CN119257791A - A three-layer structure small-caliber artificial blood vessel and its preparation method - Google Patents

Abstract

The invention discloses a three-layer structured small-caliber artificial blood vessel and a preparation method thereof, wherein the wall of the artificial blood vessel is 3 layers, the inner layer is an ordered fiber layer, the middle layer is an unordered fiber layer, the outer layer is an ordered fiber layer, the preparation methods of the inner layer and the outer layer are molten near-field direct writing, and the preparation method of the middle layer is one of molten near-field direct writing or electrostatic spinning. The middle disordered fiber layer has finer fibers and smaller pore diameter, the fiber diameter and the pore diameter of the fiber layer are adjustable, the fiber has good elasticity and compliance, the inner ordered fiber layer and the outer ordered fiber layer can realize ordered stacking of fibers at a specific angle, simulate the arrangement of collagen fibers of a human body blood vessel, and rapidly induce endothelialization and smooth muscle layer reconstruction, thereby effectively promoting blood vessel regeneration, and the raw material is a synthetic or natural degradable high molecular polymer, has good biocompatibility, simple preparation process and no addition of organic solvent or only use of a small amount of organic solvent.

Description

Three-layer structured small-caliber artificial blood vessel and preparation method thereof

Technical Field

The invention belongs to the technical field of artificial vascular graft preparation, and particularly relates to a three-layer structure small-caliber artificial blood vessel and a preparation method thereof.

Background

Cardiovascular disease is the leading cause of death worldwide. The main cause of cardiovascular disease is arterial occlusion, which results in a decrease in blood flow to the target organ. Vascular procedures, such as coronary bypass grafting and arteriovenous shunts, require biologically active vascular grafts. Autografts, such as saphenous vein and internal mammary artery, are gold standard grafts for treating vascular occlusions, and generally require two procedures, the first procedure to harvest the patient's own artery or vein, and the second procedure to replace the original occluded artery with a graft, restoring blood flow, which has the disadvantage of easily causing damage to the donor site of the patient, and in which patients without available autografts cannot be cured in this way. Vascular replacement and reconstructive surgery is widely practiced worldwide, and aims to rescue numerous patients with cardiovascular and cerebrovascular diseases and accidental injury victims. Synthetic vascular grafts not only avoid autologous vascular harvesting procedures, but also provide additional surgical opportunities for the patient. Although vascular grafts are commonly used in the field of vascular surgery, patients and doctors often suffer from the challenges of thrombosis, insufficient mechanical properties, mismatching of compliance and the like, and the problems particularly and remarkably influence the success rate of small-diameter vascular graft replacement surgery and become the main source of surgery failure. For example, traditional synthetic grafts based on polyethylene terephthalate (dacron) and expanded polytetrafluoroethylene (ePTFE) have been very successful in replacing the aorta (> 6 mm) in the clinic. However, the clinical application of such non-degradable synthetic vascular grafts in small-caliber (< 6 mm) vascular grafts such as coronary arteries is not ideal, mainly due to low long-term patency, easy thrombosis and embolism formation, and severe intimal hyperplasia. Currently, the problem of poor vascular graft adaptability significantly exacerbates the patient's suffering and financial burden.

The natural blood vessel of healthy people has excellent mechanical property, hemodynamic efficiency and antithrombotic capability by the unique three-layer structure of the natural blood vessel, namely an inner membrane, a middle membrane and an outer membrane. Specifically, the outer membrane layer has a high proportion of collagen fibers and thus has high strength, and can suppress excessive expansion and rupture under physiological pressure. The middle layer mainly comprises smooth muscle cells, collagen and elastin, and can adapt to the contraction and expansion of blood vessels under physiological pressure. The intima is mainly composed of endothelial cells and plays an important role in preventing thrombosis. Unfortunately, most of the existing vascular grafts on the market are of single-layer structures, and comprehensive performance standards of natural blood vessels are difficult to fully reach. In view of this, development of a novel vascular graft having high compliance and capable of simulating superior adaptation to natural blood vessels has been an urgent expectation for patients and doctors. In addition, if the growing microenvironment of endothelial cells is not ideal, the regenerated endothelial cells gradually fall off, resulting in thrombosis. The tunica media not only can maintain healthy endothelium, but also can inhibit vascular stenosis. For example, studies have shown that contact-dependent communication between smooth muscle cells and endothelial cells can promote proliferation of endothelial cells, whereas damaged smooth muscle cells induce inflammation or their hyper-proliferation induce restenosis. Therefore, the smooth muscle reconstruction plays a key role in the blood vessel regeneration process, accelerates the autologous smooth muscle reconstruction, is favorable for quickly recovering the compliance, adapts to the vascular pulsation, induces spontaneous endothelialization, and finally ensures the long-term smoothness of the blood vessel.

The arrangement of the natural extracellular matrix collagen fibers in human tissue plays an important role in maintaining tissue mechanics and function. In the three-layer structure of human blood vessels, different orientations of each layer of collagen fibers can regulate the mechanical behavior and cell arrangement of the blood vessels, and the cell arrangement plays a critical role in the maturation and regeneration of functional tissues. Collagen fibers in the smooth muscle layer are arranged circumferentially at an angle of 65 °, and smooth muscle cells are also arranged circumferentially. Notably, the directional growth of vascular smooth muscle cells along the circumferential direction of vascular grafts is critical to the regeneration of small diameter vessels, and its specific arrangement plays a critical role in the maturation and regeneration process of natural blood vessels. Therefore, vascular grafts capable of guiding the circumferential arrangement of smooth muscle cells can effectively promote revascularization. Electrospinning is the mainstream technology for manufacturing artificial vascular grafts at present, however, due to the fact that micro-nano fibers are deposited to cause small pore diameters and fibers are stacked in an unordered manner, cell infiltration and tissue regeneration in the vascular grafts are limited, regenerated tissues in the vascular grafts are gradually degenerated along with the extension of implantation time, and vascular walls are calcified, so that the grafts can be finally disabled. Currently, there is no vascular graft specifically designed for effective promotion of vascular endothelial cell regeneration and vascular smooth muscle cell regeneration.

