Artificial blood vessel and method for manufacturing artificial blood vessel

Abstract

The purpose of the present invention is to provide an artificial blood vessel having high flexibility and a method for manufacturing the artificial blood vessel. An artificial blood vessel (VE) according to the present invention is an artificial blood vessel (VE) comprising expanded polytetrafluoroethylene having nodes and fibrils formed between the nodes, in which high-density regions (R1) and low-density regions (R2) are alternately provided in the axial direction (D1) of the artificial blood vessel (VE), the high-density region (R1) is a region in which nodes and fibrils are compressed and dense in the axial direction (D1), and the low-density region (R2) is a region in which nodes and fibrils are in a lower-density state than the high-density region (R1).

Description

Technical Field

[0001] The present invention relates to an artificial blood vessel and a method for manufacturing the artificial blood vessel. Background Art

[0002] An artificial blood vessel made of expanded polytetrafluoroethylene (ePTFE) is used as the material. This ePTFE artificial blood vessel is formed by rapidly stretching polytetrafluoroethylene (PTFE) into a tube, resulting in a structure with nodes and fibrils formed between the nodes, as described in Patent Document 1.

[0003] Prior art literature Patent Literature Patent Document 1: Japanese Patent Application No. 2005-530549

[0004] Problems to be solved by the invention

[0005] An artificial blood vessel made of ePTFE is biocompatible and flexible, but an artificial blood vessel made of ePTFE that is even more flexible is being demanded. Summary of the Invention

[0006] Therefore, an object of the present invention is to provide an artificial blood vessel with high flexibility and a method for producing the artificial blood vessel.

[0007] Technical solutions to problems

[0008] The artificial blood vessel of the present invention is an artificial blood vessel composed of expanded polytetrafluoroethylene, wherein the expanded polytetrafluoroethylene has nodes and fibrils formed between the nodes, wherein high-density areas and low-density areas are alternately arranged in the axial direction of the artificial blood vessel, the high-density areas are areas where the nodes and the fibrils are compressed in the axial direction and become dense, and the low-density areas are areas where the nodes and the fibrils are in a low-density state compared to the high-density areas.

[0009] In addition, the manufacturing method of the artificial blood vessel of the present invention includes the following steps: a) providing a tubular artificial blood vessel substrate composed of expanded polytetrafluoroethylene, wherein the expanded polytetrafluoroethylene has nodes and fibrils formed between the nodes; b) compressing the artificial blood vessel substrate in the axial direction of the artificial blood vessel substrate while inserting a core material into the inner side of the artificial blood vessel substrate; c) releasing the force compressing the artificial blood vessel substrate to extend the artificial blood vessel substrate; d) compressing the extended artificial blood vessel substrate again one or more times; and e) extending the artificial blood vessel substrate compressed in step d) again.

[0010] Effects of the Invention

[0011] According to the artificial blood vessel and the method for manufacturing an artificial blood vessel of the present invention, an artificial blood vessel with high flexibility can be provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 This is a schematic diagram of an artificial blood vessel according to one embodiment of the present invention. Figure 2 yes Figure 1 An enlarged schematic diagram of area A1. Figure 3 This is a SEM photograph at 25 times the magnification of the surface of a sample piece obtained by cutting a portion of the artificial blood vessel in the thickness direction. Figure 4 yes Figure 3 A 100x SEM photograph of area A2. Figure 5 This is a diagram showing an artificial blood vessel substrate preparation step in a method for manufacturing an artificial blood vessel. Figure 6 This is a diagram showing the first firing step in the method for producing an artificial blood vessel. Figure 7 This is a diagram showing a marker coating step in a method for producing an artificial blood vessel. Figure 8 This is a diagram showing the first compression step in the method for manufacturing an artificial blood vessel. Figure 9 This is a diagram showing a strip-shaped portion forming step in a method for manufacturing an artificial blood vessel. Figure 10 This is a diagram showing the first stretching step in the method for manufacturing an artificial blood vessel. Figure 11 This is a diagram showing an additional compression step in the method for manufacturing an artificial blood vessel. Figure 12 This is a diagram showing an additional stretching step in the method for manufacturing an artificial blood vessel. Figure 13 This is a 33x SEM photograph of a sample piece obtained by cutting a portion of the artificial blood vessel from an oblique direction. Figure 14 This is a SEM photograph showing a cross-section of a sample piece obtained by cutting a portion of the artificial blood vessel, taken at 130 times the magnification of the sample piece in the axial direction. Figure 15 This is a photograph showing the band-shaped portion of an artificial blood vessel. Figure 16 This is a schematic diagram showing a method for evaluating the flexibility of an artificial blood vessel. Figure 17 This is a microscope image of a sample piece obtained by partially cutting the artificial blood vessel in the thickness direction.

