JP2017221692A - Bellows-like lumen structure - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a lumen structure having improved kink resistance and strength.SOLUTION: A bellows-like neurotization tube is molded from a braid 10 formed by braiding yarns 9. The height of a crest of the bellows part of the bellows-like neurotization tube is 1-40% with respect to the internal diameter of the bellows-like neurotization tube. Further, a fiber forming the yarn is formed of a biodegradable polymer. Furthermore, the bellows-like neurotization tube can be manufactured by braiding the yarns to fabricate a braid with a braiding angle of 30-85°, repetitively compressing and extending the braid in the longitudinal direction using a core material 3 with an external diameter of 2 mm or more to mold it into a bellows-like shape, and compressing the braid again in the longitudinal direction.SELECTED DRAWING: Figure 3

Description

  The present invention relates to a bellows-like lumen structure.

  When tissues or organs such as human nerves and tendons are damaged due to accidents, disasters, diseases, etc., and the damaged part cannot be cured by self-recovery power, the perception, sensation, motor ability, etc. are impaired. For such patients, with the development of technology to connect the damaged site under the microscope in recent years, surgical sutures that connect the cut site, self nerves and tendons, etc. are collected from other sites, Treatment such as autologous nerve transplantation that recovers the function lost by transplantation has been performed.

  However, if the missing area is too large, repair by connection as described above is impossible, and even if a certain degree of failure occurs, it is from other parts that seem to be less important than the damaged part Nerves must be collected and transplanted to the site of injury. In such a case, although it is less important than the injury of the site where it first occurred, the nerves of other healthy parts that are not damaged are collected, so that the site has sensory, sensory, motor skills, etc. Will cause a failure. Therefore, a treatment method capable of repairing the damaged part without causing any trouble to other parts is eagerly desired.

  For example, in order to overcome the adverse effects of autologous nerve transplantation, various studies have been made to restore the original function by replacing the damaged site with an artificial instrument.

  In Patent Document 1, the outer surface of a tubular body knitted with ultrafine fibers made of a plurality of biodegradable polymers is coated by applying it multiple times with a collagen solution, and further manufactured by filling the inside of the tubular body with collagen. A nerve regeneration-inducing tube is disclosed.

  In Patent Documents 2 and 3, a collagen solution is applied to a PGA tube obtained using a braided cord making machine using polyglycolic acid (PGA) fibers, filled with a collagen solution, and then freeze-dried and thermally crosslinked. A tubular tissue regeneration member containing collagen therein is produced.

  In Patent Document 4, a tubular body made of an aliphatic ester resin and having a bellows structure in which peaks and valleys are continuous along the tube axis direction is provided. A nerve regeneration tube is disclosed in which a plurality of through-holes leading to a surface are formed, and the plurality of through-holes are holes formed by laser processing.

JP 2010-269185 A JP 2013-031730 A International Publication No. 08/001952 JP 2011-206203 A

  However, the nerve regeneration induction tube and tissue regeneration member described in Patent Documents 1 to 3 have a problem that kink resistance is low and strength is low.

  Further, Patent Document 4 has a problem that although it is a bellows-like structure, it does not have substance permeability such as water, electrolytes, and growth factors required for nerve regeneration unless a hole is made with a laser or the like.

  Therefore, an object of the present invention is to provide a lumen structure with improved kink resistance and strength.

  Another object of the present invention is to provide a bellows-like lumen structure having a material-permeable gap in the entire structure without drilling by using braids.

  The present inventors conducted various studies to solve the above problems. As a result, it has been found that the above problems can be solved by an accordion-like lumen structure formed from braided braided yarn formed from a plurality of organic polymer fibers, and the present invention has been completed. .

  That is, the present invention is a bellows-like lumen structure formed of a braid formed by braiding yarns formed from a plurality of organic polymer fibers.

  According to the present invention, a bellows-like lumen structure with improved kink resistance and strength is provided. In addition, according to the present invention, a bellows-like lumen structure having a substance-permeable gap in the entire structure without drilling is provided by using a braid.

It is a schematic diagram which shows the definition of a group angle. It is a schematic diagram which shows the measuring method of the distance of the major axis direction of the height of a bellows peak, an outer diameter, and five peaks. It is a schematic diagram which shows an example of the braiding machine used suitably in order to manufacture the braiding which comprises the bellows-like lumen structure of this invention. It is an expansion schematic diagram which shows an example of the yarn winding bobbin and carrier with which a braiding machine is equipped. It is a figure which shows the result of the canine radial nerve embedding experiment using the nerve regeneration tube which is not made from the bellows shape produced from the normal braid. It is a figure which shows the result of the canine radial nerve embedding experiment using the bellows-like nerve regeneration tube produced from the braid formed in the bellows shape.

  The present invention is a bellows-like lumen structure formed from a braid made by braiding yarn. By setting it as such a structure, it becomes a lumen structure with improved kink resistance and strength.

