Artificial blood vessel based on electrostatic spinning and preparation device thereof

Abstract

The invention discloses an artificial blood vessel based on electrostatic spinning and a preparation device thereof, and relates to the technical field of biomedices.The artificial blood vessel is of a double-layer hollow circular tube structure and comprises an inner layer and an outer layer, the inner layer is made of polymer electrospun fibers containing heparin, the outer layer is made of polymer electrospun fibers, and the artificial blood vessel has good blood compatibility and is used for preparing the artificial blood vessel. According to the preparation device, the movable seat is arranged, the collecting pipe is arranged on the movable seat, when the blood vessel is manufactured, the movable seat drives the collecting pipe to move, the spinning mechanism is in a relatively fixed state, and therefore it is guaranteed that sprayed spinning is stable and uniform enough, and the stability of the quality of the artificial blood vessel is guaranteed.

Description

Technical Field

[0001] The invention relates to the technical field of biomedicine, and in particular to an artificial blood vessel based on electrostatic spinning and a preparation device thereof. Background Art

[0002] In recent years, with the increase in the number of patients with cardiovascular diseases, diabetes, and uremia, the use of artificial blood vessels to replace damaged autologous blood vessels for transplantation has become one of the clinical options. At present, large and medium-caliber artificial blood vessels have been successfully commercialized and used in clinical practice, but small-caliber blood vessels (diameter <6mm) are prone to platelet deposition and thrombosis due to slow blood flow, leading to vascular stenosis and obstruction. How to improve blood compatibility is a key issue in promoting the clinical application of small-caliber artificial blood vessels.

[0003] Heparin is a commonly used anticoagulant drug. In recent years, many patents have been devoted to covalently bonding heparin to the wall of artificial blood vessels to prevent blood coagulation. However, covalent bonding often requires additional plasma equipment or complex synthesis steps.

[0004] To this end, an artificial blood vessel based on electrospinning and a preparation device thereof are proposed. Summary of the invention

[0005] The object of the present invention is to provide an artificial blood vessel based on electrospinning and a preparation device thereof, so as to solve the problems raised in the above background technology.

[0006] In order to solve the above technical problems, the present invention provides the following technical solutions: an artificial blood vessel based on electrospinning, wherein the artificial blood vessel is a double-layer hollow circular tube structure, including an inner layer and an outer layer, wherein the inner layer is a polymer electrospun fiber containing heparin, and the outer layer is a polymer electrospun fiber.

[0007] According to the above technical solution, the outer diameter of the artificial blood vessel is 1-6 mm.

[0008] According to the above technical solution, the production of the artificial blood vessel includes the following steps:

[0009] The production of the artificial blood vessel comprises the following steps:

[0010] S1. dissolving the polymer in a solvent to prepare a uniform solution having a polymer concentration of 10% to 16%;

[0011] S2, adding Span80 at a ratio of 1-10 μL / mL to the uniform solution prepared in S1, stirring evenly, then adding the heparin aqueous solution at a ratio of 1-10 mg / mL, stirring vigorously for 12 hours, to obtain an inner layer electrospun fiber solution;

[0012] S3, preparing an inner layer fiber tube by electrospinning the inner layer electrospun fiber solution prepared in S2, wherein the thickness of the inner layer fiber tube is 100-400 μm;

[0013] S4. Using the uniform solution prepared in S1 to prepare an outer fiber tube on the surface of the inner fiber tube prepared in S3 by electrospinning, an artificial blood vessel is obtained, wherein the thickness of the outer fiber tube is 100-400 μm.

[0014] According to the above technical scheme, the polymer described in S1 is selected from one or more of polyurethane, polylactic acid, polycaprolactone, and polylactic acid-caprolactone copolymer, and the solvent described in S1 is selected from one or more of dichloromethane, tetrahydrofuran, dimethylacetamide, and hexafluoroisopropanol, selected from one or more of lactone and polylactic acid-caprolactone copolymer.

