Method for manufacturing biomedical implant, and biomedical implant

Abstract

A method for manufacturing a biomedical implant (100) comprises a circumferential diameter reduction step for preparing a porous structure for use in a biological implant, which is to include a diameter-expandable tubular stent (10) and a porous structure (20) arranged to cover the stent and configured to expand as the stent expands, and reducing the diameter of the porous structure in the circumferential direction from a state where the porous structure has an outer diameter larger than a first outer diameter when mounting the porous structure onto the stent.

Description

Method for manufacturing a biological implant and biological implant

[0001] The present invention relates to a method for manufacturing a biological implant and a biological implant.

[0002] A stent is an medical device that is delivered to a lesion in a biological lumen by a stent delivery system and then implanted to treat various diseases caused by stenosis or occlusion of a biological lumen such as a blood vessel. It expands a lesion such as a stenosis or occlusion and secures the lumen.

[0003] For example, Patent Document 1 discloses a mesh-covered stent in which a mesh is arranged so as to cover the outer periphery of the stent in order to prevent peripheral embolism during stent implantation. The mesh-covered stent has a mesh having an expandable mesh structure that expands following the expansion of the stent, thereby preventing the scattering of plaque and thrombus when the stent expands.

[0004] International Publication No. 2006 / 126182

[0005] The mesh attached to the stent may cause a phenomenon in which the mesh-like structure deforms so as to bulge radially outward after the stent is attached, increasing the outer diameter due to the properties and shape of the linear members (filamentous members) constituting the mesh-like structure, leading to an increase in the stent profile. When bulging occurs in the mesh, problems such as deterioration of delivery performance and detachment of the mesh may occur.

[0006] [[ID=第十八条]] The present invention has been made in view of the above problems, and an object thereof is to provide a method for manufacturing a biological implant and a biological implant that can suppress the occurrence of a phenomenon in which a porous structure arranged so as to cover a stent deforms so as to bulge radially outward and the outer diameter increases.

[0007] The above object of the present invention can be achieved by any one of the following means (1) to (10).

[0008] (1) A method for manufacturing a biological implant, comprising: (1) preparing a porous structure to be used in a biological implant, which comprises an expandable cylindrical stent and a porous structure arranged to cover the stent and configured to expand in accordance with the expansion of the stent; and a circumferential diameter reduction step of reducing the diameter of the porous structure in the circumferential direction, which has an outer diameter larger than a first outer diameter when the porous structure is mounted on the stent.

[0009] (2) The method for manufacturing a biological implant according to (1), wherein the circumferential diameter reduction step reduces the diameter of the porous structure while applying heat to the porous structure.

[0010] (3) A method for manufacturing a biological implant according to (1) or (2), comprising an axial diameter reduction step, which involves stretching the porous structure along the axial direction of the porous structure to reduce its diameter, either before or after the circumferential diameter reduction step.

[0011] (4) The method for manufacturing a biological implant as described in (3), wherein the axial diameter reduction step is performed before the circumferential diameter reduction step.

[0012] (5) The method for manufacturing a biological implant according to (3) or (4), wherein the axial diameter reduction step reduces the diameter of the porous structure while applying heat to the porous structure.

[0013] (6) The method for manufacturing a biological implant according to any one of (1) to (5), wherein the porous structure is composed of a filamentous member containing a polymer material braided to have a mesh-like skeletal structure and a plurality of voids partitioned by the skeletal structure.

[0014] (7) A method for manufacturing a biological implant according to any one of (1) to (6), further comprising a mounting step of arranging the porous structure after the circumferential diameter reduction step has been performed so as to cover the outer surface of the stent before the diameter expansion step, and mounting the porous structure to the stent.

[0015] (8) A biological implant comprising: an expandable cylindrical stent; and a porous structure disposed to cover the stent and configured to expand as the diameter of the stent expands, wherein the porous structure has a mesh-like skeletal structure and a plurality of voids partitioned by the skeletal structure, the skeletal structure has a plurality of loop structures whose width along the circumferential direction of the voids gradually increases toward one side in the axial direction of the porous structure, each loop structure having a vertex having the largest circumferential width and a base having the smallest circumferential width, one loop and another loop adjacent to the first loop and on the axial base end are connected via locking portions in which parts of both intersect and lock together, the locking portions being located closer to the base of the other loop than to the vertex of the other loop.

[0016] (9) The biological implant according to (8), wherein the ratio of the overlap between the one loop portion and the other loop portion in the axial direction with respect to the axial length of the loop portion is 25% or more in at least a part of the porous structure.

[0017] (10) The biological implant according to (8) or (9), wherein the spiral angle formed by a virtual line passing through the locking portion along the circumferential direction of the porous structure and a virtual straight line parallel to the axial direction of the porous structure is 80° or more and less than 90°.