  Hereinafter, the bellows-like lumen structure of the present invention will be described in detail.

[Bellows-like lumen structure]
In the present invention, the lumen structure is a structure having a lumen penetrating to the outside, and has a shape such as a cylindrical shape, a rectangular tube shape, a truncated cone shape, and a truncated pyramid shape. Of these, a cylindrical shape is preferable. In addition, examples of the cross-sectional shape include a circle, an ellipse, an egg, a fan, a bow, or a polygon (triangle, quadrangle, pentagon, hexagon, octagon, etc.). Of these, the shape is preferably circular. Hereinafter, the lumen structure is also simply referred to as “tube” in the present specification.

  Further, in the present invention, “accordion-like” means a state in which peaks and valleys are alternately and continuously formed, and “an bellows-like lumen structure made of braid” This means that the luminal structure is made of braid.

  Furthermore, in the present invention, the “yarn” is a bundle of fibers, and the number of fibers is not particularly limited, but is usually 1 to 50. The fiber here means a fiber bundle in which a plurality of fibers are arranged without being twisted, a yarn knitted in a braided shape, or a yarn that has been twisted. Even in this form, it can be used.

  As the fiber forming the yarn, an organic polymer fiber is preferable. Examples of the organic polymer fiber include, for example, polyester resins such as polyethylene terephthalate resin, polytrimethylene terephthalate resin, polybutylene terephthalate resin, polyethylene naphthalate resin, and liquid crystal polyester resin, and polyolefins such as polyethylene resin, polypropylene resin, and polybutylene. Polyamide resin such as resin, nylon 6 resin, nylon 66 resin, nylon 12 resin, nylon 610 resin, styrene resin, polyoxymethylene resin, polycarbonate resin, polymethylene methacrylate resin, polyvinyl chloride resin, polyphenylene sulfide resin, polyphenylene ether resin , Polyimide resin, polyamideimide resin, polyetherimide resin, polysulfone resin, polyethersulfone resin, polyketone resin, Polyether ketone resin, polyether ether ketone resin, polyacrylate resin, polyether nitrile resin, phenol resin, phenoxy resin, thermoplastic resin such as fluororesin, polystyrene, polyolefin, polyurethane, polyester, polyamide, polybutadiene And fibers formed from organic polymers such as thermoplastic elastomers such as polyisoprene and fluorine, or copolymer resins and modified resins thereof.

  Moreover, the fiber formed from a biodegradable polymer is also preferably used as the organic polymer fiber. By using a biodegradable polymer, a nerve tissue regeneration member as described later, that is, a nerve regeneration tube, a subcutaneous tissue, a submucosa, a biological membrane tissue, a fat tissue, a muscle tissue, a skin tissue, a gingival tissue, etc. It is suitably used as a member for regeneration, replacement, or transplantation.

  Specific examples of the biodegradable polymer include, for example, polyglycolic acid (PGA), polylactic acid (D, L, DL form), polyε-caprolactone, polyhydroxybutyric acid, cellulose, polyhydroxybutyrate valeric acid, Alternatively, a polyorthoester, a copolymer, a mixture, or a composite thereof can be used. Among these, polyglycolic acid, a copolymer of polylactic acid and polyglycolic acid, and a copolymer of polyε-caprolactone and polyglycolic acid are preferable.

  In addition, you may use the said organic polymer fiber individually or in combination of 2 or more types. Commercially available products or synthetic products may be used for the organic polymer fibers and the yarns formed from the organic polymer fibers. Furthermore, the braid constituting the bellows-like lumen structure of the present invention may have a single-layer structure or a multilayer structure of two or more layers. In the case of a multilayer structure, the type of material (organic polymer fiber) of each layer may be the same or different.

  The braid angle before the bellows molding of the braid constituting the bellows-like lumen structure of the present invention is not particularly limited, and may be any braid angle. Here, the braiding angle refers to an acute angle formed by the braiding yarn (yarn) with respect to the axial direction (θ in FIG. 1), and the small braiding angle means that the braiding yarn (yarn) is nearly parallel to the axial direction ( It means that the braid angle is close to the direction perpendicular to the axial direction. The braid angle can be measured by a method using a CCD camera described in the examples described later, and the braid angle of the braid constituting the bellows-like lumen structure of the present invention before the bellows molding is arbitrary. Measured values at one location are adopted.

  The braid angle is controlled by controlling the braiding speed and the take-up speed of the braid when the braid is manufactured by the braiding machine (knitting machine), and the braid is gathered from the yarn exit of the carrier. This can be done by controlling the difference in height to the position to be generated, h) in FIG.

  The inner diameter of the bellows-like lumen structure of the present invention is preferably in the range of 0.5 to 20 mm, and the total length is preferably in the range of 5 to 100 mm.

