CN114010368A - Helical multi-layer composite artificial blood vessel and preparation method thereof - Google Patents

Abstract

Translated fromChinese

本申请公开了一种螺旋型多层复合人工血管及其制备方法，该制备方法包括如下步骤：模具制备：3D打印螺旋型不锈钢模具；脱模层制备：在所述模具外侧涂覆至少一层脱模层；浸涂层制备：在所述至少一层脱模层外侧涂覆多层PLCL涂层；静电纺丝层制备：在所述多层PLCL涂层外侧纺丝，形成静电纺丝层；脱模：将成型的多层复合管与模具分离，得到螺旋型多层复合人工血管。该螺旋型多层复合人工血管制备方法，血管厚度可控且具有一定均匀性，制得的人工血管为呈螺旋状的小口径人工血管，能够产生旋动流，从而提高近壁面血流流速和壁面剪切应力，并能减少有害物质在血管内壁的沉积，对降低小口径人工血管移植后的再狭窄、提高长期通畅性具有重要意义。

The present application discloses a spiral-type multi-layer composite artificial blood vessel and a preparation method thereof. The preparation method includes the following steps: mold preparation: 3D printing a spiral stainless steel mold; mold release layer preparation: coating at least one layer on the outside of the mold mold release layer; dip coating preparation: coating the outer side of the at least one mold release layer with multiple layers of PLCL coating; electrospinning layer preparation: spinning on the outer side of the multilayer PLCL coating to form an electrospinning layer ; Demoulding: separate the formed multi-layer composite tube from the mold to obtain a spiral multi-layer composite artificial blood vessel. The preparation method of the helical multi-layer composite artificial blood vessel has controllable thickness of the blood vessel and a certain uniformity. It can reduce the wall shear stress and reduce the deposition of harmful substances on the inner wall of the blood vessel, which is of great significance for reducing restenosis after small-diameter artificial blood vessel transplantation and improving long-term patency.

Description

Spiral multilayer composite artificial blood vessel and preparation method thereof

Technical Field

The application relates to a spiral multilayer composite artificial blood vessel and a preparation method thereof.

Background

Artificial blood vessels are a substitute for many severely stenotic or occluded blood vessels, and large and medium-caliber artificial blood vessels are clinically used and achieve satisfactory results at present. The problems of restenosis, low patency rate and the like caused by easy occurrence of thrombus and intimal hyperplasia after the small-caliber artificial blood vessel operation are not solved.

The swirling flow state is a typical blood flow state of a human body, and on one hand, the flow state can stabilize blood flow and reduce turbulence; on the other hand, the vascular wall can be smoothly washed, and the deposition of harmful substances in blood on the vascular wall is reduced, so that the burden of the artery is reduced, and the artery is protected from the pathological influences of atherosclerosis, thrombosis and intimal hyperplasia. Research has shown that the formation of a swirling flow is related to the shape of a blood vessel, such as the three-dimensional helically twisted structure of a human aorta, so that the blood flow there assumes a swirling state during systole. The flow state is applied to the design of the small-caliber artificial blood vessel, and has important significance for reducing restenosis after the small-caliber artificial blood vessel is transplanted and improving long-term patency.

Disclosure of Invention

The purpose of the application is to provide a preparation method of the spiral multilayer composite artificial blood vessel, and the prepared small-caliber spiral multilayer composite artificial blood vessel can reduce the restenosis problem after the small-caliber artificial blood vessel is transplanted and improve the patency after the small-caliber artificial blood vessel is transplanted by forming blood swirling flow.

The technical scheme adopted by the application is as follows: the preparation method of the spiral multilayer composite artificial blood vessel comprises the following steps:

(1) preparing a mould: 3D printing a stainless steel mold, wherein the mold is in a spiral shape;

(2) preparing a demolding layer: coating at least one layer of demoulding layer on the outer side of the mould by adopting a lifting dipping film coating machine;

(3) preparing a dip coating: coating a plurality of PLCL coatings on the outer side of the at least one demolding layer by using a dip coating machine;

(4) preparing an electrostatic spinning layer: spinning for a preset time on the outer side of the multilayer PLCL coating by using an electrostatic spinning machine to form an electrostatic spinning layer;

(5) demolding: and separating the multilayer composite pipe formed on the mould from the mould to obtain the spiral multilayer composite artificial blood vessel.