[0015] A device for preparing an artificial blood vessel based on electrospinning, the device comprising a spinning mechanism and a collecting mechanism, the spinning mechanism being arranged on one side of the collecting mechanism, the collecting mechanism comprising a movable seat, a collecting tube being rotatably arranged above the movable seat, and driving mechanisms being arranged at both ends of the movable seat for driving the movable seat to move along the axial direction of the collecting tube.

[0016] According to the above technical solution, the driving mechanism includes a guide rail, a movable plate is movably provided on the guide rail, connecting plates are provided at both ends of the guide rail, and a driving screw is rotatably provided between the two connecting plates, the driving screw is threadedly connected to the connecting plate, and the movable seat is fixedly connected to the upper surface of the connecting plate.

[0017] According to the above technical solution, a positioning plate is provided on the upper surface of the movable seat, and the number of the positioning plates is two. The opposite surfaces of the positioning plates are provided with grooves, and the inner surfaces of the grooves are respectively provided with top blocks movably, and the two ends of the collecting pipe are respectively arranged inside the grooves, and the collecting pipe is located outside the top block.

[0018] According to the above technical solution, a circular groove is penetrated on the end surface of the groove, a rotating plate is rotatably arranged in the circular groove, a cavity structure is arranged in the rotating plate, the top block is movably arranged on the surface of the rotating plate, an adjusting screw which is threadedly connected to the top block and drives the top block to slide is rotatably arranged inside the rotating plate, one end of the adjusting screw is coaxially connected with a gear, a crown gear is rotatably arranged inside the rotating plate, the gears are respectively meshed with the crown gears, and a knob which is coaxially connected with the crown gear is rotatably arranged on the outer side of the rotating plate.

[0019] According to the above technical solution, a positioning ring is fixedly connected to the outer side of the knob corresponding to the outer surface of the rotating plate, and a fastening bolt is penetrated through the end surface of the positioning ring.

[0020] According to the above technical solution, the positioning plate is movably connected to the movable seat, a rotating sleeve is rotatably provided inside the movable seat, a rotating ring is rotatably provided on the positioning plate and is sleeved on the rotating sleeve and movably connected to the rotating sleeve, the rotating ring and the corresponding rotating plate are linked by a transmission mechanism, a transmission shaft that passes through the rotating sleeve and drives the rotating sleeve to rotate is rotatably provided between the connecting plates, and a screw that is threadedly connected to the positioning plate is provided inside the movable seat.

[0021] Compared with the prior art, the beneficial effects achieved by the present invention are as follows: the artificial blood vessel proposed in the present invention is a double-layer structure, the inner layer is a polymer electrospun fiber containing heparin, so it has good blood compatibility, and the outer layer gives the artificial blood vessel good toughness and strength; while in traditional electrostatic spinning equipment, a moving spinneret sprays the spinning onto a rotating tubular object, and the spinning solidifies on the surface of the tubular object to form an artificial blood vessel. Since the spinneret is in a moving state during operation, the ejected spinning cannot be guaranteed to be sufficiently uniform and stable, which affects the quality of the artificial blood vessel. The present invention arranges a movable seat, and a collecting tube is arranged on the movable seat. When the blood vessel is made, the collecting tube is driven to move by the movable seat, and the spinneret is in a relatively fixed state, thereby ensuring that the ejected spinning is sufficiently stable and uniform, and ensuring the stability of the quality of the artificial blood vessel. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The accompanying drawings are used to provide a further understanding of the present invention and constitute a part of the specification. Together with the embodiments of the present invention, they are used to explain the present invention and do not constitute a limitation of the present invention. In the accompanying drawings:

[0023] Figure 1 This is an ultrasound detection image of the polyurethane artificial blood vessel prepared in Example 1 of the present invention implanted into the abdominal aorta of SD rats 2 months later;

[0024] Figure 2 This is a HE-stained section of the polyurethane artificial blood vessel prepared in Example 1 of the present invention implanted into the abdominal aorta of SD rats for 2 months;

[0025] Figure 3 It is a schematic diagram of the structure of the present invention;

[0026] Figure 4 It is a schematic diagram of the structure of the movable seat of the present invention;

[0027] Figure 5 It is a schematic diagram of the main cross-sectional structure of the movable seat of the present invention;