  The inner diameter is the maximum when the narrowest nerve bundle is less than 0.5 mm, and when the stump of the reticular nerve around the prostate is bundled and inserted into the nerve regeneration tube in the nerve reconstruction after radical prostatectomy. The above range is preferable because an inner diameter of about 20 mm is sufficient.

  The outer diameter of the bellows-like lumen structure of the present invention is preferably 1 to 30 mm. The outer diameter of the bellows-like lumen structure of the present invention is preferably 101 to 210% of the inner diameter of the bellows-like lumen structure of the present invention.

  The outer diameter is preferably in the above range in consideration of the preferred inner diameter, wall thickness, peak height, etc. of the bellows structure.

  The height of the peak of the bellows portion (bellows height) of the bellows-like lumen structure of the present invention is preferably 0.1 to 4 mm. The height of the peak of the bellows portion (bellows height) of the bellows-like lumen structure of the present invention is preferably 1 to 40% of the inner diameter of the bellows-like lumen structure.

  The height of the mountain is structurally most stable in the above range. When the tube is bent, it is considered that it is advantageous to absorb stress by shifting each knitted yarn.

  In the bellows portion of the bellows-like lumen structure of the present invention, the distance in the major axis direction for five peaks is preferably 1 to 40 mm. In the bellows portion of the bellows-like lumen structure of the present invention, the distance in the major axis direction for five peaks is preferably 10 to 350% of the inner diameter of the bellows-like lumen structure.

  In the present specification, the height of the peak of the bellows-like lumen structure is the average of the heights (a and b in A of FIG. 2) measured on both sides of the peak as shown in A of FIG. The value is defined as the height of the peak, and the average value of the values measured at a total of three locations near both ends and the center of the lumen structure is defined as the height of the bellows portion (bellows height).

  As for the outer diameter, as shown in FIG. 2B, the value obtained by measuring the apex of the peak of the bellows portion is taken as the outer diameter at that location, and this is the total of the vicinity of both ends and the center of the lumen structure. The average value of the values measured at three locations is defined as the outer diameter of the bellows-like lumen structure.

  Regarding the inner diameter, the outer diameter of the core material used at the time of manufacturing the braid is defined as the inner diameter of the bellows-like lumen structure as it is.

  Further, as shown in FIG. 2C, the distance in the major axis direction for the five bellows peaks is a value obtained by measuring the distance of five peaks near the center of the lumen structure. It is defined as the distance in the major axis direction.

[Method of manufacturing bellows-like lumen structure]
The manufacturing method of the bellows-like lumen structure of the present invention is not particularly limited, but there is a method in which a braid is produced using a core material formed from polytetrafluoroethylene or the like, and then the braid is formed into a bellows shape. preferable.

  The method for producing the braid is not particularly limited, and examples thereof include a method of using 4 to 48 yarns on a braiding machine (braiding machine) and assembling the outer periphery of the core material. Examples include 4 braids, 8 braids, 16 braids, 32 braids, 48 braids, etc. The assembling method (braiding method) includes round punching, square punching, flat punching, etc. These may be combined to form a string. Other assembly methods include regular blade (1 wire 2 over 2 under), diamond pattern full load (2 wire 2 over 2 under), diamond pattern half load (1 wire 1 over 1 under), and the like.

  In the present invention, the form of the braiding machine (braiding machine) and its assembling method (braiding method) are not limited at all.

  Hereinafter, an example of a method for manufacturing a braid according to the present invention will be described in detail with reference to the drawings.

  FIG. 3 is a schematic diagram showing an example of a braiding machine that is preferably used to manufacture the braiding constructing the lumen structure of the present invention. FIG. 4 is an enlarged schematic view showing an example of a yarn winding bobbin and a carrier provided in the braiding machine.

  In the braiding machine shown in FIG. 3, 1 is a feeding device, 2 is a core material winding drum, 3 is a core material, 4 is a delivery guide pulley, 5 is a gear box, 6 is a flyer drive motor, 7 is a flyer, and 8 is a thread. A winding bobbin, 9 is a yarn, 10 is a braid with core material, 11 is a winding guide pulley, 12 is a braid winding drum with core material, 13 is a winding device, 14 is a winding device drive motor, and 15 is The carrier 16 is an outlet for the carrier yarn.

  The braiding machine shown in FIG. 3 includes a feeding mechanism, a braiding mechanism, and a winding mechanism.

  The delivery mechanism includes a delivery device 1 and a delivery guide pulley 4. A core winding drum 2 is attached to the delivery device 1. That is, the delivery mechanism is configured to attach the core material winding drum 2 to the delivery device 1 and then send the core material 3 from the core material winding drum 2 through the delivery guide pulley 4.

  Next, the braiding mechanism includes a fryer driving motor, a fryer driven by the fryer driving motor, and a plurality of shield wire winding bobbin delivery devices (carriers) installed on the fryer.

