JP5453774B2 - Nerve regeneration substrate and parts for nerve regeneration substrate - Google Patents

Description

  The present invention relates to a nerve regeneration substrate made of a biodegradable material.

  Human nerves may be damaged by diseases or injuries, and nerve damage may not be cured by self-recovery. Such nerve damage can cause movement disorders and organ dysfunction. On the other hand, an operation for suturing a damaged nerve and a treatment for collecting and transplanting a nerve from another part of the self are performed.

  Patent Document 1 discloses a precursor of a tissue regeneration device in which a filamentous material is fixed in an inner space of a cylindrical body made of a biodegradable material.

  Patent Document 2 discloses a nerve regeneration induction tube in which a nerve regeneration induction path is formed by a sponge-like matrix or the like inside a tubular body made of a biodegradable material.

JP 2008-43597 A JP 2004-208808 A

  The tissue regeneration device and nerve regeneration induction tube disclosed in Patent Document 1 and Patent Document 2 are used as a base material for regenerating cord tissue such as nerves and tendons. However, there are places where the nerves do not necessarily have a streak, so a cylindrical body or a tubular body is not suitable for such nerves.

  For example, in motor nerves, nerve fibers run in a bundle to form a bundle, so when the nerve is torn, insert the broken end of the nerve into both ends of the tubular body or tubular body, respectively, and suture it. Can do. On the other hand, in the autonomic nerve, there are parts where nerve fibers branch thinly and spread radially, and when the nerve is torn, a plurality of radially spread nerve fibers are bundled into a cylindrical shape Inserting and suturing a body or tubular body is an extremely complicated operation.

  The present invention has been made in view of these circumstances, and an object thereof is a nerve regeneration group suitable for regenerating relatively thin nerve fibers in an autonomic nerve or the like without requiring a special instrument or operation. The purpose is to provide materials.

  The nerve regeneration substrate according to the present invention is made of a biodegradable material, and at least one of at least one of the first sheet and the second sheet and the other of at least one pair of the first sheet and the second sheet sandwiching the nerve to be regenerated is the other. Are provided in parallel along the direction connecting the first end side and the second end side where the nerve tear ends are respectively arranged on the surface layer on the opposite side, and the one surface layer is bonded to the other surface layer. A first adhesive layer and a second adhesive layer to be obtained.

  The nerve regeneration substrate according to the present invention is for joining the fractured ends of nerves by nerve regeneration. In particular, this nerve regeneration base material is suitably used for the purpose of joining the fractured ends of the autonomic nerves by nerve regeneration. In the present specification, nerve fibers may be simply referred to as nerves. Nerve tears are not limited to the cause of the tear, but are severed or injured due to injury or disease, tears or defects associated with excision of organs or tissues, nerve cutting for the purpose of nerve transplantation, etc. A wide variety of causes are included.

  The first sheet and the second sheet have a thin sheet shape made of a biodegradable material. The planar shape of the first sheet and the second sheet is not particularly limited, and a rectangular shape, a circular shape, an elliptical shape, a cloud shape, or the like can be adopted, but a rectangular shape is preferable for the convenience of packaging and work. Although the size of the first sheet and the second sheet is not particularly limited, for example, if the rectangular sheet is used for autonomic nerve regeneration in the abdominal cavity, each dimension of length x width x thickness is 10 to 100 mm x 10 The thing of about 100 mm x 0.01-5.0 mm is suitable. More desirably, the first sheet and the second sheet have a length × width × thickness of about 15 to 30 mm × 15 to 30 mm × 0.1 to 2.0 mm.

  A biodegradable material is a material that can be decomposed in vivo, and preferably can be absorbed after decomposition. Examples of the biodegradable material include polylactic acid, polyglycolic acid, ε-aminocaprolactone, collagen, and chitosan. Among these, collagen is preferable from the viewpoint that an inflammatory reaction does not occur in humans and the rate of degradation and absorption by a living body can be controlled by a crosslinking treatment or the like.

  Collagen is a major protein component constituting the connective tissue of animals, and the main chain structure of the molecule is (Gly-XY), (Gly-Pro-X) and (Gly-Pro-Hyp). It means what is composed. Here, X and Y are natural or non-natural amino acids other than glycine, proline and hydroxyproline.