As an improvement to the above, in the step (2), the step of applying a release layer includes:

fixing the die on a bayonet of a pulling and dipping coating machine, immersing the die into a 10-20% demolding solution at the speed of 4500-5500 mu m/s, and staying for 2-5 s;

withdrawing the mold from the demolding solution at a speed of 500-600 μm/s, and drying at room temperature for 10-15 min;

and (3) placing the mould in an oven, and drying for 25-35 min at 40-60 ℃.

As an improvement on the scheme, the demolding solution is a PVA solution, and the solvent of the PVA solution is a mixed solution of 50:50 deionized water and absolute ethyl alcohol.

As an improvement to the above, in the step (3), applying the multilayered PLCL coating includes:

fixing the mold which finishes the coating of the demolding layer on a bayonet of a pulling and dipping coating machine, and dipping the mold into a PLCL solution with the concentration of 14% -15% at the speed of 4500-5500 mu m/s for 2-5 s;

withdrawing the mould from the PLCL solution at a speed of 400-800 μm/s;

placing the mold in a fume hood, and drying for 8-15 min to form a PLCL coating;

repeating the above steps at least once.

As an improvement to the scheme, the solvent of the PLCL solution is hexafluoroisopropanol, the PLCL solution comprises PEG, and the concentration of the PEG is 0.55-0.65%.

As an improvement to the above solution, in the step (4), spinning outside the multilayer PLCL coating comprises:

injecting the electrostatic spinning solution with the concentration of 8-15% into a positive pressure injection pump and a negative pressure injection pump of an electrostatic spinning machine;

fixing the die for coating the multilayer PLCL on a collecting device of an electrostatic spinning machine;

and starting the electrostatic spinning machine, wherein the collecting device drives the die to rotate, and the positive pressure spinning needle and the negative pressure spinning needle of the collecting device jet spinning preset time from two sides to the die.

As an improvement to the scheme, the electrostatic spinning solution is a PLCL solution with hexafluoroisopropanol as a solvent, and the advancing speeds of the positive pressure injection pump and the negative pressure injection pump are 0.2-0.5 mL/h.

As an improvement to the above scheme, the positive pressure spinning needle is connected with a high voltage direct current power supply with the voltage of 4-6 kV, and the negative pressure spinning needle is connected with a high voltage direct current power supply with the voltage of-6-4 kV; the distance between the positive pressure spinning needle and the negative pressure spinning needle is 25-30 cm; the distance between the positive pressure spinning needle head and the negative pressure spinning needle head and the collecting device is 10-16 cm; the rotating speed of the collecting device is 300-500 rpm; the spinning temperature is less than 32 ℃, and the spinning relative humidity is less than 55%.

As an improvement to the above, the step (5) of separating the multilayer composite pipe molded on the mold from the mold includes:

taking down the die from the electrostatic spinning machine, and drying in a fume hood for 12-24 h;

soaking the die in deionized water for 48-72 h;

and taking out the mold, holding one end of the mold, clamping the multilayer composite pipe at the other end by using tweezers, and dragging and rotating to separate the multilayer composite pipe from the mold.

The technical scheme adopted by the application is as follows: the spiral multilayer composite artificial blood vessel is prepared by the preparation method of the spiral multilayer composite artificial blood vessel, and comprises a dip coating layer and an electrostatic spinning layer which are sequentially compounded from inside to outside, wherein the thickness of the dip coating layer is 60-120 mu m, and the thickness of the electrostatic spinning layer is 80-120 mu m;

the diameter of the spiral multilayer composite artificial blood vessel is 1-6 mm, the number of turns is not less than 2 turns, the spiral pitch is 40-60 mm, and the spiral amplitude is 2-5 mm.

Be different from prior art, the compound artificial blood vessel preparation method of helical form multilayer that this application provided, blood vessel thickness is controllable and have certain homogeneity, the artificial blood vessel that makes is the heliciform small-bore artificial blood vessel, the vascular wall comprises the dip-coating layer and the electrostatic spinning layer complex that have pore structure, this small-bore artificial blood vessel can produce the swirling flow to improve nearly wall blood flow velocity and wall shear stress, and can reduce the deposit of harmful substance at the vascular inner wall, to reducing the restenosis after the transplantation of small-bore artificial blood vessel, improve long-term patency and have the significance.

Drawings

Fig. 13D schematically illustrates printing a stainless steel mold.