[0013] Description of labels 1 node 2 Fibrils B band C core material D1 Axial D2 Circumferential D3 radial E1, E2 contacts F Fixed platform FR Fixing table reference surface L is the vertical length from the base plane of the fixing platform to the distal end of the artificial blood vessel. M mark N1 and N2 node parts P1 Part of the strip P2 Other parts of the strip P3 The inner part of the bend of the artificial blood vessel P4 The outer part of the curved part of the artificial blood vessel R1 High-density area R2 low-density area T The front end of the artificial blood vessel VE artificial blood vessels VEB artificial blood vessel substrate X Axis of the graft θ is the angle of the strip relative to the axis of the artificial blood vessel θE Angle between the node parts DETAILED DESCRIPTION

[0014] Hereinafter, an artificial blood vessel and a method for manufacturing an artificial blood vessel according to an embodiment of the present invention will be described with reference to the accompanying drawings. The embodiment shown below is merely an example, and the artificial blood vessel and the method for manufacturing an artificial blood vessel according to the present invention are not limited to the following embodiment.

[0015] In this specification, "perpendicular to A" and similar expressions do not refer only to a direction that is completely perpendicular to A, but also include situations where it is approximately perpendicular to A. Furthermore, in this specification, "parallel to B" and similar expressions do not refer only to a direction that is completely parallel to B, but also include situations where it is approximately parallel to B. Furthermore, in this specification, "C-shaped" and similar expressions do not refer only to a perfect C-shape, but also include situations where a shape reminiscent of a C-shape in appearance (approximately a C-shape).

[0016] An artificial blood vessel VE according to one embodiment of the present invention (see Figure 1) For example, it is used to replace a diseased biological blood vessel and bypass the biological blood vessel. The artificial blood vessel VE is composed of a cylindrical body with a predetermined length.

[0017] The diameter of the artificial blood vessel VE can be varied depending on the intended location and other factors, and is not particularly limited. For example, the artificial blood vessel VE can be a large-caliber artificial blood vessel with an inner diameter of 10 mm or greater (for use in the thoracic and abdominal aorta), a medium-caliber artificial blood vessel with an inner diameter of 6 mm or greater but less than 10 mm (for use in arteries in the lower limbs, neck, and axillary regions), or a small-caliber artificial blood vessel with an inner diameter of less than 6 mm, such as 4 mm or 5 mm. The thickness of the artificial blood vessel VE can be varied appropriately depending on the inner diameter and length of the artificial blood vessel used, and is not particularly limited. For example, the thickness of the artificial blood vessel VE can be set to 0.1 to 2 mm. For example, if the inner diameter of the artificial blood vessel VE is 5 to 6 mm, the wall thickness can be 0.3 to 0.7 mm, and preferably 0.4 to 0.6 mm.

[0018] The length of the artificial blood vessel VE in the axial direction D1 can be changed according to the site of use, etc., and is not particularly limited. For example, the length of the artificial blood vessel VE in the axial direction D1 can be set to 50 to 1000 mm.

[0019] The artificial blood vessel VE of this embodiment is made of expanded polytetrafluoroethylene (ePTFE). Figure 4 As shown, the artificial blood vessel VE is composed of expanded polytetrafluoroethylene having nodes 1 and fibrils 2 formed between the nodes 1. In addition, Figure 3 This is a 25x SEM photograph taken from the outer surface of the artificial blood vessel VE along the thickness direction after the sample piece was flattened by cutting a tubular artificial blood vessel VE manufactured by the manufacturing method described below with a cutter. Figure 4 It will Figure 3 A partially enlarged photograph of area A2.

[0020] An artificial blood vessel made of expanded polytetrafluoroethylene (EPTFE), for example, is prepared by mixing a lubricant with unsintered PTFE powder and adjusting the mixture, as described in Japanese Patent Publication No. 42-13560. The mixture is extruded into a tubular shape using a plunger extrusion molding device, and then the tube is stretched axially at a desired stretch ratio. The resulting tube is fixed in a manner that prevents shrinkage, and the stretched structure, which has been heated to a sintering temperature or higher, is sintered and fixed, thereby obtaining a cylindrical artificial blood vessel substrate made of expanded polytetrafluoroethylene. The artificial blood vessel substrate is then subjected to a prescribed treatment described below to obtain an artificial blood vessel VE. Furthermore, the method for manufacturing an artificial blood vessel (artificial blood vessel substrate) made of expanded polytetrafluoroethylene is not limited to the above method, as long as it can obtain a structure having nodes and fibrils.

[0021] The porosity and fibril length of the artificial vascular substrate can be arbitrarily set by adjusting the stretching ratio and the tensile strain rate. The tube forming the basis of the artificial vascular substrate is stretched in a uniaxial direction. The stretching ratio is not particularly limited and can be selected, for example, from a range of 1.2 to 15 times, preferably 2 to 10 times, and more preferably 2 to 5 times. The sintering temperature of the artificial vascular substrate is not particularly limited and can be, for example, 350 to 800°C.