[0018] According to the method for manufacturing a biological implant and the biological implant itself, the occurrence of a phenomenon in which a porous structure positioned to cover the stent deforms to bulge radially outward, thereby increasing its outer diameter, can be suppressed.

[0019] This is a schematic plan view showing a stent delivery system equipped with a biological implant according to an embodiment. This is a plan view showing the reduced diameter state of the biological implant according to an embodiment. This is an enlarged view showing a part of the expanded diameter state of the biological implant according to an embodiment. This is a plan view showing a part of the porous structure according to an embodiment. This is an enlarged view for explaining the structure of the porous structure according to an embodiment. This is a diagram for schematically explaining the manufacturing method of the porous structure according to an embodiment.

[0020] Embodiments of the present invention will be described below with reference to the attached drawings. Note that the following description does not limit the technical scope or meaning of terms as defined in the claims. Furthermore, the dimensional ratios in the drawings are exaggerated for illustrative purposes and may differ from actual ratios.

[0021] An embodiment will be described with reference to Figures 1 to 6.

[0022] Figure 1 shows a stent delivery system 300 equipped with a biological implantation 100 according to an embodiment of the present invention.

[0023] Figures 2 to 5 are diagrams illustrating the biological implant 100, stent 10, and porous structure 20 according to the embodiment, and Figure 6 is a diagram illustrating the manufacturing method of the biological implant 100 according to the embodiment. Specifically, Figure 2 is a schematic plan view showing the reduced diameter state of the stent 10 and porous structure 20 according to the embodiment. Figure 3 is a schematic plan view showing the expanded diameter state of the stent 10 according to the embodiment. Figures 4 and 5 are enlarged views illustrating the characteristic parts of the porous structure 20 according to the embodiment, showing the state before the porous structure 20 expands.

[0024] For the sake of clarity, the following directions are defined in this specification.

[0025] The longitudinal direction in which the stent 10 and the porous structure 20 extend is defined as the "axial direction." The axial direction is the direction from the tip 10A to the base 10B (or from the base 10B to the tip 10A) as shown in Figure 2, and is indicated by arrows X1-X2 in each figure.

[0026] In the stent 10 and the porous structure 20, the side inserted into the living body is referred to as the "proximal side," and the side opposite the proximal side, on which the surgeon operates the stent delivery system 300, is referred to as the "proximal side." The "proximal portion" refers to the part that includes a certain range extending from the proximal (frontmost) end towards the proximal end, and the "proximal end" refers to the part that includes a certain range extending from the proximal (very proximal) end towards the proximal end. Furthermore, the rotational direction relative to the axial direction is defined as the circumferential direction.

[0027] <Stent Delivery System 300> As shown in Figure 1, the biological implantation 100 according to this embodiment is positioned on the outer circumference of the expandable and deflated balloon 220 provided by the balloon catheter 200.

[0028] The balloon catheter 200 comprises a long catheter body 210, a balloon 220 provided at the tip of the catheter body 210, and a hub 230 fixed to the base end of the catheter body 210.

[0029] The balloon catheter 200 to which the implanted biological device 100 is attached constitutes a stent delivery system 300. The stent delivery system 300 delivers the implanted biological device 100, to which the porous structure 20 is attached, in a deflated state to the lesion site, and expands the stent 10 and the porous structure 20 as the balloon 220 expands, thereby allowing the stent 10 and the porous structure 20 to be placed in the lesion site.

[0030] The balloon catheter 200 can be configured as a rapid exchange type balloon catheter, for example, by introducing a guidewire W from near the tip of the catheter body 210 and inserting the guidewire W through to the tip of the balloon 220. Alternatively, the balloon catheter 200 can also be configured as a so-called over-the-wire type balloon catheter.

[0031] For example, organic polymer materials can be used as the material constituting the balloon 220. Specifically, polymer materials such as polyolefins (e.g., polyethylene, polypropylene, polybutene, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer, ionomer, or mixtures of two or more of these), polyvinyl chloride, polyamide, polyamide elastomer, polyurethane, polyurethane elastomer, polyimide, fluororesin, or mixtures thereof, or elastic resin materials such as two or more of the above polymer materials can be used, and among these, polyamide resins can be preferably used as the main material.

[0032] <Biological implant 100> The biological implant 100 according to this embodiment is used to treat narrowing or obstruction in blood vessels, bile ducts, trachea, esophagus, urethra, or other biological tubular lumens. The stent 10 used in the biological implant 100 is configured as a so-called balloon-expandable medical device, which is placed in a crimped state on a folded balloon 220, delivered to the lesion, and then expanded and placed in the lesion.

