A highly impermeable artificial blood vessel and its preparation method

Abstract

This invention provides a highly impermeable artificial blood vessel and its preparation method. The artificial blood vessel is designed by mimicking the three-layer structure of the intima, media, and adventitia of human blood vessels. The inner layer is a collagen coating, forming the inner functional area of ​​the artificial blood vessel. The collagen coating is dense and smooth, providing excellent impermeability. The middle layer is a relatively loose satin or twill weave fabric layer, allowing the collagen from the inner layer to easily penetrate into the middle fabric layer, forming anchoring points to increase the bonding force between the collagen coating and the middle fabric of the artificial blood vessel, ensuring the integrity of the entire artificial blood vessel. Simultaneously, the middle fabric layer and collagen together form the middle functional area of ​​the artificial blood vessel. The outer layer is a tightly woven plain weave fabric layer, making it difficult for the collagen from the inner layer to penetrate into the plain weave structure. The outer fabric layer serves as the outer functional area of ​​the artificial blood vessel.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, specifically to a highly leak-proof artificial blood vessel and its preparation method. Background Technology

[0002] Textile-based artificial blood vessels are now widely used in clinical practice and have achieved good medical results. However, woven artificial blood vessels, made by weaving warp and weft yarns on a loom, form microporous structures between the yarns. While these micropores facilitate the invasion and growth of recipient tissue, encapsulate the vascular prosthesis, and promote its healing, a disadvantage is that they can cause a large amount of blood to leak through the vessel wall into the interstitial space during implantation.

[0003] Currently, there are related technologies that reduce leakage by weaving tightly and reducing pores. For example, patent CN101069757A discloses a double-layer woven structure textile artificial blood vessel. The outer wall fiber has a larger diameter, larger pores, and a sparse structure, while the inner wall fiber has a smaller diameter, smaller pores, and a tighter structure. The outer structure with larger pores is conducive to cell tissue ingrowth, while the inner structure with smaller pores avoids excessive bleeding during surgery. Furthermore, patent CN102206888A discloses an integrated three-layer woven simulated artificial blood vessel, comprising an outer woven structure, a middle woven structure, and an inner woven structure, connected together by knotted yarns. The outer woven structure uses a twill or satin weave, the middle woven structure uses a twill weave, and the inner woven structure uses a plain weave. The outer layer has a lower density and larger pores between the yarns, facilitating cell and tissue ingrowth. The middle layer is loose and elastic, with moderate pores, providing good elasticity to the blood vessel wall and space for nutrient-rich blood vessel growth. The inner layer has a higher density, smaller pores, and a smooth wall, facilitating blood flow and effectively preventing bleeding during transplantation of the woven artificial blood vessel. The finer monofilaments in the multifilament are beneficial for endothelial cell growth. While the tight weave in the aforementioned patent reduces leakage, it also affects the mechanical properties of the inner fabric, making it stiffer and consequently affecting the elasticity of the artificial blood vessel.

[0004] Currently, a method of sealing gaps with a coating can also be used to reduce blood leakage. For example, patent CN200610112213.9 discloses injecting a collagen-mixed coating solution into a section of a woven artificial blood vessel using a syringe, so that the coating solution is evenly coated on the inner wall of the lumen. After the coated artificial blood vessel dries, it is placed in a vacuum drying oven at 90-110℃ for cross-linking for 16-20 hours. The average blood permeability of the resulting artificial blood vessel is 0.024 ml / min*cm. 2 The permeability of the artificial blood vessel with three coating layers was 2.5 ml / min*cm. 2However, this method has the following problems: (1) The collagen-mixed coating solution is allowed to flow freely and be coated on the inner wall of the tube by injecting a syringe. The uniformity of the collagen coating cannot be guaranteed, and the interfacial bonding force between the collagen coating and the inner wall of the tube is also poor, making the collagen coating easy to fall off; (2) Multiple coatings are required, resulting in low production efficiency; (3) Cross-linking reaction is required at high temperature (90-110℃), which can easily damage the structure of collagen. Summary of the Invention

[0005] This invention provides a highly impermeable artificial blood vessel and its preparation method. The artificial blood vessel has excellent impermeability, good mechanical properties, and a simple preparation method.

[0006] To solve the above-mentioned technical problems, the technical solution of the present invention is as follows:

[0007] A highly impermeable artificial blood vessel, comprising a three-layer structure: an inner layer of collagen coating, a middle layer of satin or twill fabric, and an outer layer of plain weave fabric.