[0022] The artificial blood vessel substrate is produced in the extrusion molding step at an extrusion molding speed calculated from the product of the extrusion reduction ratio (hereinafter sometimes referred to as "extrusion RR") and the punch speed (mm / min), which is used in the production of known artificial blood vessel substrates.

[0023] In order to improve the extrusion forming property under high speed, it can be thought that preferably makes liquid lubricant higher with respect to the mixing ratio of PTFE unsintered powder, but if coordinates excessive liquid lubricant, then sometimes cause the intensity reduction of artificial blood vessel base material.Therefore, with respect to PTFE unsintered powder 100 mass parts, the mixing ratio of liquid lubricant is preferably below 30 mass parts, more preferably below 26 mass parts.With respect to PTFE unsintered powder 100 mass parts, the lower limit of the mixing ratio of liquid lubricant is preferably 15 mass parts, more preferably 18 mass parts, is preferably particularly 20 mass parts.With respect to the mixing amount of the liquid lubricant of PTFE unsintered powder 1kg, preferably suppress as below 380ml, more preferably suppress as below 330ml.

[0024] Nodes 1 are three-dimensionally connected in the artificial blood vessel VE (refer to Figure 3 、 Figure 4 、 Figure 13 and Figure 14 Specifically, the node 1 is located in the axial direction D1, circumferential direction D2 and radial direction D3 of the artificial blood vessel VE (refer to Figure 1 ). In addition, Figure 4 As shown, the fibril 2 extends in such a manner as to connect a portion of the node 1 separated in the axial direction D1 to another portion of the node 1 in the axial direction D1 .

[0025] In this embodiment, if Figure 2 and Figure 3 As shown, high-density regions R1 and low-density regions R2 are alternately arranged in the axial direction D1 of the artificial blood vessel VE, wherein the high-density region R1 is a region where the nodes 1 and the fibrils 2 are compressed and dense in the axial direction D1, and the low-density region R2 is a region where the nodes 1 and the fibrils 2 are in a low-density state compared with the high-density region R1.

[0026] The high-density region R1 is a region where the density of nodes 1 and fibrils 2 (especially nodes 1) is relatively higher than that of the low-density region R2. The high-density region R1 is a compressed region where the nodes 1 and fibrils 2 are compressed in the axial direction D1 of the artificial blood vessel VE and are densely packed. Figure 2 and Figure 3 As shown, the high-density region R1 is provided in an annular shape in the circumferential direction D2 of the artificial blood vessel VE. The structure and formation method of the high-density region R1 are not particularly limited as long as the high-density region R1 is configured such that the nodes 1 and fibrils 2 are denser in the compressed state than in other regions (low-density regions R2). In this embodiment, the high-density region R1 is formed when the cylindrical artificial blood vessel base material VEB is compressed in the axial direction D1 (see FIG. Figure 8 ) is formed by the compression stripe portion (a curved portion of the artificial vascular base material VEB centered at the bottom of the valley portion, which is contracted into a wrinkled shape by compressing the artificial vascular base material VEB in the axial direction D1). In addition, in this embodiment, the high-density region R1 provided as the compression stripe is formed on the core material C (see Figure 8 In a state where the artificial vascular substrate VEB is inserted (e.g., etc.), the artificial vascular substrate VEB is compressed in the axial direction D1. In this case, a portion displaced outward in the radial direction D3 and a portion displaced inward in the radial direction D3 are generated in the artificial vascular substrate VEB. The portion displaced inward in the radial direction D3 is in contact with the core material C and is likely to become high-density. In addition, the width of each of the high-density region R1 and the low-density region R2 in the axial direction D1 and the ratio of their widths to each other can be appropriately changed according to the compression method of the artificial vascular substrate and the artificial vascular substrate used, and are not particularly limited. In addition, the boundary between the high-density region R1 and the low-density region R2 is as follows: Figure 3 While not explicitly defined, it suffices to confirm the alternating presence of high-density regions R1 (dark regions when visually observed) and low-density regions R2 (light regions when visually observed) with a density lower than that of the high-density regions R1 when magnified in an SEM photograph or the like. Alternatively, the boundary between the high-density regions R1 and the low-density regions R2 can be determined using brightness contrast or other methods in an image of the high-density regions R1 and the low-density regions R2. The density of the nodes 1 and fibrils 2 in the high-density region R1 is not limited to a specific value as long as the density of the nodes 1 and fibrils 2 is relatively high compared to the density of the nodes 1 and fibrils 2 in the low-density region R2.