[0033] Furthermore, the stent 10 can also be constructed as a so-called self-expanding medical device, made of a self-expanding material.

[0034] As shown in Figures 2 and 3, the biological implantation device 100 comprises an expandable stent 10 and a porous structure 20 positioned to cover the stent 10 and configured to expand in accordance with the expansion of the stent 10.

[0035] <Stent 10> As shown in Figures 2 and 3, the stent 10 has a cylindrical shape that extends in the axial direction. The porous structure 20 is arranged to cover the outer circumference of the stent 10 and has a cylindrical shape similar to the stent 10.

[0036] As shown in Figure 3, the stent 10 has linear rings 11 that form the outer circumference of a cylindrical shape with gaps, and link portions 12 that connect the rings 11 in gaps partitioned between adjacent linear rings 11 in the axial direction.

[0037] The ring 11 extends circumferentially around the stent 10 in a wave-like pattern that reciprocates in the axial direction.

[0038] The ring 11 has multiple first strut portions 14, which are straight or curved; second strut portions 15, which are straight or curved; and curved portions 17, which are formed between the first strut portions 14 and the second strut portions 15.

[0039] Furthermore, as shown in Figure 3, the ring 11 has a plurality of third strut portions 16, which are straight or curved, and are adjacent to one side of the link portion 12 in the axial direction and are provided in pairs in the circumferential direction.

[0040] The rings 11 are arranged sequentially along the axial direction. Adjacent rings 11 in the axial direction are connected and integrated by link portions 12.

[0041] The stent 10 can be configured as a drug-eluting stent, for example, in which at least a portion of the stent 10 is coated with a drug. The drug coated on the stent 10 can be configured as a drug-carrying portion supported by a predetermined polymer, for example. As the polymer, a biodegradable polymer can be used.

[0042] The drug-carrying portion can be positioned, for example, on the outer surface of the first strut portion 14 and / or the outer surface of the third strut portion 16 of the ring 11. By not forming the drug-carrying portion on the curved portion 17 and the link portion 12 of the ring 11 (the parts where stress concentrates and / or distortion occurs as the stent 10 expands in diameter), it is possible to avoid peeling or detaching the drug-carrying portion due to stress concentration and bending or distortion that occurs in the drug-carrying portion when the stent 10 expands in diameter.

[0043] The stent 10 can be made of, for example, a metallic material. The metallic material constituting the stent 10 is not particularly limited, and any metallic material known in the medical field and used in metallic stents can be used. Specifically, examples include stainless steels such as SUS304, SUS316, SUS316L, SUS420J2, and SUS630, tantalum, titanium, nickel-titanium alloys, tantalum-titanium alloys, nickel-aluminum alloys, Inconel, gold, platinum, iridium, tungsten, and cobalt-chromium (Co-Cr) alloys. Among stainless steels, SUS316L is preferred because it has the best corrosion resistance. Among cobalt-based alloys, MP35N and L605 are preferred.

[0044] Furthermore, the stent 10 can be made of, for example, a polymer material. The polymer material constituting the stent 10 is not particularly limited, and polymer materials used in polymer stents (biodegradable stents) known in the medical field can be used. For example, materials similar to those exemplified as the material for the porous structure 20 described later can be used.

[0045] Also, there is no particular limitation on the type of drug applied to the stent 10, and any one can be selected from those used in known drug-eluting stents.

[0046] <Porous structure 20> The porous structure 20 is arranged to cover the outer periphery of the stent 10 and can expand (increase in diameter) following the expansion (increase in diameter) of the stent 10.

[0047] The porous structure 20 includes a plurality of void portions 50 as described later. The area of each of the plurality of void portions 50 is preferably smaller than the gap between the rings 11 of the stent 10. By adopting such a configuration, it is possible to prevent the scattering of plaques and thrombi accompanying the expansion of the stent 10. On the other hand, the size of the void portion 50 is preferably larger than the area of a single blood cell contained in the blood. Thereby, the blood cells can pass through the void portion 50. Furthermore, the void portion 50 enables the porous structure 20 to be provided with extensibility. Therefore, when the stent 10 expands, the porous structure 20 also elongates in the circumferential direction along with the expansion of the stent 10, and can exhibit good followability (expandability) with respect to the expansion of the stent 10.