When using traditional synthetic vascular grafts, both doctors and patients often face multiple challenges including thrombosis, mechanical property deficiencies, compliance mismatch, material non-degradability, and significant intimal hyperplasia problems. The existing artificial blood vessel is mainly produced by an electrostatic spinning technology, and the deposition of micro-nano fibers is easy to form fibers with small pore diameters and unordered arrangement, so that the infiltration of cells in the blood vessel and the capability of tissue regeneration are limited.

Disclosure of Invention

The invention aims to provide a three-layer structured small-caliber artificial blood vessel and a preparation method thereof, which solve the problem that the prior art cannot accurately construct a microstructure which is favorable for regeneration of vascular endothelial cells and vascular smooth muscle cells, thereby accelerating the natural regeneration process of the blood vessel.

The wall of the artificial blood vessel is 3 layers, the inner layer is an ordered fiber layer, the middle layer is an unordered fiber layer, and the outer layer is an ordered fiber layer.

The inner layer and the outer layer are ordered fiber layers, the middle layer is a disordered fiber layer, and the artificial blood vessel is designed to simulate a complex structure of a natural blood vessel and promote biocompatibility and functionality of the artificial blood vessel.

The three-layer structure design of the invention, especially the combination of the ordered fiber layers of the inner layer and the outer layer and the unordered fiber layer of the middle layer, can simulate the complex structure of the blood vessel to a certain extent. In human tissue, the arrangement of collagen fibers within the natural extracellular matrix is critical to maintaining tissue mechanical properties and function. In particular to a fine structure of a blood vessel, which consists of three layers, wherein the unique arrangement direction of collagen fibers in each layer accurately controls the mechanical behavior and the cell distribution mode of the blood vessel. The ordered arrangement of cells is a core element in the process of functional tissue maturation and regeneration.

Preferably, the diameter of the inner layer fiber of the artificial blood vessel is 3 nm-30 μm, the diameter of the middle layer fiber is 3 nm-30 μm, the diameter of the outer layer fiber is 3 nm-30 μm, and the distance between the inner layer fiber and the outer layer fiber is 5 μm-300 μm.

Preferably, the number of fiber layers of the inner and outer ordered fiber layers of the artificial blood vessel is 2-50.

The invention strictly controls the diameter and the distance between the inner layer fiber and the outer layer fiber and the number of layers of the inner layer ordered fiber layer and the outer layer ordered fiber layer, ensures the accuracy and the consistency of the artificial blood vessel structure, and is beneficial to the adhesion and the proliferation of cells due to the smaller fiber diameter, smaller pore diameter and ordered structure. By precisely controlling these parameters, it is ensured that the vascular prosthesis has a structure and properties similar to those of natural blood vessels at a microscopic level, thereby better simulating its physiological function. The consistency is not only beneficial to the quality control of the product, but also helps to improve the reliability and safety of the product in clinical application. The precise control of the diameter, the spacing and the layer number of the fibers is also beneficial to optimizing the mechanical properties of the artificial blood vessel. By adjusting the parameters, the accurate regulation and control of key performance indexes such as the tensile strength, the elastic modulus and the like of the blood vessel can be realized. When the diameter, spacing and number of layers of the fibers are optimized, the surface morphology and chemistry of the blood vessel will also change accordingly, affecting its interaction with the surrounding tissue. By reducing unnecessary roughness and non-specific adsorption sites, the risk of inflammatory and rejection reactions can be reduced, promoting fusion and repair of blood vessels with surrounding tissues.

Preferably, the inner ordered fiber layer fiber of the artificial blood vessel has a specific crossing angle of-20 degrees to 80 degrees, and the outer ordered fiber layer fiber of the artificial blood vessel has a specific crossing or circumferential orientation distribution angle of-20 degrees to 80 degrees.

The inner layer and the outer layer ordered fiber layer have specific crossed or circumferential orientation distribution angles, and are aimed at simulating the mechanical property, blood flow property and biological property of natural blood vessel, and the arrangement of collagen fibers in natural extracellular matrix in human tissue has key effect on maintaining the mechanical property and function of tissue. In the complex structure of the blood vessel, the blood vessel is composed of three layers, the specific arrangement direction of the collagen fibers in each layer can finely regulate the mechanical response and the cell layout of the blood vessel, and the ordered arrangement of the cells is a core element of the development, maturation and regeneration of functional tissues.

Preferably, the crossing angle of the inner ordered fiber layer fibers of the artificial blood vessel is 60-70 degrees, and the crossing or circumferential orientation distribution angle of the outer ordered fiber layer fibers of the artificial blood vessel is 60-70 degrees.

Preferably, the intersection angle of the fibers of the inner ordered fiber layer of the artificial blood vessel is 65 degrees, and the intersection or circumferential orientation distribution angle of the fibers of the outer ordered fiber layer of the artificial blood vessel is 65 degrees.

Preferably, the vascular prosthesis is biodegradable and the material is selected from synthetic polymers (e.g., polylactic acid, polycaprolactone, lactide-caprolactone copolymers, polydioxanone, lactide-glycolide copolymers, polyurethane, etc.), natural polymers (e.g., chitosan, hyaluronic acid, alginate, cellulose, starch, chondroitin sulfate, gelatin, silk fibroin, collagen, fibrin, serum albumin, elastin, etc.), or combinations thereof.

The present invention uses biodegradable materials including synthetic polymers (e.g., polylactic acid, polycaprolactone, lactide-caprolactone copolymer, polydioxanone, lactide-glycolide copolymer, polyurethane, etc.), natural polymers (e.g., chitosan, hyaluronic acid, alginate, cellulose, starch, chondroitin sulfate, gelatin, silk fibroin, collagen, fibrin, serum albumin, elastin, etc.), or combinations thereof, so that the artificial blood vessel can be gradually absorbed by the body after accomplishing its substitution function, reducing long-term foreign body reaction.

