Fabrication of carbon nanofiber yarn nerve scaffolds

Abstract

To provide a method for fabricating nerve scaffold.SOLUTION: A nerve scaffold includes a tubular outer housing fabricated from a biocompatible polymer, within which a plurality of carbon nanofiber yarns are disposed. The carbon nanofiber yarns, which can be separated by distances roughly corresponding to an average nerve fiber diameter, provide surfaces on which nerve fibers can regrow. Because the adjacent carbon nanofiber yarns can support individual nerve fibers, a nerve can be regenerated with a reduced likelihood of undesirable outcomes, such as nerve pain or reduced nerve function.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present disclosure relates generally to carbon nanofibers. Specifically, the present disclosure relates to carbon nanofibers. The present study relates to the fabrication of nanofiber yarn nerve scaffolds. [Background technology]

[0002] Nerve injury is a difficult disease to treat. In particular, when a nerve is severed, the nerve regrowth is Limited recovery of nerve function, leading to persistent nerve pain (sometimes called neuropathy) Unlike other types of tissue, you can simply sew the two ends of a severed nerve back together. However, this is often insufficient to promote complete nerve recovery and healing. Several experimental techniques have been developed to study the mechanism of action of the severed nerve endings. and the development of cells (Schwann tissue) that the body can use to regenerate nerve cells. ) is often included. Summary of the Invention

[0003] Example 1 is a method of manufacturing a nerve scaffold, the method including: Place the adhesive strip on the roller and rotate the roller to make the navy blue strip around the roller. a step of winding the nanofiber yarn, the wound nanofiber yarn being A bundle of aligned segments of the nanofiber yarn is formed on a roller, and the nanofiber yarn is first bonded. The adhesive strip is passed over the step and the strip is split into two parts. separating the bundle of aligned segments of nanofiber yarn; removing the bundle of aligned segments of nanofiber yarn from the roller; Folding the bundle of aligned segments, the bundle of aligned segments includes a first end and a second end opposite the first end; and a bundle of aligned nanofiber yarn segments configured to be placed in a tube. This includes achieving the above.

[0004] Example 2 includes the subject matter of Example 1, but places a second adhesive strip on the roller. The method further includes the step of: The gap between them is defined.

[0005] Example 3 includes the subject matter of example 2, wherein the step of separating the nanofiber yarn bundles further comprises: occurs in a gap defined by the first adhesive strip and the second adhesive strip. .

[0006] Example 4 includes the subject matter of any of the preceding examples, further comprising aligning the nanofiber yarns. The bundle of segments includes a midpoint, and the folding step includes folding the bundle of nanofiber yarns at the midpoint. This includes folding.

[0007] Example 5 includes the subject matter of Example 4, but the midpoint of the folded bundle is a pull-out structure (d The folded bundle is connected to a rawing structure, and the drawing structure is used to place the folded bundle into the tube. It is used for this purpose.

[0008] Example 6 includes the subject matter of Example 5, and is directed to an aligned folded nanofiber yarn. The method further includes cutting the first and second ends of the bundle of segments.

[0009] Example 7 includes the subject matter of Example 6, further comprising: Cutting the first end and the second end of the bundle results in an aligned nanofiber yarn. The bundle of segments is expanded to fill the cross section of the tube.

[0010] Example 8 includes the subject matter of any of the preceding examples, and further includes a folded nanofiber. The yarn bundle contains 1000 to 8000 aligned segments of nanofiber yarn.

[0011] Example 9 contains the subject matter of any of the preceding examples, with the folded stack positioned The weight ratio of the folded nanofiber yarn bundle to the tube being fabricated is about 0.65 to about 1.

[0012] Example 10 includes the subject matter of any of the preceding examples, wherein the nanofiber yarn has a diameter of 5. It has a diameter of 30 μm to 30 μm.

[0013] Example 11 includes the subject matter of any of the preceding examples, wherein the nanofiber yarn comprises: It has a diameter of 3 μm to 15 μm.

[0014] Example 12 includes the subject matter of any of the preceding examples, wherein the nanofiber yarn is It is composed of carbon nanotubes.

[0015] Example 13 includes the subject matter of any of the preceding examples, including a surgical suture material. forming a cylindrical helix, the cylindrical helix defining an interior; Then, carbon nanofibers are placed around the cylindrical helix, inside the cylindrical helix and on the surface of the opposite helix. and wrapping the sheet to form a tube.

[0016] Example 14 includes the subject matter of any of the preceding examples, further comprising: The mass is 1.5% to 2.5% by mass of the total mass of the nerve scaffold including the bundles and the tube in which the bundles are placed. %.

[0017] Example 15 includes the subject matter of any of the preceding examples, further comprising: The mass is 4.5% to 5.5% by mass of the total mass of the bundle and the tube in which the bundle is placed.

[0018] Example 16 includes the subject matter of any of the preceding examples, further comprising: The mass is 9.5% to 10.5% by mass of the total mass of the bundle and the tube in which the bundle is placed.

[0019] Example 17 includes the subject matter of any of the preceding examples, wherein the nanofiber yarn is a hypothetical It is a twisted nanofiber yarn.

[0020] Example 18 includes the subject matter of any of the preceding examples, wherein the nanofiber yarn is It is a single-ply false twisted nanofiber yarn.

[0021] Example 19 includes the subject matter of any of the preceding examples, further comprising: has surface topography features larger than 1 μm above or below the surface of the nanofiber yarn It is not something that can be achieved.

[0022] Example 20 includes the subject matter of any of the preceding examples, further comprising: has surface topography features less than 0.1 μm above or below the surface of the nanofiber yarn do.

[0023] Example 21 includes the subject matter of any of the preceding examples, further comprising: The bundle of segments is 1-5%, 1-10%, 1-20% of the volume of the pipe in which the bundle is placed. , 1-30%, 1-40%, or 1-50%.

[0024] Example 22 includes the subject matter of any of the preceding examples, and further includes a nanoparticle disposed within a tube. The average distance between adjacent aligned segments of the fiber yarn is 5 μm to 15 μm. do.

[0025] Example 23 includes the subject matter of any of the preceding examples, and further includes a nanoparticle disposed within a tube. The average distance between adjacent aligned segments of the fiber yarn is 5 μm to 12 μm. do.

