Preparation method for integrally forming electrostatic spinning variable cross-section special-shaped artificial blood vessel

Abstract

The invention relates to a preparation method for integrally forming an electrostatic spinning variable-cross-section special-shaped artificial blood vessel, and the artificial blood vessel prepared by the preparation method for integrally forming the electrostatic spinning variable-cross-section special-shaped artificial blood vessel can be integrally formed and quickly demoulded regardless of the inherent irregular shape of a supporting piece, so that the loss is reduced, and the efficiency is improved; meanwhile, the original irregular morphology of the blood vessel is kept. The method provided by the invention is simple in preparation, is suitable for individual case customization in the medical field, is adjustable in section and morphology, and has a good clinical application prospect.

Description

Technical Field

[0001] The invention belongs to the field of artificial blood vessels, and particularly relates to a preparation method for integrally forming an electrostatically spun variable-section special-shaped artificial blood vessel. Background Art

[0002] An artificial blood vessel is a device used to replace the function of natural blood vessels in the human body. They are usually made of biological or synthetic materials and are used to repair damaged or blocked blood vessels. Artificial blood vessels are designed to mimic the structure and function of natural blood vessels to ensure good blood flow and reduce the risk of blood clots.

[0003] Electrospun artificial blood vessels are made of nano-scale fiber structures and materials with good biocompatibility. They have the advantages of high specific surface area, good mechanical properties and controllability. This artificial blood vessel can better simulate the microstructure of natural blood vessels, promote the growth of endothelial cells, reduce the risk of thrombosis, and can be used as a drug carrier. Therefore, electrospun artificial blood vessels are regarded as a potential vascular replacement material that can be used in cardiovascular surgery and other vascular reconstruction fields.

[0004] However, most of the natural blood vessels in the human body are irregular and heterogeneous. For example, the aortic root is an irregular bifurcated blood vessel. When using aortic root replacement to treat patients with Marfan syndrome whose clinical life expectancy does not exceed 30 years old, the best option is to use artificial blood vessels that are 1:1 replicas of the natural blood vessels in the patient's body for replacement. However, the preparation of such variable-section, one-piece, suture-free heterogeneous artificial blood vessels by electrospinning is still a challenge.

[0005] At present, the vascular models prepared by electrospinning technology are all conventional "straight-tube" artificial blood vessels with constant cross-sections. Therefore, it is still impossible to prepare variable-section one-piece suture-free special-shaped artificial blood vessels. If the method of preparing "straight-tube" artificial blood vessels is simply transplanted to prepare variable-section irregular artificial blood vessels, it will cause serious demoulding problems due to steric hindrance, destroying the integrity of the artificial blood vessels. Summary of the invention

[0006] In view of the defects of the prior art, the technical problem to be solved by the present invention is to provide a method for preparing an electrospun variable-section special-shaped artificial blood vessel by one-piece molding, so as to solve the problem that the existing artificial blood vessels cannot replicate the original morphology and properties of the patient's natural blood vessels.

[0007] The present invention provides a method for preparing an electrospinning integrated molding material, comprising:

[0008] (1) Forming of flexible support parts:

[0009] The solid model is completely immersed in the elastic material solution, and after drying, it is demoulded to obtain a support member;

[0010] (2) Regulation of the electric potential of the flexible support:

[0011] In order to allow the electrospun fibers to finally be deposited on the surface of the prepared support, the support is filled with liquid, and the grounding wire or negative pressure wire is immersed in the liquid, and the support is sealed and installed;

[0012] (3) The spinning solution is electrospun, and the electrospun fibers are deposited on the surface of the support, and demolded to obtain an electrospun integrated molding material.

[0013] The support member in step (1) is a flexible support member.

[0014] Preferably, the material of the solid model in step (1) includes but is not limited to one or more of polymers and metals; the surface of the solid model is smooth; and the solid model includes a variable cross-section artificial blood vessel model or a constant cross-section model.

[0015] The solid model: according to the preset design shape and size of the artificial blood vessel, the shape of the natural blood vessel is reproduced in a 1:1 ratio using polymer or metal or other materials (such as wood, stone, glass, ceramic and other fixed materials), and the size of the prepared solid model is guaranteed to be stable and its surface is smooth.

[0016] Preparation of solid model: According to the preset design shape and size of the artificial blood vessel, a solid model with a smooth surface is prepared using polymer or metal.

