Spiral multilayer composite artificial blood vessel and preparation method thereof

Abstract

The present application discloses a spiral multilayer composite artificial blood vessel and a preparation method thereof, the preparation method comprising the following steps: mold preparation: 3D printing a spiral stainless steel mold; mold release layer preparation: coating at least one mold release layer on the outside of the mold; dip coating layer preparation: coating multiple layers of PLCL coating on the outside of the at least one mold release layer; electrospinning layer preparation: spinning on the outside of the multiple layers of PLCL coating to form an electrospinning layer; demoulding: separating the formed multilayer composite tube from the mold to obtain a spiral multilayer composite artificial blood vessel. The spiral multilayer composite artificial blood vessel preparation method has controllable blood vessel thickness and a certain uniformity. The obtained artificial blood vessel is a spiral small-caliber artificial blood vessel, which can generate swirling flow, thereby increasing the near-wall blood flow velocity and wall shear stress, and can reduce the deposition of harmful substances on the inner wall of the blood vessel, which is of great significance for reducing restenosis after small-caliber artificial blood vessel transplantation and improving long-term patency.

Description

Technical Field

[0001] The present application relates to a spiral multi-layer composite artificial blood vessel and a preparation method thereof. Background Art

[0002] Artificial blood vessels are substitutes for many severely narrowed or occluded blood vessels. Currently, large and medium-caliber artificial blood vessels have been used clinically and achieved satisfactory results. However, small-caliber artificial blood vessels are prone to thrombosis and intimal hyperplasia after surgery, resulting in restenosis and low patency, which has always been an unsolved problem.

[0003] Swirling flow is a typical blood flow pattern in the human body. On the one hand, this flow pattern can stabilize blood flow and reduce turbulence; on the other hand, it can make the blood vessel wall smooth and flush, reduce the deposition of harmful substances in the blood on the blood vessel wall, thereby reducing the burden on the arteries and protecting the arteries from the pathological effects of atherosclerosis, thrombosis and intimal hyperplasia. Studies have shown that the formation of swirling flow is related to the shape of blood vessels. For example, the three-dimensional spiral twisted structure of the human aorta makes the blood flow there present a swirling state during the heart contraction period. Applying this flow pattern to the design of small-caliber artificial blood vessels is of great significance to reducing restenosis after small-caliber artificial blood vessels are transplanted and improving long-term patency. Summary of the invention

[0004] The purpose of the present application is to provide a method for preparing a spiral multilayer composite artificial blood vessel. The prepared small-caliber spiral multilayer composite artificial blood vessel can form a swirling blood flow, reduce the restenosis problem of small-caliber artificial blood vessels after transplantation, and improve the patency of small-caliber artificial blood vessels after transplantation.

[0005] A technical solution adopted in the present application is to provide a method for preparing a spiral multi-layer composite artificial blood vessel, comprising the following steps:

[0006] (1) Mold preparation: 3D printing a stainless steel mold, wherein the mold is spiral-shaped;

[0007] (2) Preparation of release layer: coating at least one layer of release layer on the outside of the mold by using a pull-up dip coating machine;

[0008] (3) Dip coating preparation: using a pull-up dip coating machine to apply multiple layers of PLCL coating on the outside of the at least one release layer;

[0009] (4) Preparation of electrospinning layer: using an electrospinning machine to spin for a predetermined time on the outside of the multi-layer PLCL coating to form an electrospinning layer;

[0010] (5) Demolding: The multi-layer composite tube formed on the mold is separated from the mold to obtain a spiral multi-layer composite artificial blood vessel.

[0011] As an improvement to the above solution, in step (2), coating the release layer comprises:

[0012] The mold is fixed on the bayonet of the pull-up immersion coating machine, and immersed in a demoulding solution with a concentration of 10% to 20% at a speed of 4500 to 5500 μm / s for 2 to 5 seconds;

[0013] The mold is removed from the demoulding solution at a speed of 500 to 600 μm / s and dried at room temperature for 10 to 15 minutes;

[0014] Place the mold in an oven and dry at 40-60°C for 25-35 minutes.