[0026] Example 24 is a cylindrical helix including a surgical suture material and defining an interior. A cylindrical spiral, a bundle of aligned carbon nanofiber yarns inside the cylindrical spiral, and a cylindrical and a carbon nanofiber sheet around the cylindrical spiral opposite the interior of the cylindrical spiral. Carbon nanofiber nerve scaffold.

[0027] Example 25 includes the subject matter of Example 24, but with aligned segments of the lattice 5′ to 5′. They are spaced apart by 1 to 15 μm.

[0028] Example 26 includes the subject matter of Examples 24-25, and the carbon nanofiber sheet is , including a bioabsorbable polymer infiltrant.

[0029] Example 27 includes the subject matter of Examples 24-26, wherein the cylindrical spiral is wound in a first direction. a first spiral wound in a second direction opposite to the first spiral; Includes:

[0030] Example 28 includes the subject matter of Examples 24-27, except that the cylindrical spiral is a crocheted circle. It is a cylindrical spiral.

[0031] Example 29 includes the subject matter of Examples 24-27, except that the cylindrical spiral is a braided cylindrical It's a spiral. [Brief description of the drawings]

[0032] [Figure 1] FIG. 1 is a schematic diagram of severed nerve fibers connected with a tubular nerve scaffold. [Diagram 2] FIG. 1 is a schematic of a severed nerve fiber connected with a tubular nerve scaffold, where the nerve fiber is regrown between two severed nerve portions. [Diagram 3] 1 shows a carbon nanofiber nerve scaffold in an example of the present disclosure. [Figure 4A] FIG. 4 shows an enlarged view of a portion of the carbon nanofiber nerve scaffold shown in FIG. 3 in an example of the present disclosure. [Figure 4B] FIG. 4B shows an enlarged view of a portion of the carbon nanofiber nerve scaffold shown in FIG. 4A in an example of the present disclosure. [Figure 5A] FIG. 4 is an exploded view of the carbon nanofiber nerve scaffold shown in FIG. 3 in an example of the present disclosure. [Figure 5B] 1 is a scanning electron microscope (SEM) image of a single-ply false-twisted nanofiber used in a carbon nanofiber nerve scaffold in an example of the present disclosure. [Figure 6] FIG. 13 is an optical microscope image of a histological specimen of a carbon nanofiber nerve scaffold having 65% mass of nanofibers relative to the total mass of the nerve scaffold in an example of the present disclosure. [Figure 7]FIG. 13 is an optical microscope image of a histological specimen of a carbon nanofiber nerve scaffold having 65% mass of nanofibers relative to the total mass of the nerve scaffold in an example of the present disclosure. [Figure 8A] FIG. 24 Electromyogram of a healthy nerve used as a control sample for comparison with a nerve regenerated using the carbon nanofiber nerve scaffold of the present disclosure. [Figure 8B] 13 is an optical image of a histological cross section of a healthy nerve used as a control sample for comparison with nerves regenerated using the carbon nanofiber nerve scaffold of the present disclosure. [Figure 8C] FIG. 8C is an enlarged view of a portion of the histological section of FIG. 8B showing neurofilaments and neuronal nuclei. [Figure 9A] FIG. 2 shows an electromyogram of a severed nerve fiber regenerated using a carbon nanofiber nerve scaffold having 2% by weight of nanofiber yarns relative to the total weight of the nerve scaffold, in an example of the present disclosure. [Figure 9B] FIG. 9B is an optical image of a histological cross-section of a nerve fiber regenerated using a carbon nanofiber nerve scaffold having 2% by weight of nanofiber yarn relative to the total weight of the nerve scaffold, as electrically analyzed in FIG. 9A, in an example of the present disclosure. [Figure 9C] FIG. 9C is a magnified view of a portion of the histological cross section of FIG. 9B showing neurofilaments and neuronal nuclei in contact with the carbon nanofiber yarns of the scaffold in an example of the present disclosure. [Figure 10A] FIG. 13 shows an electromyogram of a severed nerve fiber regenerated using a carbon nanofiber nerve scaffold with 5% by weight of nanofiber yarns relative to the total weight of the nerve scaffold in an example of the present disclosure. [Figure 10B] FIG. 10B is an optical image of a histological cross-section of a nerve fiber regenerated using a carbon nanofiber nerve scaffold with 5% by weight nanofiber yarns, as electrically analyzed in FIG. 10A, in an example of the present disclosure. [Figure 11A] FIG. 13 shows an electromyogram of severed nerve fibers regenerated using a carbon nanofiber nerve scaffold with 10% nanofiber yarns by weight relative to the total weight of the nerve scaffold, in an example of the present disclosure. [Figure 11B]FIG. 11B is an optical image of a histological cross-section of a nerve fiber regenerated using a carbon nanofiber nerve scaffold with 10% nanofiber yarn by weight, as electrically analyzed in FIG. 11A, in an example of the present disclosure. [Figure 11C] FIG. 11C is a magnified view of a portion of the histological cross-section of FIG. 11B showing neurofilaments and neuronal nuclei in contact with carbon nanofiber yarn in an example of the present disclosure. [Figure 12] FIG. 1 illustrates a method flow diagram of an exemplary method for manufacturing a nerve scaffold, according to an embodiment. [Figure 13] 1 is a schematic diagram of an exemplary method for forming a bundle of aligned nanofiber yarn segments on a roller and placing the bundle in a tube, in one embodiment. [Figure 14] 1 is a schematic diagram of an exemplary method for forming a bundle of aligned nanofiber yarn segments on a roller and placing the bundle in a tube, in one embodiment. [Figure 15] 1 is a schematic diagram of an exemplary method for forming a bundle of aligned nanofiber yarn segments on a roller and placing the bundle in a tube, in one embodiment. [Figure 16] 1 is a schematic diagram of an exemplary method for forming a bundle of aligned nanofiber yarn segments on a roller and placing the bundle in a tube, in one embodiment. [Figure 17] 1 is a schematic diagram of an exemplary method for forming a bundle of aligned nanofiber yarn segments on a roller and placing the bundle in a tube, in one embodiment. [Figure 18] 1 is a schematic diagram of an exemplary method for forming a bundle of aligned nanofiber yarn segments on a roller and placing the bundle in a tube, in one embodiment. [Figure 19] 1 is a schematic diagram of an exemplary method for forming a bundle of aligned nanofiber yarn segments on a roller and placing the bundle in a tube, in one embodiment. [Figure 20] 1 is a schematic diagram of an exemplary method for forming a bundle of aligned nanofiber yarn segments on a roller and placing the bundle in a tube, in one embodiment. [Figure 21] 1 is a schematic diagram of an exemplary method for forming a bundle of aligned nanofiber yarn segments on a roller and placing the bundle in a tube, in one embodiment. [Figure 22] 1 is a schematic diagram of an exemplary method for forming a bundle of aligned nanofiber yarn segments on a roller and placing the bundle in a tube, in one embodiment. [Figure 23] 1 is a schematic diagram of an exemplary method for forming a bundle of aligned nanofiber yarn segments on a roller and placing the bundle in a tube, in one embodiment. [Figure 24] 1 is a schematic diagram of an exemplary method for forming a bundle of aligned nanofiber yarn segments on a roller and placing the bundle in a tube, in one embodiment. [Diagram 25] 1 is a schematic diagram of an exemplary method for forming a bundle of aligned nanofiber yarn segments on a roller and placing the bundle in a tube, in one embodiment. [Figure 26] FIG. 1 illustrates a side view of a carbon nanofiber nerve scaffold in one embodiment. [Figure 27] 27A-27C are cross-sectional views illustrating exemplary stages in the step-by-step fabrication of the carbon nanofiber nerve scaffold shown in FIG. 26 according to one embodiment. [Figure 28] 1 is a micrograph of an exemplary forest of nanofibers on a substrate according to one embodiment. [Figure 29] FIG. 2 is a schematic diagram of an exemplary reactor for nanofiber growth, according to one embodiment. [Diagram 30] FIG. 2 is a schematic diagram of a nanofiber sheet, identifying the relative dimensions of the sheet and generally illustrating the nanofibers within the sheet aligned end-to-end in a plane parallel to the surface of the sheet, according to one embodiment. [Diagram 31] FIG. 29 is a SEM micrograph that is an image of a nanofiber sheet being pulled laterally from a nanofiber forest in which the nanofibers are aligned end-to-end, as shown generally in FIG. 28, in one embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0033] The drawings depict various embodiments of the present disclosure for illustrative purposes only. and other embodiments will become apparent from the following detailed description. The drawings, which are not necessarily drawn to scale, illustrate the described embodiments. It is not intended to be limited to any particular configuration. For example, some of the figures may be generally linear, rectangular, or Although the drawings show straight lines and smooth surfaces, actual implementations of the disclosed technology may include less than perfect straight lines and right angles. Some features may be based on surface topography, taking into account real-world limitations of the manufacturing process. In short, the drawings are merely illustrative of example structures. Provided for illustration purposes.

