Artificial blood vessel for coronary artery bypass grafting and preparation method thereof

Abstract

The invention relates to the technical field of artificial blood vessels, and discloses an artificial blood vessel for coronary artery bypass grafting and a preparation method thereof. The artificial blood vessel is prepared from the following raw materials: collagen and a solvent, the solid-to-liquid ratio of the collagen to the solvent is (3-5) g: 100mL. The artificial blood vessel provided by the invention takes collagen as a raw material, the raw material composition is simple, the inner caliber of the artificial blood vessel is 1.61 + / -0.1 mm, the length is greater than or equal to 13mm, the wall thickness is 298 + / -35 microns, and the suture retention strength is 2.1 + / -0.2 N; compared with coronary arteries of a left atrial anterior branch, a left atrial rotary branch, a sinus atrial node branch and a right atrial anterior branch, the coronary artery has no obvious difference in inner caliber, wall thickness and suture retention strength, has equivalent mechanical properties, and is suitable for being used as a substitute material of autologous blood vessels of the parts.

Description

Technical Field

[0001] The present invention relates to the technical field of artificial blood vessels, and in particular to an artificial blood vessel for coronary artery bypass grafting and a preparation method thereof. Background Art

[0002] Cardiovascular diseases such as coronary heart disease pose a great threat to human health. Coronary artery bypass grafting surgery, as an important means of treating severe coronary heart disease, has been widely used in clinical practice, but it still faces many challenges in the selection of surgical materials.

[0003] On the one hand, autologous blood vessels have good biocompatibility and mechanical properties and have always been the preferred material for coronary artery bypass surgery. However, the source of autologous blood vessels is limited and it is difficult to meet clinical needs. In addition, the process of obtaining autologous blood vessels may bring additional trauma and risks to patients, increasing the complexity and uncertainty of the operation.

[0004] On the other hand, in order to alleviate the problem of donor blood vessel shortage, synthetic material stents are widely used in coronary artery bypass surgery. However, the biocompatibility and mechanical properties of these stents are often difficult to match with natural coronary blood vessels, and the parameters such as the caliber, length and thickness of existing stent products are difficult to achieve accurate matching with the lesion site. Especially for lesion replacement surgery of small blood vessels such as the left atrial anterior branch, left atrial circumflex branch, sinoatrial node branch, and right atrial anterior branch, the caliber of the coronary vessels in these parts is about 1.6±0.1mm, the thickness is about 327±50μm, and the length is about 13-30mm. These small-caliber coronary blood vessels are prone to plaques formed by the accumulation of cholesterol and its substances, which can cause stenosis or occlusion of the arterial wall, leading to myocardial ischemia, hypoxia or necrosis, triggering chest pain, chest tightness and other discomforts. With the accumulation of plaques, the stenosis of the lumen will prevent blood from flowing smoothly, leading to chest pain or discomfort. In severe cases, it can also lead to heart failure and arrhythmias. Although the length of existing artificial blood vessels can be matched by cutting long tubes short, there are still difficulties in matching the inner diameter and wall thickness. Therefore, it is of great significance to develop small-caliber artificial blood vessels with excellent biocompatibility and mechanical properties, which can be applied to coronary artery bypass surgery for lesions of small blood vessels such as the left atrial anterior branch, left atrial circumflex branch, sinoatrial node branch, and right atrial anterior branch, as a substitute material for autologous blood vessels. Summary of the invention

[0005] The present invention aims to solve at least one of the above-mentioned technical problems existing in the prior art. To this end, one of the purposes of the present invention is to provide an artificial blood vessel; the second purpose of the present invention is to provide a method for preparing such an artificial blood vessel; the third purpose of the present invention is to provide the application of such an artificial blood vessel.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is:

[0007] The first aspect of the present invention provides an artificial blood vessel, comprising the following preparation materials: collagen and a solvent; the solid-liquid ratio of the collagen and the solvent is (3-5) g:100 mL.

[0008] In some embodiments of the present invention, the solid-to-liquid ratio of the collagen and the solvent is (4-5) g:100 mL.

[0009] In some specific embodiments of the present invention, the artificial blood vessel is prepared from collagen and a solvent.

