°C and a cooling temperature of 25°C, the polyester is melt-extruded into original polyester monofilaments with a diameter of 0.6±0.02 mm, and then the original polyester monofilaments are solid-state drawn into monofilaments with diameters of 0.15±0.02 mm and 0.30±0.02 mm.

[0041] Step 4: Weave the thicker polyester monofilament along a spiral direction on the inner layer of the blood vessel, and then fix the two ends of the monofilament with pins, and then weave the relatively thinner polyester monofilament along the opposite spiral direction perpendicular to the axis of the stent. After weaving, anneal the sample in a vacuum oven at 100°C for one hour to obtain a dense middle layer.

[0042] Step 5: Use double-needle electrospinning technology to spin the electrospinning solution B onto the outer surface of the dense middle layer to obtain a three-layer artificial blood vessel. The electrospinning receiver used has a diameter of 5 mm, a distance of 16 cm, a voltage of 16 kV, a flow rate of 1.5 ml / h, and a collection speed of 100 rpm.

[0043] Step 6: Place the three-layer artificial blood vessel in a vacuum drying oven at 60°C to dry.

[0044] Step 7: Prepare heparin crosslinking liquid. Each 5 ml crosslinking liquid contains 20 mM 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC), 20 mM N-hydroxysuccinimide (NHS), 50 mM (-N-morpholino)ethanesulfonic acid (MES) and 8000 U heparin sulfate. The pH is adjusted to 6.5. Immerse the dried three-layer artificial blood vessel in the crosslinking liquid and shake it at 37°C for 36 hours. After completion, wash it with sterile PBS solution and dry it.

[0045] Example 4 Step 1: Clean the polyhydroxyalkanoate and polyurethane with sterile PBS solution, dry them in a vacuum drying oven at 55°C to constant weight, dissolve the polyhydroxyalkanoate in a dichloromethane solution with a mass fraction of 2% to obtain electrospinning solution A; dissolve the polyurethane in a mixed solution of N,N-dimethylformamide (DMF) and tetrahydrofuran (THF) (v:v, 1:1) with a mass fraction of 13% to obtain electrospinning solution B.

[0046] Step 2: Spinning the electrospinning solution A using double-needle electrospinning technology to obtain an electrospun membrane as the inner layer of the blood vessel, the electrospinning receiver used has a diameter of 5 mm, a distance of 16 cm, a voltage of 16 kV, and a flow rate of 1.5 ml / h; the collection core shaft has a diameter of 2 mm and a rotation speed of 100 rpm; Step 3: At a melt temperature of 240°C and a cooling temperature of 25°C, the polyester is melt-extruded into original polyester monofilaments with a diameter of 0.6±0.02 mm, and then the original polyester monofilaments are solid-state drawn into monofilaments with diameters of 0.15±0.02 mm and 0.30±0.02 mm.

[0047] Step 4: Weave the thicker polyester monofilament along a spiral direction on the inner layer of the blood vessel, and then fix the two ends of the monofilament with pins, and then weave the relatively thinner polyester monofilament along the opposite spiral direction perpendicular to the axis of the stent. After weaving, anneal the sample in a vacuum oven at 100°C for one hour to obtain a dense middle layer.

[0048] Step 5: Use double-needle electrospinning technology to spin the electrospinning solution B onto the outer surface of the dense middle layer to obtain a three-layer artificial blood vessel. The electrospinning receiver used has a diameter of 5 mm, a distance of 16 cm, a voltage of 16 kV, a flow rate of 1.5 ml / h, and a collection speed of 100 rpm.

[0049] Step 6: Place the three-layer artificial blood vessel in a vacuum drying oven at 60°C to dry.

[0050] Step 7: Prepare heparin crosslinking liquid. Each 5 ml crosslinking liquid contains 20 mM 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC), 20 mM N-hydroxysuccinimide (NHS), 50 mM (-N-morpholino)ethanesulfonic acid (MES) and 8000 U heparin sulfate. The pH is adjusted to 6.5. Immerse the dried three-layer artificial blood vessel in the crosslinking liquid and shake it at 37°C for 36 hours. After completion, wash it with sterile PBS solution and dry it.

[0051] Example 5 Step 1: Clean the polyhydroxyalkanoate and polyurethane with sterile PBS solution, dry them in a vacuum drying oven at 55°C to constant weight, dissolve the polyhydroxyalkanoate in a dichloromethane solution with a mass fraction of 5% to obtain electrospinning solution A; dissolve the polyurethane in a mixed solution of N,N-dimethylformamide (DMF) and tetrahydrofuran (THF) (v:v, 1:1) with a mass fraction of 16% to obtain electrospinning solution B.

[0052] Step 2: Spinning the electrospinning solution A using double-needle electrospinning technology to obtain an electrospun membrane as the inner layer of the blood vessel, the electrospinning receiver used has a diameter of 5 mm, a distance of 16 cm, a voltage of 16 kV, and a flow rate of 1.5 ml / h; the collection core shaft has a diameter of 2 mm and a rotation speed of 100 rpm; Step 3: At a melt temperature of 250°C and a cooling temperature of 25°C, the polyester is melt-extruded into original polyester monofilaments with a diameter of 0.6±0.02 mm, and then the original polyester monofilaments are solid-state drawn into monofilaments with diameters of 0.15±0.02 mm and 0.30±0.02 mm.

[0053] Step 4: Weave the thicker polyester monofilament along a spiral direction on the inner layer of the blood vessel, and then fix the two ends of the monofilament with pins, and then weave the relatively thinner polyester monofilament along the opposite spiral direction perpendicular to the axis of the stent. After weaving, anneal the sample in a vacuum oven at 100°C for one hour to obtain a dense middle layer.