The biological degradation characteristic enables the artificial blood vessel made of the materials to be naturally integrated into the body environment after completing the function of the artificial blood vessel as a blood vessel substitute, and avoids long-term foreign body reaction possibly caused by the traditional non-degradation materials. Along with the gradual degradation of the material, the interface between the artificial blood vessel and surrounding tissues is gradually blurred, so that the foreign body stimulation is reduced, and the risk of long-term foreign body reaction is reduced. The selection of the biodegradable material not only improves the safety of the artificial blood vessel, but also improves the effectiveness thereof by promoting the mechanism of blood vessel regeneration and the like.

The vascular prosthesis may be surface modified, and the modifying material includes polymers (e.g., polyacrylonitrile, polydimethylsiloxane, polyvinyl alcohol, polyacrylic acid, polyvinylpyrrolidone, polystyrene, etc.), inorganic nanomaterials (e.g., silica, carbon nanotubes, titania, graphene, silver nanoparticles, etc.), growth factors (e.g., epidermal growth factor, vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factor, keratinocyte growth factor, insulin-like growth factor, etc.), and other substances (e.g., natural polyphenols, polydopamine, biological enzymes, surfactants, antimicrobial agents, silane coupling agents, etc.).

The artificial blood vessel can be loaded with drugs or bioactive substances, including antibacterial agents (such as antibiotics, antibacterial peptides and the like), anti-inflammatory drugs (such as glucocorticoids, nonsteroidal anti-inflammatory drugs and the like), analgesics (such as ibuprofen, acetaminophen and the like), antiviral drugs (such as acyclovir, oseltamivir and the like), antitumor drugs (such as paclitaxel, doxorubicin and the like), natural flavones or polyphenols (such as quercetin, tea polyphenols and the like), growth factors (such as epidermal growth factors, vascular endothelial growth factors and the like), antioxidants (such as vitamin C, vitamin E and the like), polypeptides or proteins (such as insulin, growth hormones and the like) and genetic drugs (such as DNA, siRNA and the like) and the like.

The invention provides a preparation method of a three-layer structure small-caliber artificial blood vessel, which comprises the steps that the preparation method of an inner layer and an outer layer is melt near-field direct writing, and the preparation method of a middle layer is one of melt near-field direct writing or electrostatic spinning.

The inner and outer ordered fiber layers are prepared by adopting a fused near-field direct writing technology, so that the precise arrangement of fibers is ensured. The micro-nano fiber prepared by the near field direct writing process is accurate and controllable, the technology has great potential in the micro-nano manufacturing field due to the characteristics of high accuracy, high resolution and strong controllability, and the precisely arranged fiber structure is important for simulating the mechanical property and biological function of a natural blood vessel. By optimizing the arrangement direction and density of the fibers, the key parameters such as the tensile strength, the elastic modulus and the like of the blood vessel can be regulated and controlled, so that the blood vessel is more similar to the performance of a natural blood vessel. The orderly arranged fiber structure can also provide proper attachment and growth environment for cells and promote bioremediation processes such as endothelialization and the like.

The invention enables a producer to flexibly select the most suitable preparation process according to different performance requirements by adopting two preparation technologies of the molten near field direct writing and the electrostatic spinning, thereby optimizing the overall performance of the product.

Preferably, the preparation method is to integrally mold or prepare the inner layer structure, the middle layer structure and the outer layer structure respectively and then assemble and heat seal the inner layer structure, the middle layer structure and the outer layer structure.

The invention provides two manufacturing processes, namely, integral molding and assembling and heat sealing after being respectively prepared, wherein the integral molding ensures the tight combination between layers by continuously printing a three-layer structure in the same process, and the assembling and heat sealing after being respectively prepared provides more processing flexibility and material selection space.

The integral molding enhances the overall structural strength of the product, also improves the durability and the service life of the product, shortens the production period and improves the production efficiency. The size, shape and materials of each part can be adjusted according to actual requirements by assembling and heat sealing. The material most suitable for the requirements of each layer can be freely selected.

Preferably, the integrated forming comprises the steps of printing an inner ordered fiber layer on a metal receiving rod with a specific diameter by using a near-field direct-writing 3D printing technology, preparing a middle unordered fiber layer on the inner ordered fiber layer by using the near-field direct-writing 3D printing technology or an electrostatic spinning technology, and finally printing an outer ordered fiber layer on the middle unordered fiber layer by using the near-field direct-writing 3D printing technology.

The invention combines the near-field direct-writing 3D printing technology and the electrostatic spinning technology, realizes the accurate construction of the small-caliber artificial blood vessel complex structure, and shows the advancement and innovation in the biomedical engineering field. Near field direct writing technology is known as high precision and high resolution, can precisely control the deposition position and shape of materials, and is very suitable for manufacturing three-dimensional structures with fine features. The electrostatic spinning fiber has high specific surface area, good flexibility and biocompatibility, and is very suitable for simulating the microstructure and function of natural blood vessel walls. The structure not only improves the mechanical property of the artificial blood vessel, but also enhances the compatibility of the artificial blood vessel and biological tissues, and promotes the adhesion and growth of cells.

Preferably, the method for respectively preparing the inner layer structure, the middle layer structure and the outer layer structure and then assembling and heat sealing comprises the following steps of respectively printing the inner layer ordered fiber layer and the outer layer ordered fiber layer by using a near-field direct-writing 3D printing technology, preparing the middle disordered fiber layer by using the near-field direct-writing 3D printing technology or an electrostatic spinning technology, sleeving and combining the three layers of structures, and then performing heat bonding treatment.

The invention provides a small-caliber artificial blood vessel with a three-layer structure, wherein an inner layer and an outer layer are constructed by adopting ordered fiber layers, fibers are orderly stacked at a specific angle (such as-20 DEG to 80 DEG, preferably 60 DEG to 70 DEG, and most preferably 65 DEG), and a structure with larger aperture and high porosity is formed so as to promote cell infiltration and growth. The middle layer is designed as a disordered fiber layer, and fibers are deposited in an disordered manner to form smaller pore diameters and lower porosity, so that good elasticity and compliance are provided for blood vessels.