[0027] The low-density region R2 is a region where the density of nodes 1 and fibrils 2 (especially nodes 1) is relatively low compared to the high-density region R1. The low-density region R2 is a non-compressed portion sandwiched between the high-density regions R1 in the axial direction D1. The high-density region R1 is a region where the nodes 1 and fibrils 2 are densely packed when compressed in the axial direction D1 of the artificial blood vessel VE. Figure 2 and Figure 3 As shown, the low-density region R2 is provided in an annular shape in the circumferential direction D2 of the artificial blood vessel VE. The structure and formation method of the low-density region R2 are not particularly limited as long as the low-density region R2 is configured such that the density of nodes 1 and fibrils 2 is lower than that of other regions (high-density region R1). In this embodiment, the low-density region R2 is provided in the axial direction D1 when the artificial blood vessel base material VEB is compressed in the axial direction D1 (see FIG. Figure 8 ) between the compressed streaks (high-density region R1). Furthermore, the density of the nodes 1 and fibrils 2 in the low-density region R2 is not limited to a specific value as long as it is relatively low relative to the density of the nodes 1 and fibrils 2 in the high-density region R1.

[0028] like Figure 2 and Figure 3 As shown, the artificial blood vessel VE of this embodiment has high-density regions R1 and low-density regions R2 arranged alternately in the axial direction D1. This improves the flexibility of the artificial blood vessel VE. Specifically, high-density regions R1, where the density of nodes 1 and fibrils 2 is high (particularly, the density of relatively hard nodes 1 is high), and low-density regions R2, where the density of nodes 1 and fibrils 2 is low (particularly, the density of relatively hard nodes 1 is low), are formed alternately in the axial direction D1 of the artificial blood vessel VE. This allows the artificial blood vessel VE to function like a wrinkle, improving the flexibility of the artificial blood vessel VE.

[0029] In this embodiment, if Figure 1 、 Figure 15 As shown, the artificial blood vessel VE further includes a strip-shaped portion B that extends continuously in a strip-like shape along the axial direction D1 of the artificial blood vessel VE in such a manner as to serve as resistance to the artificial blood vessel VE (artificial blood vessel base material VEB) from stretching in the axial direction D1 to a length exceeding a predetermined length after the artificial blood vessel VE (artificial blood vessel base material VEB) is compressed in the axial direction D1.

[0030] As will be described in detail later, the band-shaped portion B acts as a resistance to the extension of the artificial vascular substrate VEB when the artificial vascular substrate VEB is compressed in the axial direction D1 and the compressive force is removed, thereby preventing the artificial vascular substrate VEB from extending beyond a predetermined length. Here, the "predetermined length" refers to a length shorter than the natural length of the artificial vascular substrate VEB before compression. Specifically, it refers to a length shorter than the length of an artificial vascular substrate VEB with the same structure except for not having the band-shaped portion B when the compressive force is removed and sufficient time has passed since compression. More specifically, the "predetermined length" is preferably 60% to 80%, and more preferably 65% ​​to 75%, of the natural length of the artificial vascular substrate VEB before compression.

[0031] The structure and formation method of the band-shaped portion B are not particularly limited, as long as it acts as a resistance to the expansion of the compressed artificial blood vessel VE (artificial blood vessel base VEB). For example, the band-shaped portion B is rigid compared to the remaining portion (the portion with alternating high-density regions R1 and low-density regions R2) where the band-shaped portion B is not formed. Thus, even if the remaining portion, which is relatively flexible compared to the band-shaped portion B, attempts to expand in the axial direction D1, the band-shaped portion B acts as a resistance to the expansion of the remaining portion. The band-shaped portion B can be formed, for example, by locally curing the artificial blood vessel base VEB by heat treatment (e.g., laser firing, heating with a heater, etc.) at specific locations on the artificial blood vessel base VEB. Alternatively, tape can be applied to the artificial blood vessel base VEB in a specific pattern, or a specific pattern of compressive force can be applied locally.

[0032] The strip-shaped portion B extends continuously in a strip-like manner along the axial direction D1 of the artificial blood vessel VE. Here, "extending continuously along the axial direction D1" means that the strip-shaped portion B is continuous from one side of the axial direction D1 to the other side, providing resistance to extension of the artificial blood vessel base material VEB beyond a predetermined length. While the strip-shaped portion B extends continuously in the axial direction D1 while being inclined relative to the axial direction D1 in this embodiment, a portion of the strip-shaped portion B may also extend parallel to the axial direction D1.

[0033] As described above, the shape of the strip portion B is not particularly limited as long as it continuously extends along the axial direction D1 in a manner that acts as a resistance to the expansion of the compressed artificial blood vessel VE (artificial blood vessel base material VEB). Figure 1 and Figure 2 As shown, the strip-shaped portion B is provided as a portion P1 of the strip-shaped portion B at a location in the axial direction D1 of the artificial blood vessel VE (refer to Figure 1 ) and another portion P2 separated from the portion P1 in the axial direction D1 (refer to Figure 1), there is an area in which high-density areas R1 and low-density areas R2 are alternately formed.