[0008] The outer and middle layers of the artificial blood vessel are interconnected by interwoven threads, and the collagen coating of the inner layer penetrates into the middle fabric layer, thereby connecting with the middle fabric layer.

[0009] The outer and middle layers of the artificial blood vessel are connected by interlacing the outer and middle yarns with a splicing yarn.

[0010] The outer layer of the artificial blood vessel has a thickness of 0.2–0.3 mm, the middle layer has a thickness of 0.3–0.5 mm, and the inner layer has a thickness of 0.1–0.3 mm.

[0011] The outer and middle layers of the artificial blood vessel fabric are one or more of polyester, polypropylene, and polytetrafluoroethylene.

[0012] The fibers used in the outer and middle layers of the artificial blood vessel fabric are 100-300D in diameter and have 40-200 filaments.

[0013] The collagen coating on the inner layer of the artificial blood vessel degrades within 60 days under the influence of blood flow and enzymatic decomposition.

[0014] The type of collagen is bovine collagen, fish collagen, or chicken collagen.

[0015] The present invention also provides a method for preparing a highly impermeable artificial blood vessel, comprising the following steps: (1) weaving an outer layer and a middle layer of fabric, and connecting the outer layer and the middle layer of fabric to obtain a double-layer artificial blood vessel;

[0016] (2) Collagen was added to an acetic acid solution to prepare a collagen solution;

[0017] (3) Fix the double-layer artificial blood vessel, take a clean cylindrical sponge and soak it in collagen solution for 5 minutes. The diameter of the cylindrical sponge is larger than the inner diameter of the double-layer artificial blood vessel. Inject 10 mL of the prepared collagen solution into one end of the fixed double-layer artificial blood vessel. Spread the collagen on the inner wall of the two layers of artificial blood vessel at a uniform speed along the path coaxial with the artificial blood vessel. A collagen coating is formed on the inner wall of the double-layer artificial blood vessel to obtain a three-layer artificial blood vessel.

[0018] (4) The obtained three-layer artificial blood vessel is placed in a vacuum drying oven at 37°C and dried for 24 hours to obtain a highly impermeable artificial blood vessel.

[0019] The highly impermeable artificial blood vessel is stored in an environment with a temperature of 25°C and a humidity of 80%–90%.

[0020] Compared with the prior art, the beneficial effects of the present invention are: (1) The artificial blood vessel with high anti-permeability provided by the present invention is designed to simulate the three-layer structure of the intima, media and adventitia of human blood vessels. The inner layer is a collagen coating, which forms the inner functional area of ​​the artificial blood vessel. The collagen coating is dense and smooth, with excellent anti-permeability effect and good adhesion properties, and is not easy to fall off. The middle layer is a relatively loose satin or twill weave fabric layer. The collagen in the inner layer can easily penetrate into the middle fabric layer to form fixing points to increase the adhesion between the collagen coating and the middle fabric of the artificial blood vessel. The bonding strength ensures the integrity of the entire artificial blood vessel. The collagen coating adheres to the fabric and will not easily detach. At the same time, the middle fabric layer and collagen together form the middle functional area of ​​the artificial blood vessel. The outer fabric layer is a tightly woven plain-weave structure, which makes it difficult for the inner collagen to enter the plain-weave structure. The outer fabric layer serves as the outer functional area of ​​the artificial blood vessel. At the same time, the dense plain-weave structure of the outer layer makes the artificial blood vessel less likely to be punctured by the needle during suturing, which is beneficial for surgical suturing. In addition, the dense fabric structure provides a guarantee for the overall mechanical properties of the artificial blood vessel.

[0021] (2) In this invention, the outer plain weave fabric layer of the artificial blood vessel is relatively dense. In order not to affect the elasticity of the artificial blood vessel, the thickness of the outer layer is 0.2 to 0.3 mm to ensure the softness of the plain weave fabric layer; the thickness of the middle layer is 0.3 to 0.5 mm to ensure the mechanical properties while ensuring the tight bonding between the inner coating and the middle layer; the thickness of the inner layer is 0.1 to 0.3 mm to avoid the problem that the coating thickness is too thin, resulting in poor permeability, and the coating thickness is too thick, resulting in poor mechanical properties.