[0034] [overview] Neurotmesis is a nerve injury in which the nerve and nerve sheath are severed. This can result in the muscles that the nerve controls being cut. This causes loss of sensation and paralysis in the affected area. Nerves generally do not recover without medical intervention. Symptoms of rupture can be treated with opioids and anti-inflammatory drugs, and restoration of the nerve and associated function can be achieved with surgery. Surgical methods to promote nerve recovery include suturing nerve endings, transferring nerve grafts, and These include implantation of a neural scaffold or implantation of a neural scaffold.

[0035] Suturing both ends of a nerve can have drawbacks. For example, suturing both ends of a nerve can This creates tension within the sutured nerve. This tension inhibits regrowth and increases the likelihood of scarring. Similarly, the use of nerve grafts may be associated with poor neurologic function. For example, removing a portion of a nerve from a living donor and donating it to a recipient The donor then experiences a loss of sensation in the part of the body previously served by the removed nerve.

[0036] The use of hollow nerve scaffolds to promote regrowth of severed nerves is an ongoing research topic. The scaffold is a biocompatible tube that is sutured to the end of the nerve. It has multiple small channels that act as guides for the regrowth of the fibers. In, the scaffold is simply a hollow tube defining a single interior chamber. Regardless of the internal configuration, The goal of the scaffold is to create an environment that promotes the regrowth of nerve fibers and helps restore muscle function. It is.

[0037] The latter scenario of a hollow tube nerve scaffold is shown diagrammatically in Figure 1. In this example, the nerve Segments 100A and 100B are cut from each other. The hollow tube nerve scaffold 104 is The nerve segments 100A and 100B are arranged to overlap each other at their respective ends. , promoting the regrowth of nerve fibers.

[0038] One drawback of some types of nerve scaffolds, such as the exemplary nerve scaffold 104, is the lack of re-grown tissue. Nerve fibers are subjected to tension as they regrow. This causes the nerve fibers to shrink in places. This can lead to decreased nerve function, nerve pain, or other undesirable outcomes. For example, as shown in FIG. 2, nerve segments 200A and 200B are and reconnected via a hollow tube nerve scaffold 204. The nerve scaffold 204 is attached to the suture 20 6A, 206B, 206C, and 206D, respectively, of nerve segments 200A and 200B. As shown in the figure, the regenerated nerve fibers 208 are attached to the nerve segment. It has an hourglass shape with a constriction between the opposing faces of 200A and 200B. This constriction within the nerve fiber 208 can cause some or all of the undesirable consequences described above. There is a possibility that.

[0039] Thus, according to some examples described herein, the present disclosure provides a method for preparing a cellular membrane comprising: A nerve scaffold having a tubular outer housing formed therein, We describe a neural scaffold in which multiple carbon nanofiber yarns are arranged on the surface of the scaffold. The number of carbon nanofiber yarns is such that adjacent yarns correspond roughly to the diameter of an average nerve fiber. They are separated by a distance, providing a surface onto which nerve fibers can regrow. Carbon nanofiber yarns can support individual nerve fibers (partially In fact, this adequate spacing between the nanofiber yarns allows the nanofibers to be attracted to the nerve fibers during regrowth. In some examples of the present disclosure, the regenerated nerve fibers are less likely to be subjected to tensile stress. The magnitude of tensile stress was regenerated using nerve scaffolds without carbon nanofiber yarn For at least these reasons, embodiments of the present disclosure When used as a nerve scaffold, there is a possibility of undesirable outcomes such as neuralgia or decreased nerve function. The effectiveness is reduced.