[0048] The porous structure 20 can be constituted by, for example, a knitted fabric (knit), a woven fabric (braid), a molded product (a member such as a film body with cuts formed), etc. When the porous structure 20 is a knitted fabric, the porous structure 20 can be constituted by a weft knitting. By constituting the porous structure 20 by weft knitting, it is possible to suppress the axial length of the porous structure 20 from becoming shorter along with the expansion of the stent 10. When the porous structure 20 is a woven fabric, the woven fabric is constituted by a known weaving method. Also, the porous structure 20 may be constituted by a molded product obtained by making holes in a cylindrical object formed by injection molding or the like. The size, shape, and number of the knitting stitches and weaving patterns of the porous structure 20 are not particularly limited as long as it is possible to prevent peripheral embolism during the expansion of the stent 10.

[0049] The porous structure 20 can be fixed to any point on the stent 10. For example, the porous structure 20 can be fixed to the stent 10 at a position other than the tip 10A and base 10B of the stent 10. Alternatively, the porous structure 20 can be fixed to all of the link portions 12 of the stent 10.

[0050] Examples of polymers that can be used to constitute the porous structure 20 include: (1) polymers selected from the group consisting of aliphatic polyesters, polyesters, polyacid anhydrides, polyorthoesters, polycarbonates, polyphosphazenes, polyphosphate esters, polyvinyl alcohols, polypeptides, polysaccharides, proteins, and cellulose; and (2) copolymers composed of two or more monomers that constitute (1) above. Here, the aliphatic polyester is not particularly limited and includes, for example, polylactic acid (PLA) such as poly-L-lactic acid (PLLA), poly-D-lactic acid (PDLA), poly-DL-lactic acid (PDLLA), polyglycolic acid (PGA), polyhydroxybutyric acid, polyhydroxyvaleric acid, polyhydroxypentanoic acid, polyhydroxyhexanoic acid, polyhydroxyheptanoic acid, poly(ε-caprolactone) (PCL), polytrimethylene carbonate, poly-2,2-dimethyltrimethylene carbonate, polydioxanone, polybutyrolactone, polyvalerolactone, polymalic acid, polyethylene adipate, polyethylene succinate, polybutylene adipate, and polybutylene succinate. Furthermore, the polycarbonate is not particularly limited and includes, for example, tyrosine-polycarbonate. Furthermore, polymers other than the biodegradable polymers mentioned above can also be used.

[0051] Furthermore, the porous structure 20 can be fixed to a predetermined location on the stent 10 using the various materials (polymers) exemplified above.

[0052] As shown in Figures 4 and 5, the porous structure 20 has a mesh-like arrangement of skeletal parts 30 and a plurality of voids 50 partitioned by the skeletal parts 30.

[0053] At least one of the skeletal portions 30 of the porous structure 20 has a plurality of loop structures in which the width W along the circumferential direction of the void portion 50 gradually increases toward one side in the axial direction of the porous structure 20.

[0054] Each loop portion 40 included in the loop structure has a vertex portion 42 having the largest circumferential width W and a base portion 43 having the smallest circumferential width W.

[0055] The loop portion 40 further includes a tip portion 41 located closer to the tip than the apex portion 42, a first transition portion 44a connecting the tip portion 41 and the apex portion 42, and a second transition portion 44b connecting the apex portion 42 and the base portion 43.

[0056] The loop portion 40 has a structure in which the tip is closed by a tip portion 41 that protrudes in a curved manner toward the tip. The loop portion 40 gradually widens in width W toward the base end at the first transition portion 44a located between the tip portion 41 and the apex portion 42. Furthermore, the loop portion 40 gradually narrows in width W toward the base end at the second transition portion 44b located between the apex portion 42 and the root portion 43.

[0057] One loop portion 40A and another loop portion 40B adjacent to the first loop portion 40A on the axial base end side are connected via a locking portion 45 in which parts of both are intersected and locked together.

[0058] In this specification, as shown in Figure 5, of a pair of axially adjacent loop portions 40, the loop portion 40 located towards the tip is referred to as "loop portion 40A," and the loop portion 40 located towards the base end than loop portion 40A is referred to as "the other loop portion 40B."

[0059] In this embodiment, in at least one pair of loop portions 40A and 40B included in the porous structure 20, the locking portion 45 is located closer to the root portion 43 of the other loop portion 40B than to the apex portion 42 of the other loop portion 40B.

[0060] The porous structure 20 having the above configuration can exhibit the following effects.

[0061] If, for example, spun filamentous members (relatively small diameter linear members) are used as the constituent material of the porous structure 20, residual stress may accumulate in the filamentous members during the manufacturing process. When a cylindrical porous structure 20 is manufactured using filamentous members with accumulated residual stress, the filamentous members forming the porous structure 20 generate a force (springback) that tries to restore them to their original shape. This causes the porous structure 20 to deform, bulging radially outward, resulting in an increase in its outer diameter. To address this problem, the porous structure 20 is equipped with locking parts 45 positioned as described above, making it difficult for the connection between adjacent loop parts 40A and 40B to be easily released. Therefore, it is possible to prevent the porous structure 20 from restoring to its linear shape immediately after spinning. This prevents the bulging phenomenon described above from occurring in the porous structure 20.