[0022] (3) In this invention, the outer and middle fabric layers of the artificial blood vessel are connected by interlaced yarns. The inner coating layer is coated on the inner wall of the middle fabric layer by a cylindrical sponge. The diameter of the cylindrical sponge is larger than the inner diameter of the middle fabric layer. Moreover, the sponge expands after absorbing the collagen solution. When the cylindrical sponge soaked in collagen solution moves within the middle fabric layer, the sponge exerts a certain pressure on the tube wall. The collagen is squeezed and covers the inner wall of the middle fabric layer and penetrates into the relatively loose middle fabric layer, thereby ensuring the integrity of the connection between the inner coating layer and the middle fabric layer. At the same time, the collagen coating itself has good adhesion and is not easy to fall off, ensuring its permeability. Furthermore, the outer fabric layer has a relatively tight plain weave structure, making it difficult for collagen to enter the outer fabric layer and not affecting the outer functional area. Attached Figure Description

[0023] Figure 1 This is a SEM image of the inner wall of the artificial blood vessel without the inner coating in this invention;

[0024] Figure 2 This is a SEM image of the inner wall of the artificial blood vessel after the inner coating is applied in this invention.

[0025] Figure 3 A cross-sectional view of the highly impermeable artificial blood vessel provided by the present invention; Detailed Implementation

[0026] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0027] This invention provides a highly leak-proof artificial blood vessel, which consists of a three-layer structure designed to mimic the intima, media, and adventitia of human blood vessels. From a biomimetic perspective, the three layers of a human blood vessel have different functions, therefore, it is necessary to differentiate their functions.

[0028] In this embodiment, the inner layer of the artificial blood vessel is a collagen coating. Collagen has excellent film-forming properties, resulting in a dense and smooth coating with superior impermeability, forming the functional inner layer of the artificial blood vessel. During surgery, unlike pure fabric blood vessels, there is no blood waste due to pre-clotting. Post-surgery, the collagen layer slowly degrades over time, and the resulting material promotes better cell proliferation.

[0029] Specifically, the collagen used is bovine collagen, fish collagen, or chicken collagen, which has good biocompatibility and is suitable for long-term use. Furthermore, its degradation time is controllable; the degradation time can be controlled by adjusting the thickness of the collagen coating. In this embodiment, the inner collagen coating completes degradation within 60 days under the influence of blood flow and enzymatic decomposition. After degradation, the collagen becomes amino acids, essential substances for the human body.

[0030] Moreover, collagen membranes have excellent adhesive properties, are not easy to fall off, and provide better impermeability.

[0031] The middle layer of the artificial blood vessel is a loosely woven satin or twill fabric layer. Collagen from the inner layer easily penetrates into this middle fabric layer, forming anchoring points to increase the adhesion between the collagen coating and the middle fabric of the artificial blood vessel, ensuring the overall integrity of the vessel. Simultaneously, the middle fabric layer and collagen together form the functional zone of the artificial blood vessel. This functional zone allows the inner collagen coating to adhere completely to the fabric, preventing it from easily detaching and reducing the possibility of collagen coating loss.

[0032] The outer layer of the artificial blood vessel is a tightly woven plain-textured fabric layer, making it difficult for collagen from the inner layer to enter the plain structure. This means the outer fabric layer serves as the functional outer layer of the artificial blood vessel. Furthermore, the dense plain-textured structure makes the artificial blood vessel less prone to being punctured by a needle during suturing, facilitating surgical closure. Simultaneously, the dense fabric structure ensures and enhances the overall mechanical properties of the artificial blood vessel.

[0033] Specifically, the outer and middle layers of the artificial blood vessel are made of one or more of polyester, polypropylene, and polytetrafluoroethylene (PTFE). Polyester, PTFE, and polypropylene are commonly used implantable materials in clinical practice, possessing excellent inertness, resistance to degradation, and good flexibility. The outer and middle layers of the artificial blood vessel are interconnected by interlacing yarns; furthermore, the connection between the outer and middle layers is achieved by interlacing the outer and middle layer yarns with knotting yarns.

[0034] In this embodiment, the fibers used in the outer and middle layers of the artificial blood vessel have a fineness of 100–300D and a single filament count of 40–200. The outer layer of the artificial blood vessel has a dense plain weave structure, resulting in slightly higher stiffness. To maintain the overall flexibility of the artificial blood vessel, the thickness of the outer layer is 0.2–0.3 mm. The middle layer is a satin or twill weave fabric. To avoid affecting the mechanical properties of the braided artificial blood vessel and to increase the bonding force between collagen and the middle layer, the thickness of the middle layer is 0.3–0.5 mm. A too-thick inner collagen coating would cause the artificial blood vessel to harden, affecting its mechanical properties; however, a too-thin coating would result in poor impermeability. Therefore, the thickness of the inner coating is 0.1–0.3 mm.