[0015] As an improvement to the above solution, the demoulding solution is a PVA solution, and the solvent of the PVA solution is a 50:50 mixture of deionized water and anhydrous ethanol.

[0016] As an improvement to the above scheme, in step (3), applying a multilayer PLCL coating comprises:

[0017] Fix the mold coated with the release layer on the bayonet of the pull-up immersion coating machine, and immerse it in a PLCL solution with a concentration of 14% to 15% at a speed of 4500 to 5500 μm / s for 2 to 5 seconds;

[0018] The mold is withdrawn from the PLCL solution at a speed of 400 to 800 μm / s;

[0019] The mold is placed in a fume hood and dried for 8 to 15 minutes to form a layer of PLCL coating;

[0020] Repeat the above steps at least once.

[0021] As an improvement to the above solution, the solvent of the PLCL solution is hexafluoroisopropanol, and the PLCL solution includes PEG, and the concentration of PEG is 0.55% to 0.65%.

[0022] As an improvement to the above scheme, in step (4), spinning outside the multilayer PLCL coating includes:

[0023] Injecting an electrospinning solution with a concentration of 8% to 15% into a positive pressure injection pump and a negative pressure injection pump of an electrospinning machine;

[0024] The mold with the multi-layer PLCL coating is fixed on the collecting device of the electrospinning machine;

[0025] The electrospinning machine is turned on, and the collecting device drives the mold to rotate, and the positive pressure spinneret needle and the negative pressure spinneret needle thereof spin toward the mold from both sides for a predetermined time.

[0026] As an improvement to the above scheme, the electrospinning solution is a PLCL solution whose solvent is hexafluoroisopropanol, and the propulsion speed of the positive pressure injection pump and the negative pressure injection pump is 0.2-0.5 mL / h.

[0027] As an improvement to the above scheme, the positive pressure spinneret needle is connected to a high voltage DC power supply with a voltage of 4 to 6 kV, and the negative pressure spinneret needle is connected to a high voltage DC power supply with a voltage of -6 to -4 kV; the spacing between the positive pressure spinneret needle and the negative pressure spinneret needle is 25 to 30 cm; the distance between the positive pressure spinneret needle, the negative pressure spinneret needle and the collecting device is 10 to 16 cm; the rotation speed of the collecting device is 300 to 500 rpm; the spinning temperature is less than 32°C, and the spinning relative humidity is less than 55%.

[0028] As an improvement to the above solution, in step (5), separating the multilayer composite tube formed on the mold from the mold includes:

[0029] The mold was removed from the electrospinning machine and placed in a fume hood to dry for 12 to 24 hours;

[0030] Soak the mold in deionized water for 48 to 72 hours;

[0031] Take out the mold, hold one end of the mold, clamp the multilayer composite tube at the other end with tweezers, drag and rotate, and separate the multilayer composite tube from the mold.

[0032] A technical solution adopted in the present application is: to provide a spiral multi-layer composite artificial blood vessel, which is prepared by the above-mentioned method for preparing a spiral multi-layer composite artificial blood vessel, wherein the spiral multi-layer composite artificial blood vessel comprises a dip coating layer and an electrospinning layer which are sequentially composited from the inside to the outside, wherein the thickness of the dip coating layer is 60 to 120 μm, and the thickness of the electrospinning layer is 80 to 120 μm;

[0033] The spiral multilayer composite artificial blood vessel has a diameter of 1 to 6 mm, a number of turns of not less than 2, a spiral pitch of 40 to 60 mm, and a spiral amplitude of 2 to 5 mm.