[0062] Furthermore, as described above, a force may act on the porous structure 20 that attempts to restore the filamentous members constituting the porous structure 20 to their straight shape immediately after spinning. Therefore, particularly near both ends in the axial direction of the porous structure 20, the force that attempts to maintain the cylindrical shape of the porous structure 20 and the force that attempts to restore the filamentous members to their straight shape may become unbalanced, and a phenomenon (flaring phenomenon) may occur in which the porous structure 20 warps upward and expands in diameter towards both ends in the axial direction. To address this problem, the porous structure 20 can appropriately maintain the connection relationship between adjacent loop portions 40A and 40B by the locking portion 45. Therefore, the occurrence of the flare phenomenon described above in the porous structure 20 can be effectively prevented.

[0063] As shown in Figure 5, the ratio of the axial overlap between one loop portion 40A and the other loop portion 40B with respect to the axial length of the loop portion 40 (length L2 of overlap L2 of one loop portion 40A over the other loop portion 40B in the axial direction / length L1 of the other loop portion 40B in the axial direction × 100 [%]) is 25% or more in at least a part of the porous structure 20. Preferably, the above ratio is achieved when the mesh count of the porous structure 20 is 50% or more.

[0064] As described above, since the length ratio (L2 / L1) is 25% or more, the porous structure 20 can have a predetermined expansion margin when mounted on the stent 10. In other words, the porous structure 20 is given a degree of freedom for expansion by the amount by which one loop portion 40A and the other loop portion 40B overlap in the axial direction. Therefore, when the stent 10 expands while the porous structure 20 is mounted on it, the porous structure 20 can avoid being pulled in the axial direction and shortening, or developing wires in the loop portions 40, and can suitably maintain a predetermined mesh shape. Furthermore, since the porous structure 20 is mounted on the stent 10 with an expansion margin, its flexibility is also improved.

[0065] Furthermore, the length ratio (L2 / L1) is preferably 30% or more and 50% or less, and more preferably 35% or more and 50% or less. In addition, when one loop portion 40A is moved axially, it comes into contact with other loop portions 40B of adjacent wales (parts of the mesh knit aligned in the axial direction), so it is preferable that the above length ratio be a maximum of 50%.

[0066] As shown in Figure 4, the spiral angle θ formed by a virtual line H1 passing through the locking portion 45 along the circumferential direction of the porous structure 20 and a virtual straight line O1 parallel to the axial direction of the porous structure 20 can be, for example, 80° or more and less than 90°, more preferably 85° or more and less than 90°.

[0067] If the spiral angle θ is provided within the range described above, the locking portions 45, which are arranged at predetermined intervals in the circumferential direction of the porous structure 20, will be positioned in close proximity in the axial direction (arranged in a single line in the vertical direction in the unfolded view of Figure 6). Therefore, even when the porous structure 20 is fixed to the stent 10 at multiple points, it becomes possible to uniformly expand each loop portion 40 of the porous structure 20 when the porous structure 20 expands.

[0068] <Method for Manufacturing the Biological Implant 100> Next, the method for manufacturing the biological implant 100 according to this embodiment will be described. In the following, the method for manufacturing the porous structure 20 will be mainly described with reference to Figures 6(A) to (C). Note that in Figures 6(A) to (C), schematic unfolded diagrams of the porous structure 20 are shown for illustrative purposes, and the actual product is not limited to those shown.

[0069] As shown in Figure 6(A), a porous structure 20 to be used in the biological implant 100 is prepared. At this stage, the porous structure 20 is prepared in a cylindrical shape having an outer diameter larger than the first outer diameter (for example, 2.5 mm or more and 7.0 mm or less, more preferably 5.0 mm or less) when mounting the porous structure 20 to the stent 10. Specifically, the porous structure 20 can be prepared as a filamentous member containing a braided polymer material having a mesh-like skeletal portion 30 and a plurality of void portions 50 partitioned by the skeletal portion 30. Note that the prepared porous structure 20 is in a state before the locking portion 45 connecting adjacent loop portions 40A and 40B are placed in the aforementioned position (see Figure 5).

[0070] A circumferential diameter reduction process (the operation shown in Figure 6(C)) is performed to reduce the diameter of the porous structure 20 in the circumferential direction, which is currently in a state where the porous structure 20 has an outer diameter larger than the first outer diameter when mounting the porous structure 20 to the stent 10.