  Examples of collagen types include type I, type II, type III and type IV. Among these, from the viewpoint of easy handling, type I and type III collagen is preferred, but the type of collagen is not particularly limited in the present invention. In addition, the collagen in the present invention includes gelatin which is heat-denatured collagen, but is preferably not heat-denatured from the viewpoint of cell adhesion.

  Collagen is produced by extraction from living tissue, chemical polypeptide synthesis, recombinant DNA method, and the like. Among these, from the viewpoint of production cost, collagen produced by extraction from living tissue is preferable. In addition, examples of the origin of biological tissue include cattle, pigs, rabbits, sheep, mice, birds, fish, and humans. Examples of biological tissues include the aforementioned animal and human skin, tendons, bones, cartilage, and organs. Needless to say, the selection of the biological tissue and the origin is appropriately performed by those skilled in the art, and the present invention is not limited to the collagen derived from the biological tissue exemplified in the present specification.

  Moreover, as a collagen, what was processed so that it can melt | dissolve in a solvent is preferable from a viewpoint of making industrial manufacture easy. Examples of such collagen include solubilized collagen such as enzyme-solubilized collagen, acid-solubilized collagen, alkali-solubilized collagen, and neutral-solubilized collagen. Of these, acid-solubilized collagen is particularly preferable from the viewpoint of easy handling. Furthermore, from the viewpoint of safety when implanted in a living body, atelocollagen that has been subjected to the removal treatment of the telopeptide that is an antigenic determinant is preferable.

  As the first sheet and the second sheet in the present invention, a film, a woven fabric, a non-woven fabric, or the like prepared using a biodegradable material as a raw material is used. The collagen fiber material (also simply referred to as “collagen fiber”) described above. In particular, it is preferably a woven or non-woven fabric of collagen fibers.

  Examples of the method for producing a collagen fiber include a wet spinning method, a dry spinning method, and a melt spinning method. The wet spinning method is preferable because the production is easy and the production cost is low. . As a wet spinning method for obtaining such collagen fibers, known spinning methods (JP 2000-93497 A, JP 2000-210376 A, JP 2000-271207 A, etc.) can be employed.

  As a non-woven fabric made of collagen fibers, for example, a first layer in which a plurality of collagen fibers are arranged in parallel is laminated with a second layer in which a plurality of collagen fibers are arranged in parallel by changing the arrangement direction of the collagen fibers. In addition, the relationship between the first layer and the second layer is similarly repeated, and a plurality of layers are laminated and bonded to each other. As a method for producing such a nonwoven fabric composed of collagen fibers, the method disclosed in Japanese Patent Application Laid-Open No. 2003-301362 can be employed.

  Examples of the knitted fabric made of collagen fibers include woven fabrics and knitted fabrics. Examples of the woven fabric include those woven by plain weave and twill weave using collagen fibers. Examples of the knitted fabric include those woven by flat knitting or rubber knitting using collagen fibers.

  It is preferable that the 1st sheet | seat and 2nd sheet | seat which consist of collagen fibers as mentioned above are the nonwoven fabrics of a collagen fiber. In the non-woven fabric of collagen fibers, as described above, since a plurality of layers in which a plurality of collagen fibers are arranged in parallel are laminated, the nerve tearing ends are arranged on the surface layer of the first sheet or the second sheet, respectively. The first sheet is formed by laminating a plurality of collagen fibers in parallel along a direction connecting the first end side and the second end side (hereinafter also referred to as “first direction”). Alternatively, nerves are regenerated along the collagen fibers arranged on the surface layer of the second sheet. That is, the regenerated nerve extends along the first direction with a guidance path between a plurality of collagen fibers.