[0034] Different from the prior art, the method for preparing a spiral multi-layer composite artificial blood vessel provided in the present application has a controllable blood vessel thickness and a certain uniformity. The artificial blood vessel prepared is a spiral small-caliber artificial blood vessel, and the blood vessel wall is composed of a dip coating with a porous structure and an electrospinning layer. The small-caliber artificial blood vessel can generate a swirling flow, thereby increasing the near-wall blood flow velocity and wall shear stress, and can reduce the deposition of harmful substances on the inner wall of the blood vessel, which is of great significance for reducing restenosis after small-caliber artificial blood vessel transplantation and improving long-term patency. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Fig. 1 Schematic diagram of 3D printed stainless steel mold. DETAILED DESCRIPTION

[0036] The present application provides a method for preparing a spiral multilayer composite artificial blood vessel, which is used to prepare a spiral small-caliber artificial blood vessel, reduce restenosis after transplantation of the small-caliber artificial blood vessel, and improve long-term patency.

[0037] In the description of the present application, unless otherwise specified, "multilayer" means two or more layers. PVA refers to polyvinyl alcohol, PEO refers to polyethylene oxide, PLCL refers to poly-L-lactide-caprolactone, and PEG refers to polyethylene glycol.

[0038] The method for preparing a spiral multi-layer composite artificial blood vessel provided in the present application comprises the following steps:

[0039] (1) Mold preparation:

[0040] 3D printed stainless steel mold, the mold is spiral-shaped, please refer to it Figure 1 , Figure 1 A schematic diagram of a 3D printed stainless steel mold is shown;

[0041] (2) Preparation of release layer: coating at least one layer of release layer on the outside of the mold by using a pull-up dip coating machine;

[0042] (3) Preparation of dip coating: using a pull-up dip coating machine to coat the outer side of the at least one release layer with multiple layers of PLCL coating;

[0043] (4) Preparation of electrospinning layer: using an electrospinning machine to spin for a predetermined time on the outside of the multi-layer PLCL coating to form an electrospinning layer;

[0044] (5) Demolding: The multi-layer composite tube formed on the mold is separated from the mold to obtain a spiral multi-layer composite artificial blood vessel.

[0045] Furthermore, in step (2), the purpose of coating a release layer on the surface of the mold is to enable the formed artificial blood vessel to be separated from the mold more smoothly. The step of coating the release layer specifically includes:

[0046] a2. The mold is fixed on the bayonet of the pull-up immersion coating machine, and immersed in a 10% to 20% concentration of the release solution at a speed of 4500 to 5500 μm / s, and retained for 2 to 5s;

[0047] b2. The mold is withdrawn from the release solution at a speed of 500 to 600 μm / s and dried at room temperature for 10 to 15 min;

[0048] c2. Place the mold in an oven and dry at 40-60°C for 25-35 minutes.

[0049] Wherein, the demoulding solution is a water-soluble polymer solution, such as a PVA solution, a PEO solution, and the like.

[0050] Preferably, the demoulding solution is a PVA solution, and the solvent of the PVA solution is a 50:50 mixture of deionized water and anhydrous ethanol.

[0051] It can be understood that the above step (2) forms a release layer on the mold. In practical applications, as needed, the above step (2) can be repeated multiple times to form at least two release layers on the mold.

[0052] Furthermore, in step (3), the step of applying a multilayer PLCL coating specifically includes:

[0053] a3. The mold coated with the release layer in step (2) is fixed on the bayonet of the pull-up immersion coating machine and immersed in a 14% to 15% PLCL solution at a speed of 4500 to 5500 μm / s for a dipping time of 2 to 5 s;

[0054] b3. The mold exits the PLCL solution at a speed of 400 to 800 μm / s;

[0055] c3. The mold is placed in a fume hood and dried for 8 to 15 minutes to form a layer of PLCL coating;

[0056] d3. Repeat steps a3-c3 at least once to form at least two layers of the PLCL coating.

[0057] It can be understood that in the actual preparation process, the number of layers of the PLCL coating to be formed can be determined according to the wall thickness requirements of the small-caliber artificial blood vessel, that is, the number of times the above steps a3-c3 are repeated.