[0010] In the present invention, collagen artificial blood vessels with excellent performance can be prepared only with collagen and solvent. Compared with existing collagen artificial blood vessels, no auxiliary agents such as cross-linking agents are used, the raw material composition is simpler, the biosafety is higher, and the cost is lower.

[0011] In some embodiments of the present invention, the collagen is selected from at least one of type I collagen, type II collagen, and type III collagen.

[0012] In some embodiments of the present invention, the endotoxin content of the collagen is less than or equal to 25 EU / g.

[0013] In some embodiments of the present invention, the solvent is selected from at least one of glacial acetic acid, hexafluoroisopropanol, and trifluoroethanol.

[0014] In some embodiments of the present invention, the inner diameter of the artificial blood vessel is 1.61±0.1 mm.

[0015] In some embodiments of the present invention, the length of the artificial blood vessel is greater than or equal to 13 mm.

[0016] In some embodiments of the present invention, the wall thickness of the artificial blood vessel is 298±35 μm.

[0017] In some specific embodiments of the present invention, the wall thickness of the artificial blood vessel is 263.07-333.74 μm.

[0018] In some embodiments of the present invention, the suture retention strength of the artificial blood vessel is 2.1±0.2N.

[0019] In some embodiments of the present invention, the artificial blood vessel has a nanofiber porous structure; the diameter of the nanofibers on the inner surface of the blood vessel is 219.8±108.5 nm, and the diameter of the nanofibers on the outer surface is 237±98 nm.

[0020] The second aspect of the present invention provides a method for preparing the artificial blood vessel according to the first aspect of the present invention, comprising the following steps:

[0021] Collagen and a solvent are mixed to obtain an electrospinning solution, and inner surface and outer surface electrospinning are performed in sequence to obtain the artificial blood vessel.

[0022] In some embodiments of the present invention, the collagen and the solvent are mixed at a temperature of 20-25° C. for 15-20 h.

[0023] In some embodiments of the present invention, the electrospinning parameters of the inner surface of the artificial blood vessel include at least one of the following parameters:

[0024] 1) The diameter of the wire collection drum is 2-4mm and the length is 1900-2100mm;

[0025] 2) The speed of the wire drum is 430-460r / min;

[0026] 3) Liquid supply linear speed is 130-160 μm / min;

[0027] 4) Line thrust is 8-12kgf;

[0028] 5) The stroke of the liquid supply channel is 110-130mm;

[0029] 6) Voltage is 11-13kV, current is 1-2mA;

[0030] 7) The receiving distance is 190-210mm;

[0031] 8) The ambient temperature is 20-25°C and the relative humidity is 40%-50%;

[0032] 9) The time is 1.5-3h.

[0033] In some specific embodiments of the present invention, the electrospinning parameters of the inner surface of the artificial blood vessel include at least one of the following parameters:

[0034] 1) The diameter of the wire collection drum is 2-4mm and the length is 1950-2050mm;

[0035] 2) The speed of the wire drum is 440-460r / min;

[0036] 3) Liquid supply linear speed is 140-160 μm / min;

[0037] 4) Line thrust is 9-11kgf;

[0038] 5) The stroke of the liquid supply channel is 115-125mm;

[0039] 6) Voltage is 11-13kV, current is 1-2mA;

[0040] 7) The receiving distance is 195-205mm;

[0041] 8) The ambient temperature is 20-25°C and the relative humidity is 40%-50%;

[0042] 9) The time is 1.5-2h.

[0043] In some embodiments of the present invention, the electrospinning parameters of the outer surface of the artificial blood vessel include at least one of the following parameters:

[0044] 1) The diameter of the wire collection drum is 2-4mm and the length is 1900-2100mm;

[0045] 2) The speed of the wire drum is 390-420r / min;

[0046] 3) Liquid supply linear speed is 80-100 μm / min;

[0047] 4) Line thrust is 10-13kgf;

[0048] 5) The stroke of the liquid supply channel is 70-100mm;

[0049] 6) Voltage is 11-13kV, current is 1-2mA;

[0050] 7) The receiving distance is 190-210mm;

[0051] 8) The ambient temperature is 20-25°C and the relative humidity is 40%-50%;

[0052] 9) The time is 18-22 hours.