[0017] The elastic material solution is used as the impregnating liquid. In order to obtain a support with a certain elasticity after drying and to prepare a flexible support for fiber deposition, the prepared front-end impregnating liquid is a solution of elastic materials such as latex, rubber, and polyurethane. The solvent and concentration can be adjusted according to the characteristics of the natural blood vessels to be replicated.

[0018] Preferably, the elastic material in step (1) includes one or more of latex, rubber, and thermoplastic elastomer; wherein the rubber includes one or more of nitrile rubber, natural rubber, and fluororubber; the thermoplastic elastomer includes polyurethane; the solvent in the elastic material solution includes one or more of tetrahydrofuran, dichloromethane, toluene, and hexane; and the mass percentage concentration of the elastomer solution is 5%-40%.

[0019] In step (1), the solid model is completely immersed in the elastic material solution, and when the surface of the fixed model is completely covered and no bubbles exist, it is taken out, dried, and demolded to obtain the support member for fiber deposition. The flexible support member model for fiber deposition has good elasticity and resilience, and its size can be easily changed during demolding, and after demolding, it can return to the full-size shape consistent with the original natural blood vessel.

[0020] Preferably, in step (1), the support member is surface treated to reduce its surface energy, which is beneficial for the subsequent separation of the fibers therefrom.

[0021] Furthermore, in step (1), the surface treatment of the support member to reduce the surface energy includes but is not limited to: treating the surface of the flexible support member to reduce its surface energy, such as spraying, dipping and coating the surface of the support member with a low surface energy material.

[0022] The low surface energy material includes polytetrafluoroethylene, silicone oil or other particles or liquids.

[0023] Preferably, the liquid in step (2) is a conductive liquid; wherein the conductive liquid is at least one of water, salt solution, acid solution, alkaline solution, ionic liquid, electrolyte solution, liquid metal, liquid containing conductive particles, etc.

[0024] Preferably, the spinning solution in step (3) is one or more of a polyurethane solution, a polyester solution, a polylactic acid solution, and a polycaprolactone solution, and the spinning solution concentration is 5%-40wt%; the electrospun fiber is at least one of a polyurethane fiber, a polyester fiber, a polylactic acid fiber, a polycaprolactone fiber, etc.

[0025] Preferably, the electrospinning process in step (3) includes: the positive pressure of electrospinning is 5kV-99kV, the negative pressure of immersion in liquid in step (2) is 0kV--99kV, and the uniformity of fiber deposition is regulated.

[0026] Fiber deposition uniformity control: During the spinning process, the support is rotated at set intervals, specifically: During the electrospinning fiber deposition process, the flexible support is rotated at a certain angle (0-360°) at set intervals (the interval time is more than 3 minutes, such as 5 minutes, 10 minutes, 15 minutes, etc.) to ensure that the amount of fiber deposited at each position on the surface of the flexible support is consistent.

[0027] Preferably, the demoulding in step (3) includes releasing the liquid in the support, separating the support from the electrospun fiber structure, and removing the support, wherein the electrospun fiber structure is an electrospun fiber 3D structure; and washing and drying are performed after the demoulding.

[0028] Furthermore, the demolding process of the deposited electrospun fibers and the flexible support member in step (3) includes releasing the liquid in the flexible support member, while the flexible support member becomes weak, its cross-sectional area changes rapidly, the structure collapses, and is physically separated from the fibers deposited on its surface, and the flexible support member is completely removed. The resulting 3D fiber structure is then cleaned and dried to obtain the prepared electrospun variable-section artificial blood vessel.

[0029] The invention provides an electrospinning integrated molding material prepared by the method.

[0030] The present invention provides an application of the electrospinning integrated molding material in an artificial blood vessel with a variable cross-section.

[0031] Beneficial Effects

[0032] The present invention provides a method for preparing an electrospinning variable-section special-shaped artificial blood vessel in one piece, including the preparation of a fiber deposition flexible support, surface treatment, and regulation of the fiber deposition process. Compared with the conventional method of preparing artificial blood vessels using electrospinning technology, the artificial blood vessel prepared by the method for preparing an electrospinning variable-section artificial blood vessel in one piece of the present invention can ignore the inherent irregular shape of the support, be formed in one piece and demould quickly, reduce loss, improve efficiency, and maintain the original irregular morphology of the blood vessel. The method provided by the present invention is simple to prepare, suitable for customization of individual cases in the medical field, and has adjustable cross-section and morphology, and has good clinical application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 This is an axial top view of the electrospun variable-section special-shaped artificial blood vessel prepared in Example 1 of the present invention;

[0034] Figure 2 A top view of the cross-section of the electrospun variable-section special-shaped artificial blood vessel prepared in Example 1 of the present invention after the deionized water is released but before the polyurethane flexible support member is removed;

[0035] Figure 3 This is a top view of the cross-section of the finished electrospun variable-section special-shaped artificial blood vessel prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0036] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms fall within the scope limited by the appended claims of the application equally.