[0058] The more layers of the PLCL coating, the thicker the wall of the small-caliber artificial blood vessel produced.

[0059] The solvent of the PLCL solution is hexafluoroisopropanol, and the PLCL solution includes PEG as a porogen, so that the dip coating has a porous structure. In the PLCL solution, the concentration of PEG is 0.55% to 0.65%.

[0060] Furthermore, in step (4), the step of spinning outside the multilayer PLCL coating specifically includes:

[0061] a4. Inject the electrospinning solution with a concentration of 8% to 15% into the positive pressure injection pump and negative pressure injection pump of the electrospinning machine;

[0062] b4. The mold coated with the multilayer PLCL coating completed in step (3) is fixed on the collecting device of the electrospinning machine;

[0063] c4. Turn on the electrospinning machine, the collecting device drives the mold to rotate, and the positive pressure spinneret and the negative pressure spinneret spinneret spin from both sides toward the mold for a predetermined time;

[0064] It is understandable that in the actual preparation process, the spinning time can be controlled according to the wall thickness requirement of the small-caliber artificial blood vessel. The longer the spinning time, the thicker the electrospinning layer, and the thicker the wall of the small-caliber artificial blood vessel.

[0065] Wherein, the electrospinning solution is a PLCL solution whose solvent is hexafluoroisopropanol, and the PLCL solution in this step does not contain a porogen.

[0066] The propulsion speed of the positive pressure injection pump and the negative pressure injection pump is 0.2-0.5 mL / h.

[0067] Among them, the electrospinning device includes two high-voltage DC power supplies, namely a positive DC power supply and a negative DC power supply. The positive DC power supply is used to output positive pressure, and the negative DC power supply is used to output negative pressure. The positive pressure spinneret needle is connected to the positive pressure DC power supply, and the negative pressure spinneret needle is connected to the negative pressure DC power supply.

[0068] The collecting device is arranged between the positive pressure spinneret needle and the negative pressure spinneret needle. The positive pressure spinneret needle and the negative pressure spinneret needle are arranged opposite to each other and are respectively located on two opposite sides above the collecting device. The positive pressure spinneret needle and the negative pressure spinneret needle spin obliquely downward from both sides toward the mold on the collecting device to form conjugate electrospinning.

[0069] Furthermore, the positive pressure spinneret needle is connected to a high voltage DC power supply with a voltage of 4 to 6 kV, and the negative pressure spinneret needle is connected to a high voltage DC power supply with a voltage of -6 to -4 kV; the spacing between the positive pressure spinneret needle and the negative pressure spinneret needle is 25 to 30 cm; the distance between the positive pressure spinneret needle, the negative pressure spinneret needle and the collecting device is 10 to 16 cm; the rotation speed of the collecting device is 300 to 500 rpm; the spinning temperature is less than 32°C, and the spinning relative humidity is less than 55%.

[0070] Furthermore, in step (5), separating the multilayer composite tube formed on the mold from the mold specifically comprises:

[0071] a5. The electrospinning mold completed in step (4) is removed from the electrospinning machine and placed in a fume hood to dry for 12 to 24 hours;

[0072] b5. Soak the mold in deionized water for 48 to 72 hours;

[0073] This step is used to remove the demoulding layer formed on the mold to facilitate the separation of the multilayer composite pipe from the mold. In practical applications, an appropriate amount of anhydrous ethanol can be added to the deionized water to promote the dissolution of the demoulding layer.

[0074] c5. Take out the mold, hold one end of the mold, clamp the multilayer composite tube at the other end with tweezers, drag and rotate to separate the multilayer composite tube from the mold, and obtain a spiral multilayer composite artificial blood vessel.

[0075] In one application scenario, the method for preparing a spiral multilayer composite artificial blood vessel provided in the present application further includes the step of drying the spiral multilayer composite artificial blood vessel obtained in step (5) for easy storage. Specifically, the spiral multilayer composite artificial blood vessel is placed in an oven and dried at 40 to 60° C. for 25 to 35 minutes, and then the artificial blood vessel is taken out of the oven and stored in a ziplock bag.