[0040] [Examples of neural scaffolds] As noted above, in some examples of the present disclosure, the neural scaffold may comprise carbon nanofibers and / or The present disclosure is directed to a method for manufacturing a carbon nanotube-based fiber optic cable comprising: Although carbon nanotubes share many of the same advantageous characteristics, they are also known as "carbon It will be recognized that the term "nano-fibers" includes the general term "carbon nano-fibers." In particular, carbon nanofiber yarns are conductive and biocompatible, and therefore are suitable for use in the fabrication of the fibers described herein. Exemplary neural scaffold components may be usefully used, for example, carbon nanofibers. When the tube is used as a scaffolding component (e.g., in the tubular component described above), adjacent Multiple pathways are defined between the carbon nanofiber yarns. Nerve fibers are located within these pathways. Carbon nanofiber yarns can be grown (or equivalently called "regenerated") by Also, the conduction from one segment of a severed nerve to another segment of this severed nerve. The presence of conductive pathways can also enhance nerve growth. It is possible to improve neural function beyond what is generally expected from regenerated nerves. In some instances, the use of carbon nanofiber yarns in nerve scaffolds can It is believed that the neurofunction of a transectioned nerve can be made to approach that of the same nerve before the transection injury. In some cases, carbon nanofibers, especially single-ply false-twisted carbon Nanofiber yarns can provide topographically smooth and nanoporous support surfaces, The surface on which nerve fibers can grow can promote regrowth of nerve fibers with low tensile stress.

[0041] An example of a nerve scaffold of the present disclosure is shown generally in FIG. 4 and a plurality of nanofiber yarns 308. Advantages of this nerve scaffold 300 include the A plurality of gaps defined by a plurality of nanofiber yarns or These gaps may be structured and configured to promote nerve growth. The dimensions allow for electrical connection between the severed nerve segments. do.

[0042] Tube 304 may perform any of a number of functions. 04 separates the area where nerve fibers can regrow from the surrounding environment. protects re-growing neurons from physical damage and other disturbances that may reduce the growth rate and continuity of the re-growing neurons. The tube 304 may also serve to protect the growing nerve fibers. Thus, the carbon nanofiber yarns are arranged in a density and arrangement that promotes the regrowth of nerve fibers. , defining a space in which carbon nanofiber yarns can be positioned and configured.

[0043] The tube 304 may be made from a biocompatible and / or bioabsorbable material. An example of such a material is silicon, which has the properties of being compliant rather than rigid. This compliance has the added benefit of being The tube 304 is attached to an adjacent nerve segment by a catheter. Other examples of biocompatible materials that can be used include poly(methyl methacrylate), poly(tetrafluoroethylene), and poly(tetrafluoroethylene). Poly(fluoroethylene), polyethylene, polyglycolide, polycaprolactam, poly(lactic acid) co-glycolic acid), polylactic acid, poly(glycerol sebacate), polysialic acid, poly Ethylene glycol, polyurethane, collagen, chitosan, silk, alginate, etc. In another set of embodiments, the tubes are made of, but not limited to, carbon nanotubes. In some embodiments, the tube 304 may be made of carbon such as a tube. In certain embodiments, the catheter may be made of carbon nanotubes. Both tubes and carbon nanotube yarns can be used together to promote nerve regeneration. .

[0044] As described above, the plurality of nanofiber yarns 308 may include real twist multi-ply and single-ply. Group-ply nanofiber yarn, no-twist multi-ply and single-ply nanofiber These include nanofiber yarns, as well as false-twisted multi-ply and single-ply nanofiber yarns. The nanofiber yarns 308 are placed within the tube 304 to form multiple nanofibers through which regenerated nerve fibers can grow. The nanofiber yarn can define the structure of the interfiber spaces where nerve fibers are formed. This provides a smooth, nanoporous surface that can support the growth of nerve fibers and provide mechanical support for re-growing nerve fibers. This mechanical support allows the re-growing nerve fibers, and the regenerating nerve as a whole, to Tensile stresses that can cause painful pain or negatively affect nerve fiber growth or are less likely to experience compressive stress.

[0045] A plurality of nanofiber yarns 308 (the manufacture of which is described below in connection with FIGS. 12-15) The nanofiber yarn can be disposed within a tube 304, as shown in FIG. Although shown as being parallel to one another and uniformly distributed within tube 304, this is not a simple It will be appreciated that this is for convenience of illustration. Rather, the nanofiber yarns are substantially spaced apart from one another. are aligned precisely in space, but not necessarily exactly parallel to one another, within the volume defined by tube 304. The nanofibers are assembled into a plurality of nanofiber threads 308 that occupy a portion of the volume. In the embodiment, the schematic arrangement of such nanofiber yarns in a plurality of nanofiber yarns 308 is shown. The arrays have pathways (gaps and / or interspersions) between the nanofiber yarns that correspond approximately to the cross-sectional diameter of the nerve fibers. This is sufficient to define a space (also called a gap) that is typically 5 μm to 10 μm in diameter. m, and in some cases between 8 μm and 10 μm. The nanofiber yarns cross or are misaligned with each other. Even in such a case, the tube 304 is at least partially continuous along its length (i.e., 10% or 20% greater along the length of the This space is sufficient to minimize these tensions and promote nerve regeneration. .

[0046] 4A and 4B are schematic diagrams illustrating an example of a carbon nanofiber yarn nerve scaffold 300 according to the present disclosure. 4A and 4B show this beneficial configuration of nanofiber yarns within a tube for This makes it easier to explain. As shown in these figures, multiple nanofiber yarns 3 The cross-sectional diameter of the nanofiber yarn at 08 is in the same direction as the cross-section of the tube 304 (+ / - 10° Similarly, the length of the tube 304 and the nanofibers in the plurality of nanofiber yarns 308 are The lengths of the nanofiber yarns are aligned in approximately the same direction (microstructure of multiple nanofiber yarns). (Allows for orientation changes on the meter and / or nanometer scale).

