Artificial blood vessel with high blood seepage prevention performance and preparation method of artificial blood vessel

Abstract

According to the high-seepage-proofing artificial blood vessel and the preparation method thereof, the artificial blood vessel is designed by simulating a three-layer structure of an inner membrane, a middle membrane and an outer membrane of a human body blood vessel, the inner layer is a collagen coating, an inner layer functional area of the artificial blood vessel is formed, and the collagen coating is compact and smooth and has an excellent seepage-proofing effect; the middle layer is a loose fabric layer of a satin weave or twill structure, collagen of the inner layer easily permeates into the middle fabric layer, fixing points are formed to increase the binding force between the collagen coating and the middle fabric of the artificial blood vessel, and the integrity of the whole artificial blood vessel is ensured. Meanwhile, the middle fabric layer and the collagen jointly form a middle functional area of the artificial blood vessel; the outer layer is a compact fabric layer with a plain structure, so that collagen in the inner layer is difficult to enter the plain structure, and the outer fabric layer is used as an outer functional area of the artificial blood vessel.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to an artificial blood vessel with high anti-blood seepage properties and a preparation method thereof. Background Art

[0002] At present, textile artificial blood vessels have been widely used in clinical practice and have achieved good medical effects. However, woven artificial blood vessels made by weaving warp and weft yarns on a loom will form microporous structures between the yarns. Although these micropores are convenient for the recipient tissue to invade and grow, wrap the vascular prosthesis and promote its healing, the disadvantage is that a large amount of blood can leak through the tube wall into the tissue gap during implantation.

[0003] Currently, there are related technologies that reduce leakage by tightly weaving and reducing porosity. For example, patent CN101069757A discloses a double-layer woven structure textile artificial blood vessel. The outer layer wall fiber diameter is coarse, the pores are large, and the structure is sparse, while the inner layer wall fiber diameter is small, the pore size is small, and the structure is tight. The outer layer structure with larger pores is conducive to the growth of cell tissues, and the inner layer structure with smaller pores avoids excessive bleeding during surgery. In addition, patent CN102206888A discloses an integrated three-layer woven simulated artificial blood vessel, including an outer woven structure, a middle woven structure and an inner woven structure, and the three woven structures are connected together by a binding yarn, the outer woven structure adopts a twill or satin weave, the middle woven structure adopts a twill weave, and the inner woven structure adopts a plain weave; the outer layer tissue density is relatively small, and the pores between the yarns are relatively large, which is conducive to the growth of cells and tissues; the middle layer structure is fluffy, has good elasticity, and has moderate pores, which provides good elasticity for the vascular wall and provides space for the growth of nutrient blood vessels; the inner layer tissue density is relatively large, the pores are relatively small, and the tube wall is smooth, which is conducive to blood flow, and can effectively prevent the bleeding of the tube wall during the transplantation of textile artificial blood vessels. The thinner monofilaments in the multifilament are conducive to the growth of endothelial cells. In the above patent, leakage can be reduced by weaving tightly through leakage, but it will also affect the mechanical properties of the inner fabric, making it hard, thereby affecting the elasticity of the artificial blood vessel.

[0004] At present, a coating method can be used to seal the gap to reduce blood leakage. For example, patent CN200610112213.9 discloses injecting a collagen mixed coating liquid from a section of a woven artificial blood vessel through a syringe, so that the coating liquid is evenly coated on the inner wall of the lumen. After the coated artificial blood vessel is dried, it is placed in a vacuum drying oven at 90-110°C for cross-linking for 16-20 hours. The average blood permeability of the obtained artificial blood vessel is 0.024ml / min*cm 2 The water permeability of the artificial blood vessel after 3 coatings is 2.5ml / min*cm 2However, this method has the following problems: (1) The collagen mixed coating liquid is allowed to flow freely through a syringe and coated on the inner wall of the lumen, the uniformity of the collagen coating cannot be guaranteed, and the interface bonding between the collagen coating and the inner wall of the lumen is also poor, and the collagen coating is easy to fall off; (2) Multiple coatings are required, and the production efficiency is low; (3) The cross-linking reaction is required at a high temperature (90-110°C), which is easy to destroy the structure of collagen. Summary of the invention

[0005] The invention provides an artificial blood vessel with high anti-blood seepage effect and a preparation method thereof. The artificial blood vessel has excellent anti-blood seepage effect, good mechanical properties and a simple preparation method.