[0076] The present application provides a method for preparing a spiral multilayer composite artificial blood vessel, wherein the thickness of the artificial blood vessel wall is controllable and has a certain uniformity. The spiral multilayer composite artificial blood vessel prepared by the preparation method is a spiral small-caliber artificial blood vessel, which can generate swirling flow, thereby increasing the near-wall blood flow velocity and wall shear stress, and can reduce the deposition of harmful substances on the inner wall of the blood vessel, thereby reducing restenosis after small-caliber artificial blood vessel transplantation and improving long-term patency.

[0077] The present application is further described in detail below in conjunction with the embodiments. It is particularly noted that the following embodiments are only used to illustrate the present application, but are not intended to limit the scope of the present application. Similarly, the following embodiments are only partial embodiments of the present application rather than all embodiments, and all other embodiments obtained by those of ordinary skill in the art without making creative work are within the scope of protection of the present application.

[0078] Embodiment 1:

[0079] This embodiment provides a method for preparing a spiral multi-layer composite artificial blood vessel, the method comprising the following steps:

[0080] (1) Mold preparation:

[0081] A 3D printed stainless steel mold is spiral-shaped, with a mold diameter of 4 mm, a spiral pitch of 60 mm, 2 turns, and a spiral amplitude of 4 mm.

[0082] (2) Preparation of release layer:

[0083] a21 weighed 7.5g PVA, prepared a 15% PVA solution, the solvent was a 50:50 mixture of deionized water and anhydrous ethanol;

[0084] b21. The mold is fixed on the bayonet of the dip-pull coating machine and immersed in the PVA solution at a speed of 5000 μm / s for 5 seconds;

[0085] c21. The mold was removed from the PVA solution at a speed of 500 μm / s, dried at room temperature for 10 min, and then removed and placed in an oven and dried at 60 ° C for 30 min;

[0086] d21. Take the mold out of the oven, fix it upside down on the clamp of the lifting and dipping coating machine, repeat the above steps b21 and c21 once to complete the preparation of the release layer.

[0087] In this embodiment, two layers of the demoulding layers are formed on the mold.

[0088] (3) Dip coating preparation:

[0089] a31 weighed 6.39g PLCL, prepared a 14.2% PLCL solution as a dip coating solution, the solvent was hexafluoroisopropanol, and 0.27g PEG was added as a porogen;

[0090] b31. The mold coated with the PVA coating is fixed to the bayonet of the pull-up dip coating machine and immersed in the dipping solution at a speed of 5000μm / s for a dipping time of 5s;

[0091] c31. The mold is withdrawn from the dipping liquid at a speed of 500μm / s;

[0092] d31. The mold was dried in a fume hood for 10 min to form a layer of PLCL coating;

[0093] e31. The mold is fixed upside down on the bayonet of the pull-up immersion coating machine, and the above steps b31-d31 are repeated to apply a second layer of PLCL coating;

[0094] f31. Repeat steps b31-e31 twice to form six layers of the PLCL coating on the outside of the release layer.

[0095] In this embodiment, the thickness of the PLCL coating is about 100 μm.

[0096] (4) Preparation of electrospinning layer:

[0097] a41. A 10% PLCL solution was prepared as an electrospinning solution, the solvent being hexafluoroisopropanol, and the electrospinning solution was injected into the positive pressure injection pump and the negative pressure injection pump of the electrospinning machine;

[0098] b41. The mold coated with six layers of PLCL coating completed in step f31 is fixed on the collecting device of the electrospinning machine;

[0099] c41. Turn on the electrospinning machine, the collecting device drives the mold to rotate, and the positive pressure spinneret and the negative pressure spinneret of the electrospinning machine spin toward the mold from both sides for 2.5h to form an electrospinning layer on the outside of the PLCL coating;

[0100] In this embodiment, the thickness of the electrospinning layer is about 100 μm.