Detailed Description

The application provides a preparation method of a spiral multilayer composite artificial blood vessel, which is used for preparing a spiral small-caliber artificial blood vessel, reducing restenosis after transplantation of the small-caliber artificial blood vessel and improving long-term patency.

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

The preparation method of the spiral multilayer composite artificial blood vessel comprises the following steps:

(1) preparing a mould:

a 3D printing stainless steel mold, the mold being a spiral type, please refer to fig. 1 together, fig. 1 shows a schematic diagram of the 3D printing stainless steel mold;

(2) preparing a demolding layer: coating at least one layer of demoulding layer on the outer side of the mould by adopting a lifting dipping film coating machine;

(3) preparing a dip coating: coating a plurality of PLCL coatings on the outer side of the at least one demolding layer by using a dip coating machine;

(4) preparing an electrostatic spinning layer: spinning for a preset time on the outer side of the multilayer PLCL coating by using an electrostatic spinning machine to form an electrostatic spinning layer;

(5) demolding: and separating the multilayer composite pipe formed on the mould from the mould to obtain the spiral multilayer composite artificial blood vessel.

Further, in the step (2), a release layer is coated on the surface of the mold for the purpose of separating the molded artificial blood vessel from the mold more smoothly, and the step of coating the release layer specifically includes:

a2. fixing the die on a bayonet of a pulling and dipping coating machine, immersing the die into a 10-20% demolding solution at the speed of 4500-5500 mu m/s, and staying for 2-5 s;

b2. withdrawing the mold from the demolding solution at a speed of 500-600 μm/s, and drying at room temperature for 10-15 min;

c2. and (3) placing the mould in an oven, and drying for 25-35 min at 40-60 ℃.

Wherein the demolding solution is a water-soluble polymer solution, such as a PVA solution, a PEO solution and the like.

Preferably, the demolding solution is a PVA solution, and the solvent of the PVA solution is a 50:50 mixture of deionized water and absolute ethyl alcohol.

It is understood that, in the above step (2), a release layer is formed on the mold, and in practical applications, the above step (2) can be repeated as many times as necessary to form at least two release layers on the mold.

Further, in the step (3), the step of applying the plurality of PLCL coatings specifically includes:

a3. fixing the die coated with the demolding layer in the step (2) on a bayonet of a pulling and dipping coating machine, and dipping the die into a PLCL solution with the concentration of 14% -15% at the speed of 4500-5500 mu m/s for 2-5 s;

b3. withdrawing the mould from the PLCL solution at a speed of 400-800 μm/s;

c3. placing the mold in a fume hood, and drying for 8-15 min to form a PLCL coating;

d3. repeating steps a3-c3 at least once to form at least two layers of the PLCL coating.

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

The more the number of PLCL coating layers, the thicker the small-caliber artificial blood vessel wall is.

Wherein, the solvent of the PLCL solution is hexafluoroisopropanol, the PLCL solution comprises PEG used as a pore-forming agent, so that the dip coating layer has a pore structure, and the concentration of the PEG in the PLCL solution is 0.55-0.65%.

Further, in the step (4), the step of spinning outside the multilayer PLCL coating specifically comprises:

a4. injecting the electrostatic spinning solution with the concentration of 8-15% into a positive pressure injection pump and a negative pressure injection pump of an electrostatic spinning machine;

b4. fixing the die coated with the multilayer PLCL coating in the step (3) on a collecting device of an electrostatic spinning machine;

c4. starting the electrostatic spinning machine, driving the die to rotate by the collecting device, and spinning for a preset time from two sides of a positive pressure spinning needle head and a negative pressure spinning needle head of the collecting device to the die;

it can be understood 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 is, the thicker the electrostatic spinning layer is, and the thicker the small-caliber artificial blood vessel wall is.

The electrostatic spinning solution is a PLCL solution with hexafluoroisopropanol as a solvent, and the PLCL solution in the step does not contain a pore-foaming agent.

The positive pressure injection pump and the negative pressure injection pump are propelled at a speed of 0.2-0.5 mL/h.

The electrostatic spinning device comprises two high-voltage direct-current power supplies, namely a positive-voltage direct-current power supply and a negative-voltage direct-current power supply, the positive-voltage direct-current power supply is used for outputting positive voltage, the negative-voltage direct-current power supply is used for outputting negative voltage, a positive-voltage spinning needle head is connected with the positive-voltage direct-current power supply, and the negative-voltage spinning needle head is connected with the negative-voltage direct-current power supply.