[0047] One result of such orientation of the nanofiber yarns is that, as described above, the nanofiber yarns The adjacent nanofibers define the space between which the nerve fibers grow during regeneration. An example of the space defined by the above is shown in the enlarged view of FIG. 4B. As shown in the figure, multiple adjacent The adjacent nanofiber yarns are separated from each other by distances represented as α1, α2, and α3. The width of the space between at least some of the nanofiber yarns, α1, to promote nerve growth , α2, and α3 are 5 μm to 10 μm, 5 μm to 12 μm, 5 μm to 8 μm, and 5 μm to Nerve fibers generally have a diameter of is about 8 μm (+ / - 10%), nanofibers with widths α1, α2, and α3 The spaces between the threads are sized and configured to support the regrowth of nerve fibers. Widths greater than α1, α2, and α3 may, in some cases, reduce tensile stress on nerve fibers. Thus, it is possible to provide adequate support for re-growing nerve fibers. , the space between nanofiber yarns is less than 20 μm, less than 15 μm, less than 12 μm, less than 10 μm It may be less than 8 μm, or less than 8 μm. The width may in some cases prevent nerve fibers from growing through multiple nanofiber yarns. or between a nerve fiber and adjacent nanofiber yarns in contact with the nerve fiber. Nerve fibers can grow in a physically restricted environment where compressive forces are present. This is a restriction on nerve function. In some cases, the spacing between the nanofiber yarns may lead to limited mobility and / or neuropathic pain. The diameter is greater than 1 μm, greater than 2 μm, greater than 3 μm, greater than 5 μm, or or larger than 7 μm.

[0048] In some examples, individual nanofiber yarns of the plurality of nanofiber yarns 308 may be false twisted, single twisted, or twisted. The nanofiber yarn is made of group-ply. The technology that can false-twist nanofiber yarn is US Patent No. 5,333,636, which is incorporated herein by reference in its entirety. No. 15 / 844,756. Without wishing to be bound by theory, , and in some cases, the relatively high tensile strength of single-ply nanofiber yarns, especially false-twisted nanofiber yarns. It is believed that smooth, nanoporous surfaces provide a surface that promotes nerve fiber regrowth. The smooth surface generally includes the nanofiber yarn surface on or below the surface. There is a surface topography that does not have any features larger than 100 nm.

[0049] FIG. 5A shows an exploded view of a nerve scaffold 300 comprising a tube 304 and a plurality of nanofiber yarns 308. As shown, the tube 304 has a length L1 and an inner diameter D1. It is sized in part according to the size of the gap between the opposing sides of the severed nerve. In the example of part, the length L1 is 1mm~2cm, 1mm~1cm, 1mm~0.5mm, 1cm The thickness may be in the range of mm to 2 cm, 1.5 cm to 2 cm, or 5 mm to 1.5 cm. The inner diameter D1 is positioned so that the tube 304 spans the severed end of the nerve, as shown in FIG. The nerve is then sewn into place and sized so that it can be attached to the end of the nerve by suturing or other means. Inner diameter D1 is 1mm~40mm, 1mm~5mm, 3mm~10mm, 1mm~15mm , 10 mm to 30 mm, or 15 mm to 40 mm.

[0050] As shown, the plurality of nanofiber yarns 308 have a length L2 and an outer diameter D2. L2 is the size of the gap between the opposing surfaces of the cut nerve and the length L of the tube 304. 1. In some cases, enough material of the tube 304 is sewn into the tube 304. Length L2 is less than or equal to length L1 so that it can overlap the ends of the nerve segments to be joined. In some cases, the length L2 is preferably longer than the length of the nerve segment that contacts the opposing sides of the nerve segment. (in other words, bridging the severed nerve) or In some cases, the length L2 is within 1 mm to 2 cm. , 1mm~1cm, 1mm~0.5mm, 1cm~2cm, 1.5cm~2cm, 5mm It may be anywhere in the range of 1.5cm.

[0051] The outer diameter D2 of the plurality of nanofiber yarns 308 is determined by the number of nanofiber yarns 308 that are arranged within the tube 304. In some examples, the outer diameter D2 is sized and configured to be placed in the inner diameter of the tube 304. The outer diameter D2 of the plurality of nanofiber yarns 308 is 2% to 10% smaller than the inner diameter D1 of the tube 304. When the dimension is slightly smaller than D1, the plurality of nanofiber yarns 308 are attached to the tube 304. small enough to be inserted into the space defined by the inner surface of the adjacent tube 304 Large enough to form an interference fit. This interference fit allows A number of nanofiber yarns 308 are secured within the tube 304 and do not unintentionally slip out. In some cases, nanofiber yarn bundles can be compressed to smaller diameters for easier assembly. It may simply be threaded through the tube. Once in the tube, the bundle may be expandable to the full inner diameter of the tube. Moreover, the plurality of nanofiber yarns 308 so dimensioned correspond to an inner diameter D1 and a length The nanofiber yarns 308 may be distributed throughout the cross section of the tube 304 perpendicular to L1. By distributing the ion beam over both the length and cross-sectional diameter of the tube 304, the nerve fibers can be formed. This provides plenty of interstitial space that can be expanded.

[0052] In some embodiments, the interstitial spaces between adjacent nanofiber yarns may accommodate nerve fiber growth. It may include one or more polymer matrices for support. The polymer matrix may be one or more of collagen, gelatin, or fibrin. In some other examples, the polymer matrix may be a There may be one or more.

[0053] In some embodiments, the interstitial spaces between adjacent nanofiber yarns may also include one or more In some instances, the protein or growth factor may include , vascular endothelial growth factor (VEGF), nerve growth factor (NGF), hepatocyte growth factor (HGF) or a fibrin matrix gel. In the example, the interstitial space contains nerve growth factor.

[0054] In yet another embodiment, the interstitial spaces between adjacent nanofiber yarns are one or more The polymer matrix may include one or more polymer matrices in combination with a number of proteins. In certain instances, the interstitial spaces include collagen in combination with nerve growth factor.

[0055] In some examples, the adjacent nanofiber yarns of the plurality of nanofiber yarns 308 shown above The appropriate spacing between the tubes should be determined based on the total mass of the nerve scaffold (i.e., the tubes plus the multiple carbon nanofibers). It is indirectly measured as a percentage of the carbon nanofiber yarn mass relative to the yarn mass. The ratio of carbon nanofibers to the total mass of the carbon nanofiber nerve scaffold can be The percentage of the yarn mass is sometimes referred to herein as "filling" for the sake of brevity. In some examples, the density of the fibers within the carbon nanofiber yarn nerve scaffolds of the present disclosure may be described as "density." The growth of nerve fibers was observed at packing densities of less than 2%, 2% to 5%, or 2% to 10%. was found to be sufficient (as described below in the context of Figures 6, 7, 9A-11C , in terms of nerve signal transmission time and regrown nerve fiber morphology). It can also be measured on an area basis, e.g., the cumulative cross-sectional area of ​​the yarns in the bundle 308 relative to the cross-sectional area (inner diameter) of the tube. The product ratio is greater than 1%, greater than 5%, greater than 10%, greater than 20%, and 3 Greater than 0%, Greater than 40%, Greater than 50%, Less than 75%, Less than 65%, 50 Less than 40%, less than 30%, less than 20%, less than 10%, less than 5%, or less than 3% It may be full.