[0101] In this embodiment, the propulsion speeds of the positive pressure injection pump and the negative pressure injection pump are both 0.5 mL / h, the positive pressure spinneret needle is connected to a high-voltage DC power supply with a voltage of 5.48 kV, and the negative pressure spinneret needle is connected to a high-voltage DC power supply with a voltage of -5.55 kV; the spacing between the positive pressure spinneret needle and the negative pressure spinneret needle is 28 cm; the distances between the positive pressure spinneret needle, the negative pressure spinneret needle and the collecting device are both 16 cm; the rotation speed of the collecting device is 300 rpm; the spinning temperature is 29°C, and the spinning relative humidity is 50%.

[0102] (5) Demolding:

[0103] a51. The electrospinning mold completed in step c41 is removed from the electrospinning machine and placed in a fume hood to dry for 16h;

[0104] b51. Soak the mold in deionized water for 48h;

[0105] c51. Take out the mold, hold one end of the mold, clamp the multilayer composite tube at the other end with tweezers, drag and rotate to separate the multilayer composite tube from the mold.

[0106] d51. Place the multilayer composite tube in an oven, dry it at 60°C for 30 minutes, then take it out and store it in a ziplock bag.

[0107] The total wall thickness of the spiral multi-layer composite artificial blood vessel prepared by the preparation method provided in this embodiment is about 200 μm.

[0108] Embodiment 2:

[0109] This embodiment provides a method for preparing a spiral multi-layer composite artificial blood vessel, the method comprising the following steps:

[0110] (1) Mold preparation:

[0111] The 3D printed stainless steel mold is spiral-shaped, with a mold diameter of 4 mm, a spiral pitch of 60 mm, 2 turns, and a spiral amplitude of 2 mm.

[0112] (2) Preparation of release layer:

[0113] a21 weighed 10g PVA, prepared a 20% PVA solution, the solvent was a 50:50 mixture of deionized water and anhydrous ethanol;

[0114] b21. The mold is fixed on the bayonet of the dip-pull coating machine and immersed in the PVA solution at a speed of 5500 μm / s for 5 seconds;

[0115] c21. The mold was removed from the PVA solution at a speed of 800 μm / s, dried at room temperature for 10 min, and then removed and placed in an oven at 50 ° C for 35 min;

[0116] d21. Take the mold out of the oven, fix it upside down on the clamp of the lifting and dipping coating machine, and repeat the above steps b21 and c21 to complete the preparation of the release layer.

[0117] In this embodiment, two layers of the demoulding layers are formed on the mold.

[0118] (3) Dip coating preparation:

[0119] a31 weighed 7.68g PLCL, prepared a 15% PLCL solution as a dip coating solution, the solvent was hexafluoroisopropanol, and 0.32g PEG was added as a porogen;

[0120] b31. The mold coated with the PVA coating is fixed to the bayonet of the pull-up dip coating machine and immersed in the dipping solution at a speed of 5500μm / s for a dipping time of 4.5s;

[0121] c31. The mold is withdrawn from the dipping liquid at a speed of 700μm / s;

[0122] d31. The mold was dried in a fume hood for 15 min to form a layer of PLCL coating;

[0123] e31. The mold is fixed upside down on the bayonet of the pull-up immersion coating machine, and the above steps b31-d31 are repeated to apply a second layer of PLCL coating;

[0124] f31. Repeat steps b31-e31 once to form four layers of the PLCL coating on the outside of the release layer.

[0125] In this embodiment, the thickness of the PLCL coating is about 70 μm.