The fiber crossing or circumferential orientation distribution angles of the inner and outer ordered fiber layers can be set independently, and the same configuration can be selected, and the different designs can be adopted to adapt to different biomechanical requirements.

The vascular material is selected from synthetic polymers (such as polylactic acid, polycaprolactone, lactide-caprolactone copolymer, polydioxanone, lactide-glycolide copolymer, polyurethane and the like), natural polymers (such as chitosan, hyaluronic acid, alginate, cellulose, starch, chondroitin sulfate, gelatin, silk fibroin, collagen, fibrin, serum albumin, elastin and the like) or combinations thereof, and ensures the biocompatibility and degradation controllability of the product.

In the preparation method, the inner and outer ordered fiber layers are precisely formed by a fused near-field direct writing technology, and the middle disordered fiber layer can be prepared by a fused near-field direct writing or electrostatic spinning technology. The construction process can be sequentially carried out layer by layer, or respectively prepared and assembled integrally, namely, the inner, middle and outer three layers of fibers are combined under precise control, and the connection is reinforced by a heat sealing technology.

The inner diameter, the thickness of each layer, the fiber diameter and the fiber spacing of the three-layer structure small-caliber blood vessel can be customized and designed and manufactured according to clinical requirements, so that the accurate regulation and control of degradation time is realized, and diversified clinical medical application scenes are met.

Compared with the prior art, the invention has the following beneficial effects:

1. The three-layer structured small-caliber artificial blood vessel provided by the invention has the advantages that the middle disordered fiber layer has thinner fibers and smaller pore diameters, the fiber diameter and the pore diameter of the fiber layer are adjustable, and the elasticity and the compliance are good.

2. The three-layer structured small-caliber artificial blood vessel provided by the invention has the advantages that the inner and outer ordered fiber layers can be orderly stacked at a specific angle, the arrangement of collagen fibers of a human blood vessel is simulated, and the endothelialization and the reconstruction of smooth muscle layers are rapidly induced, so that the regeneration of the blood vessel is effectively promoted.

3. The raw material of the product is synthetic or natural degradable high molecular polymer, the biocompatibility is good, the preparation process is simple, and no organic solvent is added or only a small amount of organic solvent is used.

Drawings

FIG. 1 is a schematic diagram of a small-caliber artificial blood vessel with a three-layer structure;

Figure 2 is a cross-sectional view of the wall of a small-caliber artificial blood vessel with a three-layer structure after implantation into a human body.

In the figure, 1, outer layer, 2, middle layer, 3, inner layer, 4, endothelial cells, 5 and smooth muscle cells.

Detailed Description

Example 1

As shown in figure 1, the invention discloses a three-layer structured small-caliber artificial blood vessel, wherein the wall of the artificial blood vessel is 3 layers, the inner layer 3 is an ordered fiber layer, the middle layer 2 is a disordered fiber layer, and the outer layer 1 is an ordered fiber layer.

The diameter of the inner layer fiber of the artificial blood vessel is 500nm, the diameter of the middle layer fiber is 30nm, the diameter of the outer layer fiber is 500nm, and the distance between the inner layer fiber and the outer layer fiber is 50 μm.

The number of the fiber layers of the inner and outer ordered fiber layers of the artificial blood vessel is 5.

The crossing angle of the fibers of the inner ordered fiber layer of the artificial blood vessel is 65 degrees, and the crossing or circumferential orientation distribution angle of the fibers of the outer ordered fiber layer of the artificial blood vessel is 65 degrees.

The artificial blood vessel is made of polylactic acid.

The inner layer and the outer layer of the artificial blood vessel belong to bionic, are similar to natural blood vessel fiber arrangement and are used for promoting adhesion proliferation and differentiation of endothelial cells (inner layer) and smooth muscle cells (outer layer), and the middle layer is of a disordered structure and is used for providing mechanical support.

Fig. 2 is a sectional view of a vessel wall after implantation of an artificial blood vessel into a human body, 4 is vascular endothelial cells after implantation into a human body, and 5 is vascular smooth muscle cells after implantation into a human body. FIG. 2 shows the growth of two types of cells on an artificial blood vessel.

Example 2

The wall of the artificial blood vessel is 3 layers, the inner layer 3 is an ordered fiber layer, the middle layer 2 is an unordered fiber layer, and the outer layer 1 is an ordered fiber layer.

The diameter of the inner layer fiber of the artificial blood vessel is 30 μm, the diameter of the middle layer fiber is 30 μm, the diameter of the outer layer fiber is 30 μm, and the distance between the inner layer fiber and the outer layer fiber is 300 μm.

The number of the fiber layers of the inner and outer ordered fiber layers of the artificial blood vessel is 25.

The crossing angle of the inner ordered fiber layer fibers of the artificial blood vessel is 60 degrees, and the crossing or circumferential orientation distribution angle of the outer ordered fiber layer fibers of the artificial blood vessel is 60 degrees.

The material of the artificial blood vessel is a combination of polycaprolactone and lactide-caprolactone copolymer.

Example 3

The wall of the artificial blood vessel is 3 layers, the inner layer 3 is an ordered fiber layer, the middle layer 2 is an unordered fiber layer, and the outer layer 1 is an ordered fiber layer.

The diameter of the inner layer fiber of the artificial blood vessel is 1 μm, the diameter of the middle layer fiber is 1 μm, the diameter of the outer layer fiber is 1 μm, and the distance between the inner layer fiber and the outer layer fiber is 250 μm.

The number of the fiber layers of the inner and outer ordered fiber layers of the artificial blood vessel is 15.

The crossing angle of the inner ordered fiber layer fibers of the artificial blood vessel is 60 degrees, and the crossing or circumferential orientation distribution angle of the outer ordered fiber layer fibers of the artificial blood vessel is 70 degrees.

The vascular prosthesis material is a combination of lactide-caprolactone copolymer and polyurethane.

Example 4

The wall of the artificial blood vessel is 3 layers, the inner layer is an ordered fiber layer, the middle layer is an unordered fiber layer, and the outer layer is an ordered fiber layer.