The collecting device is arranged between the positive pressure spinning needle head and the negative pressure spinning needle head, the positive pressure spinning needle head and the negative pressure spinning needle head are oppositely arranged and are respectively positioned on two opposite sides above the collecting device, and the positive pressure spinning needle head and the negative pressure spinning needle head obliquely downwards from two sides to the die on the collecting device to perform spinning so as to form conjugated electrostatic spinning.

Furthermore, the positive pressure spinning needle head is connected with a high-voltage direct-current power supply with the voltage of 4-6 kV, and the negative pressure spinning needle head is connected with a high-voltage direct-current power supply with the voltage of-6-4 kV; the distance between the positive pressure spinning needle and the negative pressure spinning needle is 25-30 cm; the distance between the positive pressure spinning needle head and the negative pressure spinning needle head and the collecting device is 10-16 cm; the rotating speed of the collecting device is 300-500 rpm; the spinning temperature is less than 32 ℃, and the spinning relative humidity is less than 55%.

Further, in the step (5), the separating the multilayer composite pipe molded on the mold from the mold specifically includes:

a5. taking down the die which finishes the electrostatic spinning in the step (4) from the electrostatic spinning machine, and drying the die in a fume hood for 12-24 hours;

b5. soaking the die in deionized water for 48-72 h;

the step is used for removing the demoulding layer formed on the mould, so that the multilayer composite pipe is convenient to separate from the mould.

c5. And taking out the mold, holding one end of the mold, clamping the multilayer composite tube at the other end by using forceps, dragging and rotating to separate the multilayer composite tube from the mold, and thus obtaining the spiral multilayer composite artificial blood vessel.

In an application scenario, the preparation method of the spiral multilayer composite artificial blood vessel further comprises a step of drying the spiral multilayer composite artificial blood vessel obtained in the step (5) so as to facilitate storage. Specifically, the spiral multilayer composite artificial blood vessel is placed in an oven, dried for 25-35 min at 40-60 ℃, taken out of the oven, and placed in a self-sealing bag for storage.

The application provides a compound artificial blood vessel of helical multilayer preparation method, the thickness of artificial blood vessel wall is controllable and have certain homogeneity, the compound artificial blood vessel of helical multilayer who is made by this preparation method, for being the heliciform small-bore artificial blood vessel, this small-bore artificial blood vessel can produce the swirling flow to improve nearly wall blood flow velocity and wall shear stress, and can reduce the deposit of harmful substance at the vascular inner wall, reduce the restenosis after the transplantation of small-bore artificial blood vessel, improve long-term patency.

The present application will be described in further detail with reference to examples. It is to be noted that the following examples are only illustrative of the present application, and do not limit the scope of the present application. Likewise, the following examples are only some examples and not all examples of the present application, and all other examples obtained by a person of ordinary skill in the art without any inventive step are within the scope of the present application.

The first embodiment is as follows:

the embodiment provides a preparation method of a spiral multilayer composite artificial blood vessel, which comprises the following steps:

(1) preparing a mould:

3D prints stainless steel mould, the mould is the spiral type, and mould diameter 4mm, spiral pitch 60mm, 2 circles of the number of turns, spiral amplitude 4 mm.

(2) Preparing a demolding layer:

a21. weighing 7.5g of PVA, preparing a 15% PVA solution with a solvent of 50:50 mixed solution of deionized water and absolute ethyl alcohol;

b21. fixing the mould on a bayonet of a dip-coating machine, dipping the mould into the PVA solution at a speed of 5000 mu m/s, and staying for 5 s;

c21. withdrawing the PVA solution from the mold at a speed of 500 μm/s, drying at room temperature for 10min, taking down, placing in an oven, and drying at 60 deg.C for 30 min;

d21. and (4) taking the die out of the oven, inversely fixing the die on a bayonet of a dip coating machine, and repeating the steps b21 and c21 once to finish the preparation of the release layer.

In this embodiment, two release layers are formed on the mold.