  The 1st end side and the 2nd end side in the surface layer of the 1st sheet or the 2nd sheet are the positions where the tearing ends of the nerves face each other and face each other on the surface layer of the 1st sheet or the 2nd sheet. In general, the vicinity of the pair of end portions. The nerve to be regenerated extends from the center of the torn end of the torn nerve fiber. Whether the central tear edge or the distal tear edge is positioned on the first end side or the second end side is determined in consideration of the specification of such nerve regeneration. When the first sheet or the second sheet is a rectangle, a pair of short sides or long sides near the rectangle is the first end side and the second end side. The direction connecting the first end side and the second end side is a pair of short sides or long sides that do not become the first end side and the second end side among a pair of short sides or long sides facing each other in the rectangle. The direction along the side. In the present specification, “direction” includes opposite directions. Therefore, the direction connecting the first end side and the second end side (first direction) includes both the direction from the first end to the second end and the direction from the second end to the first end. .

  The first sheet and the second sheet obtained as described above may be further subjected to various known physical or chemical crosslinking treatments. The stage at which this crosslinking treatment is performed is not particularly limited. Two or more crosslinking treatments may be used, and the order thereof is not limited.

  The crosslinking treatment described above can significantly delay the time taken for decomposition and absorption when the nerve regeneration substrate is implanted in the living body compared to the uncrosslinked material. This is useful in that the physical strength of the material is improved. That is, it becomes easy to maintain the necessary physical strength during the period until the portion where the nerve is lost is reproduced using the nerve regeneration substrate.

  Examples of the physical crosslinking described above include γ-ray irradiation, ultraviolet irradiation, electron beam irradiation, plasma irradiation, and crosslinking treatment by thermal dehydration reaction. Examples of chemical crosslinking methods include reactions with aldehydes such as dialdehyde and polyaldehyde, epoxies, carbodiimides, isocyanates, tannin treatment, chromium treatment, and the like.

  Further, the first sheet or the second sheet obtained as described above may be coated with a biodegradable substance. Examples of biodegradable substances used for coating include collagen and hyaluronic acid. Furthermore, the first sheet or the second sheet may be impregnated with various growth factors, drugs, and the like. Nerve regeneration can be promoted by the action of these growth factors and drugs.

  At least one of the first sheet and the second sheet has a surface layer on the side facing the other, the first adhesive layer and the second layer along the direction (first direction) connecting the first end side and the second end side. An adhesive layer is provided in parallel.

  The first pressure-sensitive adhesive layer and the second pressure-sensitive adhesive layer are layers having adhesion performance capable of adhering the surface layer of the first sheet and the surface layer of the second sheet, and a substance having such adhesion performance is laminated on the surface layer, It can be formed by processing a part of the surface layer to exert adhesive performance. The first adhesive layer and the second adhesive layer may be provided on at least one of the first sheet and the second sheet. For example, the first adhesive layer and the second adhesive layer are provided on the surface layer of the first sheet. The first adhesive layer and the second adhesive layer on the surface of the second sheet, the first adhesive layer on the surface of the first sheet, and the second adhesive on the surface of the second sheet An embodiment in which a layer is provided is mentioned. Of course, the first adhesive layer or the second adhesive layer may be provided on both the surface layer of the first sheet and the surface layer of the second sheet.

  Specifically, the aspect which apply | coats the biomedical adhesive to the surface layer of a 1st sheet or the surface layer of a 2nd sheet as a 1st adhesion layer and a 2nd adhesion layer is mention | raise | lifted. A bioadhesive is a material that can be decomposed in vivo, and preferably can be absorbed after decomposition. Examples of the biomedical adhesive include those mainly composed of fibrin using a blood coagulation reaction.

  In the surface layer of the first sheet or the second sheet, the first adhesive layer and the second adhesive layer provided in parallel along the direction connecting the first end side and the second end side are the first end side and the second sheet. They are separated in a direction intersecting with the direction connecting the end sides (hereinafter also referred to as “second direction”). Therefore, when the first sheet and the second sheet are bonded to each other with the surface layers facing each other by the first pressure-sensitive adhesive layer and the second pressure-sensitive adhesive layer, between the first pressure-sensitive adhesive layer and the second pressure-sensitive adhesive layer, A space continuous in the direction is formed between the surface layer of the first sheet and the surface layer of the second sheet. In this space, the surface layer of the first sheet and the surface layer of the second sheet are not bonded. On the other hand, since the surface layer of the first sheet and the surface layer of the second sheet are bonded by the first adhesive layer and the second adhesive layer, the space cannot enter the space from the outside in the second direction. The nerve is regenerated in this space.