[0028] Figure 6 It is a schematic diagram of the left cross-sectional structure of the positioning plate of the present invention;

[0029] In the figure: 1. movable seat; 2. collecting tube; 3. guide rail; 4. movable plate; 5. connecting plate; 6. driving screw; 7. positioning plate; 8. groove; 9. top block; 10. circular groove; 11. rotating plate; 12. adjusting screw; 13. gear; 14. crown gear; 15. knob; 16. positioning ring; 17. fastening bolt; 18. rotating sleeve; 19. rotating ring; 20. transmission shaft; 21. screw. DETAILED DESCRIPTION

[0030] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0031] Example 1

[0032] An artificial blood vessel based on electrospinning, the artificial blood vessel is a double-layer hollow circular tube structure, including an inner layer and an outer layer, the inner layer is a polymer electrospun fiber containing heparin, and the outer layer is a polymer electrospun fiber;

[0033] Specifically, the production of artificial blood vessels includes the following steps:

[0034] Dissolve polyurethane in dimethylacetamide to prepare 10 mL of a uniform solution with a polyurethane concentration of 14%. Take 5 mL of the uniform solution and add 20 μL of Span80. After stirring evenly, add 30 mg of heparin and continue stirring for 12 hours to obtain an inner layer electrospun fiber solution.

[0035] The inner fiber tube and the outer fiber tube were prepared in sequence by electrospinning method, and received by metal roller, with spinning voltage of 12kV, flow rate of 1.6mL / h, and receiving distance of 12cm. After spinning, the tube was removed and vacuum dried for 24h. The inner diameter of the prepared artificial blood vessel was 3mm, the thickness of the inner fiber tube was 200μm, and the thickness of the outer fiber tube was 200μm.

[0036] The artificial blood vessel was implanted into the abdominal aorta of SD rats. Ultrasound showed that the artificial blood vessel was still patency after 2 months. Figure 1 The artificial blood vessel was taken out and sliced, showing that the wall was smooth and there was no thrombosis. Figure 2 shown.

[0037] Example 2

[0038] An artificial blood vessel based on electrospinning, the artificial blood vessel is a double-layer hollow circular tube structure, including an inner layer and an outer layer, the inner layer is a polymer electrospun fiber containing heparin, and the outer layer is a polymer electrospun fiber;

[0039] Specifically, the production of artificial blood vessels includes the following steps:

[0040] Dissolve polycaprolactone in dichloromethane to prepare 10 mL of a uniform solution with a polycaprolactone concentration of 10%. Take 3 mL of the uniform solution and add 6 μL of Span80. After stirring evenly, add 18 mg of heparin and continue stirring for 12 hours to obtain an inner layer electrospun fiber solution.

[0041] The inner fiber tube and the outer fiber tube were prepared in sequence by electrospinning method, and received by metal roller, with spinning voltage of 12kV, flow rate of 1.5mL / h, and receiving distance of 10cm. After spinning, the tube was removed and vacuum dried for 24h. The outer diameter of the prepared artificial blood vessel was 2mm, the thickness of the inner fiber tube was 100μm, and the thickness of the outer fiber tube was 250μm.

[0042] Example 3

[0043] A method for preparing an artificial blood vessel containing heparin comprises the following steps:

[0044] Polylactic acid was dissolved in hexafluoroisopropanol to prepare 10 mL of a uniform solution with a polylactic acid concentration of 16%. 6 mL of the uniform solution was added with 60 μL of Span80, stirred evenly, and then 60 mg of heparin was added and stirred for 12 hours to obtain an inner layer electrospun fiber solution.

[0045] The inner fiber tube and the outer fiber tube were prepared in sequence by electrospinning, and received by a metal roller. The spinning voltage was 14 kV, the flow rate was 1.8 mL / h, and the receiving distance was 15 cm. After spinning, the tube was removed and vacuum dried for 24 hours. The inner diameter of the prepared artificial blood vessel was 3 mm, the thickness of the inner fiber tube was 400 μm, and the thickness of the outer fiber tube was 280 μm.