(3) Preparing a dip coating:

a31. weighing 6.39g of PLCL, preparing a PLCL solution with the concentration of 14.2 percent as a dip coating solution, taking hexafluoroisopropanol as a solvent, and simultaneously adding 0.27g of PEG as a pore-foaming agent;

b31. fixing the mould coated with the PVA coating on a bayonet of a pulling dip coating machine, and dipping the mould into the dip coating liquid at the speed of 5000 mu m/s for 5 s;

c31. withdrawing the die from the dip-coating solution at a speed of 500 μm/s;

d31. drying the mould in a fume hood for 10min to form a PLCL coating;

e31. the mould is reversely fixed on a bayonet of a dip coating machine, the operations of the steps b31-d31 are repeated, and the coating of the second PLCL coating is carried out;

f31. repeating steps b31-e31 twice to form six layers of the PLCL coating outside the release layer.

In this example, the thickness of the PLCL coating is approximately 100 μm.

(4) Preparing an electrostatic spinning layer:

a41. preparing a PLCL solution with the concentration of 10% as an electrostatic spinning solution, wherein a solvent is hexafluoroisopropanol, and injecting the electrostatic spinning solution into a positive pressure injection pump and a negative pressure injection pump of an electrostatic spinning machine;

b41. fixing the die coated with the six-layer PLCL coating in step f31 on a collecting device of an electrospinning machine;

c41. starting the electrostatic spinning machine, driving the die to rotate by the collecting device, and spinning for 2.5 hours from two sides of a positive pressure spinning needle head and a negative pressure spinning needle head of the electrostatic spinning machine to the die to form an electrostatic spinning layer on the outer side of the PLCL coating;

in this example, the thickness of the electrospun layer was about 100 μm.

In the embodiment, the propulsion speeds of the positive pressure injection pump and the negative pressure injection pump are both 0.5mL/h, the positive pressure spinning needle head is connected with a high-voltage direct-current power supply with the voltage of 5.48kV, and the negative pressure spinning needle head is connected with a high-voltage direct-current power supply with the voltage of-5.55 kV; the distance between the positive pressure spinning needle head and the negative pressure spinning needle head is 28 cm; the distances between the positive pressure spinning needle head and the negative pressure spinning needle head and the collecting device are all 16 cm; the rotating speed of the collecting device is 300 rpm; the spinning temperature is 29 ℃, and the spinning relative humidity is 50%.

(5) Demolding:

a51. taking the die which finishes the electrostatic spinning in the step c41 off the electrostatic spinning machine, and drying the die in a fume hood for 16 hours;

b51. soaking the mold in deionized water for 48 h;

c51. and taking out the mold, holding one end of the mold, clamping the multilayer composite pipe at the other end by using tweezers, and dragging and rotating to separate the multilayer composite pipe from the mold.

d51. And (3) placing the multilayer composite tube in an oven, drying for 30min at the temperature of 60 ℃, taking out, and placing in a self-sealing bag for storage.

The total wall thickness of the spiral multilayer composite artificial blood vessel prepared by the preparation method provided by the embodiment is about 200 μm.

Example two:

the embodiment provides a preparation method of a spiral multilayer composite artificial blood vessel, which comprises the following steps:

(1) preparing a mould:

3D prints stainless steel mould, the mould is the spiral type, and mould diameter 4mm, spiral pitch 60mm, 2 circles of the number of turns, spiral amplitude 2 mm.

(2) Preparing a demolding layer:

a21. weighing 10g of PVA, preparing a PVA solution with the concentration of 20 percent, and mixing deionized water and absolute ethyl alcohol with the solvent of 50: 50;

b21. fixing the die on a bayonet of a dip-coating machine, immersing the die into the PVA solution at a speed of 5500 mu m/s, and staying for 5 s;

c21. withdrawing the PVA solution from the mold at a speed of 800 μm/s, drying at room temperature for 10min, taking down, placing in an oven, and drying at 50 deg.C for 35 min;

d21. and (4) taking the die out of the oven, inversely fixing the die on a bayonet of a dip coater, and repeating the steps b21 and c21 to finish the preparation of the release layer.

In this embodiment, two release layers are formed on the mold.

(3) Preparing a dip coating:

a31. weighing 7.68g of PLCL, preparing a PLCL solution with the concentration of 15% as a dip coating solution, taking hexafluoroisopropanol as a solvent, and simultaneously adding 0.32g of PEG as a pore-foaming agent;

b31. fixing the mould coated with the PVA coating on a bayonet of a pulling dip coating machine, and dipping the mould into the dip coating liquid at a speed of 5500 mu m/s for 4.5 s;

c31. the mould is withdrawn from the dip-coating liquid at the speed of 700 mu m/s;

d31. drying the mould in a fume hood for 15min to form a PLCL coating;

e31. the mould is reversely fixed on a bayonet of a dip coating machine, the operations of the steps b31-d31 are repeated, and the coating of the second PLCL coating is carried out;

f31. repeating steps b31-e31 once to form four layers of the PLCL coating outside the release layer.