[0006] In order to solve the above technical problems, the technical solution of the present invention is:

[0007] The invention discloses an artificial blood vessel with high anti-bleeding property. The artificial blood vessel is composed of a three-layer structure, wherein the inner layer is a collagen coating, the middle layer is a fabric layer with a satin or twill structure, and the outer layer is a fabric layer with a plain weave structure.

[0008] The outer layer and the middle layer of the artificial blood vessel are connected to each other in an interlaced manner, and the collagen coating of the inner layer penetrates into the middle fabric layer, thereby being connected to the middle fabric layer.

[0009] The outer layer and the middle layer of the artificial blood vessel are connected by interweaving the outer layer yarns and the middle layer yarns through the binding yarns.

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

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

[0012] The thickness of the fibers used in the outer layer and the middle layer fabrics of the artificial blood vessel is 100-300D, and the number of monofilaments is 40-200.

[0013] The collagen coating of the inner layer of the artificial blood vessel is completely degraded within 60 days under the action of blood flow flushing and enzyme decomposition.

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

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

[0016] (2) adding collagen to acetic acid solution to prepare a collagen solution;

[0017] (3) Fixing the double-layer artificial blood vessel, taking a clean cylindrical sponge and soaking it in the collagen solution for 5 minutes, wherein the diameter of the cylindrical sponge is larger than the inner diameter of the double-layer artificial blood vessel, injecting 10 mL of the prepared collagen solution into one end of the fixed double-layer artificial blood vessel, and applying the collagen to the inner walls of the two layers of the artificial blood vessel at a uniform speed along the same axis as the artificial blood vessel, forming a collagen coating on the inner wall of the double-layer artificial blood vessel, and obtaining 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 an artificial blood vessel with high anti-bleeding properties.

[0019] The artificial blood vessel with high anti-blood seepage property is stored in an environment with a temperature of 25° C. and a humidity of 80% to 90%.

[0020] Compared with the prior art, the present invention has the following beneficial effects: (1) The highly anti-blood seepage artificial blood vessel provided by the present invention is designed by simulating the three-layer structure of the human vascular intima, middle membrane and outer membrane. The inner layer is a collagen coating, forming the inner functional area of ​​the artificial blood vessel. The collagen coating is dense and smooth, has excellent anti-seepage effect, and has good adhesion properties and is not easy to fall off; the middle layer is a relatively loose satin or twill fabric layer, and the collagen of the inner layer can easily penetrate into the middle fabric layer to form fixed points to increase the adhesion between the collagen coating and the middle fabric of the artificial blood vessel. The bonding force ensures the integrity of the entire artificial blood vessel. The collagen coating is attached to the fabric as a whole and will not fall off easily. At the same time, the middle fabric layer and the collagen together form the middle functional area of ​​the artificial blood vessel. The outer layer is a fabric layer with a tight plain weave structure, which makes it difficult for the collagen in the inner layer 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 it difficult for the artificial blood vessel to be hooked by the needle during suturing, which is conducive to surgical suturing. At the same time, the dense fabric structure provides a guarantee for the overall mechanical properties of the artificial blood vessel.

[0021] (2) The outer plain woven fabric layer of the artificial blood vessel of the present invention is relatively dense. In order not to affect the elasticity of the artificial blood vessel, the thickness of the outer layer is 0.2-0.3 mm to ensure the softness of the plain woven fabric layer; the thickness of the middle layer is 0.3-0.5 mm to ensure that the inner coating and the middle layer are tightly combined while ensuring the mechanical properties; the thickness of the inner layer is 0.1-0.3 mm to avoid the problem of poor leakage due to too thin a coating and poor mechanical properties due to too thick a coating.