[0054] Step 5: Use double-needle electrospinning technology to spin the electrospinning solution B onto the outer surface of the dense middle layer to obtain a three-layer artificial blood vessel. The electrospinning receiver used has a diameter of 5 mm, a distance of 16 cm, a voltage of 16 kV, a flow rate of 1.5 ml / h, and a collection speed of 100 rpm.

[0055] Step 6: Place the three-layer artificial blood vessel in a vacuum drying oven at 60°C to dry.

[0056] Step 7: Prepare heparin crosslinking liquid. Each 5 ml crosslinking liquid contains 20 mM 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC), 20 mM N-hydroxysuccinimide (NHS), 50 mM (-N-morpholino)ethanesulfonic acid (MES) and 8000 U heparin sulfate. The pH is adjusted to 6.5. Immerse the dried three-layer artificial blood vessel in the crosslinking liquid and shake it at 37°C for 36 hours. After completion, wash it with sterile PBS solution and dry it.

[0057] In the description of this specification, the description with reference to the terms "one embodiment", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0058] It is known from common technical knowledge that the present invention can be implemented by other embodiments that do not deviate from its spirit or essential features. Therefore, the above disclosed embodiments are only illustrative in all respects and are not exclusive. All changes within the scope of the present invention or within the scope equivalent to the present invention are included in the present invention.

Claims

1. A biodegradable coated artificial blood vessel, characterized in that: It includes a polyhydroxyalkanoate-heparin cross-linked inner layer, a dense middle layer and a polyurethane-heparin cross-linked outer layer.

2. A method for preparing the biodegradable coated artificial blood vessel according to claim 1, characterized in that: The steps include: Step 1, spinning a pre-configured electrospinning solution A to obtain a tubular electrospun membrane as the inner layer of the blood vessel; wherein the electrospinning solution A is a polyhydroxyalkanoate solution; Step 2, using the pre-prepared polyester monofilament to weave on the inner layer of the blood vessel to obtain a dense middle layer; Step 3, spinning on the dense middle layer with a pre-configured electrospinning solution B to obtain a blood vessel outer layer; wherein the electrospinning solution B is a polyurethane solution; Step 4: After the outer layer of the blood vessel is prepared on the dense middle layer, the entire blood vessel is placed in a pre-configured heparin cross-linking liquid for cross-linking. After the cross-linking is completed, a degradable coated artificial blood vessel with a polyhydroxyalkanoate-heparin cross-linked inner layer, a dense middle layer and a polyurethane-heparin cross-linked outer layer is obtained.

3. The preparation method according to claim 2, characterized in that: In step 1, the electrospinning solution A is prepared as follows: The polyhydroxyalkanoate is dissolved in a dichloromethane solution to obtain an electrospinning solution A.

4. The preparation method according to claim 2, characterized in that: In step 2, the polyester monofilament includes a polyester monofilament with a first diameter and a polyester monofilament with a second diameter; wherein the first diameter is greater than the second diameter.

5. The preparation method according to claim 2, characterized in that: In step 2, the preparation method of the polyester monofilament is as follows: melt-extruding polyester into raw polyester monofilaments; The original polyester monofilament is solid-state drawn into a polyester monofilament with a first diameter and a polyester monofilament with a second diameter; wherein the first diameter is greater than the second diameter.

6. The preparation method according to claim 4 or 5, characterized in that: In step 2, the pre-prepared polyester monofilament is used to weave on the inner layer of the blood vessel, and the specific steps are as follows: fixing the starting point of the polyester monofilament of the first diameter to the first end of the inner layer of the blood vessel; Starting from the first end of the blood vessel inner layer, a polyester monofilament of a first diameter is woven on the blood vessel inner layer along a first spiral direction; when the polyester monofilament of the first diameter is woven to the second end of the blood vessel inner layer, an end point of the polyester monofilament of the first diameter is fixed to the second end of the blood vessel inner layer; fixing the starting point of the polyester monofilament of the second diameter to the first end or the second end of the inner layer of the blood vessel; Starting from any end of the blood vessel inner layer, a polyester monofilament of a second diameter is woven on the blood vessel inner layer along a second spiral direction; when the polyester monofilament of the second diameter is woven to the other end of the blood vessel inner layer, an end point of the polyester monofilament of the second diameter is fixed to a corresponding end of the blood vessel inner layer; wherein the first spiral direction intersects with the second spiral direction; After the second diameter polyester monofilament is braided, the blood vessel is annealed at a set temperature to obtain a dense middle layer.

7. The preparation method according to claim 2, characterized in that: In step 3, the electrospinning solution B is prepared as follows: The polyurethane is dissolved in a mixed solution of N,N-dimethylformamide and tetrahydrofuran to obtain an electrospinning solution B.

8. The preparation method according to claim 2, characterized in that: In step 4, the heparin cross-linking liquid includes 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC), N-hydroxysuccinimide (NHS) and (-N-morpholino)ethanesulfonic acid (MES) in a molar mass ratio of (1.5-2.5):(1.5-2.5):(4.5-5.5).

9. The preparation method according to claim 2, characterized in that: In step 4, the entire blood vessel is placed in a pre-configured heparin cross-linking liquid for cross-linking, specifically: The whole blood vessel was immersed in the heparin cross-linking liquid and incubated on a constant temperature shaker at a preset temperature for a preset time.

10. The preparation method according to claim 2, characterized in that: In both step 1 and step 3, spinning is performed using double-needle electrospinning technology.

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