In this example, the thickness of the PLCL coating is about 70 μm.

(4) Preparing an electrostatic spinning layer:

a41. preparing a PLCL solution with the concentration of 15% as an electrostatic spinning solution, wherein a solvent is hexafluoroisopropanol, and injecting the electrostatic spinning solution into a positive pressure injection pump and a negative pressure injection pump of an electrostatic spinning machine;

b41. fixing the die coated with the four PLCL coatings in step f31 on a collecting device of an electrospinning machine;

c41. starting the electrostatic spinning machine, driving the die to rotate by the collecting device, and spinning for 2h from two sides of a positive pressure spinning needle and a negative pressure spinning needle of the electrostatic spinning machine to the die to form an electrostatic spinning layer on the outer side of the PLCL coating;

in this example, the thickness of the electrospun layer was about 90 μm.

In the embodiment, the propulsion speeds of the positive pressure injection pump and the negative pressure injection pump are both 0.5mL/h, the positive pressure spinning needle is connected with a high-voltage direct-current power supply with the voltage of 5.84kV, and the negative pressure spinning needle is connected with a high-voltage direct-current power supply with the voltage of-5.25 kV; the distance between the positive pressure spinning needle and the negative pressure spinning needle is 24 cm; the distances between the positive pressure spinning needle head and the negative pressure spinning needle head and the collecting device are all 13 cm; the rotating speed of the collecting device is 400 rpm; the spinning temperature is 29.8 ℃, and the spinning relative humidity is 48%.

(5) Demolding:

a51. taking the die which finishes the electrostatic spinning in the step c41 off the electrostatic spinning machine, and drying the die in a fume hood for 20 hours;

b51. soaking the mold in deionized water for 60 hours;

c51. and taking out the mold, holding one end of the mold, clamping the multilayer composite pipe at the other end by using tweezers, and dragging and rotating to separate the multilayer composite pipe from the mold.

d51. And (3) placing the multilayer composite tube in an oven, drying for 35min at the temperature of 45 ℃, taking out, and placing in a self-sealing bag for storage.

The total wall thickness of the spiral multilayer composite artificial blood vessel prepared by the preparation method provided by the embodiment is about 160 mu m.

The application also provides a spiral multilayer composite artificial blood vessel which is prepared by the preparation method of the spiral multilayer composite artificial blood vessel, the spiral multilayer composite artificial blood vessel comprises a dip coating layer and an electrostatic spinning layer which are sequentially compounded from inside to outside, the thickness of the dip coating layer is 60-120 mu m, and the thickness of the electrostatic spinning layer is 80-120 mu m.

Wherein the dip coating layer is a multilayer pore structure and comprises at least two PLCL coating layers.

The diameter of the spiral multilayer composite artificial blood vessel is 1-6 mm, the number of turns is not less than 2 turns, the spiral pitch is 40-60 mm, and the spiral amplitude is 2-5 mm.

This compound artificial blood vessel of screw-tupe multilayer for being spiral helicine small-bore artificial blood vessel, the vascular wall comprises the dip-coating layer and the electrostatic spinning layer combination that have pore structure, and this small-bore artificial blood vessel can produce the swirling flow to improve nearly wall blood flow velocity and wall shear stress, and can reduce the deposit of harmful substance at the vascular inner wall, to reducing the restenosis after the small-bore artificial blood vessel transplants, improve long-term patency and have the significance.

The above description is only an example of the present application and is not intended to limit the scope of the present application, and all modifications of equivalent structures and equivalent processes, which are made by the contents of the specification and the drawings, or which are directly or indirectly applied to other related technical fields, are intended to be included within the scope of the present application.