  The core 3 delivered from the delivery mechanism is delivered upward from below the opening at the center of the flyer 7 of the braiding mechanism.

  Here, the flyer 7 is rotated in the circumferential direction by the flyer drive motor 6. A plurality of yarn winding bobbins 8 are mounted on an upper portion of the fryer 7 so as to be rotatable and moved in a zigzag manner to a feeding device (not shown). Then, the circumferential rotation of the fryer 7 and the rotation and movement of the plurality of yarn winding bobbins 8 pass through the carrier 15 from the plurality of yarn winding bobbins 8 and feed the yarn 9 from the yarn outlet 16 respectively. However, it is braided onto the core material 3 (see also FIG. 4).

  The winding mechanism includes a winding guide pulley 11, a winding device 13, and a winding device drive motor 14 that drives the winding device 13. That is, the braid 10 with the core material is wound around the braid winding drum 12 with the core material by the winding device 13 driven by the winding device drive motor 14 via the winding guide pulley 11.

  In the braiding machine used in the present invention, a noise sensor, a temperature sensor, or the like can be attached as a sensor.

  The braid angle is controlled by controlling the braid knitting speed, that is, the frequency of the flyer drive motor, the braid winding speed, that is, the frequency of the take-up device drive motor, and the like. Can be performed by controlling the difference in height to the position where the braids are gathered and generated.

  The wall thickness of the braid before being formed into a bellows shape is preferably 0.01 to 2 mm.

  The method for forming the braid into a bellows shape is not particularly limited, but at least one annular peak is formed while the braid is repeatedly compressed and stretched in the major axis direction while the core material is still contained. Then, while repeating the same operation little by little from that part, the part that swells the annular crest toward both ends is trimmed and formed into a mountain shape. At this time, the swelled portion naturally swells regularly at a certain number of stitch intervals. After that, the braid is compressed again in the major axis direction as much as possible, and then returned to the target compression amount to obtain a bellows-like lumen structure. At this time, since the bellows-like lumen structure tends to extend in the long axis direction, the lumen structure and the core material are clipped at the end of the bellows-like lumen structure, for example. It is preferable to prevent the elongation of.

  The above compression amount is the percentage of the total length after compression relative to the total length of the luminal structure before compression. For example, when the total length before compression is 100 mm and the total length after compression is 30 mm, compression is performed. The amount will be 30%. The amount of compression is preferably less than 70%, more preferably 50% or less, from the viewpoint of kink resistance and strength improvement. The lower limit of the compression amount is not particularly limited, but is preferably 10% or more, and more preferably 20% or more.

  After the bellows molding, in order to fix the bellows shape, it is preferable to perform an annealing treatment at a temperature of 50 to 200 ° C. for 30 minutes to 48 hours, and an annealing treatment at a temperature of 90 to 150 ° C. for 30 minutes to 24 hours. It is more preferable.

  The manufacturing method as described above is a manufacturing method that can be applied regardless of the braid angle (for example, 30 to 85 °), but when the braid angle is large (for example, 40 to 85 °), a bellows is formed. Before doing this, it is preferable to replace the core material with a small outer diameter and extend the braid once in the long axis direction to reduce the braid angle. By performing this operation, it becomes easier to form the bellows.

  Then, the bellows-like lumen structure of the present invention is obtained by extracting the core material.

  That is, the principle of bellows molding in the present invention is that when a braid with a small braid angle is compressed in the major axis direction, the braid angle becomes large, but at that time the length of the yarn becomes longer than the outer periphery of the core material, and the surplus Minutes are extruded at regular intervals in the outer direction of the diameter, forming peaks and forming bellows.

[Use]
The use of the bellows-like luminal structure of the present invention is not particularly limited. For example, the tissue of an animal body such as a human, rat, dog, cat, monkey, horse, cow, or sheep is regenerated, transplanted, or replaced. It can be used as a member for More preferably, it is a member for regenerating, transplanting or replacing human body tissue.

  Since the bellows-like luminal structure of the present invention has a gap unique to the braid, it can pass gas or liquid while it does not pass cells, and can provide a place advantageous for nerve regeneration. Moreover, since it has a bellows structure, a contact area with a biological tissue decreases and adhesion with a biological tissue can be reduced. Furthermore, since it has a bellows structure, even if a force is applied in the diametrical direction of the bellows-like lumen structure of the present invention, a space can be secured without completely closing the lumen, and it becomes a scaffold for tissue regeneration. In addition, by adopting a bellows structure, even when the lumen is crushed in the diameter direction over time and the lumen is completely blocked, the bellows supports the encapsulated tissue from the inside until just before the lumen structure is disassembled, thereby securing a space. It is possible to form a cavity after complete disappearance.