[0035] This invention also provides a method for preparing a highly impermeable artificial blood vessel, specifically including the following steps: (1) weaving an outer and middle layer of fabric, and connecting the outer and middle layers of fabric to obtain a double-layer artificial blood vessel, the SEM image of which is shown below. Figure 1 As shown;

[0036] (2) Collagen was added to an acetic acid solution to prepare a collagen solution;

[0037] (3) Fix the double-layer artificial blood vessel, take a clean cylindrical sponge and soak it in collagen solution for 5 minutes. The diameter of the cylindrical sponge is larger than the inner diameter of the double-layer artificial blood vessel. Inject 10 mL of the prepared collagen solution into one end of the fixed double-layer artificial blood vessel. Apply the collagen to the inner wall of the two layers of artificial blood vessel at a uniform speed along a path coaxial with the artificial blood vessel. A collagen coating is formed on the inner wall of the double-layer artificial blood vessel, resulting in a three-layer artificial blood vessel. The thickness of the coating can be controlled by controlling the application speed and the number of applications.

[0038] (4) The obtained three-layer artificial blood vessel was dried in a vacuum drying oven at 37°C for 24 hours to obtain a highly impermeable artificial blood vessel. The SEM image of its inner wall is shown below. Figure 2 As shown, by Figure 1 and Figure 2 It can be seen that the above steps successfully formed a relatively smooth and dense coating on the surface of the relatively loose fabric layer. The artificial blood vessel was stored in an environment with a temperature of 25°C and a humidity of 80%–90%.

[0039] Parallel samples of highly impermeable artificial blood vessels were prepared according to the above steps and numbered 1#, 2#, 3#, 4#, 5#, 6#, and 7#, respectively. The weight of the uncoated double-layer artificial blood vessel and the weight of the three-layer artificial blood vessel after drying were recorded, and the weight gain rate after coating was calculated.

[0040]

[0041] The weight gain rate data is shown in the table below:

[0042] Sample number Weight gain rate (%) 1# 4.21 2# 4.75 3# 4.20 4# 4.86 5# 4.03 6# 4.57 7# 5.01

[0043] The weight gain data show that the weight gain of the seven samples was between 4% and 5%, with very little difference.

[0044] The highly impermeable artificial blood vessel prepared in step (4) was broken, and its cross-section was observed. The SEM image of the cross-section is shown below. Figure 3 As shown in the figure, the artificial blood vessel has a three-layer structure with reliable bonding between the layers. The outer layer is a relatively dense fabric layer, the middle layer is a fabric layer with a lot of gel-like substance adhering to it, and the two form a groove morphology. That is to say, the collagen solution is penetrated into the middle fabric layer under the pressure of the cylindrical sponge, and the inner layer is a smooth and dense gel-like substance layer.

[0045] The weight gain data, combined with scanning electron microscopy images, show that the coating is relatively uniformly attached to the inner wall of the artificial blood vessel.

[0046] If conventional methods of pouring or impregnation are used to prepare the inner coating, it is difficult to control the coating to form only on the inner wall of the fabric layer. Furthermore, because pouring or impregnation methods require high solution flowability, it is difficult to control the coating thickness on the fabric surface and to ensure coating uniformity. In this invention, a cylindrical sponge is used to uniformly coat the inner layer. The sponge expands after absorbing the collagen solution, generating pressure on the sponge wall, allowing the collagen solution to penetrate the satin or twill weave structure of the middle layer, ensuring the adhesion between the inner collagen coating and the middle fabric layer. Moreover, when using a cylindrical sponge, the viscosity of the prepared collagen solution is relatively high, preventing the solution from flowing too quickly and ensuring coating uniformity during application.

[0047] Performance testing

[0048] (1) Leakage resistance test

[0049] The highly impermeable artificial blood vessels prepared above were subjected to leakage tests. For an artificial blood vessel with an inner diameter of 10 mm and a length of 101 mm, 4.22 mL of water leaked within 60 seconds under a pressure of 16 kPa. The leakage value was calculated. The leakage values ​​of artificial blood vessels prepared with inner coatings of different thicknesses are shown in the table below:

[0050] Thickness (mm) of the inner coating in artificial blood vessels <![CDATA[Leakage value (mL·min -1 ·cm -2 )]]> 0.1 43.76 0.2 13.43 0.3 0.13

[0051] As shown in the table above, when the thickness of the inner coating in the artificial blood vessel is 0.3 mm, the leakage rate of the artificial blood vessel is 0.13 mL·min. -1 ·cm -2 The resulting artificial blood vessels have good permeability.