[0053] In some specific embodiments of the present invention, the electrospinning parameters of the outer surface of the artificial blood vessel include at least one of the following parameters:

[0054] 1) The diameter of the wire collection drum is 2-4mm and the length is 1950-2050mm;

[0055] 2) The speed of the wire drum is 400-420r / min;

[0056] 3) Liquid supply linear speed is 80-90 μm / min;

[0057] 4) Line thrust is 11-13kgf;

[0058] 5) The stroke of the liquid supply channel is 70-90mm;

[0059] 6) Voltage is 11-13kV, current is 1-2mA;

[0060] 7) The receiving distance is 195-205mm;

[0061] 8) The ambient temperature is 20-25°C and the relative humidity is 40%-50%;

[0062] 9) The time is 18-20h.

[0063] The third aspect of the present invention provides use of the artificial blood vessel described in the first aspect of the present invention in preparing a medical device for treating cardiovascular diseases.

[0064] In some embodiments of the invention, the cardiovascular disease comprises coronary artery obstruction of the left atrial anterior branch and / or the left atrial circumflex branch and / or the sinoatrial node branch and / or the right atrial anterior branch.

[0065] Compared with the prior art, the present invention has the following beneficial effects:

[0066] 1) The artificial blood vessel provided by the present invention uses collagen as a raw material, and the raw material composition is simple. The inner diameter of the artificial blood vessel is 1.61±0.1 mm, the length is greater than or equal to 13 mm, the wall thickness is 298±35 μm, and the suture retention strength is 2.1±0.2N. There is no significant difference in inner diameter, wall thickness and suture retention strength with small-caliber coronary arteries such as the coronary artery of the left atrial anterior branch, the left atrial circumflex branch, the sinoatrial node branch and the right atrial anterior branch, and the mechanical properties are comparable, so the artificial blood vessel is suitable as a substitute material for autologous blood vessels in these parts;

[0067] 2) The preparation method of the artificial blood vessel provided by the present invention controls the diameter of the nanofibers on the inner and outer surfaces of the artificial blood vessel by adjusting the electrospinning parameters, so that the artificial blood vessel has a structure more similar to that of the natural coronary artery, which helps to promote the growth and integration of host cells. This structure not only improves the biocompatibility of the artificial blood vessel, but also helps to reduce postoperative complications, such as infection and calcification;

[0068] 3) The artificial blood vessel provided by the present invention has been verified by animal experiments to be able to maintain lumen patency and arterial blood flow patterns in the replacement area, with host endothelial cells growing on the inner surface and host smooth muscle cells growing on the outer surface, good biocompatibility, a 1-year patency rate of not less than 82%, a lumen loss rate of not more than 18%, and no adverse events such as infection and calcification. It can be well used in the preparation of medical devices for the treatment of cardiovascular diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0069] Figure 1 is a cross-sectional SEM image of a natural coronary artery;

[0070] Figure 2 This is a cross-sectional SEM image of a collagen artificial blood vessel;

[0071] Figure 3 This is a cross-sectional SEM image of an expanded polytetrafluoroethylene artificial blood vessel;

[0072] Figure 4 Statistical results of the inner diameter (a), wall thickness (b) and suture retention strength (c) of natural coronary arteries, collagen artificial blood vessels and expanded polytetrafluoroethylene artificial blood vessels;

[0073] Figure 5 Circumferential (a) and longitudinal (b) uniaxial tensile stress-strain curves of natural coronary arteries, collagen artificial blood vessels and expanded polytetrafluoroethylene artificial blood vessels;

[0074] Figure 6 Circumferential (a) and longitudinal (b) cyclic elastic test stress-strain curves of natural coronary arteries and collagen artificial blood vessels;

[0075] Figure 7 This is a SEM image of the inner surface of a natural coronary artery;

[0076] Figure 8 This is a SEM image of the outer surface of a natural coronary artery;

[0077] Fig. 9 This is a SEM image of the inner surface of the collagen artificial blood vessel;

[0078] Fig.10 This is a SEM image of the outer surface of the collagen artificial blood vessel;