Claims (10)

Translated fromChinese

1.一种螺旋型多层复合人工血管的制备方法，其特征在于，包括如下步骤：1. a preparation method of helical multi-layer composite artificial blood vessel, is characterized in that, comprises the steps:(1)模具制备：3D打印不锈钢模具，所述模具呈螺旋型；(1) Mold preparation: 3D printing stainless steel mold, the mold is spiral;(2)脱模层制备：采用提拉浸渍镀膜机在所述模具外侧涂覆至少一层脱模层；(2) Preparation of mold release layer: at least one layer of mold release layer is coated on the outside of the mold by using a pull-up dip coating machine;(3)浸涂层制备：采用提拉浸渍镀膜机在所述至少一层脱模层外侧涂覆多层PLCL涂层；(3) Preparation of dip coating: using a pull-up dip coating machine to coat a multilayer PLCL coating on the outside of the at least one release layer;(4)静电纺丝层制备：采用静电纺丝机在所述多层PLCL涂层外侧纺丝预定时间，形成静电纺丝层；(4) Electrospinning layer preparation: using an electrospinning machine to spin the outer side of the multilayer PLCL coating for a predetermined time to form an electrospinning layer;(5)脱模：将成型在所述模具上的多层复合管与模具分离，得到螺旋型多层复合人工血管。(5) Demoulding: separating the multi-layer composite tube formed on the mold from the mold to obtain a spiral-type multi-layer composite artificial blood vessel.2.根据权利要求1所述的螺旋型多层复合人工血管的制备方法，其特征在于，步骤(2)中，涂覆脱模层包括：2. the preparation method of spiral type multi-layer composite artificial blood vessel according to claim 1, is characterized in that, in step (2), coating release layer comprises:将所述模具固定在提拉浸渍镀膜机的卡口上，以4500～5500μm/s的速度浸入到浓度10％～20％的脱模溶液中，滞留2～5s；Fixing the mold on the bayonet of the pull-dipping coating machine, immersing the mold in a release solution with a concentration of 10%-20% at a speed of 4500-5500 μm/s, and staying for 2-5s;将模具以500～600μm/s的速度退出所述脱模溶液，在室温条件下干燥10～15min；The mold is withdrawn from the mold release solution at a speed of 500-600 μm/s, and dried at room temperature for 10-15 minutes;将模具放置于烘箱中，在40～60℃条件下干燥25～35min。Place the mold in an oven and dry at 40-60°C for 25-35 minutes.3.根据权利要求2所述的螺旋型多层复合人工血管的制备方法，其特征在于，所述脱模溶液为PVA溶液，该PVA溶液的溶剂为50:50的去离子水和无水乙醇混合液。3. the preparation method of helical multi-layer composite artificial blood vessel according to claim 2, is characterized in that, described demoulding solution is PVA solution, and the solvent of this PVA solution is deionized water and dehydrated alcohol of 50:50 mixture.4.根据权利要求1所述的螺旋型多层复合人工血管的制备方法，其特征在于，步骤(3)中，涂覆多层PLCL涂层包括：4. the preparation method of helical multi-layer composite artificial blood vessel according to claim 1, is characterized in that, in step (3), coating multi-layer PLCL coating comprises:将完成脱模层涂覆的模具固定于提拉浸渍镀膜机的卡口上，以4500～5500μm/s的速度浸入到浓度14％～15％的PLCL溶液中，浸涂时间2～5s；将所述模具以400～800μm/s的速度退出PLCL溶液；Fix the mold with the release layer coating on the bayonet of the pull-up dip coating machine, and immerse it in a PLCL solution with a concentration of 14%-15% at a speed of 4500-5500 μm/s, and the dip coating time is 2-5s; The mold exits the PLCL solution at a speed of 400-800 μm/s;将所述模具放置在通风橱中，干燥8～15min，形成一层PLCL涂层；The mold is placed in a fume hood and dried for 8-15 minutes to form a layer of PLCL coating;重复上述步骤至少一次。Repeat the above steps at least once.5.根据权利要求4所述的螺旋型多层复合人工血管的制备方法，其特征在于，所述PLCL溶液的溶剂为六氟异丙醇，所述PLCL溶液包括PEG，PEG浓度为0.55％～0.65％。5. The preparation method of the helical multi-layer composite artificial blood vessel according to claim 4, wherein the solvent of the PLCL solution is hexafluoroisopropanol, the PLCL solution comprises PEG, and the PEG concentration is 0.55%～ 0.65%.6.