  The surface layer of either the first sheet or the second sheet is provided with a third adhesive layer or a fourth adhesive layer on the first end side and the second end side for fixing the tearing end of the nerve, respectively. Preferably it is.

  The third pressure-sensitive adhesive layer and the fourth pressure-sensitive adhesive layer are layers having adhesive performance capable of adhering nerves to the surface layer of the first sheet or the surface layer of the second sheet, and a substance having such adhesive performance is laminated on the surface layer. It can be formed by processing a part of the surface layer to exert the adhesive performance. The third adhesive layer and the fourth adhesive layer may be provided on at least one of the first sheet and the second sheet. For example, the third adhesive layer and the fourth adhesive layer are provided on the surface layer of the first sheet. A mode in which the third adhesive layer and the fourth adhesive layer are provided on the surface layer of the second sheet, a third adhesive layer is provided in the surface layer of the first sheet, and a fourth adhesive layer is provided on the surface layer of the second sheet. An embodiment in which a layer is provided can be mentioned. Of course, the 3rd adhesion layer or the 4th adhesion layer may be provided in any of the surface layer of the 1st sheet, and the surface layer of the 2nd sheet.

  Specifically, the aspect which apply | coats the biomedical adhesive to the surface layer of a 1st sheet or the surface layer of a 2nd sheet as a 3rd adhesion layer and a 4th adhesion layer is mention | raise | lifted. A bioadhesive is a material that can be decomposed in vivo, and preferably can be absorbed after decomposition. Examples of the biomedical adhesive include those mainly composed of fibrin using a blood coagulation reaction.

  It is preferable that the 5th adhesion layer which can adhere | attach a 1st sheet or a 2nd sheet | seat with a biological tissue is provided in the back surface side with respect to the surface layer in a 1st sheet | seat or a 2nd sheet | seat.

  The fifth adhesive layer is a layer having an adhesive performance capable of adhering the surface layer or the second sheet of the first sheet to the living tissue, and a substance having such an adhesive performance is disposed on the back surface side of the first sheet or the second sheet. It can be formed by laminating or by processing a part of the back side to exhibit adhesive performance. Moreover, although the 5th adhesion layer should just be provided in either the 1st sheet | seat or the 2nd sheet | seat, you may provide in both.

  Specifically, the aspect which apply | coats the biomedical adhesive to the back surface side of a 1st sheet | seat or a 2nd sheet | seat as a 5th adhesion layer is mention | raise | lifted. A bioadhesive is a material that can be decomposed in vivo, and preferably can be absorbed after decomposition. Examples of the biomedical adhesive include those mainly composed of fibrin using a blood coagulation reaction.

  The nerve regeneration substrate according to the present invention is preferably sterilized by a known method such as γ-ray sterilization or ultraviolet sterilization before being used for medical purposes. In the nerve regeneration substrate according to the present invention, the first sheet and the second sheet do not necessarily have to be integrally packaged as a pair. For example, the first sheet and the second sheet are individually packaged. It may be.

  According to the present invention, at least one of at least one pair of the first sheet and the second sheet sandwiching the nerve to be regenerated, on the surface layer on the side facing the other, the first end side where the nerve tearing ends are respectively disposed; Since the first adhesive layer and the second adhesive layer are provided in parallel along the direction connecting the second end side, a relatively thin nerve fiber in the autonomic nerve or the like can be easily connected to the first sheet without using sutures. And can be reproduced by being sandwiched between the second sheets.

  In addition, at least one surface layer of the first sheet and the second sheet has a third adhesive layer or a fourth adhesive layer for fixing the fractured end of the nerve to the first end side and the second end side, respectively. Since it is provided, relatively thin nerve fibers in the autonomic nerve or the like can be easily fixed to the first sheet or the second sheet without using sutures.