[0046] See also Figure 3-6 A preparation device for an artificial blood vessel based on electrostatic spinning, the preparation device includes a spinneret mechanism and a collecting mechanism, the spinneret mechanism is arranged on one side of the collecting mechanism, the collecting mechanism includes a movable seat 1, a collecting tube 2 is rotatably arranged above the movable seat 1, and driving mechanisms for driving the movable seat 1 to move along the axial direction of the collecting tube 2 are arranged at both ends of the movable seat 1. The spinneret mechanism adopts the existing technology and can continuously spray out electrospun fibers. The collecting tube 2 can be made of metal material. The collecting tube 2 rotates, and the electrospun fibers are sprayed on the surface of the collecting tube 2 and solidified to complete the production of the blood vessel. In this process, the collecting tube 2 is driven by the movable seat 1 to move, so that the spinneret mechanism is in a relatively fixed state, ensuring stable and uniform spinning.

[0047] Specifically, the driving mechanism includes a guide rail 3, such as Figure 3As shown, the guide rail 3 is extended in the same direction as the axial direction of the collecting tube 2, and a movable plate 4 is movably provided on the guide rail 3. The guide rail 3 is a strip plate with a wedge-shaped cross-section. The movable plate 4 is provided with a wedge-shaped groove movably connected to the guide rail 3. Connecting plates 5 are provided at both ends of the guide rail 3, and a driving screw 6 is rotatably provided between the two connecting plates 5. The driving screw 6 is screwed to the connecting plate 5, and the movable seat 1 is fixedly connected to the upper surface of the connecting plate 5. A driving motor for driving the driving screw 6 to rotate is connected to one side of the connecting plate 5. The movement of the movable plate 4 is controlled by rotating the driving screw 6.

[0048] Specifically, a positioning plate 7 is provided on the upper surface of the movable seat 1, and the number of the positioning plates 7 is two. Figure 5 As shown, the opposite surface of the positioning plate 7 is provided with a groove 8, and the groove 8 is circular. The inner surface of the groove 8 is movably provided with a top block 9, and the top block 9 can move along the radial direction of the groove 8. The two ends of the collecting tube 2 are respectively arranged inside the groove 8 and located on the outside of the top block 9. The top block 9 moves outward to press against the inner wall of the collecting tube 2 to fix the collecting tube 2. Therefore, the collecting tube 2 is detachable to facilitate the removal of the blood vessel, and the collecting tube 2 of different types of materials can also be replaced.

[0049] Specifically, a circular groove 10 is provided through the end surface of the groove 8, a rotating plate 11 is rotatably provided in the circular groove 10, a cavity structure is provided in the rotating plate 11, a top block 9 is movably provided on the surface of the rotating plate 11, the collecting tube 2 is connected to the rotating plate 11 through the top block 9, and the rotating plate 11 can also drive the collecting tube 2 to rotate between the positioning plates 7, and an adjusting screw 12 which is screwed to the top block 9 and drives the top block 9 to slide is provided inside the rotating plate 11, and the adjusting screw 12 extends along the radial direction of the groove 8, and one side of the adjusting screw 12 is provided. The ends are coaxially connected with gears 13, the internal rotation of the rotating plate 11 is provided with a crown gear 14, the gears 13 are respectively meshed with the crown gears 14, and the outer rotation of the rotating plate 11 is provided with a knob 15 coaxially connected with the crown gear 14. By rotating the knob 15, the crown gear 14 is driven to rotate, and the gear 13 is driven to rotate synchronously, and then the adjusting screw 12 is rotated synchronously. Under the action of the thread cooperation, the top block 9 is controlled to move synchronously, so that the top block 9 can fix the collecting tube 2, and at the same time maintain good concentricity, so that the rotation process of the collecting tube 2 is more stable.

[0050] Specifically, a positioning ring 16 is fixedly connected to the outer side of the knob 15 on the outer surface of the rotating plate 11, and a fastening bolt 17 is penetrated through the end face of the positioning ring 16. In order to prevent the knob 15 from rotating relative to the rotating plate 11 when the rotating plate 11 rotates and causing the top block 9 to loosen, the fastening bolt 17 can be tightened to keep the knob 15 and the positioning ring 16 relatively fixed, thereby achieving a locking function.