[0079] Fig.11 The statistical results of nanofiber diameters on the inner surface (a) and outer surface (b) of collagen artificial blood vessels and natural coronary arteries;

[0080] Fig.12 The anatomical follow-up observation results of the collagen artificial vascular stent in the experimental case at the time of replacement surgery (a), 4 weeks after surgery (b), and 1 year after surgery (c);

[0081] Fig.13 This is the angiographic image of the collagen artificial vascular stent in the test example 4 weeks after surgery;

[0082] Fig.14 This is a cross-sectional VVG staining image of the collagen artificial vascular scaffold in the experimental example 4 weeks after surgery;

[0083] Fig.15 This is a SEM image of the inner surface of the collagen artificial vascular stent in the test example 4 weeks after surgery;

[0084] Fig.16 This is the SEM image of the outer surface of the collagen artificial vascular stent in the test example 4 weeks after surgery;

[0085] Fig.17 This is the color Doppler ultrasound spectrum detection result of the collagen artificial vascular stent in the test example one year after surgery. DETAILED DESCRIPTION

[0086] The present invention is further described in detail below by specific examples. Unless otherwise specified, the raw materials, reagents or devices used in the examples and comparative examples can be obtained from conventional commercial sources or can be obtained by prior art methods. Unless otherwise specified, the experiments or test methods are conventional methods in the art.

[0087] Example

[0088] In this embodiment, an artificial blood vessel is prepared using type I collagen and hexafluoroisopropanol as raw materials, and the steps are as follows:

[0089] Take 0.5g of medical grade Type I collagen (endotoxin content ≤25EU / g), put it in a 15mL glass flask, add 10mL of hexafluoroisopropanol, and dissolve it under magnetic stirring at 25℃ in water-soluble state for 18h to obtain a fully dissolved electrospinning solution.

[0090] The dissolved electrospinning solution was fixed to the reciprocating platform of the precision injection pump of the electrospinning machine by extraction and injection with a pipette. The inner surface electrospinning parameters were adjusted: the receiving device was an aluminum roller with a diameter of 3 mm, the roller length was 2000 mm, the roller speed was 450 r / min, the liquid supply line speed was 150 μm / min, the line thrust was 10 kgf, the liquid supply channel stroke was 120 mm, the voltage was 13 kV, the current was 1 mA, the receiving distance was 200 mm, the ambient temperature was 25 ° C, the relative humidity was 40%, the exhaust was running uninterruptedly, and the inner surface was obtained by electrospinning for 2 h. Adjust the electrospinning parameters of the outer surface: the receiving device is an aluminum roller with a diameter of 3 mm, the roller length is 2000 mm, the roller speed is 410 r / min, the liquid supply line speed is 90 μm / min, the line thrust is 11 kgf, the liquid supply channel stroke is 80 mm, the voltage is 12.7 kV, the current is 1 mA, the receiving distance is 200 mm, the ambient temperature is 25 ° C, the relative humidity is 40%, the exhaust is running uninterruptedly, and the electrospinning is performed for 20 hours to obtain the outer surface. Maintain the ambient temperature at 25 ° C, the relative humidity is 40%, the continuous exhaust system is maintained for 48 hours, the ultraviolet sterilization mode is turned on, the roller rotation speed is 60 r / min, sterilization is performed for 0.5 hours, and the mold is demolded with sterile ultrapure water to obtain a collagen artificial blood vessel (Collagen) with a nanofiber porous structure, cut it into the required length with sterile scissors, and place it in a sterile culture dish for storage.

[0091] Comparative Example

[0092] The commercially available expanded polytetrafluoroethylene (ePTFE) artificial blood vessel was used as a comparison.

[0093] Performance Testing

[0094] 1. The cross sections of the artificial blood vessels in the examples and comparative examples were characterized by SEM and compared with the cross sections of natural coronary arteries:

[0095] Before characterization using SEM, samples were sectioned to expose the luminal, extraluminal, and cross-sectional areas: tissue samples were initially washed in fresh saline and fixed in methanol for 10 min, samples were dehydrated in a gradient ethanol solution (50%, 70%, 80%, 90%, 100%, 100%), and then freeze-dried overnight, and before SEM imaging, they were sputter-coated with gold at 30 mA for 120 s and observed under SEM at an accelerating voltage of 10 kV.