The diameter of the inner layer fiber of the artificial blood vessel is 900nm, the diameter of the middle layer fiber is 150nm, the diameter of the outer layer fiber is 800nm, and the distance between the inner layer fiber and the outer layer fiber is 80 mu m.

The number of the fiber layers of the inner and outer ordered fiber layers of the artificial blood vessel is 50.

The crossing angle of the inner ordered fiber layer fibers of the artificial blood vessel is 80 degrees, and the crossing or circumferential orientation distribution angle of the outer ordered fiber layer fibers of the artificial blood vessel is-20 degrees.

The artificial blood vessel is made of lactide-caprolactone copolymer.

Example 5

The preparation method of the three-layer structured small-caliber artificial blood vessel comprises the steps of inner layer cross distribution ordered near field direct writing, middle layer disordered electrostatic spinning and outer layer cross distribution ordered near field direct writing, and specifically comprises the following steps:

1) The preparation of the inner layer cross-distributed ordered near-field direct-writing fiber layer comprises the steps of loading selected polymer materials into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path according to the design requirements of the ordered layer (determining fiber diameter, fiber distance and cross angle), and starting a program to complete printing of the inner layer cross-distributed ordered fiber layer.

2) The preparation of the middle disordered electrostatic spinning fiber layer comprises the steps of dissolving a selected polymer material in a solvent, preparing an electrostatic spinning solution, loading the electrostatic spinning solution into a syringe, mounting the syringe on electrostatic spinning equipment, selecting the inner diameter of a spinning nozzle, and setting spinning parameters (flow speed, voltage, receiving rod rotating speed and needle to receiving rod distance). And (3) carrying out electrostatic spinning on the inner ordered fiber layer prepared in the step (1), and finally obtaining the middle unordered electrostatic spinning fiber layer.

3) The preparation of the outer layer cross-distributed ordered near-field direct-writing fiber layer comprises the steps of loading selected polymer materials into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path according to the design requirements of the ordered layer (determining fiber diameter, fiber distance and cross angle), and completing the printing of the outer layer cross-distributed ordered fiber layer on the middle unordered fiber layer prepared in the step 2) by a starting procedure.

4) And (3) demolding, namely removing the sample prepared in the step 3 from the receiving rod to obtain the small-caliber artificial blood vessel with the three-layer structure.

The invention introduces a near-field direct writing technology, accurately constructs a fiber structure with orderly stacked inner and outer layers, and remarkably promotes infiltration and proliferation of vascular endothelial cells and vascular smooth muscle cells, thereby overcoming the limitation of the traditional technology.

The invention has the advantages that:

1. the middle disordered fiber layer adopts finer fibers and an adjustable diameter/aperture design, so that the artificial blood vessel has good elasticity and compliance, can be more suitable for complex physiological environments, and improves the stability and durability of the artificial blood vessel in vivo application.

2. Promoting revascularization, namely, the inner and outer ordered fiber layers are orderly stacked through a specific angle, and the arrangement mode of collagen fibers in natural blood vessels of a human body is simulated. The design can accelerate the reconstruction and endothelialization processes of the smooth muscle layer, thereby effectively promoting the regeneration and repair of vascular tissues and improving the biocompatibility and the functionality of the artificial blood vessel.

3. The product adopts synthetic or natural degradable high molecular polymer as raw material, has good biocompatibility, and ensures the safety and reliability of the product. Meanwhile, the preparation process is relatively simple, and no or only a small amount of organic solvent is needed, so that the preparation process is environment-friendly, the production cost is reduced, and the production efficiency is improved.

Example 6

As shown in figure 1, the preparation method of the three-layer structured small-caliber artificial blood vessel comprises the steps of inner layer cross distribution ordered near field direct writing, middle layer disordered electrostatic spinning and outer layer circumference orientation distribution ordered near field direct writing.

1) The preparation of the inner layer cross-distributed ordered near-field direct-writing fiber layer comprises the steps of loading selected polymer materials into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path according to the design requirements of the ordered layer (determining fiber diameter, fiber distance and cross angle), and starting a program to complete printing of the inner layer cross-distributed ordered fiber layer.

2) The preparation of the middle disordered electrostatic spinning fiber layer comprises the steps of dissolving a selected polymer material in a solvent, preparing an electrostatic spinning solution, loading the electrostatic spinning solution into a syringe, mounting the syringe on electrostatic spinning equipment, selecting the inner diameter of a spinning nozzle, and setting spinning parameters (flow speed, voltage, receiving rod rotating speed and needle to receiving rod distance). And (3) carrying out electrostatic spinning on the inner ordered fiber layer prepared in the step (1), and finally obtaining the middle unordered electrostatic spinning fiber layer.

3) The preparation of the ordered near-field direct-writing fiber layer with the outer circumferential orientation distribution comprises the steps of loading a selected polymer material into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path according to the design requirements of the ordered layer (determining the fiber diameter, the fiber distance and the circumferential orientation distribution angle), and completing the printing of the ordered fiber layer with the outer circumferential orientation distribution on the middle unordered fiber layer prepared in the step 2) by a starting procedure.

4) And (3) demolding, namely removing the sample prepared in the step 3 from the receiving rod to obtain the small-caliber artificial blood vessel with the three-layer structure.

Example 7

The preparation method of the three-layer structured small-caliber artificial blood vessel comprises the steps of inner layer cross distribution ordered near field direct writing, middle layer disordered near field direct writing and outer layer cross distribution ordered near field direct writing.

1) The preparation of the inner layer cross-distributed ordered near-field direct-writing fiber layer comprises the steps of loading selected polymer materials into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path according to the design requirements of the ordered layer (determining fiber diameter, fiber distance and cross angle), and starting a program to complete printing of the inner layer cross-distributed ordered fiber layer.

2) And 3) preparing a middle disordered near-field direct-writing fiber layer, namely loading the selected polymer material into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a used pinhead, setting the temperature of the charging barrel, the temperature of the pinhead, the distance between the pinhead and a receiving rod, printing voltage and air pressure, writing a printing path, starting a program, and printing on the inner ordered fiber layer prepared in the step 1) to finally obtain the middle disordered near-field direct-writing fiber layer.