[0052] (2) Mechanical properties

[0053] The mechanical properties of the highly impermeable artificial blood vessels prepared above were tested. The mechanical property data of artificial blood vessels with inner coatings of different thicknesses are shown in the table below:

[0054] Inner coating thickness (mm) Fracture stress (MPa) Elongation at break (%) 0.1 112.56 185.69 0.2 118.77 199.26 0.3 113.25 197.56

[0055] (3) Softness test

[0056] The softness properties of the inner collagen coating were tested using a hand-feel softness meter. The softness data for collagen coatings of different thicknesses are shown in the table below:

[0057] Collagen coating thickness (mm) Softness (mN) 0.1 1256 0.2 1859 0.3 2672

[0058] As shown in the table above, the flexibility of the inner coating of artificial blood vessels decreases with increasing thickness. When the inner coating is thicker, it can cause the artificial blood vessels to harden, affecting the overall flexibility of the artificial blood vessels.

[0059] (4) Peel force performance

[0060] The highly impermeable artificial blood vessels prepared above were subjected to peel force tests. The peel force data of artificial blood vessels with different middle layer thicknesses are shown in the table below:

[0061] Thickness of the middle layer (mm) Peel strength (N / m) 0.2 52.9 0.3 70.5 0.4 85.2 0.5 93.5

[0062] As shown in the table above, with the increase of the thickness of the middle layer, the bonding force between the collagen coating and the middle layer fabric is greater, and the collagen coating is more firmly bonded to the middle layer fabric of the artificial blood vessel.

Claims

1. A highly leak-proof artificial blood vessel, characterized in that: The artificial blood vessel consists of three layers: an inner layer of collagen coating, a middle layer of satin or twill fabric, and an outer layer of plain weave fabric. The outer and middle layers are interconnected by interwoven threads. The inner coating is applied to the inner wall of the middle fabric layer using a cylindrical sponge with a diameter larger than the inner diameter of the middle fabric layer. The sponge expands after absorbing the collagen solution. As the collagen-soaked sponge moves within the middle fabric layer, it exerts pressure on the vessel wall, compressing and covering the collagen within the looser middle fabric layer, thus ensuring the seamless connection between the inner coating and the middle fabric layer. The outer layer of the artificial blood vessel has a thickness of 0.2–0.3 mm, the middle layer has a thickness of 0.3–0.5 mm, and the inner layer has a thickness of 0.1–0.3 mm.

2. The highly leak-proof artificial blood vessel according to claim 1, characterized in that: The outer and middle layers of the artificial blood vessel are connected by interlacing the outer and middle yarns with a splicing yarn.

3. The highly impermeable artificial blood vessel according to claim 1, characterized in that: The outer and middle layers of the artificial blood vessel fabric are one or more of polyester, polypropylene, and polytetrafluoroethylene.

4. The highly impermeable artificial blood vessel according to claim 1, characterized in that: The fibers used in the outer and middle layers of the artificial blood vessel fabric are 100-300D in diameter and have 40-200 filaments.

5. The highly leak-proof artificial blood vessel according to claim 1, characterized in that: The collagen coating on the inner layer of the artificial blood vessel degrades within 60 days under the influence of blood flow and enzymatic decomposition.

6. The highly leak-proof artificial blood vessel according to claim 1, characterized in that: The type of collagen is bovine collagen, fish collagen, or chicken collagen.

7. A method for preparing a highly impermeable artificial blood vessel according to any one of claims 1-6, characterized in that... Includes the following steps: (1) Weave the outer and middle fabric layers and connect the outer and middle fabric layers to obtain a double-layer artificial blood vessel; (2) Collagen is added to acetic acid solution to prepare collagen solution; (3) Fix the double-layer artificial blood vessel, take a clean cylindrical sponge and soak it in collagen solution for 5 minutes. The diameter of the cylindrical sponge is larger than the inner diameter of the double-layer artificial blood vessel. Inject 10 mL of the prepared collagen solution into one end of the fixed double-layer artificial blood vessel. Spread the collagen on the inner wall of the two layers of artificial blood vessel at a uniform speed along the path coaxial with the artificial blood vessel. A collagen coating is formed on the inner wall of the double-layer artificial blood vessel to obtain a three-layer artificial blood vessel. (4) The obtained three-layer artificial blood vessel is placed in a vacuum drying oven at 37°C for 24 hours to obtain a highly impermeable artificial blood vessel.

8. The method for preparing a highly impermeable artificial blood vessel according to claim 7, characterized in that: The highly impermeable artificial blood vessel is stored in an environment with a temperature of 25°C and a humidity of 80% to 90%.

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