根据权利要求1所述的螺旋型多层复合人工血管的制备方法，其特征在于，步骤(4)中，在所述多层PLCL涂层外侧纺丝包括：6. The preparation method of helical multi-layer composite artificial blood vessel according to claim 1, characterized in that, in step (4), spinning on the outside of the multi-layer PLCL coating comprises:将浓度8％～15％的静电纺丝液注入静电纺丝机的正压注射泵和负压注射泵；将完成多层PLCL涂覆的模具固定在静电纺丝机的收集装置上；Inject the electrospinning solution with a concentration of 8% to 15% into the positive pressure injection pump and the negative pressure injection pump of the electrospinning machine; fix the multi-layer PLCL coating mold on the collecting device of the electrospinning machine;开启该静电纺丝机，所述收集装置带动所述模具转动，其正压喷丝针头、负压喷丝针头从两侧朝向所述模具喷丝预定时间。When the electrospinning machine is turned on, the collecting device drives the mold to rotate, and the positive-pressure spinneret and the negative-pressure spinneret are spun toward the mold for a predetermined time from both sides.7.根据权利要求6所述的螺旋型多层复合人工血管的制备方法，其特征在于，所述静电纺丝液为溶剂为六氟异丙醇的PLCL溶液，所述正压注射泵和负压注射泵的推进速度为0.2～0.5mL/h。7. The preparation method of the helical multi-layer composite artificial blood vessel according to claim 6, wherein the electrospinning solution is a PLCL solution whose solvent is hexafluoroisopropanol, and the positive pressure syringe pump and the negative The propelling speed of the pressure syringe pump is 0.2 to 0.5 mL/h.8.根据权利要求6所述的螺旋型多层复合人工血管的制备方法，其特征在于，所述正压喷丝针头连接电压为4～6kV的高压直流电源，所述负压喷丝针头连接电压为-6～-4kV的高压直流电源；所述正压喷丝针头和负压喷丝针头的间距为25～30cm；所述正压喷丝针头、负压喷丝针头与收集装置的距离为10～16cm；所述收集装置的转速为300～500rpm；纺丝温度小于32℃，纺丝相对湿度小于55％。8 . The preparation method of the helical multi-layer composite artificial blood vessel according to claim 6 , wherein the positive pressure spinneret is connected to a high voltage DC power supply with a voltage of 4 to 6kV, and the negative pressure spinneret is connected to A high voltage DC power supply with a voltage of -6 to -4kV; the distance between the positive pressure spinneret and the negative pressure spinneret is 25 to 30cm; the distance between the positive pressure spinneret and the negative pressure spinneret and the collection device The rotating speed of the collecting device is 300-500 rpm; the spinning temperature is less than 32°C, and the spinning relative humidity is less than 55%.9.根据权利要求1所述的螺旋型多层复合人工血管的制备方法，其特征在于，步骤(5)中，将成型在所述模具上的多层复合管与模具分离包括：9. The preparation method of the helical multi-layer composite artificial blood vessel according to claim 1, wherein in step (5), separating the multi-layer composite tube formed on the mold from the mold comprises:将所述模具自静电纺丝机上取下，置于通风橱中干燥12～24h；Remove the mold from the electrospinning machine and place it in a fume hood to dry for 12-24 hours;将模具浸泡于去离子水中48～72h；Soak the mold in deionized water for 48-72h;取出模具，握持模具的一端，用镊子夹住另一端的多层复合管，拖拽旋转，使多层复合管与模具分离。Take out the mold, hold one end of the mold, clamp the other end of the multi-layer composite tube with tweezers, and drag and rotate to separate the multi-layer composite tube from the mold.10.一种螺旋形多层复合人工血管，其特征在于，由权利要求1所述的螺旋型多层复合人工血管的制备方法制得，该螺旋形多层复合人工血管包括从内到外依次复合的浸涂层和静电纺丝层，所述浸涂层的厚度为60～120μm，所述静电纺丝层的厚度为80～120μm；10. A spiral-shaped multi-layer composite artificial blood vessel, characterized in that, obtained by the preparation method of the spiral-shaped multi-layer composite artificial blood vessel according to claim 1, wherein the spiral-shaped multi-layer composite artificial blood vessel comprises sequentially from inside to outside. A composite dip coating and an electrospinning layer, wherein the dip coating has a thickness of 60-120 μm, and the electrospinning layer has a thickness of 80-120 μm;该螺旋形多层复合人工血管的直径为1～6mm，匝数不少于2匝，螺旋节距为40～60mm，螺旋振幅为2～5mm。The diameter of the spiral multi-layer composite artificial blood vessel is 1-6 mm, the number of turns is not less than 2, the spiral pitch is 40-60 mm, and the spiral amplitude is 2-5 mm.

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