[0022] (3) The outer fabric layer and the middle fabric layer of the artificial blood vessel of the present invention are interwoven and connected by the binding yarn, and the inner coating 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, and the sponge will swell after absorbing the collagen solution. When the cylindrical sponge soaked with the collagen solution moves in the middle fabric layer, the sponge exerts a certain pressure on the tube wall, and the collagen is squeezed and covered on the inner wall of the middle fabric layer and penetrates into the relatively loose middle fabric layer, thereby ensuring the connection and integrity of the inner coating 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 leakage. In addition, the outer fabric layer is a relatively tight plain weave structure, and collagen is not easy to enter the outer fabric layer, and will not affect the outer functional area. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is a SEM image of the inner wall of the artificial blood vessel when the inner layer coating is not applied in the present invention;

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

[0025] Figure 3 A cross-sectional view of an artificial blood vessel with high anti-blood seepage properties provided by the present invention; DETAILED DESCRIPTION

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

[0027] The present invention provides an artificial blood vessel with high anti-bleeding properties. The artificial blood vessel is composed of a three-layer structure and is designed by simulating the three-layer structure of the intima, middle membrane and adventitia of human blood vessels. From the perspective of bionics, the three-layer structure of human blood vessels has different functions, so it is necessary to distinguish the functions of the three-layer structure.

[0028] The inner layer of the artificial blood vessel in this embodiment is a collagen coating. Collagen has good film-forming properties, and the coating is dense and smooth, with excellent anti-seepage effect, forming the inner functional area of ​​the artificial blood vessel. Compared with pure fabric blood vessels, there is no waste of blood due to pre-coagulation during surgery. After surgery, the collagen layer will slowly degrade over time, and the materials produced by degradation can enable cells to proliferate better.

[0029] Specifically, the type of collagen is bovine collagen, fish collagen or chicken collagen, which has good biocompatibility and is suitable for long-term use. Moreover, its degradation time is controllable, and the degradation time can be controlled by adjusting the thickness of the collagen coating. In this embodiment, the inner layer of the collagen coating is degraded within 60 days under the action of blood flow and enzyme decomposition. After degradation, the collagen will become amino acids, which become a substance necessary for the human body.

[0030] Moreover, the collagen membrane has excellent adhesion properties, is not easy to fall off, and is better at preventing seepage.

[0031] The middle layer of the artificial blood vessel is a relatively loose satin or twill fabric layer. The inner layer collagen can easily penetrate into the middle fabric layer, forming fixed points to increase the bonding strength between the collagen coating and the middle fabric of the artificial blood vessel, ensuring the integrity of the entire artificial blood vessel; at the same time, the middle fabric layer and collagen together form the middle functional area of ​​the artificial blood vessel. The middle functional area can make the inner layer collagen coating adhere to the fabric as a whole, and will not easily fall off, reducing the possibility of the collagen coating falling off.

[0032] The outer layer of the artificial blood vessel is a fabric layer with a tight plain weave structure, which makes it difficult for the collagen in the inner layer to enter the plain weave structure, that is, the outer fabric layer alone serves as the outer functional area of ​​the artificial blood vessel, and the outer layer's dense plain weave structure makes the artificial blood vessel less likely to be pierced by a needle during suturing, which is conducive to surgical suturing. At the same time, the dense fabric structure provides a guarantee for the overall mechanical properties of the artificial blood vessel, thereby improving the overall mechanical properties of the artificial blood vessel.

[0033] Specifically, the outer and middle fabrics of the artificial blood vessel are one or more of polyester, polypropylene, and polytetrafluoroethylene, which are commonly used implantable materials in clinical practice, have good inertness, are not easy to degrade, and have good flexibility. The outer and middle layers of the artificial blood vessel are connected to each other in an interwoven manner; further, the outer and middle layers of the artificial blood vessel are connected by interweaving the outer yarn and the middle yarn through a binding yarn.

[0034] The thickness of the fibers used in the outer and middle fabrics of the artificial blood vessel in this embodiment is 100-300D, and the number of monofilaments is 40-200. At the same time, the outer fabric layer of the artificial blood vessel is a dense plain weave structure, so the hardness is slightly larger. In order to maintain the softness of the entire artificial blood vessel, the thickness of the outer fabric layer is 0.2-0.3mm. The middle layer is a satin or twill fabric. In order not to affect the mechanical properties of the woven artificial blood vessel and to increase the bonding force between the collagen and the middle fabric, the thickness of the middle fabric layer ranges from 0.3 to 0.5mm. If the inner collagen coating is too thick, the artificial blood vessel will become hard and affect its mechanical properties, but if the coating is too thin, its anti-seepage effect will be poor. Therefore, the thickness of the inner coating is 0.1-0.3mm.