[0056] Although the packing density is a macroscopic measurement, the packing density is the individual nanofibers of the plurality of nanofibers 308. It has been shown experimentally that the average diameter of the spaces between the fibers can be predicted. and a plurality of nanofiber yarns 308 configured to promote nerve fiber growth. For example, the false twist of a single ply in the range of 2% to 10% can be easily measured. The packing density of the nanofiber yarns is between 8 μm and 10 μm in diameter, as described in more detail below. As mentioned above, the cross-sectional area of ​​many nerve fibers is Therefore, the diameter of the nanofiber yarn in this invention has a packing density of 2% to 10%. The carbon nanofiber nerve scaffolds presented here lowered tensile stress on nerve fibers compared to empty tube scaffolds. The devices are configured to reduce the amount of blood flow to the tissue and promote the regrowth of many different types of nerve fibers. In addition, the carbon nanofiber yarn nerve scaffolds of the present disclosure have a cross-sectional diameter smaller than that of nerve fibers. This reduces the compressive stress on the nerve fibers from the gaps in the graft.

[0057] In other examples, the packing density is within the range of 1% to 40%, 2% to 35%, or 2% to 65%. However, too high a packing density (e.g., greater than 65%) may result in the The spaces between the nanofiber yarns are too small for nerve fibers to grow (e.g., less than 5 μm). It will be appreciated that the packing density will be low (in some cases, less than 2 μm). , which has been found to be less than 5%), the spacing between adjacent nanofiber yarns is Upon regrowth, the nanofibers become too large to provide a structure to physically support the nanofiber yarn. This can result in tensile stresses on the fibres, as discussed above.

[0058] In some cases, depending on the outer diameter of the individual nanofiber yarns themselves, the To achieve this, 1000-8000 single-ply false-twisted nanofiber yarns are The tubes 304 may be configured to have the above packing density for a cross-sectional diameter of It is known that it is possible.

[0059] In addition, the more uniformly the carbon nanofiber yarns are aligned, the more the nerve growth is promoted. This has been experimentally observed. The experimental results are shown below.

[0060] FIG. 5B shows a scanning electron microscope (SE) image of a single-ply false-twisted nanofiber yarn of the present disclosure. M) Image of the false twisting technique. As noted above, the false twisting technique is incorporated herein by reference in its entirety. No. 15 / 844,756, which is incorporated herein by reference. In some examples, the carbon nanofiber nerve fibers of the present disclosure, such as those shown in FIG. The single-ply false-twisted nanofiber yarns used in the scaffolds range from 5 μm to 40 μm, 5 μm ~30μm, 5μm~20μm, 10μm~30μm, 50μm~40μm, 25μm~ 35μm, less than 40μm, less than 30μm, less than 20μm, more than 5μm, more than 10μm The cross-sectional diameter is in the range of either 20 μm or more (in the case of FIG. 5A, both directions The nanowires shown in FIG. 5B can have a length of 100 mm. In a particular example of a fiber yarn, the cross-sectional diameter is about 15 μm. One advantage of the illustrated embodiment is that the nanofiber yarns provide a smooth surface onto which nerve fibers can grow. The nanofiber yarn shown in FIG. 5B has a surface area above or below the average position of the yarn surface. have surface topography features smaller than 1 μm (and in some cases smaller than 0.1 μm) (The average position is measured from the circumference of the yarn over the length of the yarn and is statistically significant.) (calculated from sampling).

[0061] [Experimental Results] 6 to 11C show various experimental examples of the present disclosure. 1 shows various embodiments that can serve as references for the embodiments shown in C. For example, FIG. 6 shows a histological cross-section of a severed nerve fiber. In this example, 65% carbon nanotube Using the disclosed nerve scaffold with a packing density of nanofiber yarn (single ply, false twist), Regeneration was attempted. Multiple threads (or multiple aligned segments of a single thread) were The diameter of the yarn was 14.5 μm. Approximately 8000 yarn segments were bundled together. In the cross section, when photographed at 10x magnification, the intervening (darker) ducts were visible from the distal and proximal ends. ) It can be seen that the regrowth of nerve fibers into the carbon nanofiber yarn is limited. 7, which is a 400x magnification of the boxed area in FIG. 6. The regeneration of nerve fibers into multiple nanofiber yarns with different densities was observed from the severed proximal nerve surface to the distal In addition, the regenerating nerve fibers did not form continuous fibers from the proximal end to the distal end. It is therefore not possible to re-establish a neurological connection between the proximal and distal ends of a severed nerve. 6 and 7 show that the proper packing density of the carbon nanofiber yarns, i.e., It is dense enough to support nerve fibers in a single layer, but also dense enough to reconnect the ends of severed nerves. The importance of selecting a neural scaffold of the present disclosure that has a density that is not so high as to inhibit growth Shows.

[0062] 8A-8C illustrate another point of reference for embodiments described herein, Neither amputated nor regenerated using any type of nerve scaffold Figure 8A shows the electromyogram of this healthy nerve. In general, the distal latency and amplitude are Two measurements are obtained using electromyography: The graph in Figure 8A characterizes the propagation speed of the electrical signal through the The nerve corresponds to a healthy nerve, the cross-sections of which are shown in Figures 8B and 8C. After sectioning, the nerve was sutured to the nerve scaffold. A summary of the electromyogram results from the sciatic nerves of three separate healthy rats combined is shown in Table 1 below. To summarize.

[0063] The image in FIG. 8B was taken at 40× optical magnification, and the image in FIG. 8C was taken at >40× optical magnification. Figure 8C was taken simply to show the continuity of the nerve fiber filaments with the cell nuclei. is provided.