[0034] In this embodiment, if Figure 1 As shown, the band-shaped portion B extends helically around the axis of the artificial blood vessel VE. In this case, the artificial blood vessel VE's resistance to outward forces in the radial direction D3 is improved. Furthermore, the helical extension of the band-shaped portion B allows it to function like a coil spring, improving the shape retention of the artificial blood vessel VE and easily preventing the artificial blood vessel VE from stretching beyond a predetermined length. Furthermore, in addition to the aforementioned helical shape, the band-shaped portion may also include, for example, multiple annular portions separated in the axial direction D1 and axial portions interconnecting the annular portions in the axial direction D1.

[0035] In the present embodiment, the strip-shaped portion B is provided to suppress the elongation of the portion where the high-density region R1 and the low-density region R2 arranged alternately adjacent to the strip-shaped portion B are arranged. This suppresses the situation where the flexibility is reduced due to the partial complete elongation that acts like wrinkles formed by the high-density region R1 and the low-density region R2 arranged alternately in the axial direction D1. In addition, the strip-shaped portion B is designed to act as a resistance to the elongation of the high-density region R1 and the low-density region R2 in a no-load state (in other words, a state of free length with no residual stress) where no force is applied to the artificial blood vessel VE, and the elongation of the artificial blood vessel VE is restricted. However, if an external force is applied to the artificial blood vessel VE, the resistance of the strip-shaped portion B allows the elongation of the high-density region R1 and the low-density region R2. Therefore, the high-density region R1 and the low-density region R2 are maintained in a state where they are easy to elongate and contract in the axial direction D1 in a state where they are not fully elongated in the axial direction D1 by the strip-shaped portion B. As shown by Figure 1 As shown by the two-dot chain line, when a bending force is applied to the artificial blood vessel VE, the high-density region R1 and the low-density region R2 tend to contract in the inner portion P3 of the bend of the artificial blood vessel VE, while the high-density region R1 and the low-density region R2 tend to expand in the outer portion P4 of the bend of the artificial blood vessel VE. Consequently, the artificial blood vessel VE is easily bent. Consequently, the high-density region R1 and the low-density region R2 are not fully extended in the axial direction D1 by the band-shaped portion B, maintaining a state where they can both expand and contract easily in the axial direction D1. This can suppress changes in the length of the artificial blood vessel VE over time (contraction or expansion of the length of the artificial blood vessel VE relative to its designed length by leaving the artificial blood vessel VE for a predetermined period of time).

[0036] The angle θ of the spiral band portion B relative to the axis X of the artificial blood vessel VE (see Figure 1) is not particularly limited; for example, in the completed artificial blood vessel VE, it is preferably greater than 45°, more preferably 50-80°, and even more preferably 60-70°. When the angle θ of the helical band portion B relative to the axis X is within this range, compression and expansion of the artificial blood vessel VE are facilitated, thereby improving the flexibility of the artificial blood vessel VE. Furthermore, as described later, the band portion B can be formed by heat treating the artificial blood vessel base material VEB while it is compressed. However, the angle θ described above refers to the angle when the artificial blood vessel base material VEB is released from compression. Furthermore, when forming the band portion B while the artificial blood vessel base material VEB is compressed, the angle of the heat treatment during formation of the band portion B can be determined by taking into account factors such as the compression rate of the artificial blood vessel base material VEB and the elongation of the artificial blood vessel base material VEB when extended from the compressed state.

[0037] The width (length in the axial direction D1) of the band portion B is not particularly limited, as long as it is configured to provide resistance to the expansion of the compressed artificial blood vessel VE (artificial blood vessel base material VEB). The width of the band portion B can be appropriately varied depending on the required flexibility and other performance characteristics of the artificial blood vessel VE. The width of the band portion B is not limited; for example, in the artificial blood vessel VE, it can be set to 1 / 6 to 1 / 4 the width of the portion excluding the band portion B (the portion where the high-density regions R1 and the low-density regions R2 are alternately arranged) (the width of the portion sandwiched by the band portion B in the axial direction D1 is 4 to 6 times the width of the band portion B).

[0038] Next, use the schematic diagram Figures 5 to 12 An example of a method for manufacturing an artificial blood vessel VE is described below. The manufacturing method described below is merely an example, and the artificial blood vessel VE of the present invention is not limited to the following manufacturing method. As long as it has the characteristics described in the claims, it can also be manufactured using other manufacturing methods.

[0039] First, if Figure 5 As shown, a tubular artificial vascular substrate VEB made of expanded polytetrafluoroethylene (ePTFE) is provided (artificial vascular substrate preparation step). The ePTFE has nodes 1 and fibrils 2 formed between the nodes 1. This artificial vascular substrate VEB is an ePTFE tube stretched to a predetermined stretch ratio. The artificial vascular substrate VEB can be obtained, for example, by mixing a lubricant with unsintered PTFE powder to prepare the mixture, extruding the mixture into a tube using a plunger extruder, and then stretching the tube in the axial direction D1 at a desired stretch ratio.

[0040] Next, the entire surface of the artificial blood vessel base material VEB is fired (first firing step. Figure 6Specifically, the entire surface of the artificial vascular substrate VEB is heated and fired. This firing roughens the entire surface of the artificial vascular substrate VEB. This allows the marker M, described later, to be easily fixed to the surface of the artificial vascular substrate VEB when applied.