  Examples of the animal tissue include nerve tissue, subcutaneous tissue, submucosal tissue, biological membrane tissue, adipose tissue, muscle tissue, skin tissue, gingival tissue, and the like, particularly suitable for nerve tissue. Can be used. More specifically, the following can be exemplified as the organization.

  Nerve tissue (eg, central nerve, peripheral nerve; sciatic nerve, median nerve, facial nerve, cranial nerve, brachial plexus, ulnar nerve, radial nerve, femoral nerve, sciatic nerve, radial nerve, sural nerve, erectile nerve, axilla Nerve); subcutaneous tissue; submucosa, oral submucosa, gastrointestinal submucosa, genital submucosa; biological membrane tissue (eg, cerebral dura mater, peritoneum, pleura, fascia, organ membrane); adipose tissue (Eg, so-called fat); muscle tissue (eg, so-called muscle); skin tissue (eg, so-called skin); gingival tissue (eg, periodontal tissue, alveolar bone, alveolar tissue); parenchymal organs (eg, liver, kidney, Lungs, pancreas, thyroid); other (eg, blood vessels, tendons, ligaments, cartilage, bones) and the like.

  The bellows-like lumen structure of the present invention is preferably used for a nerve tissue regeneration member, that is, a nerve regeneration tube. The bellows-like lumen structure of the present invention can be used as a nerve regeneration tube, a subcutaneous tissue, a submucosal tissue, or the like. When used for a regeneration member such as biological membrane tissue, adipose tissue, muscle tissue, skin tissue, gingival tissue, the outer surface of the bellows-like lumen structure may be coated with collagen, The interior (lumen) may be filled with collagen. As the collagen, collagen conventionally used as a scaffold for nerve regeneration, for example, may be used, and examples thereof include type I collagen, type III collagen, type IV collagen, and the like. You may mix and use the above. Collagen may also contain laminin, heparan sulfate proteoglycan, entactin and growth factors. As growth factors, EGF (epidermal growth factor), βFGF (fibroblast growth factor), NGF (nerve growth factor), PDGF (platelet-derived growth factor), IGF-1 (insulin-like growth factor), TGF-β ( Transforming growth factors).

  The bellows-like luminal structure coated and filled with collagen is preferably subjected to freezing, lyophilization, and crosslinking treatment to crosslink the collagen. Freezing is preferably performed at a temperature of −196 ° C. to −10 ° C. for 3 to 48 hours. By freezing, fine ice is formed between collagen molecules, and the collagen solution undergoes phase separation and becomes sponge. Next, the frozen collagen solution is freeze-dried under vacuum, preferably at −80 to 30 ° C., preferably for 12 to 48 hours. By freeze-drying, fine ice between collagen molecules is vaporized and the collagen sponge is refined. Examples of the crosslinking method include γ-ray crosslinking, ultraviolet crosslinking, electron beam crosslinking, thermal dehydration crosslinking, glutaraldehyde crosslinking, epoxy crosslinking, and water-soluble carbodiimide crosslinking, but it is easy to control the degree of crosslinking and perform crosslinking treatment. Thermal dehydration crosslinking that does not affect the living body is preferred. The thermal dehydration crosslinking treatment is performed under a vacuum, for example, at a temperature of 105 to 150 ° C., preferably 120 to 150 ° C., for example, for 6 to 24 hours, preferably 10 to 15 hours.

  EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited thereto.

1. Production of bellows-shaped tube (1) Braiding machine Separated motors for knitting and take-off for braiding machine (model number: 101-K) manufactured by KOKUBUN LIMITED Co., Ltd. and equipped with a medium 48-carrier braider. It was installed and remodeled so that the speed could be changed independently.

(2) Polyglycolic acid (PGA) yarn Product name: Trisorb, size: USP7-0 manufactured by Samyang (Korea) was used.

(3) Fabrication of braids As described below, a total of 6 types of braids, each having an inner diameter of 2 mm, 4 mm, and 6 mm, each having a large braid angle and a small braid, were fabricated.

(3-1) Braid with an inner diameter of 2 mm The above two PGA yarns were combined to form a yarn and wound around a bobbin. Forty-eight bobbins were prepared, attached to the braiding machine, and braided with a polytetrafluoroethylene tube having an outer diameter of 2 mm as a core material. Thereafter, the core material was extracted to obtain a tube.

  At this time, the braiding angle was changed by adjusting the take-up speed of the braid to adjust the knitting position (the difference in height from the yarn exit of the carrier to the position where the yarn gathers and the braid is generated).

  When producing a braid with a large braiding angle in Example 1, the take-up speed was slow (knitting speed: motor frequency 41.99 to 50.12 Hz, take-up speed: motor frequency 1.04 to 1.40 Hz).

  When producing the braid with a small braiding angle of Example 2, the take-up speed was increased (knitting speed: motor frequency 50.02 to 55.00 Hz, take-up speed: motor frequency 2.30 to 2.56 Hz).