[0096] Figure 1 This is a cross-sectional SEM image of a natural coronary artery. Figure 2 This is a cross-sectional SEM image of a collagen artificial blood vessel. Figure 3 This is a cross-sectional SEM image of an expanded polytetrafluoroethylene artificial blood vessel. Figure 1-Figure 3 It can be seen that compared with the expanded polytetrafluoroethylene artificial blood vessel in the comparative example, the collagen artificial blood vessel prepared in the example has a cross-section that is visually more similar to a natural coronary artery.

[0097] A plurality of collagen artificial blood vessels were prepared by referring to the method in the embodiment, and the average inner diameter was 1.60 mm, the average wall thickness was 298 μm, the manufacturing accuracy was ±0.1 mm, and the average suture retention strength was 1.9 N, which was slightly higher than that of natural coronary arteries and significantly lower than that of expanded polytetrafluoroethylene artificial blood vessels on the market. Figure 4 The statistical results of the inner diameter (a), wall thickness (b) and suture retention strength (c) of natural coronary arteries, collagen artificial blood vessels and expanded polytetrafluoroethylene artificial blood vessels are shown in Table 1. Figure 4 It can be seen that the collagen artificial blood vessel provided by the present invention has no significant difference in inner caliber, wall thickness and suture retention strength compared with the natural coronary artery, while the existing expanded polytetrafluoroethylene artificial blood vessel has significant difference in inner caliber and suture retention strength compared with the natural coronary artery (p < 0.001), indicating that the collagen artificial blood vessel provided by the present invention has a shape and size more similar to the natural coronary artery, and has greater application potential in replacing autologous blood vessels as surgical materials, especially in replacing the left atrial anterior branch, left atrial circumflex branch, sinoatrial node branch, right atrial anterior branch and other blood vessels with an inner caliber of about 1.6±0.1mm, a thickness of about 327±50μm, and a length of about 13-30mm.

[0098] 2. Perform uniaxial tensile tests on the artificial blood vessels in the examples and comparative examples, and the natural coronary arteries:

[0099] The artificial blood vessels and natural coronary artery samples in the examples and comparative examples were cut longitudinally into 20 mm wide hollow tubes, cut along the tube wall to obtain concentric nanofiber membranes, and the circumferential and longitudinal directions were marked. The slices were subjected to uniaxial tensile tests in circumferential and longitudinal extensions, and the tissue slices were subjected to uniaxial tensile tests in the tensile mode of a dynamic mechanical analyzer equipped with a 5N load cell, with a tensile displacement of 5 mm / min.

[0100] Figure 5 Circumferential (a) and longitudinal (b) uniaxial tensile stress-strain curves of natural coronary arteries, collagen artificial blood vessels, and expanded polytetrafluoroethylene artificial blood vessels. Figure 5 It can be seen that the collagen artificial blood vessel prepared in the embodiment has circumferential and longitudinal ultimate tensile strengths of 5.82 MPa and 5.97 MPa, respectively, and elongations at break of 93.7% and 150.6%, respectively. Compared with the expanded polytetrafluoroethylene artificial blood vessel in the comparative example, the stress-strain curve change trends of the collagen artificial blood vessel in the embodiment and the natural coronary artery are more similar, whether in circumferential or lateral uniaxial stretching, indicating that the two have more similar elastic modulus and yield strength, and more similar mechanical properties.

[0101] 3. Perform cyclic elasticity test on the collagen artificial blood vessels and natural coronary arteries in the examples:

[0102] Before testing, the clamped tissue sections were equilibrated in a 37°C water bath for 3 min. The elastic mechanical properties of the sections were characterized by stretching the tissue sections to a preload of 1 N and then subjecting them to 20 stretching cycles at a displacement rate of 5 mm / min. The stretching was equivalent to 0.7 times the sample gauge length (i.e., 70% strain) to describe the elastic mechanical properties in the longitudinal direction of the blood vessel.