  In addition, since a fifth adhesive layer capable of adhering the first sheet or the second sheet to the living tissue is provided on the back surface side with respect to the surface layer of the first sheet or the second sheet, nerve fibers are intraperitoneally or the like. The first sheet and the second sheet sandwiched and integrated can be easily fixed to a living tissue such as an organ without using suturing.

  Hereinafter, preferred embodiments of the present invention will be described. In addition, this embodiment is only one embodiment of this invention, and it cannot be overemphasized that an embodiment can be changed in the range which does not change the summary of this invention.

[Explanation of drawings]
FIG. 1 is a perspective view showing an external configuration of nerve regeneration sheets 11 and 12 according to an embodiment of the present invention. FIG. 2 is a schematic view showing a method for producing a nonwoven fabric of collagen thread 21. FIG. 3 is a schematic diagram showing a method for regenerating the autonomic nerve 40 using the nerve regeneration sheets 11 and 12.

[Nerve regeneration sheets 11, 12]
The nerve regeneration substrate according to the present embodiment includes a pair of nerve regeneration sheets 11 and 12. The nerve regeneration sheets 11 and 12 correspond to the first sheet and the second sheet, respectively, in the present invention, and each correspond to the component for nerve regeneration base material in the present invention.

  As shown in FIG. 1, each of the nerve regeneration sheets 11 and 12 is a thin rectangular sheet. The two nerve regeneration sheets 11 and 12 have the same shape. The nerve regeneration sheets 11 and 12 sandwich the broken end of the nerve and promote nerve regeneration inside thereof.

  The nerve regeneration sheets 11 and 12 are nonwoven fabrics of collagen thread 21. In detail, the collagen thread 21 is wound around the winding plate 20 while producing the collagen thread 21 by the wet spinning method. The winding plate 20 is a rectangular flat plate that is substantially the same as the nerve regeneration sheets 11 and 12. In winding the collagen thread 21, as shown in FIG. 2A, the direction 101 in which the collagen thread 21 is supplied and the rotation axis 102 of the winding plate 20 are orthogonal to each other.

  The winding plate 20 is inclined so that the long side direction 103 of the winding plate 20 intersects with the rotation axis 102 and is rotated with respect to the rotation axis 102, so that the collagen filament 21 becomes the long side of the winding plate 20. The film is wound on the winding plate 20 at an angle not orthogonal to the direction 103. Further, the winding plate 20 is slid in one direction relative to the collagen filament 21 along the rotation axis 102 while being rotated. This slide speed is set in consideration of the arrangement pitch of the collagen thread 21. As a result, the collagen filaments 21 are wound in parallel on the winding plate 20 from one end side to the other end side in the long side direction 103 of the winding plate 20, and the collagen filaments 21 are arranged in a certain direction. Is produced.

  Next, as shown in FIG. 2B, the inclination angle between the long side direction 103 and the rotation axis 102 in the winding plate 20 is changed, and the winding plate 20 is rotated with respect to the rotation axis 102. As a result, the collagen filament 21 is at an angle that is not orthogonal to the long side direction 103 of the take-up plate 20 and is different from the arrangement direction of the collagen filament 21 that has been previously taken up. It is wound up. Further, the winding plate 20 is slid in one direction relative to the collagen filament 21 along the rotation axis 102 while being rotated. As a result, the collagen filament 21 is wound in parallel on the winding plate 20 from the other end side in the long side direction 103 of the winding plate 20 to the one end side. A layer of the collagen thread 21 is laminated.

  As described above, the inclination angle between the long side direction 103 and the rotation axis 102 in the winding plate 20 is changed every time the collagen thread 21 is laminated, and the collagen thread 21 is wound on the winding plate 20. It is done. Finally, as shown in FIG. 2C, the long side direction 103 of the winding plate 20 and the rotation axis 102 are orthogonal to each other, and the winding plate 20 is rotated with respect to the rotation axis 102. Thereby, the collagen filament 21 is wound around the winding plate 20 along the long side direction 103 of the winding plate 20. The winding plate 20 is slid in one direction relative to the collagen filament 21 along the rotation axis 102 while being rotated. Thereby, the layer of the collagen filament 21 arranged in the direction along the long side direction 103 in the winding plate 20 is laminated on the outermost side of the winding plate 20. This collagen thread 21 corresponds to the collagen fiber in the present invention.