[0071] In carrying out the circumferential diameter reduction process, a mandrel having a predetermined diameter is inserted into the lumen of the porous structure 20 in order to prevent the lumen of the porous structure 20 from collapsing and to reduce the diameter of the porous structure 20 to a predetermined outer diameter. It is preferable to select a mandrel that can adjust the dimensional difference between the inner diameter of the porous structure 20 after circumferential diameter reduction and the outer diameter of the stent 10 on which the porous structure 20 is mounted to an appropriate size. For example, if the mandrel is extremely thin, the inner diameter of the porous structure 20 after circumferential diameter reduction will become excessively small, making it difficult to mount the porous structure 20 to the stent 10. As a result, when mounting the porous structure 20 to the stent 10, it becomes necessary to forcibly expand the diameter of the porous structure 20, which disrupts the mesh of the porous structure 20. Consequently, the effect of suppressing the aforementioned swelling and flaring phenomena is diminished. On the other hand, if the core is extremely thick, the inner diameter of the porous structure 20 after circumferential reduction will be excessively large, requiring the porous structure 20 to be reduced in diameter again when mounting it to the stent 10. Furthermore, there is a possibility that the mesh of the porous structure 20 may be damaged during this process.

[0072] Considering the above points, for example, if the outer diameter of the stent 10 is 1.5 mm or more and 6.0 mm or less, it is preferable to use a core metal having a diameter of 1.5 mm or more and 5.5 mm or less, preferably 2.5 mm or less, in the circumferential diameter reduction process.

[0073] In the circumferential diameter reduction process, a diameter reduction force is applied to the cylindrical porous structure 20 along the circumferential direction, as shown by arrow T2 in Figure 6(C). By performing the circumferential diameter reduction process, the porous structure 20 can be shaped into a form (see Figure 5) that includes the aforementioned loop portions 40 (one loop portion 40A, the other loop portion 40B) and locking portions 45. As a result, the porous structure 20 can suppress the occurrence of the aforementioned swelling and flare phenomena. Furthermore, as the porous structure 20 is shaped by the circumferential diameter reduction, adjacent loop portions 40 along the circumferential direction of the porous structure 20 partially overlap each other in the circumferential direction. As a result, the porous structure 20 can have a predetermined expansion margin, and when the stent 10 is expanded, the loop portions 40 are pulled in the circumferential direction, preventing the entire porous structure 20 from shortening towards the axial center or causing wire runoff in the loop portions 40, thus maintaining a predetermined mesh shape favorably.

[0074] In the circumferential diameter reduction process, the porous structure 20 can be reduced in diameter while heat is applied to it. By performing this circumferential diameter reduction process, crystallization of the porous structure 20 can be promoted, making it possible to more reliably maintain the porous structure 20 in a predetermined shape (see Figures 5 and 6).

[0075] In the circumferential diameter reduction process, the temperature at which the porous structure 20 is heated can be set to a temperature approximately midway between the glass transition temperature and the melting temperature of the constituent material of the porous structure 20. For example, if the porous structure 20 is made of a filamentous member made of polyglycolic acid (PGA), the temperature at which the porous structure 20 is heated can be set to 150°C or higher and 175°C or lower, preferably around 150°C.

[0076] In the manufacturing method according to this embodiment, as shown in Figure 6(B), an axial diameter reduction step can be performed to reduce the diameter of the porous structure 20 by stretching it along the axial direction of the porous structure 20, either before or after the circumferential diameter reduction step.

[0077] In carrying out the axial diameter reduction process, a core metal having a predetermined diameter is inserted into the lumen of the porous structure 20 in order to prevent the lumen of the porous structure 20 from collapsing and to reduce the diameter of the porous structure 20 to a predetermined outer diameter. For the same reasons as when carrying out the circumferential diameter reduction described above, it is preferable to select a core metal that can adjust the dimensional difference between the inner diameter of the porous structure 20 after axial diameter reduction and the outer diameter of the stent 10 on which the porous structure 20 is mounted to an appropriate size. For example, if the outer diameter of the stent 10 is 1.5 mm or more and 6.0 mm or less, it is preferable to use a core metal having a diameter of 1.5 mm or more and 5.5 mm or less, more preferably 2.5 mm or less, in the axial diameter reduction process.

[0078] In the axial diameter reduction process, tensile stress is applied to both ends of the cylindrical porous structure 20 in the axial direction, as shown by arrow T1 in Figure 6(B). By performing the axial diameter reduction process, the outer diameter of the porous structure 20 can be reduced to a predetermined size, while the mesh of the porous structure 20 can be uniformly arranged along the axial direction.