[0041] After the entire surface of the artificial blood vessel base material VEB is sintered, a linear mark M extending in the axial direction D1 is applied to the surface of the artificial blood vessel base material VEB (mark application step. Figure 7 ). The mark M is provided to confirm the linearity of the artificial blood vessel VE. In the present embodiment, the mark M is made of cobalt and is applied as a linear coating layer extending in the axial direction D1 of the artificial blood vessel substrate VEB. After the mark M is applied, the entire artificial blood vessel substrate VEB is further fired (second firing process. Not shown). Specifically, the artificial blood vessel substrate VEB is fired by heating the entire periphery of the artificial blood vessel substrate VEB. Thus, the artificial blood vessel substrate VEB is completed. In addition, in the first firing process, the second firing process, etc., the periphery of the artificial blood vessel substrate VEB is heated and fired by the heating unit, thereby confirming that the nodes 1 and fibrils 2 on the surface of the artificial blood vessel substrate VEB are partially melted and densely packed close to each other to form concave and convex portions that repeat along the axial direction D1 (refer to Figure 13 and Figure 14 As a result, the recesses between the nodes 1 become deeper than before firing the artificial blood vessel base material VEB, and the concavities and convexities of the artificial blood vessel base material VEB are clearly formed. Consequently, compared to a flat surface or a case where the height difference between the concavities and convexities is small, the flexibility of the artificial blood vessel VE is improved, and the artificial blood vessel VE is more easily fixed to the surrounding tissue when placed in a living body.

[0042] Then, if Figure 8 As shown, with the core material C inserted inside the artificial vascular base material VEB, the artificial vascular base material VEB is compressed in the axial direction D1 of the artificial vascular base material VEB (first compression step). This step is performed, for example, by applying force to the artificial vascular base material VEB in the axial direction D1 while the core material C is inserted inside the artificial vascular base material VEB. The compression ratio of the artificial vascular base material VEB (relative to the original state of the artificial vascular base material VEB) is Figure 8 After compression ( Figure 8 The percentage of the length of the artificial blood vessel base material VEB (the solid line state) is not particularly limited, and can be, for example, 40 to 70%, preferably 50 to 60%.

[0043] Next, a strip-shaped portion B is provided on the artificial blood vessel base material VEB compressed in the first compression step (see strip-shaped portion forming step). Figure 9The strip-shaped portion B extends continuously in a strip-like manner along the axial direction D1 of the artificial vascular base material VEB, providing resistance to the artificial vascular VE extending in the axial direction D1 beyond a predetermined length. The method for forming the strip-shaped portion B is not particularly limited. For example, the strip-shaped portion B can be formed by sintering the surface of the compressed artificial vascular base material VEB into a predetermined pattern using a heating unit that partially heats the compressed artificial vascular base material VEB. In this embodiment, the strip-shaped portion B is formed helically about the axis of the compressed artificial vascular base material VEB. More specifically, the helical strip-shaped portion B is formed by rotating the artificial vascular base material VEB about its axis while moving the heating unit in the axial direction D1 to apply heat (or, by applying heat while the heating unit helically moves relative to the artificial vascular base material VEB).

[0044] Next, the force compressing the artificial blood vessel base material VEB is released, and the artificial blood vessel base material VEB is extended to a predetermined length (first extension step. Figure 10 In the first elongation step, the artificial blood vessel base material VEB is elongated to a length of, for example, 75 to 85% of the length of the artificial blood vessel base material VEB in the above-mentioned artificial blood vessel base material preparation step.

[0045] After the artificial vascular base material VEB is stretched in the first stretching step, in this embodiment, in addition to the first compression step and the first stretching step, a step of again compressing the stretched artificial vascular base material VEB one or more times (an additional compression step) and a step of again stretching the artificial vascular base material VEB compressed in the additional compression step (an additional stretching step) are included (see Figure 11 and Figure 12 The artificial blood vessel base material VEB is pulled out from the core material C and stretched to the desired length required as an artificial blood vessel VE.

[0046] This additional compression and extension step combines the compression and extension of the artificial vascular substrate VEB into a single set. By performing these multiple sets of compression and extension, the alternating compression striations of high-density regions R1 and low-density regions R2 can be more clearly formed compared to a single compression and extension. Furthermore, during the additional compression and extension steps, repeated compression and extension along the axial direction D1 of the artificial vascular substrate VEB repeatedly bend the hard nodes 1, forming bend marks (creases) (which would not occur in a single compression step or would disappear when the artificial vascular substrate VEB is extended). This gradually softens the hard nodes 1, making the artificial vascular substrate VE more flexible. In this embodiment, the additional compression and extension steps described above enhance the flexibility of the artificial vascular substrate VE by utilizing the synergistic effect of the sharpening of the compression striations of the alternating high-density regions R1 and low-density regions R2 and the formation of the bend marks (creases) of the hard nodes 1.