[0064] 9A, 9B, and 9C show regeneration using the disclosed nerve scaffold with a packing density of 2%. Figure 9A is an example of an electromyogram for one example of this embodiment. FIG. 9B is a histological section taken at 40× optical magnification. FIG. 9C is a histological section taken at >40× optical magnification. 9C is a magnified image of a portion of the cross-section of FIG. 9B taken with optical magnification.

[0065] The electromyogram corresponding to FIG. 9A has the distal latencies and amplitudes summarized in Table 1 below. In contrast to Figures 6 and 7, Figures 9B and 9C show a reconnection of both ends of a severed nerve. The rightmost part of the nerve shows the formed nerve fibers (including the neurofilaments and the nuclei of the nerve cells). The nerve gap between the cerebellum and the central part of the nerve is an artifact of the sectioning process and re Moreover, as can be seen in the enlarged view of Figure 9C, As mentioned above, neurofilaments and neuronal nuclei are closely associated with carbon nanotube yarns. The presence of both neurofilaments and nuclei in close proximity to carbon nanofibers suggests that This suggests a functioning regenerated nerve, which lacks a functioning nerve nucleus and nerve fibers. This is in contrast to regenerated tissue, which is primarily scar tissue. The results of this sample are also shown by the electromyogram results described below. The nerve regeneration and restoration of nerve function provided by the nerve scaffolds of the present disclosure, including electromyogram results The advantages of

[0066] 10A and 10B show regenerated nerve tissue using the disclosed nerve scaffold with 5% packing density. 10A is an exemplary electromyogram of the illustrated embodiment. B is a histological cross-section taken at 40x optical magnification. Similarly, the EMG data and images themselves may be used to re-establish nerve function between previously severed nerve endings. The neurofilaments and neuronal nuclei are in close contact with the carbon nanofiber yarn so that shows regrowth of

[0067] 11A, 11B, and 11C show the results of a neural scaffold of the present disclosure at a packing density of 10%. FIG. 11A is an example of an electromyogram of one example of this embodiment, corresponding to a regenerated severed nerve. FIG. 11B is a histological section taken at 40x optical magnification. 11C is an image of a portion of the cross section of FIG. 11B taken at an optical magnification of 1x.

[0068] As with the previous example, FIGS. 11A-11C show a carbon nanotube yarn that is in intimate contact with the The figure shows the nerve fibers that were cut and the continuous nerve pathway between the previously severed nerve endings.

[0069] The electromyogram data for the aforementioned experimental example is summarized in Table 1 below. As shown in the table, The disclosed 2%, 5%, and 10% packing density embodiments each serve as a benchmark for health. In fact, the 2% packing density produced distal latencies and amplitudes within 2.5 times of the normal nerve. One of the three samples tested for this embodiment showed distal latency comparable to that of a healthy nerve. and produced an amplitude. [Table 1]

[0070] [method] FIG. 12 illustrates an exemplary method by which an embodiment of the present disclosure may be manufactured. 25 shows diagrams of various stages of manufacture of the exemplary method shown in FIG. 25 will make the explanation easier.

[0071] The method 1200, as described above, includes, upon insertion into the vessel, expanding within the vessel and promoting nerve regrowth. FIG. 1 is an exemplary method for assembling a bundle of nanofibers having interfiber spacing that is consistent with the method of the present invention. do.

[0072] The method 1200 includes providing at least two adhesive strips, as shown in FIG. Placing 1304A and 1304B (collectively 1304) on roller 1308 The adhesive strip 1304 and roller 1308, as described above, Tubes of any desired diameter while providing spacing between fibers to facilitate nerve regeneration The amount and configuration of the nanofibers are expanded to satisfy the above requirements, thereby improving the convenience of bundling multiple nanofibers. This binding is achieved by rotating a roller 1308 of diameter D in the direction indicated by the arrow in FIG. While wrapping the nanofiber yarn or yarns 1316 around the roller 1308, This is achieved by:

[0073] Two adhesive strips 1304 secure the two regions of the bundle together, as described below. , thereby improving the ability to manipulate the bundle during processing. The strips may be spaced apart from one another to define a gap 1312 therebetween. The dimensions of the strips are: The size of the roller and the amount of nanofiber yarn collected (the number of turns of the yarn around the roller and the In some embodiments, the strip diameter may vary based on a number of factors, including the The length of the loop is about 1mm to about 1000mm (or depending on the diameter of the thread and the number of rotations of the roller). The thickness of the strip may range from about 5 mm to 100 mm. In one example, a 14.5 mm diameter thread may be applied to the roller 1308 at a distance of 55 mm to 65 mm. The adhesive strip was wrapped 4000 times over the length of the strip, resulting in 8 nanofiber yarns. A nerve scaffold was fabricated with 0.000 aligned segments at a packing density of 65%. So, a 14.5 mm diameter thread is applied to roller 1308 with a 1.0 mm to 1.2 mm adhesive strip. The nanofiber yarn was wrapped 80 times over the length of the loop, resulting in 190 aligned nanofiber yarns. Nerve scaffolds were fabricated with the segments at a charging density of 2%.

[0074] The two adhesive strips 1304 can be of any type of adhesive. For example, the adhesive 1304 may be formed using an adhesive tape or an adhesive coated backing. The present invention may include the use of adhesives on any of a variety of combinations of materials. In some embodiments, the adhesive strip may be a sticky tape. Sticky tapes can be made of paper, plastic, or other materials. The adhesive comprises an adhesive coated onto a backing material such as a backing film, cloth, or metal foil. Adhesives are applied to a surface by applying pressure, without the application of heat or activating solvents. In another example, the adhesive 1304 may be applied to the roller 1308 or to an intermediate substrate (e.g., a polymer The non-carrier adhesive layer may include a "non-carrier adhesive" layer disposed on the non-carrier adhesive layer. The adhesive layer is not disposed on a polymer backing and can be applied to any surface (e.g., roller 1308 The adhesive is a self-supporting strip of adhesive that can be applied directly to a flexible substrate (such as a flex substrate) placed on the adhesive.