3) The preparation of the outer layer cross-distributed ordered near-field direct-writing fiber layer comprises the steps of loading selected polymer materials into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path according to the design requirements of the ordered layer (determining fiber diameter, fiber distance and cross angle), and completing the printing of the outer layer cross-distributed ordered fiber layer on the middle unordered fiber layer prepared in the step 2) by a starting procedure.

4) And (3) demolding, namely removing the sample prepared in the step 3 from the receiving rod to obtain the small-caliber artificial blood vessel with the three-layer structure.

Example 8

The preparation method of the three-layer structured small-caliber artificial blood vessel comprises the steps of inner layer crossed distribution ordered near field direct writing, middle layer disordered near field direct writing and outer layer circumferential orientation distribution ordered near field direct writing.

1) The preparation of the inner layer cross-distributed ordered near-field direct-writing fiber layer comprises the steps of loading selected polymer materials into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path according to the design requirements of the ordered layer (determining fiber diameter, fiber distance and cross angle), and starting a program to complete printing of the inner layer cross-distributed ordered fiber layer.

2) And 3) preparing a middle disordered near-field direct-writing fiber layer, namely loading the selected polymer material into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a used pinhead, setting the temperature of the charging barrel, the temperature of the pinhead, the distance between the pinhead and a receiving rod, printing voltage and air pressure, writing a printing path, starting a program, and printing on the inner ordered fiber layer prepared in the step 1) to finally obtain the middle disordered near-field direct-writing fiber layer.

3) The preparation of the ordered near-field direct-writing fiber layer with the outer circumferential orientation distribution comprises the steps of loading a selected polymer material into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path according to the design requirements of the ordered layer (determining the fiber diameter, the fiber distance and the circumferential orientation distribution angle), and completing the printing of the ordered fiber layer with the outer circumferential orientation distribution on the middle unordered fiber layer prepared in the step 2) by a starting procedure.

4) And (3) demolding, namely removing the sample prepared in the step 3 from the receiving rod to obtain the small-caliber artificial blood vessel with the three-layer structure.

Example 9

The preparation method of the three-layer structured small-caliber artificial blood vessel comprises the steps of inner layer cross distribution ordered near field direct writing, middle layer disordered electrostatic spinning and outer layer cross distribution ordered near field direct writing, and heat sealing is respectively prepared.

1) The preparation of the inner layer cross-distributed ordered near-field direct-writing fiber layer comprises the steps of loading selected polymer materials into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path according to the design requirements of the ordered layer (determining fiber diameter, fiber distance and cross angle), and starting a program to complete printing of the inner layer cross-distributed ordered fiber layer.

2) The preparation of the middle disordered electrostatic spinning fiber layer comprises the steps of dissolving a selected polymer material in a solvent, preparing an electrostatic spinning solution, loading the electrostatic spinning solution into a syringe, mounting the syringe on electrostatic spinning equipment, selecting the inner diameter of a spinning nozzle, and setting spinning parameters (flow speed, voltage, receiving rod rotating speed and needle to receiving rod distance). And (3) carrying out electrostatic spinning on the receiving rod to finally obtain the middle-layer disordered electrostatic spinning fiber layer.

3) The preparation of the outer layer cross-distributed ordered near-field direct-writing fiber layer comprises the steps of loading selected polymer materials into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path according to the design requirements of the ordered layer (determining fiber diameter, fiber distance and cross angle), and starting a program to complete printing of the outer layer cross-distributed ordered fiber layer.

4) And (3) assembling and heat sealing, namely demolding and taking down the unordered electrostatic spinning fiber layer obtained in the step (2) from the receiving rod, and sleeving the unordered electrostatic spinning fiber layer on the ordered near-field direct-writing fiber layer obtained in the step (1). And then demolding the ordered near-field direct-writing fiber layer obtained in the step 3) from the receiving rod, and sleeving the ordered near-field direct-writing fiber layer on the unordered electrostatic spinning fiber layer in the step 2). And finally, keeping the temperature at 65 ℃ for a period of time, cooling to room temperature, and demoulding and taking down to obtain the three-layer structure small-caliber artificial blood vessel.

Example 10

The preparation method of the three-layer structured small-caliber artificial blood vessel comprises the steps of inner layer cross distribution ordered near field direct writing, middle layer unordered electrostatic spinning and outer layer circumference orientation distribution ordered near field direct writing, and heat sealing is respectively prepared.

1) The preparation of the inner layer cross-distributed ordered near-field direct-writing fiber layer comprises the steps of loading selected polymer materials into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path according to the design requirements of the ordered layer (determining fiber diameter, fiber distance and cross angle), and starting a program to complete printing of the inner layer cross-distributed ordered fiber layer.

2) The preparation of the middle disordered electrostatic spinning fiber layer comprises the steps of dissolving a selected polymer material in a solvent, preparing an electrostatic spinning solution, loading the electrostatic spinning solution into a syringe, mounting the syringe on electrostatic spinning equipment, selecting the inner diameter of a spinning nozzle, and setting spinning parameters (flow speed, voltage, receiving rod rotating speed and needle to receiving rod distance). And (3) carrying out electrostatic spinning on the receiving rod to finally obtain the middle-layer disordered electrostatic spinning fiber layer.

3) The preparation of the ordered near-field direct-writing fiber layer distributed by the outer circumference orientation comprises the steps of loading a selected polymer material into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path according to the design requirements of the ordered fiber layer (determining the fiber diameter, the fiber distance and the circumference orientation distribution angle), and completing the printing of the ordered fiber layer distributed by the outer circumference orientation by a starting program.

4) And (3) assembling and heat sealing, namely demolding and taking down the unordered electrostatic spinning fiber layer obtained in the step (2) from the receiving rod, and sleeving the unordered electrostatic spinning fiber layer on the ordered near-field direct-writing fiber layer obtained in the step (1). And then demolding the ordered near-field direct-writing fiber layer obtained in the step 3) from the receiving rod, and sleeving the ordered near-field direct-writing fiber layer on the unordered electrostatic spinning fiber layer in the step 2). And finally, keeping the temperature at 65 ℃ for a period of time, cooling to room temperature, and demoulding and taking down to obtain the three-layer structure small-caliber artificial blood vessel.