(3-2) Braid with an inner diameter of 4 mm The above four PGA yarns were combined to form a yarn and wound around a bobbin. Forty-eight bobbins were prepared and attached to the braiding machine, and a braid was produced using a polytetrafluoroethylene tube having an outer diameter of 4 mm as a core material. Thereafter, the core material was extracted to obtain a tube. At this time, the braiding angle was changed by adjusting the take-up speed of the braid to adjust the knitting position (the difference in height from the yarn exit of the carrier to the position where the yarn gathers and the braid is generated).

  When producing a braid with a large braiding angle in Example 3, the take-up speed was slow (knitting speed: motor frequency 42.00 Hz, take-up speed: motor frequency 1.68 to 1.78 Hz).

  When producing a braid with a small braiding angle of Example 4, the take-up speed was increased (knitting speed: motor frequency 42.00 Hz, take-up speed: motor frequency 2.94 to 3.12 Hz).

(3-3) Braid with an inner diameter of 6 mm The above 6 PGA yarns were combined to form a yarn and wound around a bobbin. Forty-eight bobbins were prepared, attached to the braiding machine, and braided with a polytetrafluoroethylene tube having an outer diameter of 6 mm as a core material. Thereafter, the core material was extracted to obtain a tube.

  At this time, the braiding angle was changed by adjusting the take-up speed of the braid to adjust the knitting position (the difference in height from the yarn exit of the carrier to the position where the yarn gathers and the braid is generated).

  When producing the braid with a large braiding angle of Example 5, the take-up speed was slow (knitting speed: motor frequency 50.00 Hz, take-up speed: motor frequency 2.57 to 2.66 Hz).

  In the case of producing the braid having a small braiding angle in Example 6, the take-up speed was increased (knitting speed: motor frequency 50.00 to 50.06 Hz, take-up speed: motor frequency 4.79 to 4.92 Hz).

(3-4) Braid with an inner diameter of 4 mm The above seven PGA yarns were combined to form a yarn and wound around a bobbin. Forty-eight bobbins were prepared and attached to the braiding machine, and a braid was produced using a polytetrafluoroethylene tube having an outer diameter of 4 mm as a core material. Thereafter, the core material was extracted to obtain a tube.

  At this time, by adjusting the braid take-up speed, the braiding angle was changed by adjusting the knitting position (the difference in height from the exit of the carrier yarn to the position where the yarn gathers and the braid is generated).

  When producing a braid having a small braiding angle in Example 7, the take-up speed was increased (knitting speed: motor frequency 42.00 Hz, take-up speed: motor frequency 3.06 to 3.29 Hz).

2. Measurement of braid angle The braid was cut into a 3.5 cm length in the major axis direction to prepare a specimen.

  In order to prevent the yarn from unraveling, both ends of the braid were melted with a heat cutter. Scissors were put in one place on the circumference of the braid, opened in the long axis direction, and sandwiched between two slide glasses. The inner surface of the tube was photographed with a CCD camera (manufactured by Keyence Corporation, VH-6300), and the assembly angle was measured with the attached software. An arbitrary set angle for one specimen was measured as described above and used as the set angle of the braid.

3. Measurement of wall thickness of braid The braid was cut into 5 cm lengths and used as specimens.

  A specimen is cut with a razor or a heat cutter in one direction of the circumference in the long axis direction, and a thickness of 3 places in total, 2 places near both ends and 1 place near the center, is a thickness gauge (SM-112, manufactured by Teclock Co., Ltd.) The average value was taken as the wall thickness of the braid.

  The structure of the obtained braid is shown in Table 1 below.

4). Forming a mountain (bellows) There are two ways to form a mountain (bellows).

(4-1) In the case of braid with a small braid angle (tube numbers 2, 4, 6, 7)
When braids with a small braid angle are used, at least one annular crest is formed while repeating compression and extension in the major axis direction with the core material (when bellows is molded) in the upper table. did. Then, while repeating the same operation little by little from that part, the part that swells the annular crest toward both ends was trimmed with fingers and formed into a mountain shape. At this time, the swelled portion naturally swells regularly at a certain number of stitch intervals.

  Then, after compressing as much as possible in the major axis direction, it was returned to the target compression amount to obtain a bellows-like tube. At this time, since the bellows-like tube tends to extend in the major axis direction, a metal clip was attached to the core material at both ends of the tube or tape was wound to prevent the tube from extending.

  A bellows-like tube compressed at 30%, 50%, 70%, and 90% using a braid of tube numbers 2 to 7 in the above table and a bellows-like tube not compressed (compression amount 100%), respectively. (Total length 70 mm).