[0037] Example 1

[0038] The method for integrally forming a variable-section special-shaped artificial blood vessel in this embodiment comprises the following steps:

[0039] (1) Preparation of solid model: Based on polypropylene material, solid model is printed by 3D printing technology;

[0040] (2) Preparation of impregnation liquid: polyurethane is dissolved in tetrahydrofuran, a volatile solvent, with a polyurethane mass fraction of 7 wt%; (3) Forming of flexible support: after polyurethane is completely dissolved in tetrahydrofuran, the surface of the solid model prepared by 3D printing is immersed in the solution, taken out, and dried. Because polyurethane is a flexible elastomer with large deformation recovery ability, it can be quickly separated to obtain a polyurethane-type flexible support by simple physical methods;

[0041] (4) Surface treatment of the flexible support: spraying the surface of the prepared flexible polyurethane support with PTFE (OKS571 from Germany) to reduce its surface energy;

[0042] (5) Control of the electric potential of the flexible support: A 1 wt% saline solution was poured into the polyurethane flexible support, and a negative pressure wire was connected, and the entire support was sealed and suspended;

[0043] (6) Fiber deposition uniformity control: Polylactic acid was dissolved in a mixed solvent of dichloromethane and tetrahydrofuran, the concentration of polylactic acid (Ingeo4032D from NatureWorks) was 12 wt%, the volume ratio of dichloromethane to tetrahydrofuran was 4:1, the positive pressure of spinning was +12 kV, and the negative pressure of immersion in saline was -1 kV. During the spinning process, the flexible support was rotated every 5 minutes to ensure that the amount of fiber deposited at each position on the surface of the flexible support was consistent;

[0044] (7) Rapid demolding and molding: The polyurethane flexible support is pierced with a fine needle, and the physiological saline inside is quickly drained. The polyurethane flexible support is automatically physically separated from the electrospun 3D fiber structure, and then washed and air-dried at 25°C to obtain the prepared polylactic acid electrospun variable-section artificial blood vessel.

[0045] The electrospun variable-section artificial blood vessel obtained in Example 1 has the advantages of rapid demoulding, one-piece molding and high degree of blood vessel restoration, which are not available in the current artificial blood vessel preparation methods.

[0046] The polylactic acid electrospun variable-section shaped artificial blood vessel in Example 1 was measured, and the largest diameter was 3.8 cm, and the shortest diameter was 2.5 cm.

[0047] Example 2

[0048] The method for integrally forming a variable-section special-shaped artificial blood vessel in this embodiment comprises the following steps:

[0049] (1) Preparation of solid model: Based on nitrile rubber material, a solid model is printed using 3D printing technology;

[0050] (2) Preparation of the impregnation liquid: dissolving nitrile rubber powder in a volatile solvent of dichloromethane, wherein the mass fraction of the nitrile rubber is 9 wt %;

[0051] (3) Forming of the flexible support: After the nitrile rubber is completely dissolved in dichloromethane, the surface of the solid model prepared by 3D printing is immersed in the solution, taken out, and dried. Because nitrile rubber is a flexible elastomer with large deformation recovery ability, the nitrile rubber-type flexible support can be quickly separated by a simple physical method;

[0052] (4) Surface treatment of the flexible support: spraying the surface of the prepared flexible nitrile rubber support with silicone oil spray to reduce its surface energy;

[0053] (5) Control of the electric potential of the flexible support: Pour tap water into the nitrile rubber flexible support, connect a negative pressure wire, and seal and hang the entire support;

[0054] (6) Fiber deposition uniformity control: Polyurethane is dissolved in N,N-dimethylformamide solvent. Polyurethane (Covestro 2590A) concentration is 17wt%, the positive pressure of spinning is +15kV, and the negative pressure of immersion in physiological saline is -1kV. During the spinning process, the flexible support is rotated every 5 minutes to ensure that the amount of fiber deposited at each position on the surface of the flexible support is consistent; (7) Rapid demoulding and molding: Use a fine needle to pierce the fixed rubber flexible support, quickly drain the tap water inside, and the nitrile rubber flexible support is automatically physically separated from the electrospun 3D fiber structure, and then washed and air-dried at 25°C to obtain the prepared polyurethane electrospun variable cross-section artificial blood vessel.