[0079] As shown in Figure 6(B), the axial diameter reduction process can be performed, for example, before the circumferential diameter reduction process. By performing the axial diameter reduction process before the circumferential diameter reduction process in this way, the porous structure 20 can be more reliably shaped into the form (see Figure 5) that includes the aforementioned loop portion 40 (one loop portion 40A, the other loop portion 40B) and locking portion 45.

[0080] Furthermore, in the axial diameter reduction process, the porous structure 20 can be reduced in diameter while heat is applied to it. As explained in the circumferential diameter reduction process described above, by reducing the diameter of the porous structure 20 while heat is applied to it, it becomes possible to more reliably maintain the porous structure 20 in a predetermined shape (see Figures 5 and 6).

[0081] In the axial diameter reduction process, the temperature at which the porous structure 20 is heated can be set to a temperature near the midpoint between the glass transition temperature and the melting temperature of the constituent material of the porous structure 20, similar to the temperature described in the circumferential diameter reduction process above. For example, if the porous structure 20 is made of a filamentous member made of polyglycolic acid (PGA), the temperature at which the porous structure 20 is heated can be set to around 150°C, as described above.

[0082] By carrying out the above steps, a porous structure 20 shaped into a predetermined form can be obtained.

[0083] Next, the porous structure 20, after the circumferential diameter reduction process (and axial diameter reduction process) has been performed, is positioned to cover the outer circumferential surface of the stent 10 before the diameter is increased, and a mounting process is performed to mount the porous structure 20 to the stent 10. The mounting process can be carried out using a predetermined crimping device, for example, in the following procedure.

[0084] In the mounting process, a crimping device equipped with at least one pressing member configured to move radially inward is used to crimp the expandable cylindrical stent 10 and the expandable porous structure 20 onto the balloon 220. In the following description, each component (balloon 220, stent 10, and porous structure 20) in its state before crimping will be referred to as "prepared parts".

[0085] The mounting process includes placing the stent 10 on the outer circumference of the balloon 220 (placement process), reducing the diameter of the stent 10 by pressing a pressing member from the outer surface of the porous structure 20 covering the outer circumference of the stent 10 (pressing process), and pressurizing the lumen 225 of the balloon 220 at least once (pressurization process).

[0086] First, the placement process is performed. In the placement process, the stent 10 is mounted on the outer circumference of the balloon 220. The stent 10 can be set in the crimping device with the porous structure 20 fixed to it, for example. There are no particular restrictions on the timing of setting the porous structure 20 in the crimping device. For example, the porous structure 20 may be mounted on the outer circumference of the stent 10 after the balloon 220 and stent 10 have been set in the crimping device.

[0087] With the workpiece set in the crimping device, a sheet-like member is placed between the porous structure 20 and the pressing member. For example, two sheet-like members can be used, and the workpiece can be sandwiched between each sheet-like member. With the workpiece sandwiched between each sheet-like member, the crimping device applies a predetermined tension to each sheet-like member.

[0088] Next, the pressing process is performed. Multiple pressing members are moved radially inward to press against the outer surface of the porous structure 20. In this embodiment, since a sheet-like member is used, the pressing members are pressed against the prepared workpiece from the outer surface of the porous structure 20 with the sheet-like member in between.

[0089] During the pressing process, a pressurizing process can be performed at least once. By performing the pressurizing process, the balloon 220 expands radially outward, and a portion of the balloon 220 enters the gap in the stent 10 (the gap formed between each strut portion 14, 15, 16 and the curved portion 17). This improves the crimping force that holds the stent 10 to the balloon 220, while reducing the profile of the implanted biological device 100 after crimping. The pressurizing process may also be performed when the pressing process is not being performed. Furthermore, the timing of starting the pressurizing process, the number of times it is performed, and the pressure in the lumen of the balloon 220 during pressurization can be arbitrarily set according to the product specifications of the implanted biological device 100.

[0090] As described above, the method for manufacturing the biological implantation 100 according to this embodiment includes preparing a porous structure 20 to be used in a biological implantation 100 which comprises an expandable cylindrical stent 10 and a porous structure 20 that is arranged to cover the stent 10 and is configured to expand in accordance with the expansion of the stent 10, and a circumferential diameter reduction step in which the porous structure 20, which has an outer diameter larger than the first outer diameter when the porous structure 20 is mounted on the stent 10, is reduced in the circumferential direction.