(4-2) In the case of braid having a large braid angle (tube numbers 1, 3, 5)
In the case of a braid with a large braiding angle, it cannot be formed into a bellows shape as it is, so the braid angle was reduced by first exchanging the core with a smaller outer diameter and extending the braid in the major axis direction. At this time, the inner diameter of the tube is reduced to the outer diameter of the core material as the braiding angle is reduced, so that the inner diameter of the tube is smaller than that at the time of manufacturing the braid. Then, it shape | molded by the method similar to said (4-1) to the bellows shape. However, tube No. 1 did not have a bellows structure with a lumen retained.

5. Annealing In order to fix the shape of the bellows-like tube, it was allowed to stand at a temperature of 140 ° C. under reduced pressure for 24 hours and annealed.

6). Dimensional measurement The height and outer diameter of the bellows tube were measured with a 50 × lens of a projector (Nikon V-12, manufactured by Nikon Corporation, production number 348155).

  As for the height of the mountain, as shown in FIG. 2A, the average value of the heights measured on both sides of the mountain (a and b in A of FIG. 2) is taken as the height of the mountain. The average value of the values measured at a total of three locations near both ends and the center of the bellows-like tube was taken as the height of the bellows portion (bellows height).

  As for the inner diameter, the outer diameter of the core material used at the time of manufacturing the braid was directly used as the inner diameter of the bellows-like tube.

  For the outer diameter, as shown in FIG. 2B, the value measured at the top of the peak is taken as the outer diameter at that location, and this is the value measured at a total of three locations near both ends and the center of the bellows-like tube. Was the outer diameter of the bellows-like tube.

  Further, as shown in FIG. 2C, the distance in the major axis direction for the five bellows peaks is a value obtained by measuring the distance of five peaks near the center of the lumen structure. The distance in the major axis direction.

  The measurement results are shown in Table 2 below. In addition, “-” in Table 2 indicates that measurement could not be performed because the peak of the bellows portion could not be determined.

7). Kink resistance test After extracting the core from the annealed bellows-shaped tube and measuring the ridge outer diameter 1 and valley outer diameter 1 near the center of the long axis, mandrels with different radii (radius 13, 10, 7, 4, 2 mm) ), The bellows-like tube was placed along 180 ° or more of the circumference of the mandrel, and the peak outer diameter 2 and the valley outer diameter 2 near the center of the major axis of the bellows-like tube when bent were measured. The percentage of the peak outer diameter 2 relative to the peak outer diameter 1 was defined as the kink ratio (%) of the peak, and the percentage of the valley outer diameter 2 relative to the valley outer diameter 1 was defined as the kink ratio (%) of the valley.

  Specifically, the kink resistance test was performed in the following procedure.

  1) A lens of 5 to 40 times was attached to a CCD camera (manufactured by Keyence Corporation, VH-6300), and a stainless steel scale (Shinwa straight silver 15 cm, product number 13005, JIS 1 grade) was photographed and calibrated.

  2) The core material was extracted from the bellows-shaped tube after annealing, and a peak near the center of the long axis was marked with a felt pen.

  3) The bellows-like tube was photographed with a CCD camera, and the crest outer diameter at the mark position and the trough outer diameter on the right side thereof were measured to obtain a crest outer diameter 1 and a trough outer diameter 1, respectively.

  4) Prepare 5 types of mandrels with different radii (radius 13mm, 10mm, 7mm, 4mm, 2mm) and photograph them with a CCD camera while curving the bellows-shaped tube along 180 ° or more of the circumference of the mandrel. The outer diameter of the crest and the outer diameter of the trough on the right side of the crest were measured to be the outer diameter 2 and the outer diameter 2 of the trough, respectively. The mandrels were used in the order of a radius of 13 mm, 10 mm, 7 mm, 4 mm, and 2 mm.

  5) The percentage of the peak outer diameter 2 relative to the peak outer diameter 1 is defined as the kink ratio (%) of the peak, and the percentage of the valley outer diameter 2 relative to the valley outer diameter 1 is defined as the valley kink ratio (%). .

  The test results are shown in Tables 3 and 4 below. Note that “−” in Tables 3 and 4 indicates that the valleys could not be determined, and thus measurement could not be performed.

  As apparent from Tables 3 and 4 above, it was found that the bellows-like lumen structure of the present invention was excellent in kink resistance. In particular, it was found that when the compression amount is less than 70%, the kink resistance is further improved.

8). Compression test The tube was cut into 3.5 cm lengths in the major axis direction to prepare specimens.

  Attach an adapter (diameter 10 mm) to the rheometer, place the specimen on the rheometer table, lower the adapter at a rate of 2 mm / min, and compress it to a distance of 75% of the tube outer diameter, then ascend at a rate of 2 mm / min The stress at the time of descending and rising (unit N) was recorded.

  The vertical axis represents stress (N), the horizontal axis represents the moving distance (mm) of the adapter, the recorded results were plotted, and the energy during compression up to 50% of the tube inner diameter display value was calculated.