  As described above, the collagen filamentous material 21 wound on the winding plate 20 is dried, and then cut along the periphery of the winding plate 20 to obtain two collagen nonwoven fabrics. In these two collagen nonwoven fabrics, the outermost surface of the winding plate 20 becomes the surface layers 13 and 14 on the inner surface side of the nerve regeneration sheets 11 and 12. Two collagen nonwoven fabrics are cut into a rectangle of a desired size as necessary.

  The obtained collagen non-woven fabric is subjected to thermal dehydration crosslinking reaction, and further impregnated with a collagen aqueous solution and again subjected to thermal dehydration crosslinking reaction, whereby membrane-like nerve regeneration sheets 11 and 12 are obtained.

  As described above, since the collagen filaments 21 laminated on the outermost side of the winding plate 20 are along the long side direction 103 in the winding plate 20, in the surface layer 13 on the inner surface side of the nerve regeneration sheet 11, Collagen filaments 21 are arranged along the long side direction 104 of the nerve regeneration sheet 11. Further, the collagen filament 21 extends over the short sides 15 and 16 of the nerve regeneration sheet 11. Similarly, in the nerve regeneration sheet 12, collagen filaments 21 are arranged along the long side direction 104 in the surface layer 14 on the inner surface side.

[Adhesion layers 31-36]
Four adhesive layers 31, 32, 33, and 34 are formed on the surface layer 13 of the nerve regeneration sheet 11. Further, two adhesive layers 35 and 36 are formed on the back surface 19 of the nerve regeneration sheet 12. In addition, the back surface 19 of the nerve regeneration sheet 12 is a surface on the opposite side of the sheet with respect to the surface layer 14.

  The adhesive layers 31 and 32 are layers having adhesive performance capable of adhering the surface layer 13 of the nerve regeneration sheet 11 and the surface layer 14 of the nerve regeneration sheet 12, and are formed by applying fibrin glue on the surface layer 13. . The adhesive layers 31 and 32 are provided along the first direction 104 along the direction connecting the pair of short sides 15 and 16 in the nerve regeneration sheet 11, that is, along the long sides 17 and 18. Each adhesive layer 31, 32 is an elongated region having the first direction 104 as the longitudinal direction, and both ends in the longitudinal direction extend to the vicinity of the short sides 15, 16. Each of the adhesive layer 31 and the adhesive layer 32 is disposed in the vicinity of the long side 17 or the long side 18, and these are arranged in a second direction 105 orthogonal to the first direction 104. In the second direction 105, none of the adhesive layers 31 to 36 exists near the center of the surface layer 13 between the adhesive layers 31 and 32. The adhesive layers 31 and 32 correspond to the first adhesive layer and the second adhesive layer in the present invention.

  The pressure-sensitive adhesive layers 33 and 34 are layers having an adhesive performance capable of adhering the surface layer 13 of the nerve regeneration sheet 11 and the nerve tear edge, and are formed by applying fibrin glue on the surface layer 13.

  The adhesive layers 33 and 34 are each provided along the second direction 105 in the surface layer 13 of the nerve regeneration sheet 11. Each adhesive layer 33, 34 is an elongated region having the second direction 105 as a longitudinal direction, and both ends in the longitudinal direction extend to the vicinity of the adhesive layers 31, 32. Each of the adhesive layer 33 and the adhesive layer 34 is disposed near the short side 15 or the short side 16. The vicinity of the short sides 15 and 16 is the position where the nerve tearing end to be reproduced is disposed, and corresponds to the first end side and the second end side in the present invention, respectively. The adhesive layers 33 and 34 correspond to the third adhesive layer and the fourth adhesive layer in the present invention.