[0126] (4) Preparation of electrospinning layer:

[0127] a41. A 15% PLCL solution was prepared as an electrospinning solution, the solvent being hexafluoroisopropanol, and the electrospinning solution was injected into the positive pressure injection pump and the negative pressure injection pump of the electrospinning machine;

[0128] b41. The mold coated with four layers of PLCL coating completed in step f31 is fixed on the collecting device of the electrospinning machine;

[0129] c41. Turn on the electrospinning machine, the collecting device drives the mold to rotate, and the positive pressure spinneret and the negative pressure spinneret of the electrospinning machine spin toward the mold from both sides for 2h to form an electrospinning layer on the outside of the PLCL coating;

[0130] In this embodiment, the thickness of the electrospinning layer is about 90 μm.

[0131] In this embodiment, the propulsion speeds of the positive pressure injection pump and the negative pressure injection pump are both 0.5 mL / h, the positive pressure spinneret needle is connected to a high-voltage DC power supply with a voltage of 5.84 kV, and the negative pressure spinneret needle is connected to a high-voltage DC power supply with a voltage of -5.25 kV; the spacing between the positive pressure spinneret needle and the negative pressure spinneret needle is 24 cm; the distances between the positive pressure spinneret needle, the negative pressure spinneret needle and the collecting device are both 13 cm; the rotation speed of the collecting device is 400 rpm; the spinning temperature is 29.8°C, and the spinning relative humidity is 48%.

[0132] (5) Demolding:

[0133] a51. The electrospinning mold completed in step c41 is removed from the electrospinning machine and placed in a fume hood to dry for 20h;

[0134] b51. Soak the mold in deionized water for 60h;

[0135] c51. Take out the mold, hold one end of the mold, clamp the multilayer composite tube at the other end with tweezers, drag and rotate to separate the multilayer composite tube from the mold.

[0136] d51. Place the multilayer composite tube in an oven, dry it at 45°C for 35 minutes, then take it out and store it in a ziplock bag.

[0137] The total wall thickness of the spiral multi-layer composite artificial blood vessel prepared by the preparation method provided in this embodiment is about 160 μm.

[0138] The present application also provides a spiral multi-layer composite artificial blood vessel, which is prepared by the above-mentioned method for preparing a spiral multi-layer composite artificial blood vessel. The spiral multi-layer composite artificial blood vessel includes a dip coating layer and an electrospinning layer composited sequentially from the inside to the outside, the thickness of the dip coating layer is 60 to 120 μm, and the thickness of the electrospinning layer is 80 to 120 μm.

[0139] Wherein, the dip coating layer is a multi-layer porous structure, and the dip coating layer includes at least two layers of PLCL coating.

[0140] The spiral multilayer composite artificial blood vessel has a diameter of 1 to 6 mm, a number of turns of not less than 2, a spiral pitch of 40 to 60 mm, and a spiral amplitude of 2 to 5 mm.

[0141] The spiral multilayer composite artificial blood vessel is a spiral small-caliber artificial blood vessel. The blood vessel wall is composed of a dip coating with a porous structure and an electrospinning layer. The small-caliber artificial blood vessel can generate swirling flow, thereby increasing the near-wall blood flow velocity and wall shear stress, and can reduce the deposition of harmful substances on the inner wall of the blood vessel. It is of great significance to reduce restenosis after small-caliber artificial blood vessel transplantation and improve long-term patency.

[0142] The above descriptions are merely embodiments of the present application and are not intended to limit the patent scope of the present application. Any equivalent structure or equivalent process transformation made using the contents of the present application specification and drawings, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present application.