[0103] Figure 6 The stress-strain curves of the circumferential (a) and longitudinal (b) cyclic elastic tests of natural coronary arteries and collagen artificial blood vessels are shown in Figure 1. Figure 6 It can be seen that the collagen artificial blood vessel prepared in the embodiment has a Young's modulus of 0.56 MPa after being subjected to 20 loading-unloading cycle tests at a strain of 120% in the circumferential direction; and a Young's modulus of 0.33 MPa after being subjected to 20 loading-unloading cycle tests at a strain of 80% in the longitudinal direction, indicating that the collagen artificial blood vessel provided by the present invention can withstand multiple repeated stretching under a specific strain without deformation, and has excellent cyclic elastic performance, which is similar to that of a natural coronary artery.

[0104] 4. SEM characterization of the inner and outer surfaces of the collagen artificial blood vessels and natural coronary arteries in the examples:

[0105] Figure 7 This is a SEM image of the inner surface of a natural coronary artery. Figure 8 This is a SEM image of the outer surface of a natural coronary artery. Fig. 9 This is a SEM image of the inner surface of the collagen artificial blood vessel. Fig.10 This is the SEM image of the outer surface of the collagen artificial blood vessel. Fig.11 The statistical results of nanofiber diameter on the inner surface (a) and outer surface (b) of collagen artificial blood vessels and natural coronary arteries are shown in Figure 2. Figure 7-Figure 11 It can be seen that the average diameter of the inner surface nanofibers of the collagen artificial blood vessel prepared in the embodiment is 183.4nm, and the average diameter of the outer surface nanofibers is 222.0nm. The diameters of the inner and outer surface nanofibers are slightly lower than those of natural coronary arteries, and there is no significant difference with natural coronary arteries (p>0.001).

[0106] Test example

[0107] Animal experiments were conducted using the collagen artificial blood vessels prepared in the examples:

[0108] 1) Preparation of the animal model of coronary artery defect: 3% sodium pentobarbital was injected intraperitoneally at 45 mg / kg body weight for anesthesia, and the surgical area was exposed. The skin of the New Zealand rabbit was prepared, disinfected, and covered with a drape. The skin and subcutaneous tissue were cut in the middle of the sternum, and the space between the suprasternal fossa and the xiphoid process was separated. The midline of the sternum was determined, and the chest was split with an electric saw. Bone wax was applied to stop bleeding, and then the incision was opened with a spreader. The pericardium was cut step by step to expose the heart. A longitudinal incision of about 1.5 cm long was made at the distal end of the right coronary artery, which was equivalent to the origin of the posterior descending branch, directly reaching the obstruction focus. A stripper was used to strip along the plane between the obstruction lesion and the external elastic membrane of the coronary artery, and the obstruction column core was freed. The fiber plug was cut off at the incision end of the arterial wall, and the plug was clamped. The stripping continued to the distal end and its branch posterior descending branch. The plug and its tail end extending into the bifurcation were removed in one piece to obtain an animal model with right atrial anterior branch coronary artery defect.

[0109] 2) Anastomose the sterilized collagen artificial vascular stent to the defective artery incision to ensure that there is no bleeding in the vascular connection and restore coronary blood flow. Observe whether there are complications such as bleeding and thrombosis at the vascular replacement site. After the blood vessel is unobstructed, suture the muscles and skin layer by layer.

[0110] 3) X-ray radiography was used to regularly detect the patency, lumen diameter and flow rate of the artificial blood vessels. Based on the coronary artery stripping method of the animal model, a stereomicroscope was used to monitor the patency and lumen diameter of the artificial blood vessels. Histochemical staining and SEM were used to detect tissue regeneration, compatibility between the stent and the host tissue, and stent degradation.

[0111] Fig.12 The anatomical follow-up observation results of the collagen artificial vascular stent in the experimental case at the time of replacement surgery (a), 4 weeks after surgery (b), and 1 year after surgery (c) are shown in the figure. Fig.12 It can be seen that the collagen artificial blood vessel scaffold provided by the present invention is well integrated with the host in the animal model, and as the scaffold degrades, new blood vessels regenerate well.