  The adhesive layers 35 and 36 are each provided along the first direction 104 on the back surface 19 of the nerve regeneration sheet 12. Each adhesive layer 35, 36 is an elongated region having the first direction 104 as a longitudinal direction, and both ends in the longitudinal direction extend to the vicinity of the short side of the nerve regeneration sheet 12. The pressure-sensitive adhesive layers 35 and 36 are layers having an adhesive performance capable of bonding the back surface 19 of the nerve regeneration sheet 12 to a living tissue, and are formed by applying fibrin glue on the back surface 19. The adhesive layers 35 and 36 correspond to the fifth adhesive layer in the present invention. In the present embodiment, two adhesive layers 35 and 36 each provided along the first direction 104 are provided, but the number, the shape of the region, and the direction of the fifth adhesive layer in the present invention are limited. It is not something. Therefore, for example, one fifth adhesive layer may be provided along the second direction 105 on the back surface 19 of the nerve regeneration sheet 12, or the fifth adhesive layer may be provided on almost the entire area of the back surface 19.

[How to use nerve regeneration sheets 11 and 12]
Hereinafter, as a method of using the nerve regeneration sheets 11 and 12, a method of joining the torn ends 41 and 42 of the autonomic nerve 40 will be described.

  First, as shown in FIG. 3A, the nerve regeneration sheet 11 is arranged in correspondence with the torn ends 41 and 42 of the autonomic nerve 40. At this time, the nerve regeneration sheet 11 has the tear edges 41 and 42 arranged near the short sides 15 and 16 on the surface layer 13 side, respectively, and the tear edges 41 and 42 are separated in the long side direction 104 of the nerve regeneration sheet 11. It is assumed that it was done. Adhesive layers 33 and 34 are formed in the vicinity of the short sides 15 and 16, respectively, so that the tear edges 41 and 42 are bonded to the surface layer 13 by the adhesive layers 33 and 34. At that time, the nerve tips at the respective tearing ends 41 and 42 are positioned closer to the center of the surface layer 13 than the adhesive layers 33 and 34.

  Subsequently, as shown in FIG. 3B, the nerve regeneration sheet 12 is superimposed on the nerve regeneration sheet 11 so that the torn ends 41 and 42 of the autonomic nerve 40 are sandwiched between the nerve regeneration sheet 11. The At this time, the surface layer 14 of the nerve regeneration sheet 12 faces the surface layer 13 of the nerve regeneration sheet 11, and the long sides and the short sides of the nerve regeneration sheet 11 and the nerve regeneration sheet 12 correspond to each other. Since the adhesive layers 31 and 32 are formed along the long sides 15 and 16 on the surface layer 13 of the nerve regeneration sheet 11, the nerve regeneration sheets 11 and 12 are pressed near the long sides 15 and 16. Two nerve regeneration sheets 11 and 12 are bonded. As a result, it is possible to prevent peripheral tissues and the like from entering the nerve regeneration sheets 11 and 12.

  Further, the adhered nerve regeneration sheets 11 and 12 are adhered to a living tissue such as an organ by the adhesive layers 35 and 36 formed on the back surface 19 of the nerve regeneration sheet 12. Thereby, the nerve regeneration sheets 11 and 12 are fixed in the living body.

  When left in the state described above, the nerve is regenerated from the torn ends 41 and 42 of the autonomic nerve 40, and the nerve between the torn ends 41 and 42 is recovered. As described above, since the collagen filaments 21 are arranged along the long-side direction 104 on the surface layers 13 and 14 of the nerve regeneration sheets 11 and 12, the tear edges 41 and 14 are aligned along the collagen filaments 21. The regenerated nerve extends from 42. That is, the regenerated nerve extends between the plurality of collagen filaments 21 as a guide route.

[Operational effects of this embodiment]
As described above, since the adhesive layers 31 and 32 are provided in parallel in the first direction 104 on the surface layer 13 of the nerve regeneration sheet 11, relatively thin nerve fibers in the autonomic nerve 40 are obtained by sewing. It is possible to easily reproduce the material by sandwiching it between the nerve regeneration sheets 11 and 12 without using it.

  In addition, the surface layer 13 of the nerve regeneration sheet 11 is provided with adhesive layers 33 and 34 for fixing the fractured ends 41 and 42 of the autonomic nerve 40 near the short sides 15 and 16, respectively. Relatively thin nerve fibers can be easily fixed to the surface layer 13 of the nerve regeneration sheet 11 without using sutures.