[0051] Specifically, the positioning plate 7 is movably connected to the movable seat 1, and the positioning plate 7 can be moved along the length direction of the collecting tube 2 to facilitate the removal and installation of the collecting tube 2. Figure 5 As shown, a cavity is provided inside the movable seat 1, and a slide groove is provided on the cavity. The positioning plate 7 is movably provided at the slide groove, so a part of the positioning plate 7 is located inside the cavity, and a rotating sleeve 18 is rotatably provided inside the movable seat 1. A rotating ring 19 which is sleeved on the rotating sleeve 18 and movably connected to the rotating sleeve 18 is rotatably provided on the positioning plate 7. The rotating ring 19 and the corresponding rotating plate 11 are linked through a transmission mechanism. A transmission cavity is provided inside the positioning plate 7, and the rotating ring 19 and the rotating plate 11 are respectively located inside the transmission cavity. Sprockets are coaxially connected to the outer surfaces of the rotating ring 19 and the rotating plate 11, and chains are provided between the sprockets. A transmission shaft 20 which passes through the rotating sleeve 18 and drives the rotating sleeve 18 to rotate is rotatably provided between the connecting plates 5. A plurality of limit grooves extending in the same direction are provided on the surface of the transmission shaft 20, and a limit strip movably connected to the limit groove is provided on the inner wall of the rotating sleeve 18. A driving motor for driving the transmission shaft 20 to rotate is arranged on the surface of the connecting plate 5 at one end. When the driving motor drives the transmission shaft 20 to rotate, the rotating sleeve 18 can be driven to rotate. The outer wall of the rotating sleeve 18 and the inner wall of the rotating ring 19 are provided with limit grooves and limit bars (not shown in the figure) that are also movably connected. When the rotating sleeve 18 rotates, the rotating ring 19 can be driven to rotate, thereby controlling the rotation of the rotating plate 11 under the action of the sprocket chain, and at the same time will not interfere with the movement of the movable plate 4 and the positioning plate 7. A screw 21 that is screwed to the positioning plate 7 can be arranged inside the movable seat 1. Figure 5 As shown, the threads at both ends of the screw rod 21 rotate in opposite directions. By rotating the screw rod 21 , the positioning plate 7 can be controlled to move synchronously in the opposite direction, thereby playing the role of adjusting the positioning of the positioning plate 7 .

[0052] When the present invention is used, the screw 21 can be rotated to drive the positioning plate 7 to move, the collecting tube 2 is placed between the positioning plates 7, the positioning plate 7 is controlled to move, and after the collecting tube 2 is inserted into the groove 8, the knob 15 is rotated to drive the crown gear 14 to rotate, the crown gear 14 drives the gear 13 to rotate, the gear 13 drives the adjusting screw 12 to rotate, and the adjusting screw 12 drives the top block 9 to move against the inner wall of the collecting tube 2. When the transmission shaft 20 rotates, it drives the rotating sleeve 18 to rotate, the rotating sleeve 18 drives the rotating ring 19 to rotate, the rotating plate 11 is driven by the rotating ring 19 to rotate, and the rotating plate 11 drives the collecting tube 2 to rotate. At the same time, the driving screw 6 controls the movable seat 1 to slide, and the spinning mechanism spins on the surface of the collecting tube 2 to form an artificial blood vessel.

[0053] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein by equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. An artificial blood vessel based on electrospinning, characterized in that: The artificial blood vessel is a double-layer hollow circular tube structure, including an inner layer and an outer layer, wherein the inner layer is polymer electrospun fibers containing heparin, and the outer layer is polymer electrospun fibers.

2. The electrospinning-based artificial blood vessel according to claim 1, characterized in that: The outer diameter of the artificial blood vessel is 1-6 mm.