  For example, since the inner diameter display value of a tube having a core material outer diameter of 4 mm is 4 mm, the energy at the time of compression up to 2 mm, which is 50%, was calculated.

  The evaluation results of the compression test are shown in Table 5 below.

  As is clear from Table 5 above, it was found that the bellows-like luminal structure of the present invention has a high energy during compression and a high strength. In particular, it has been found that the strength is higher when the compression amount is less than 70%.

[Embedding experiment]
<Canine radial nerve implantation experiment>
The following two types of nerve regeneration tubes were prepared using braids having an inner diameter of 4 mm prepared using PGA yarn.

(1) Nerve regeneration tube made from a normal braided cord (2) A bellows-like nerve regeneration tube made from a braided cord (the bellows-like tube of Example 7-2, compression amount 50%)
A nerve regeneration tube was prepared as follows. Water was added to collagen, hydrochloric acid was added to dissolve it with stirring, pH was adjusted to 3, and a collagen solution with a final concentration of 1 w / v% was prepared. This collagen solution was applied to the outer surface of a normal braid and a braid formed into a bellows shape using a brush and air-dried. This operation was repeated 20 times. The lumens of the coated normal braid and the braid formed into a bellows were filled with the 1 w / v% collagen solution and frozen in a freezer (freezing conditions: −80 ° C., 3 to 5 hours). The ordinary braid frozen in the freezer and the braid formed into a bellows shape were transferred to a freeze dryer container, and the drying under reduced pressure was started immediately and dried at room temperature for about 16 to 20 hours. Thereafter, the ordinary lyophilized braid and the braid shaped into a bellows were transferred into an oven and heated at 140 ° C. under reduced pressure for 24 hours to carry out thermal dehydration crosslinking. Next, EOG (ethylene oxide gas) sterilization was performed. After completion of sterilization, it was transferred to an oven and dried at 50 ° C. under reduced pressure for about 3 days to obtain a nerve regeneration tube and a bellows-like nerve regeneration tube that were not bellows-like.

  For (1), the entire length of the tube was cut to 70 mm, a 60 mm defect was created in the right hind limb radial nerve, and connected to the nerve stump and embedded. For (2), the entire length of the tube was cut to 45 mm, a 35 mm defect was created in the right hind limb radial nerve, and it was connected to the nerve stump and embedded.

  Thereafter, ultrasonic echo inspection was performed over time to confirm the presence state of the tube. FIG. 5 shows the result of embedding (1), and FIG. 6 shows the result of embedding (2).

  As a result, 4 weeks after implantation, (1) was completely crushed and the lumen was occluded, but (2) was slightly crushed but the lumen was not occluded. It was patent without being blocked.

  From these results, by forming the braid into a bellows shape and improving the kink resistance and the compressive strength, the lumen can be opened even at the time of four weeks when the strength of the PGA becomes the minimum, and the bellows according to the present invention. The superiority of the tubular lumen structure was shown. Furthermore, for (2), the wall of the bellows-like tube supports the encapsulated tissue from the inside to secure a space even when the lumen is almost occluded in 6 weeks. (Tunnel) can be created and an effective place for nerve regeneration can be provided.

1 sending device,
2 core winding drum,
3 core material,
4 Delivery guide pulley,
5 Gearbox,
6 Flyer drive motor,
7 Flyer,
8 Thread winding bobbin,
9 Yarn,
10 Braid with core material,
11 Take-up guide pulley,
12 cored braid winding drum,
13 winding device,
14 Winding device drive motor.
15 carrier,
16 Carrier thread exit.

Claims (6)

  A bellows-like nerve regeneration tube formed from braided braided yarn.   The bellows-like nerve regeneration tube according to claim 1, wherein a height of a peak of the bellows portion of the bellows-like nerve regeneration tube is 1 to 40% with respect to an inner diameter of the bellows-like nerve regeneration tube.   The bellows-like nerve regeneration tube according to claim 1 or 2, wherein the fiber forming the yarn is a fiber formed from a biodegradable polymer.   After braiding the yarn to produce a braid having a braid angle of 30 to 85 °, the braid is compressed into and stretched in the long axis direction using a core material having an outer diameter of 2 mm or more to form a bellows shape. A method for manufacturing a bellows-like nerve regeneration tube, which comprises forming and compressing the braid again in the long axis direction.   The method of manufacturing a bellows-like nerve regeneration tube according to claim 4, wherein the amount of compression when the braid is compressed again in the long axis direction is less than 70% of the total length of the braid before the bellows is formed.   After obtaining the bellows-like nerve regeneration tube by the production method according to claim 4 or 5, the outer surface of the bellows-like nerve regeneration tube is coated with collagen, further filled with collagen, and freeze-dried, A method for producing a collagen-coated bellows-like nerve regeneration tube, comprising thermal dehydration crosslinking.