Claims

1. A method for preparing a spiral multilayer composite artificial blood vessel, characterized in that: The steps include: (1) Mold preparation: 3D printing a stainless steel mold, wherein the mold is spiral-shaped; (2) Preparation of release layer: coating at least one layer of release layer on the outside of the mold by using a pull-up dip coating machine; (3) Preparation of dip coating: using a pull-up dip coating machine to coat the outer side of the at least one release layer with multiple layers of PLCL coating; (4) Preparation of electrospinning layer: using an electrospinning machine to spin for a predetermined time on the outside of the multi-layer PLCL coating to form an electrospinning layer; (5) demolding: separating the multi-layer composite tube formed on the mold from the mold to obtain a spiral multi-layer composite artificial blood vessel; In step (2), applying the release layer comprises: The mold is fixed on the bayonet of the lifting and dipping coating machine, and immersed in a demoulding solution with a concentration of 10% to 20% at a speed of 4500 to 5500 μm / s for 2 to 5 seconds. The demoulding solution is a PVA solution, and the solvent of the PVA solution is a 50:50 mixture of deionized water and anhydrous ethanol; The mold is removed from the demoulding solution at a speed of 500 to 600 μm / s and dried at room temperature for 10 to 15 minutes; Place the mold in an oven and dry at 40-60°C for 25-35 minutes; In step (3), applying a multilayer PLCL coating comprises: Fix the mold coated with the release layer on the bayonet of the pull-up immersion coating machine, immerse it in a PLCL solution with a concentration of 14% to 15% at a speed of 4500 to 5500 μm / s, and the immersion time is 2 to 5 seconds. The solvent of the PLCL solution is hexafluoroisopropanol, and the PLCL solution includes PEG, and the PEG concentration is 0.55% to 0.65%; The mold is withdrawn from the PLCL solution at a speed of 400 to 800 μm / s; The mold is placed in a fume hood and dried for 8 to 15 minutes to form a layer of PLCL coating; Repeat the above steps at least once; In step (4), spinning outside the multilayer PLCL coating comprises: Injecting an electrospinning solution with a concentration of 8% to 15% into a positive pressure injection pump and a negative pressure injection pump of an electrospinning machine, wherein the electrospinning solution is a PLCL solution whose solvent is hexafluoroisopropanol, and the propulsion speed of the positive pressure injection pump and the negative pressure injection pump is 0.2 to 0.5 mL / h; The mold with the multi-layer PLCL coating is fixed on the collecting device of the electrospinning machine; The electrospinning machine is turned on, and the collecting device drives the mold to rotate, and the positive pressure spinneret needle and the negative pressure spinneret needle thereof spin toward the mold from both sides for a predetermined time.

2. The method for preparing a spiral multi-layer composite artificial blood vessel according to claim 1, characterized in that: The positive pressure spinneret needle is connected to a high voltage DC power supply with a voltage of 4 to 6 kV, and the negative pressure spinneret needle is connected to a high voltage DC power supply with a voltage of -6 to -4 kV; the spacing between the positive pressure spinneret needle and the negative pressure spinneret needle is 25 to 30 cm; the distance between the positive pressure spinneret needle, the negative pressure spinneret needle and the collecting device is 10 to 16 cm; the rotation speed of the collecting device is 300 to 500 rpm; the spinning temperature is less than 32°C, and the spinning relative humidity is less than 55%.

3. The method for preparing a spiral multi-layer composite artificial blood vessel according to claim 1, characterized in that: In step (5), separating the multilayer composite tube formed on the mold from the mold comprises: The mold was removed from the electrospinning machine and placed in a fume hood to dry for 12 to 24 hours; Soak the mold in deionized water for 48 to 72 hours; Take out the mold, hold one end of the mold, clamp the multilayer composite tube at the other end with tweezers, drag and rotate, and separate the multilayer composite tube from the mold.

4. A spiral multi-layer composite artificial blood vessel, characterized in that: The spiral multi-layer composite artificial blood vessel is prepared by the preparation method of claim 1, wherein the spiral multi-layer composite artificial blood vessel comprises a dip coating layer and an electrospinning layer which are sequentially composited from the inside to the outside, wherein the thickness of the dip coating layer is 60 to 120 μm, and the thickness of the electrospinning layer is 80 to 120 μm; The spiral multilayer composite artificial blood vessel has a diameter of 1 to 6 mm, a number of turns of not less than 2, a spiral pitch of 40 to 60 mm, and a spiral amplitude of 2 to 5 mm.

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