[0047] Furthermore, in this embodiment, the formation of the band-shaped portion B prevents the artificial blood vessel VE from stretching beyond a specified length. This makes it easier to maintain the compression striations and the bend mark at the node 1, thus maintaining the artificial blood vessel VE in a flexible state. Specifically, even if the artificial blood vessel base material VEB alternates between high-density regions R1 and low-density regions R2, if the artificial blood vessel base material VEB is left for a sufficient period of time, the density of the high-density regions R1 will gradually decrease due to elongation. However, the band-shaped portion B prevents this elongation, thus preventing the high-density regions R1 from fully extending in the axial direction D1. Furthermore, the bend mark (fold) at the node 1 is also retained by the band-shaped portion B. Therefore, by maintaining the alternating high-density regions R1 and low-density regions R2 and the bend mark at the node 1, the flexibility of the artificial blood vessel VE can be enhanced. Furthermore, since the artificial blood vessel VE can easily expand and contract in the axial direction D1, the stretching limit of the artificial blood vessel VE can be determined by the elongation of the artificial blood vessel VE during anastomosis and drawing, thus facilitating the surgical procedure.

[0048] Figure 4 、 Figure 13 and Figure 14 , SEM photos of the surface and cross section of the artificial blood vessel VE manufactured by the above-mentioned manufacturing method are shown in FIG. Figure 4 As shown, on the surface of the artificial blood vessel VE, the portion of the node 1 extending in a direction perpendicular to the extending direction of the fibril 2 ( Figure 4 The portion extending in the vertical direction) is curved in a wave shape. In this way, when the additional compression step and the additional extension step are included, the node 1 is displaced in a wave shape in the axial direction D1 as it advances in the circumferential direction D2. In addition, as Figure 13 and Figure 14 As shown in FIG. 1 , on the surface of the artificial blood vessel VE, it is observed that the depth of the concavity and convexity formed between a pair of nodes 1 and 1 and the width in the axial direction D1 are increased. Figure 17In the photograph shown, the node 1 of the artificial blood vessel VE includes a pair of node portions N1 and N2 adjacent to each other in the axial direction D1. The pair of node portions N1 and N2 are connected by a pair of contact points E1 and E2 on either side of the circumferential direction D2 of the artificial blood vessel VE. In this embodiment, folds (fold lines) are provided so that the angle θE formed by the pair of node portions N1 and N2 at the contact points E1 and E2 varies. Specifically, through the aforementioned manufacturing method (additional compression and extension steps), the folds (fold lines) are provided at the contact points E1 and E2, making them easier to bend. Therefore, during expansion and contraction in the axial direction D1, the angle θE formed between the node portions N1 and N2 easily varies. This change in angle θE facilitates the approach and separation of the portions of the node portions N1 and N2 connected by the contact points E1 and E2, facilitating expansion and contraction of the artificial blood vessel VE.

[0049] The number of additional compression steps and additional elongation steps is not particularly limited, and may be, for example, 1 to 20 times, preferably 5 to 15 times. Furthermore, the total length of the artificial blood vessel VE in the axial direction D1 after the final additional elongation step is not limited, but is preferably 100% of the total length of the artificial blood vessel base material VEB ( Figures 5 to 7 The total length of the artificial blood vessel VE in the axial direction D1 after the final additional stretching step is longer than that of the artificial blood vessel base material VEB ( Figure 10 state) is shorter than the full length.

[0050] Next, the effect of improving the flexibility brought about by the presence or absence of the additional compression step and the additional stretching step will be described. Figure 16As shown, a portion of the artificial blood vessel VE was attached so that it protruded from a fixing table F, 150 mm from the distal end. The vertical length L from the reference plane FR of the fixing table F to the distal end T of the curved artificial blood vessel VE was measured to evaluate flexibility. The samples, without the additional compression and extension steps (Comparative Example) and with the additional compression and extension steps (Example), used the same artificial blood vessel substrate under the same conditions. Specifically, an ePTFE artificial blood vessel substrate with a thickness of 0.6 mm, an outer diameter of 7.2 mm, a length of 207 mm, and a stretching ratio of 2.9 was used. Regarding the manufacturing method, the Example performed the additional compression and extension steps ten times, while the Comparative Example performed only one compression and extension step without the additional compression and extension steps. The result was that the vertical length L from the reference plane FR of the fixing table F to the distal end T of the curved artificial blood vessel VE in the Comparative Example was 17.3 mm. In contrast, in the embodiment, the vertical length L from the reference plane FR of the fixing base F to the distal end T of the curved artificial blood vessel VE is 80 mm. This shows that the flexibility of the artificial blood vessel VE is significantly improved by performing the additional compression and extension steps.

[0051] Although the embodiment of the present invention has been described above, the present invention is not limited to the above embodiment. In addition, the above embodiment mainly describes the invention having the following structure.