3. The electrospinning-based artificial blood vessel according to claim 1, characterized in that: The production of the artificial blood vessel comprises the following steps: S1. dissolving the polymer in a solvent to prepare a uniform solution having a polymer concentration of 10% to 16%; S2, adding Span80 at a ratio of 1-10 μL / mL to the uniform solution prepared in S1, stirring evenly, then adding the heparin aqueous solution at a ratio of 1-10 mg / mL, stirring vigorously for 12 hours, to obtain an inner layer electrospun fiber solution; S3, preparing an inner layer fiber tube by electrospinning the inner layer electrospun fiber solution prepared in S2, wherein the thickness of the inner layer fiber tube is 100-400 μm; S4. Using the uniform solution prepared in S1 to prepare an outer fiber tube on the surface of the inner fiber tube prepared in S3 by electrospinning, an artificial blood vessel is obtained, wherein the thickness of the outer fiber tube is 100-400 μm.

4. The electrospinning-based artificial blood vessel according to claim 3, characterized in that: The polymer in S1 is selected from one or more of polyurethane, polylactic acid, polycaprolactone, and polylactic acid-caprolactone copolymer, and the solvent in S1 is selected from one or more of dichloromethane, tetrahydrofuran, dimethylacetamide, and hexafluoroisopropanol.

5. A device for preparing an artificial blood vessel based on electrospinning, characterized in that: The preparation device comprises a spinning mechanism and a collecting mechanism, wherein the spinning mechanism is arranged on one side of the collecting mechanism, and the collecting mechanism comprises a movable seat (1), a collecting tube (2) is rotatably arranged above the movable seat (1), and driving mechanisms are arranged at both ends of the movable seat (1) to drive the movable seat (1) to move along the axial direction of the collecting tube (2).

6. The device for preparing an artificial blood vessel based on electrospinning according to claim 5, characterized in that: The driving mechanism comprises a guide rail (3), a movable plate (4) is movably provided on the guide rail (3), connecting plates (5) are provided at both ends of the guide rail (3), and a driving screw (6) is rotatably provided between the two connecting plates (5), the driving screw (6) is screwed to the connecting plate (5), and the movable seat (1) is fixedly connected to the upper surface of the connecting plate (5).

7. The device for preparing an artificial blood vessel based on electrospinning according to claim 6, characterized in that: A positioning plate (7) is provided on the upper surface of the movable seat (1), and the number of the positioning plates (7) is two. The surfaces opposite to the positioning plates (7) are provided with grooves (8), and the inner surfaces of the grooves (8) are respectively provided with top blocks (9) movably, and the two ends of the collecting tube (2) are respectively arranged inside the grooves (8), and the collecting tube (2) is located outside the top blocks (9).

8. The device for preparing an artificial blood vessel based on electrospinning according to claim 7, characterized in that: A circular groove (10) is provided through the end surface of the groove (8), a rotating plate (11) is rotatably provided in the circular groove (10), a cavity structure is provided in the rotating plate (11), the top block (9) is movably provided on the surface of the rotating plate (11), an adjusting screw (12) which is threadedly connected with the top block (9) and drives the top block (9) to slide is rotatably provided inside the rotating plate (11), one end of the adjusting screw (12) is coaxially connected with a gear (13), a crown gear (14) is rotatably provided inside the rotating plate (11), the gear (13) is respectively meshed with the crown gear (14), and a knob (15) which is coaxially connected with the crown gear (14) is rotatably provided on the outer side of the rotating plate (11).

9. The device for preparing an artificial blood vessel based on electrospinning according to claim 8, characterized in that: A positioning ring (16) is fixedly connected to the outer side of the rotating plate (11) corresponding to the outer side of the knob (15), and a fastening bolt (17) is penetrated through the end surface of the positioning ring (16).

10. The device for preparing an artificial blood vessel based on electrospinning according to claim 7, characterized in that: The positioning plate (7) is movably connected to the movable seat (1); a rotating sleeve (18) is rotatably provided inside the movable seat (1); a rotating ring (19) is rotatably provided on the positioning plate (7) and is sleeved on the rotating sleeve (18) and movably connected to the rotating sleeve (18); the rotating ring (19) and the corresponding rotating plate (11) are linked via a transmission mechanism; a transmission shaft (20) is rotatably provided between the connecting plates (5) and passes through the rotating sleeve (18) and drives the rotating sleeve (18) to rotate; a screw (21) is provided inside the movable seat (1) and is threadedly connected to the positioning plate (7).

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