[0091] Furthermore, the biological implantation device 100 according to this embodiment comprises an expandable cylindrical stent 10 and a porous structure 20 arranged to cover the stent 10 and configured to expand as the diameter of the stent 10 expands. The porous structure 20 has a mesh-like skeletal portion 30 and a plurality of void portions 50 partitioned by the skeletal portion 30. The skeletal portion 30 has a plurality of loop structures in which the width W along the circumferential direction of the void portions 50 gradually increases toward one side in the axial direction of the porous structure 20. Each loop portion 40 included in the loop structure has a vertex portion 42 having the largest circumferential width W and a root portion 43 having the smallest circumferential width W. One loop portion 40A and another loop portion 40B adjacent to the axial base end of the first loop portion 40A are connected via a locking portion 45 in which parts of both intersect and lock together. The locking portion 45 is located closer to the root portion 43 of the other loop portion 40B than to the vertex portion 42 of the other loop portion 40B.

[0092] According to the method for manufacturing the biological implant 100 and the biological implant 100 of this embodiment, the porous structure 20, which is arranged to cover the stent 10, deforms to bulge radially outward, thereby suppressing the occurrence of a phenomenon in which the outer diameter increases.

[0093] Although the method for manufacturing a biological implant and the biological implant according to the present invention have been described above through embodiments, the present invention is not limited to the configuration described in the embodiments and can be modified as appropriate based on the claims.

[0094] For example, the manufacturing method of a biological implant can be modified as needed, with the omission or addition of other steps (e.g., axial diameter reduction steps) being arbitrary, as long as at least a circumferential diameter reduction step can be performed. Furthermore, the other components of a biological implant (such as the stent's structure and shape, constituent materials, relative positions of components, and stent fixing structure) can be arbitrarily modified as long as one axially adjacent loop portion and other loop portions in the porous structure are locked in a predetermined positional relationship.

[0095] This application is based on Japanese Patent Application No. 2024-168256, filed on 27 September 2024, the disclosures of which are incorporated herein by reference in their entirety.

[0096] 10 Stent 11 Ring 12 Link section 14 First strut section 15 Second strut section 16 Third strut section 17 Curved section 20 Porous structure 30 Skeleton section 40 Loop section 40A First loop section 40B Other loop sections 41 Tip section 42 Apex section 43 Root section 44a First transition section 44b Second transition section 45 Locking section 50 Gap section 100 Indwelling body 200 Balloon catheter 220 Balloon 300 Stent delivery system θ Helical angle

Claims

1. A method for manufacturing a biological implant, comprising: preparing a porous structure for use in a biological implant, which comprises an expandable cylindrical stent and a porous structure disposed to cover the stent and configured to expand in accordance with the expansion of the stent; and a circumferential diameter reduction step of reducing the diameter of the porous structure in the circumferential direction, which has an outer diameter larger than a first outer diameter when the porous structure is mounted on the stent.

2. The method for manufacturing a biological implant according to claim 1, wherein the circumferential diameter reduction step reduces the diameter of the porous structure while applying heat to the porous structure.

3. A method for manufacturing a biological implant according to claim 1, comprising an axial diameter reduction step, which involves stretching the porous structure along the axial direction of the porous structure to reduce its diameter, either before or after the circumferential diameter reduction step.

4. The method for manufacturing a biological implant according to claim 3, wherein the axial diameter reduction step is performed before the circumferential diameter reduction step.

5. The method for manufacturing a biological implant according to claim 3 or claim 4, wherein the axial diameter reduction step reduces the diameter of the porous structure while applying heat to the porous structure.

6. The method for manufacturing a biological implant according to claim 1, wherein the porous structure is composed of a filamentous member containing a polymer material braided to include a mesh-like skeletal structure and a plurality of voids partitioned by the skeletal structure.

7. A method for manufacturing a biological implant according to claim 1, further comprising a mounting step of arranging the porous structure after the circumferential diameter reduction step has been performed so as to cover the outer circumferential surface of the stent before the diameter expansion step, and mounting the porous structure to the stent.

8. A biological implant comprising: an expandable cylindrical stent; and a porous structure disposed to cover the stent and configured to expand as the stent expands, wherein the porous structure has a mesh-like skeletal structure and a plurality of voids partitioned by the skeletal structure, the skeletal structure has a plurality of loop structures whose width along the circumferential direction of the voids gradually increases toward one side in the axial direction of the porous structure, each loop structure having a vertex having the largest circumferential width and a base having the smallest circumferential width, one loop and another loop adjacent to the first loop on the axial base side are connected via locking portions in which parts of both intersect and lock together, the locking portions being located closer to the base of the other loop than to the vertex of the other loop.

9. The biological implant according to claim 8, wherein the ratio of the overlap between the one loop portion and the other loop portion in the axial direction with respect to the axial length of the loop portion is 25% or more in at least a part of the porous structure.

10. The biological implant according to claim 8, wherein the spiral angle formed by a virtual line passing through the locking portion along the circumferential direction of the porous structure and a virtual straight line parallel to the axial direction of the porous structure is 80° or more and less than 90°.

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