  In addition, since the adhesive layers 35 and 36 that can bond the nerve regeneration sheet 12 to the living tissue are provided on the back surface 19 of the nerve regeneration sheet 12, the nerve regeneration integrated with the autonomic nerve 40 sandwiched in the abdominal cavity or the like. The sheets 11 and 12 can be easily fixed to a living tissue such as an organ without using sutures.

  In the present embodiment, the adhesive layers 31 to 34 are provided only on the surface layer 13 of the nerve regeneration sheet 11, but the adhesive layers 31 to 34 are provided only on the surface layer 14 of the nerve regeneration sheet 12, for example. Alternatively, they may be provided on the surface layers 13 and 14 of the nerve regeneration sheets 11 and 12, respectively. Similarly, the adhesive layers 35 and 36 may be provided only on the back surface of the nerve regeneration sheet 11 or may be provided on the back surfaces of the nerve regeneration sheets 11 and 12, respectively.

FIG. 1 is a perspective view showing an external configuration of nerve regeneration sheets 11 and 12 according to an embodiment of the present invention. FIG. 2 is a schematic view showing a method for producing a nonwoven fabric of collagen thread 21. FIG. 3 is a schematic diagram showing a method for regenerating the autonomic nerve 40 using the nerve regeneration sheets 11 and 12.

Explanation of symbols

11, 12 ... nerve regeneration sheet (first sheet, second sheet, nerve regeneration substrate)
13, 14 ... surface layers 15, 16 ... short sides (first end side, second end side)
21 ... Collagen filament (collagen fiber, biodegradable material)
31-36 ... adhesive layer (first adhesive layer, second adhesive layer, third adhesive layer, fourth adhesive layer, fifth adhesive layer)
40: Autonomic nerve 41, 42 ... Rupture end

Claims (9)

Made of a biodegradable material, at least a pair of a first sheet and a second sheet sandwiching a nerve to be regenerated,
At least one of the first sheet and the second sheet is provided in parallel along the direction connecting the first end side and the second end side where the nerve tearing ends are respectively disposed on the surface layer facing the other side. A first adhesive layer and a second adhesive layer capable of adhering the one surface layer to the other surface layer ,
The first sheet and the second sheet are made of collagen fibers,
The collagen fibers, at least one surface layer of the one surface or the other above, nerve regeneration substrate that is a plurality of arranged along a direction connecting the said first end side and the second end side.   The third adhesive layer or the fourth adhesive layer is provided on the first end side and the second end side of the surface layer of either the one or the other, respectively, for fixing the tearing end of the nerve, respectively. The nerve regeneration substrate as described.   The nerve according to claim 1 or 2, wherein a fifth adhesive layer capable of adhering the first sheet or the second sheet to a living tissue is provided on the back surface side of the surface layer of the first sheet or the second sheet. Recycled substrate.   The nerve regeneration substrate according to any one of claims 1 to 3, wherein the first sheet and the second sheet are a film, a woven fabric, or a nonwoven fabric. The nerve regeneration substrate according to any one of claims 1 to 4 , wherein each of the adhesive layers is made of a bioadhesive. The nerve regeneration substrate according to claim 5 , wherein the bioadhesive is fibrin. A first end side and a second end side, each of which is one of at least a pair of sheets that are made of a biodegradable material and sandwich the nerve to be regenerated, and in which the nerve tearing ends are respectively disposed on the surface layer facing the other The first adhesive layer and the second adhesive layer capable of adhering the one surface layer to the other surface layer are provided in parallel along the direction connecting the two ,
One of the pair of sheets is composed of collagen fibers,
The collagen fibers are in one of the surface layer described above, nerve regeneration base component material that is a plurality of arranged along a direction connecting the said first end side and the second end side. The nerve regeneration base material according to claim 7 , wherein a third adhesive layer and a fourth adhesive layer are provided on the first layer side and the second end side of the surface layer, respectively, for fixing nerve tearing ends. parts. The part for nerve regeneration base materials of Claim 7 or 8 in which the 5th adhesion layer which can adhere | attach the said sheet | seat with a biological tissue was provided in the back surface side with respect to the said surface layer.

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