[0035] The present invention also provides a method for preparing an artificial blood vessel with high anti-blood seepage properties, which specifically comprises the following steps: (1) weaving an outer layer and a middle layer of fabric layers, and connecting the outer layer and the middle layer of fabric layers to obtain an artificial blood vessel with a double-layer structure, the inner wall of which is shown in the SEM image as follows: Figure 1 As shown;

[0036] (2) adding collagen to 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 the 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 walls of the two layers of the artificial blood vessel at a uniform speed along the same axis as the artificial blood vessel. Form a collagen coating on the inner wall of the double-layer artificial blood vessel to obtain a three-layer artificial blood vessel. The thickness of the coating can be controlled by controlling the coating speed and the number of coatings.

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

[0039] According to the above steps, parallel samples of artificial blood vessels with high anti-blood seepage were prepared, numbered 1#, 2#, 3#, 4#, 5#, 6#, and 7#, respectively. The weight of the double-layer artificial blood vessels without coating and the weight of the three-layer artificial blood vessels obtained after drying were recorded, and the weight gain rate after coating was calculated:

[0040]

[0041] The weight gain rate data are shown in the following table:

[0042] Sample No. 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] From the weight gain rate data, it can be seen that the weight gain rates of the seven samples prepared are around 4% to 5%, with a small difference.

[0044] The highly anti-blood seepage artificial blood vessel obtained in step (4) was broken and its cross section was observed. The SEM image of the cross section is as follows: Figure 3 As shown in the figure, it can be observed that the artificial blood vessel has a three-layer structure, and the layers are reliably connected. The outer layer is a relatively dense fabric layer, and the middle layer is a fabric layer with more colloid adhered to it. The two form a groove morphology, that is, the collagen solution is immersed in the middle fabric layer under the squeezing of the cylindrical sponge, and the inner layer is a smooth and dense colloid layer.

[0045] The weight gain rate data combined with the scanning electron microscope image show that the prepared coating is relatively evenly attached to the inner wall of the artificial blood vessel.

[0046] If the inner coating is prepared by conventional perfusion or dipping, it is difficult to control the coating to be formed only on the inner wall of the fabric layer; at the same time, since the perfusion or dipping method has high requirements on the fluidity of the solution, it is difficult to control the coating to form a certain thickness on the surface of the fabric layer, and the uniformity of the coating cannot be guaranteed. However, in the present invention, a cylindrical sponge is used to evenly coat the coating. After the sponge absorbs the collagen solution, it will expand and exert a certain pressure on the tube wall, so that the collagen solution is immersed in the satin or twill structure of the middle layer, ensuring the bonding force between the inner collagen coating and the middle fabric layer; and when using a cylindrical sponge coating, the viscosity of the prepared collagen solution is relatively high, and the collagen solution will not flow too fast, so the uniformity of the coating can be guaranteed during coating.

[0047] Performance Testing

[0048] (1) Anti-leakage performance test

[0049] The artificial blood vessels with high anti-blood seepage prepared above were subjected to leakage test. The artificial blood vessels with inner diameter of 10 mm and length of 101 mm were tested. Under the pressure of 16 KPa, 4.22 mL of water was seeped in the artificial blood vessels within 60 seconds. The leakage value was calculated. The leakage values ​​of artificial blood vessels made with different thickness of inner layer coating are shown in the following table:

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

[0051] As can be seen from the table above, when the thickness of the inner coating of the artificial blood vessel is 0.3 mm, the leakage value of the artificial blood vessel is 0.13 mL·min -1 cm -2 The artificial blood vessel has good leakage

[0052] (2) Mechanical properties

[0053] The mechanical properties of the artificial blood vessels with high anti-blood seepage prepared above were tested. The mechanical properties of the artificial blood vessels prepared with different thicknesses of the inner coating are shown in the following table:

[0054] Thickness of inner coating (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 of the inner collagen coating was tested by a hand-feel softness tester. The softness data of collagen coatings of different thicknesses are shown in the following table:

[0057] Thickness of collagen coating (mm) Softness(mN) 0.1 1256 0.2 1859 0.3 2672

[0058] It can be seen from the above table that the softness of the inner coating in the artificial blood vessel deteriorates as the thickness increases. When the inner coating is thicker, it will cause the artificial blood vessel to harden, affecting the overall softness of the artificial blood vessel.