[0055] Example 3

[0056] The method for integrally forming a variable-section special-shaped artificial blood vessel in this embodiment comprises the following steps:

[0057] (1) Preparation of solid model: A solid model with a smooth surface forged from stainless steel;

[0058] (2) Preparation of the impregnation liquid: dissolve the natural rubber particles in a mixed solution of toluene and hexane, the mass fraction of natural rubber is 4%, and the volume ratio of the mixed solvent is 1:1;

[0059] (3) Forming of the flexible support: After the natural rubber is completely dissolved, the surface of the solid model forged from stainless steel is immersed in the solution, taken out, and dried. Because natural rubber is a flexible elastomer with large deformation recovery ability, the natural rubber-type flexible support can be quickly separated by simple physical methods;

[0060] (4) Surface treatment of the flexible support member: immersing the surface of the obtained natural rubber flexible support member in silicone oil to reduce its surface energy;

[0061] (5) Control of the electric potential of the flexible support: Pour tap water into the natural rubber flexible support, connect a negative pressure wire, and seal and hang it as a whole;

[0062] (6) Fiber deposition uniformity control: Polycaprolactone is dissolved in dichloromethane solvent. TM 6500) with a concentration of 10wt%, a spinning positive pressure of +11kV, and a negative pressure of -1kV when immersed in saline. During the spinning process, the flexible support was rotated every 5 minutes to ensure that the amount of fiber deposited at each position on the surface of the flexible support was consistent;

[0063] (7) Rapid demolding and molding: The natural rubber flexible support is pierced with a fine needle, and the tap water inside is quickly drained. The natural rubber flexible support is automatically physically separated from the electrospun 3D fiber structure, and then washed and air-dried at 25°C to obtain the prepared polycaprolactone electrospun variable-section artificial blood vessel.

Claims

1. A method for preparing an electrospinning integrated molding material, comprising: (1) immersing the solid model in an elastic material solution, drying, and demolding to obtain a support member; (2) Fill the support with liquid, immerse the ground wire or negative pressure wire in the liquid, and seal and install the support; (3) The spinning solution is electrospun, and the electrospun fibers are deposited on the surface of the support, and demolded to obtain an electrospun integrated molding material.

2. The preparation method according to claim 1, characterized in that: In the step (1), the material of the solid model includes one or more of polymers and metals; the surface of the solid model is smooth; and the solid model includes a variable cross-section artificial blood vessel model or a constant cross-section model.

3. The preparation method according to claim 1, characterized in that: In step (1), the elastic material includes one or more of latex, rubber, and thermoplastic elastomer; the solvent in the elastic material solution includes one or more of tetrahydrofuran, dichloromethane, toluene, and hexane; the mass percentage concentration of the elastomer solution is 5%-40%; The rubber includes one or more of nitrile rubber, natural rubber and fluororubber; the thermoplastic elastomer includes polyurethane.

4. The preparation method according to claim 1, characterized in that: In step (1), the support member is subjected to surface treatment to reduce surface energy.

5. The preparation method according to claim 1, characterized in that: The liquid in step (2) is a conductive liquid; wherein the conductive liquid is one or more of water, salt solution, acid solution, alkaline solution, ionic liquid, electrolyte solution, liquid metal, and liquid containing conductive particles.

6. The preparation method according to claim 1, characterized in that: In the step (3), the spinning solution is one or more of a polyurethane solution, a polyester solution, a polylactic acid solution, and a polycaprolactone solution; the spinning solution concentration is 5%-40wt%; and the electrospun fiber is one or more of a polyurethane fiber, a polyester fiber, a polylactic acid fiber, and a polycaprolactone fiber.

7. The preparation method according to claim 1, characterized in that: The electrospinning process in step (3) includes: the positive pressure of electrospinning is 5kV-99kV, the negative pressure of immersion in the liquid is 0kV~-99kV, and during the spinning process, the support is rotated at set intervals.

8. The preparation method according to claim 1, characterized in that: The demoulding in step (3) includes releasing the liquid in the support, separating the support from the electrospun fiber structure, and removing the support; washing and drying are performed after the demoulding.

9. An electrospinning integrated molding material prepared by the method of claim 1.

10. Use of the electrospun integrated molding material according to claim 9 in an artificial blood vessel with a variable cross-section.

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