Example 11

The preparation method of the three-layer structured small-caliber artificial blood vessel comprises the steps of inner layer cross distribution ordered near field direct writing, middle layer disordered near field direct writing and outer layer cross distribution ordered near field direct writing, and heat sealing is respectively prepared.

1) The preparation of the inner layer cross-distributed ordered near-field direct-writing fiber layer comprises the steps of loading selected polymer materials into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path according to the design requirements of the ordered layer (determining fiber diameter, fiber distance and cross angle), and starting a program to complete printing of the inner layer cross-distributed ordered fiber layer.

2) And (3) preparing the middle disordered near-field direct-writing fiber layer, namely loading the selected polymer material into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path, starting a program, and printing on the receiving rod to finally obtain the middle disordered near-field direct-writing fiber layer.

3) The preparation of the outer layer cross-distributed ordered near-field direct-writing fiber layer comprises the steps of loading selected polymer materials into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path according to the design requirements of the ordered layer (determining fiber diameter, fiber distance and cross angle), and starting a program to complete printing of the outer layer cross-distributed ordered fiber layer.

4) And (3) assembling and heat sealing, namely demolding and taking down the unordered near-field direct-write fiber layer obtained in the step (2) from the receiving rod, and sleeving the unordered near-field direct-write fiber layer on the ordered near-field direct-write fiber layer obtained in the step (1). And then demolding the ordered near-field direct-write fiber layer obtained in the step 3) from the receiving rod, and sleeving the ordered near-field direct-write fiber layer on the unordered near-field direct-write fiber layer in the step 2). And finally, keeping the temperature at 65 ℃ for a period of time, cooling to room temperature, and demoulding and taking down to obtain the three-layer structure small-caliber artificial blood vessel.

Example 12

The preparation method of the three-layer structured small-caliber artificial blood vessel comprises the steps of inner layer cross distribution ordered near field direct writing, middle layer disordered near field direct writing and outer layer circumference orientation distribution ordered near field direct writing, and heat sealing is respectively prepared.

1) The preparation of the inner layer cross-distributed ordered near-field direct-writing fiber layer comprises the steps of loading selected polymer materials into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path according to the design requirements of the ordered layer (determining fiber diameter, fiber distance and cross angle), and starting a program to complete printing of the inner layer cross-distributed ordered fiber layer.

2) And (3) preparing the middle disordered near-field direct-writing fiber layer, namely loading the selected polymer material into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path, starting a program, and printing on the receiving rod to finally obtain the middle disordered near-field direct-writing fiber layer.

3) The preparation of the ordered near-field direct-writing fiber layer distributed by the outer circumference orientation comprises the steps of loading a selected polymer material into a charging barrel of an extrusion type 3D printer, selecting the inner diameter of a needle head, setting the temperature of the charging barrel, the temperature of the needle head, the distance between the needle head and a receiving rod, printing voltage and air pressure, writing a printing path according to the design requirements of the ordered fiber layer (determining the fiber diameter, the fiber distance and the circumference orientation distribution angle), and completing the printing of the ordered fiber layer distributed by the outer circumference orientation by a starting program.

4) And (3) assembling and heat sealing, namely demolding and taking down the unordered near-field direct-write fiber layer obtained in the step (2) from the receiving rod, and sleeving the unordered near-field direct-write fiber layer on the ordered near-field direct-write fiber layer obtained in the step (1). And then demolding the ordered near-field direct-write fiber layer obtained in the step 3) from the receiving rod, and sleeving the ordered near-field direct-write fiber layer on the unordered near-field direct-write fiber layer in the step 2). And finally, keeping the temperature at 65 ℃ for a period of time, cooling to room temperature, and demoulding and taking down to obtain the three-layer structure small-caliber artificial blood vessel.

The invention relates to a three-layer structured small-caliber artificial blood vessel and a preparation method thereof:

1. novel design of three-layer structure small-caliber artificial blood vessel

The small-caliber artificial blood vessel with a unique three-layer structure is provided, wherein the inner layer and the outer layer are ordered fiber layers, and the middle layer is a disordered fiber layer. The design aims to simulate the complex structure of a natural blood vessel and improve the biocompatibility and the functionality of the artificial blood vessel.

2. Diversity of preparation methods

The inner and outer ordered fiber layers are prepared by adopting a fused near field direct writing technology, so that the accurate arrangement of fibers is ensured, the middle disordered fiber layer can be prepared by adopting a fused near field direct writing or electrostatic spinning technology, and flexible process selection is provided so as to adapt to different performance requirements.

3. Precise fiber size and precise control

The diameter and the distance between the inner layer fiber and the outer layer fiber and the number of layers of the inner layer and the outer layer ordered fiber layer are strictly controlled, and the accuracy and the consistency of the artificial blood vessel structure are ensured.

4. Specific fiber orientation

The inner and outer ordered fiber layers have specific cross or circumferential orientation distribution angles designed to simulate the mechanical, blood flow and biological properties of natural blood vessels.

5. Selection of biodegradable materials

Biodegradable materials including synthetic polymers (e.g., polylactic acid, polycaprolactone, lactide-caprolactone copolymer, polydioxanone, lactide-glycolide copolymer, polyurethane, etc.), natural polymers (e.g., chitosan, hyaluronic acid, alginate, cellulose, starch, chondroitin sulfate, gelatin, silk fibroin, collagen, fibrin, serum albumin, elastin, etc.), or combinations thereof are used, so that the vascular prosthesis is gradually absorbed by the body after accomplishing its replacement function, reducing long-term foreign body reactions.

6. Flexible manufacturing process

Two manufacturing processes are provided, namely, integral molding and assembling and heat sealing after being respectively prepared. The integrated forming ensures the tight combination between layers by continuously printing three-layer structures in the same process, and the assembled heat seal after being respectively prepared provides more processing flexibility and material selection space.