[0059] (4) Peel force performance

[0060] The peeling force test of the artificial blood vessels with high anti-blood seepage prepared above was carried out. The peeling force data of artificial blood vessels with different middle layer thicknesses are shown in the following table:

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

[0062] It can be seen from the above table that as the thickness of the middle layer increases, the bonding force between the collagen coating and the middle layer fabric is greater, and the bonding between the collagen coating and the middle layer fabric of the artificial blood vessel is firm.

Claims

1. An artificial blood vessel with high anti-bleeding properties, characterized in that: The artificial blood vessel is composed of a three-layer structure, wherein the inner layer is a collagen coating, the middle layer is a fabric layer with a satin or twill structure, and the outer layer is a fabric layer with a plain weave structure.

2. The artificial blood vessel with high anti-blood seepage properties according to claim 1, characterized in that: The outer layer and the middle layer of the artificial blood vessel are connected to each other in an interlaced manner, and the collagen coating of the inner layer penetrates into the middle fabric layer, thereby being connected to the middle fabric layer.

3. The artificial blood vessel with high anti-blood seepage properties according to claim 1, characterized in that: The outer layer and the middle layer of the artificial blood vessel are connected by interweaving the outer layer yarns and the middle layer yarns through the binding yarns.

4. The artificial blood vessel with high anti-blood seepage properties according to claim 1, characterized in that: The thickness of the outer layer of the artificial blood vessel is 0.2-0.3 mm, the thickness of the middle layer of the artificial blood vessel is 0.3-0.5 mm, and the thickness of the inner layer of the artificial blood vessel is 0.1-0.3 mm.

5. The artificial blood vessel with high anti-blood seepage properties according to claim 1, characterized in that: The outer layer and middle layer fabrics of the artificial blood vessel are one or more of polyester, polypropylene and polytetrafluoroethylene.

6. The artificial blood vessel with high anti-blood seepage properties according to claim 1, characterized in that: The thickness of the fibers used in the outer layer and the middle layer fabrics of the artificial blood vessel is 100-300D, and the number of monofilaments is 40-200.

7. The artificial blood vessel with high anti-blood seepage properties according to claim 1, characterized in that: The collagen coating of the inner layer of the artificial blood vessel is completely degraded within 60 days under the action of blood flow flushing and enzyme decomposition.

8. The artificial blood vessel with high anti-blood seepage properties according to claim 1, characterized in that: The type of collagen is bovine collagen, fish collagen or chicken collagen.

9. A method for preparing an artificial blood vessel with high anti-blood seepage properties according to any one of claims 1 to 8, characterized in that The following steps are involved: (1) weaving an outer fabric layer and a middle fabric layer, and connecting the outer fabric layer and the middle fabric layer to obtain an artificial blood vessel with a double-layer structure; (2) adding collagen to acetic acid solution to prepare a collagen solution; (3) Fixing the double-layer artificial blood vessel, taking a clean cylindrical sponge and soaking it in the collagen solution for 5 minutes, wherein the diameter of the cylindrical sponge is larger than the inner diameter of the double-layer artificial blood vessel, injecting 10 mL of the prepared collagen solution into one end of the fixed double-layer artificial blood vessel, and applying the collagen to the inner walls of the two layers of the artificial blood vessel at a uniform speed along the same axis as the artificial blood vessel, forming a collagen coating on the inner wall of the double-layer artificial blood vessel, and obtaining a three-layer artificial blood vessel; (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 an artificial blood vessel with high anti-bleeding properties.

10. The method for preparing an artificial blood vessel with high anti-blood seepage properties according to claim 9, characterized in that: The artificial blood vessel with high anti-blood seepage property is stored in an environment with a temperature of 25° C. and a humidity of 80% to 90%.

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