[0052] (1) An artificial blood vessel, comprising expanded polytetrafluoroethylene, wherein the expanded polytetrafluoroethylene has nodes and fibrils formed between the nodes, wherein: High-density areas and low-density areas are alternately arranged in the axial direction of the artificial blood vessel. The high-density areas are areas where the nodes and the fibrils are compressed in the axial direction and become dense, and the low-density areas are areas where the nodes and the fibrils are in a low-density state compared to the high-density areas.

[0053] (2) In the artificial blood vessel described in (1), the artificial blood vessel further comprises a band-shaped portion, The strip-shaped portion extends continuously in a strip shape along the axial direction of the artificial blood vessel so as to serve as resistance to the artificial blood vessel being stretched in the axial direction to a predetermined length or more after the artificial blood vessel is compressed in the axial direction.

[0054] (3) In the artificial blood vessel described in (1) or (2), the node has a pair of node portions adjacent to each other in the axial direction, the pair of node portions are connected by a pair of docking points on both sides in the circumferential direction of the artificial blood vessel, the pair of docking points have a fold (fold line portion), and the fold (fold line portion) is configured so that the angle formed by the pair of node portions at the docking point changes.

[0055] (4) A method for manufacturing an artificial blood vessel, wherein the method for manufacturing an artificial blood vessel comprises the following steps: a) providing a cylindrical artificial blood vessel substrate composed of expanded polytetrafluoroethylene, wherein the expanded polytetrafluoroethylene has nodes and fibrils formed between the nodes; b) compressing the artificial vascular base material in the axial direction of the artificial vascular base material while the core material is inserted into the inner side of the artificial vascular base material; c) releasing the force compressing the artificial blood vessel substrate, thereby extending the artificial blood vessel substrate; d) compressing the stretched artificial vascular substrate again one or more times; and e) re-stretching the artificial blood vessel substrate compressed in step d).

[0056] (5) In the method for manufacturing an artificial blood vessel described in (4), the method for manufacturing an artificial blood vessel further includes the following step: providing a strip-shaped portion on the artificial blood vessel base material compressed in the step b), wherein the strip-shaped portion extends continuously in a strip-shaped manner along the axial direction of the artificial blood vessel base material in a manner that becomes a resistance to the artificial blood vessel being extended in the axial direction to a length exceeding a predetermined length.

[0057] (6) In the method for manufacturing an artificial blood vessel described in (4) or (5), the strip-shaped portion extends helically around the axis of the artificial blood vessel.

Claims

1. An artificial blood vessel, comprising expanded polytetrafluoroethylene, wherein the expanded polytetrafluoroethylene has nodes and fibrils formed between the nodes, wherein: High-density areas and low-density areas are alternately arranged in the axial direction of the artificial blood vessel. The high-density areas are areas where the nodes and the fibrils are compressed in the axial direction and become dense, and the low-density areas are areas where the nodes and the fibrils are in a low-density state compared to the high-density areas.

2. The artificial blood vessel according to claim 1, wherein: The artificial blood vessel further comprises a band-shaped portion, The strip-shaped portion extends continuously in a strip shape along the axial direction of the artificial blood vessel so as to serve as resistance to the artificial blood vessel being stretched in the axial direction to a predetermined length or more after the artificial blood vessel is compressed in the axial direction.

3. The artificial blood vessel according to claim 1, wherein: The node has a pair of node parts adjacent to each other in the axial direction, and the pair of node parts are connected by a pair of docking points on both sides in the circumferential direction of the artificial blood vessel. The docking point has a fold, and the fold is configured so that the angle formed by the pair of node parts at the docking point changes.

4. A method for manufacturing an artificial blood vessel, wherein: The method for manufacturing the artificial blood vessel comprises the following steps: a) providing a cylindrical artificial blood vessel substrate composed of expanded polytetrafluoroethylene, wherein the expanded polytetrafluoroethylene has nodes and fibrils formed between the nodes; b) compressing the artificial vascular base material in the axial direction of the artificial vascular base material while the core material is inserted into the inner side of the artificial vascular base material; c) releasing the force compressing the artificial blood vessel substrate, thereby extending the artificial blood vessel substrate; d) compressing the stretched artificial vascular substrate again one or more times; and e) re-stretching the artificial blood vessel substrate compressed in step d).

5. The method for manufacturing an artificial blood vessel according to claim 4, wherein: The method for manufacturing the artificial blood vessel further includes the step of providing a strip-shaped portion on the artificial blood vessel base material compressed in step b), wherein the strip-shaped portion extends continuously in a strip-like manner along the axial direction of the artificial blood vessel base material so as to provide resistance to the artificial blood vessel extending in the axial direction to a length exceeding a predetermined length.

6. The method for manufacturing an artificial blood vessel according to claim 5, wherein: The band-shaped portion extends helically around the axis of the artificial blood vessel.

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