[0112] Fig.13 This is the angiography image of the collagen artificial vascular stent in the test example 4 weeks after surgery. Fig.14 This is a VVG staining image of the cross section of the collagen artificial vascular stent in the test example 4 weeks after surgery. Fig.15 This is the SEM image of the inner surface of the collagen artificial vascular stent in the test example 4 weeks after surgery. Fig.16 This is a SEM image of the outer surface of the collagen artificial vascular stent in the test example 4 weeks after surgery. Figure 13-Figure 16 It can be seen that after the replacement surgery, as the collagen artificial vascular scaffold degrades, elastin grows into the scaffold to reshape the extracellular matrix, and the host endothelial cells and smooth muscle cells grow into the collagen artificial vascular scaffold.

[0113] Fig.17 The color Doppler ultrasound spectrum test results of the collagen artificial vascular stent in the test case one year after surgery are shown in Figure 1. Fig.17 It can be seen that the collagen artificial vascular stent can maintain long-term patency in the anastomosis area, with a 1-year patency rate of no less than 82%, a lumen loss rate of no more than 18%, no adverse events such as infection and calcification, and is consistent with the coronary artery blood flow pattern.

Claims

1. An artificial blood vessel, characterized in that: The preparation method comprises the following raw materials: collagen and solvent; the solid-liquid ratio of the collagen and the solvent is (3-5) g:100 mL.

2. The artificial blood vessel according to claim 1, characterized in that: The collagen is selected from at least one of type I collagen, type II collagen, and type III collagen; And / or, the solvent is selected from at least one of glacial acetic acid, hexafluoroisopropanol, and trifluoroethanol.

3. The artificial blood vessel according to claim 1, characterized in that: The inner diameter of the artificial blood vessel is 1.61±0.1 mm; And / or, the length of the artificial blood vessel is greater than or equal to 13 mm; And / or, the wall thickness of the artificial blood vessel is 298±35 μm.

4. The artificial blood vessel according to claim 1, characterized in that: The suture retention strength of the artificial blood vessel is 2.1±0.2N.

5. The artificial blood vessel according to claim 1, characterized in that: The artificial blood vessel has a nanofiber porous structure; the diameter of the nanofibers on the inner surface of the blood vessel is 219.8±108.5 nm, and the diameter of the nanofibers on the outer surface is 237±98 nm.

6. The method for preparing an artificial blood vessel according to claim 5, characterized in that: The following steps are involved: Collagen and a solvent are mixed to obtain an electrospinning solution, and inner surface and outer surface electrospinning are performed in sequence to obtain the artificial blood vessel.

7. The preparation method according to claim 6, characterized in that: The electrospinning parameters of the inner surface of the artificial blood vessel include at least one of the following parameters: 1) The diameter of the wire collection drum is 2-4mm and the length is 1900-2100mm; 2) The speed of the wire drum is 430-460r / min; 3) Liquid supply linear speed is 130-160 μm / min; 4) Line thrust is 8-12kgf; 5) The stroke of the liquid supply channel is 110-130mm; 6) Voltage is 11-13kV, current is 1-2mA; 7) The receiving distance is 190-210mm; 8) The ambient temperature is 20-25°C and the relative humidity is 40%-50%; 9) The time is 1.5-3h.

8. The preparation method according to claim 6, characterized in that: The electrospinning parameters of the outer surface of the artificial blood vessel include at least one of the following parameters: 1) The diameter of the wire collection drum is 2-4mm and the length is 1900-2100mm; 2) The speed of the wire drum is 390-420r / min; 3) Liquid supply linear speed is 80-100 μm / min; 4) Line thrust is 10-13kgf; 5) The stroke of the liquid supply channel is 70-100mm; 6) Voltage is 11-13kV, current is 1-2mA; 7) The receiving distance is 190-210mm; 8) The ambient temperature is 20-25°C and the relative humidity is 40%-50%; 9) The time is 18-22 hours.

9. Use of the artificial blood vessel according to any one of claims 1 to 5 in the preparation of medical devices for treating cardiovascular diseases.

10. The use according to claim 9, characterized in that: The cardiovascular disease includes coronary artery obstruction of the left atrial anterior branch and / or the left atrial circumflex branch and / or the sinoatrial node branch and / or the right atrial anterior branch.

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