The invention combines the near-field direct-writing 3D printing technology and the electrostatic spinning technology to realize the accurate construction of the small-caliber artificial blood vessel complex structure.

The above embodiments do not limit the scope of the present invention. It will be apparent to those skilled in the art that various modifications, combinations, sub-combinations and alternatives can occur depending upon design requirements and other factors. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the scope of the present invention.

Claims (12)

1. The small-caliber artificial blood vessel with the three-layer structure is characterized in that the wall of the artificial blood vessel is 3 layers, the inner layer (3) is an ordered fiber layer, the middle layer (2) is an unordered fiber layer, and the outer layer (1) is an ordered fiber layer.

2. The three-layer structured small-caliber artificial blood vessel according to claim 1, wherein the fiber diameter of the inner layer (3) is 3 nm-30 μm, the fiber diameter of the middle layer (2) is 3 nm-30 μm, the fiber diameter of the outer layer (1) is 3 nm-30 μm, and the fiber distance between the inner layer (3) and the outer layer (1) is 5 μm-300 μm.

3. The three-layer structured small-caliber artificial blood vessel according to claim 1 or 2, wherein the number of fiber layers of the inner layer (3) and the outer layer (1) of the artificial blood vessel is 2-50.

4. The three-layer structured small-caliber artificial blood vessel according to claim 1 or 2, wherein the inner layer (3) ordered fiber layer fiber of the artificial blood vessel has a specific crossing angle of-20 degrees to 80 degrees, and the outer layer (1) ordered fiber layer fiber of the artificial blood vessel has a specific crossing or circumferential orientation distribution angle of-20 degrees to 80 degrees.

5. The three-layer structured small caliber artificial blood vessel according to claim 4, wherein the crossing angle of the fibers of the inner layer (3) of the artificial blood vessel is 65 degrees, and the crossing or circumferential orientation distribution angle of the fibers of the outer layer (1) of the artificial blood vessel is 65 degrees.

6. The three-layer structured small caliber artificial blood vessel according to claim 1 wherein the artificial blood vessel is biodegradable and the material is selected from synthetic polymers, natural polymers or combinations thereof;

The synthetic polymers include, but are not limited to, polylactic acid, polycaprolactone, lactide-caprolactone copolymers, polydioxanone, lactide-glycolide copolymers, and polyurethane;

The natural polymers include, but are not limited to, chitosan, hyaluronic acid, alginate, cellulose, starch, chondroitin sulfate, gelatin, silk fibroin, collagen, fibrin, serum albumin, and elastin.

7. The three-layer structured small caliber artificial blood vessel according to claim 1, wherein the artificial blood vessel can be surface-modified, and the modifying material comprises polymers, inorganic nano materials, growth factors and other substances;

Polymers include, but are not limited to, polyacrylonitrile, polydimethylsiloxane, polyvinyl alcohol, polyacrylic acid, polyvinylpyrrolidone, and polystyrene;

inorganic nanomaterials include, but are not limited to, silica, carbon nanotubes, titania, graphene, and silver nanoparticles;

Growth factors include, but are not limited to, epidermal growth factor, vascular endothelial growth factor, platelet derived growth factor, fibroblast growth factor, keratinocyte growth factor, and insulin-like growth factor;

Other materials include, but are not limited to, natural polyphenols, polydopamine, biological enzymes, surfactants, antimicrobial agents, and silane coupling agents.

8. The three-layer structured small caliber artificial blood vessel according to claim 1, wherein the artificial blood vessel can be loaded with a drug or a bioactive substance, including an antibacterial agent, an anti-inflammatory drug, an analgesic agent, an antiviral drug, an antitumor drug, a natural flavone or polyphenol, a growth factor, an antioxidant, a polypeptide or a protein, and a gene drug;

Antibacterial agents include, but are not limited to, antibiotics and antibacterial peptides, anti-inflammatory agents including, but not limited to, glucocorticoids and non-steroidal anti-inflammatory agents, analgesics including, but not limited to, ibuprofen and acetaminophen, antiviral agents including, but not limited to, acyclovir and oseltamivir, antitumor agents including, but not limited to, paclitaxel and doxorubicin, natural flavones or polyphenols including, but not limited to, quercetin and tea polyphenols, growth factors including, but not limited to, epidermal growth factors and vascular endothelial growth factors, antioxidants including, but not limited to, vitamin C and vitamin E, polypeptides or proteins including, but not limited to, insulin and growth hormones, genetic drugs including, but not limited to, DNA and siRNA.

9. A method for preparing a three-layer structured small-caliber artificial blood vessel according to any one of claims 1 to 8, wherein the preparation method of the inner layer (3) and the outer layer (1) is melt near-field direct writing, and the preparation method of the middle layer (2) is one of melt near-field direct writing and electrostatic spinning.

10. The preparation method according to claim 9, wherein the preparation method is to integrally mold or prepare the inner layer (3), the middle layer (2) and the outer layer (1) separately, and then assemble and heat seal the structures.

11. The method according to claim 10, wherein the integral molding comprises the steps of printing the inner layer (3) ordered fiber layer on a metal receiving rod with a specific diameter by using a near field direct writing 3D printing technology, preparing the middle layer (2) ordered fiber layer on the inner layer (3) by using a near field direct writing 3D printing technology or an electrostatic spinning technology, and finally printing the outer layer (1) ordered fiber layer on the middle layer (2) by using a near field direct writing 3D printing technology.

12. The preparation method of the composite material according to claim 10, wherein the method for preparing the inner layer (3), the middle layer (2) and the outer layer (1) respectively and then assembling and heat-sealing the composite material comprises the following steps of printing ordered fiber layers of the inner layer (3) and the outer layer (1) respectively by using a near-field direct-writing 3D printing technology, preparing an unordered fiber layer of the middle layer (2) by using a near-field direct-writing 3D printing technology or an electrostatic spinning technology, sleeving and combining the three layers, and then performing heat bonding treatment.