[0075] A gap 1312 is defined by (and between) two strips 1304. The gap 1312 is the space that is filled by the nanofiber due to its adhesion to the strip 1304. While the fiber end is fixed, the nanofiber wrapped around the roller is removed from the roller. In this way the bundles can be conveniently handled together. This allows the cut nanofiber yarns to be further processed into nanofiber yarn bundles, This allows the scaffold to be used for nerve repair / regrowth. The gap 1312 is used to connect the thread. It must be large enough to accommodate the blade / cutting technology while not separating from the adhesive. In an embodiment, the gap 1312 may range from 1 mm to 50 mm. A gap as defined by two strips is not required, and a single strip of adhesive is used. It will be appreciated that a strip of adhesive may be used instead. The adhesive strip is attached to the two parts of the cup (adhered on the strip) The nanofibers are then cut into two pieces (along with the nanofibers) and can be removed from the roller.

[0076] The roller 1308 is a circular or axially extending roller on which the aligned nanofiber yarn bundles can be wound. The cross section of the roller may be that of an elliptical cylinder. The size of the roller is defined by its diameter D. The diameter D is a factor used to determine the length of the collected nanofiber yarn bundle. In the example of a roller with a large diameter, a long nanofiber yarn bundle is generated (after cutting) and the diameter D is small. Other examples of die rollers produce (after cutting) short bundles of nanofiber yarns. In an embodiment, the diameter D may be in the range of about 10 cm to 3 m.

[0077] The volume of nanofibers in the bundle is determined by the number of revolutions of the nanofiber yarn around the roller 1308. Each revolution of the yarn corresponds to a linear distance of the yarn that is a function of the circumference of the roller. A roller with a higher nanofiber yarn rotation speed produces a nanofiber-rich bundle, and A roller of the same size with fewer revolutions of the yarn will produce a bundle with fewer nanofibers. In some embodiments, the number of turns of the nanofiber yarn around the roller is between 10 and 100,000. In one embodiment, the number of turns of the nanofiber yarn is 2000-4000.

[0078] Once the two adhesive strips are placed on the roller 1308 (1204), (e.g. The nanofiber yarn is rolled by rotating the roller (as shown by the arrow in Figure 13). The nanofiber 1316 can be wrapped around the ferromagnetic layer (1208). The adhesive may be wound around a portion of the roller so as to contact the adhesive strip. The adhesive strip facilitates removal of the nanofiber bundle from roller 1308 .

[0079] In some embodiments, the nanofiber yarn is wound around a roller while applying tension to the yarn. Maintaining tension on the yarn during winding improves the alignment of the nanofiber yarn on the roller. In some cases, rotating the rollers at a slower speed improves the alignment of the nanofibers. The volume of nanofibers in the bundle can also be adjusted to improve the alignment of the fibers. The tension of the yarn wound around the roller under tension may be a function of the tension of the yarn in the roller. The bundle volume is smaller than that of yarn wound around a roller with little or no tension. Low or no tension can result in poor alignment and more space. In some cases, maintaining tension on the yarn as it is wound onto the rollers can be problematic. The nanofiber yarn can be tensioned using a bobbin that holds the nanofiber. In some examples, the guide can be configured to provide tension to the nanofiber yarn. Alternatively, tension can be applied using a pulley system. The tension applied is , which is large enough to induce alignment between nanofiber yarns and is less than the ultimate tensile strength of the yarns. That's fine.

[0080] Referring to FIG. 14, as the nanofiber yarn is wrapped around a roller (1208), A bundle 1404 of aligned nanofiber yarn segments is formed on roller 1308. The nanofiber yarn bundle 1404 is attached at two ends to two adhesive strips. 1304. As described above, the bundle of aligned nanofiber yarns is The length is proportional to the circumference of the roller 1308, and the bundle volume and number of yarn segments in the bundle are The length of the desired bundle 1404 is proportional to the number of times the yarn is wrapped around the roller. The size of the nerve scaffold to be used, the size of the nerve injury to be repaired, and the length of the severed nerve to be regenerated are all determined. The volume of the bundle 1404 may be affected by factors such as the length of the gap between the ends. , the diameter of the tube (described below), the volume percentage of the tube that is filled with nanofibers, and the volume of each bundle within the tube. This may be affected by factors such as the number of folds that the protein undergoes before being placed in the do.

[0081] A nanofiber yarn bundle 1404 is formed (1212) around the roller 1308, and the yarn The bundle is split (1216) or cut at the gap 1312. The ends of the bundle are further apart (121 6) A linear configuration of the bundle can be formed. A single adhesive strip instead of two In instances where a wide adhesive strip is used, the wide adhesive strip may be secured to the strip. The bundle of nanofiber yarns is then cut together and the ends are separated.

[0082] Various techniques can be used to cut the nanofiber yarn bundles 1404, including precision blades, lasers, etc. The nanofiber yarn bundle 1404 can be formed by bonding the nanofiber yarn to two adhesives. It is cut while still attached to strip 1304. (Instead of two adhesive strips In embodiments where a single wide adhesive strip is used, a single cutting technique or two Different cutting techniques are applied to cut the adhesive strips and the nanofiber yarn bundles 1404. It can be said that.

[0083] As shown in FIG. 16, when separated at 1216, the nanofiber yarn bundles 1404 are Removed from La 1308 (1220).

[0084] After removing 1220 the nanofiber yarn bundle 1404 from the roller 1308, the bundle 14 04 can be folded into half its original length (or some other subunit) The fold (1224) of the nanofiber yarn bundle 1404 is formed by folding the two ends ( In this example, this corresponds to adhesive strips 1304A, 1304B) as indicated by arrows 170 in FIG. This can be accomplished by bringing the two components together as shown in FIG. 4A and 1704B.

[0085] As shown in FIG. 18, the nanofiber bundle 1404 is folded in half to form a nanofiber bundle. A folded bundle 1804 of fiber yarn is produced. The folded bundle 1804 has a unit length of The number of nanofiber yarns per bundle is doubled compared to bundle 1404. The folded bundle 1804 is defined by two adhesive strips superimposed on each other. A folded bundle of nanofiber yarns with a first end 1808 and no adhesive strip support. The second end 1812 is defined by a first end 1814 and a second end 1815 defined by a second end 1816.

[0086] When the nanofiber yarn bundle 1404 is folded 1224, the folded bundle 1804 can be further processed to place the nanofiber yarn bundle within a tube 1916. To place the folded bundle 1804 in a tube (1228), a second end 1812 of the bundle is , the nanofiber yarn is narrower (as indicated by arrows 1912A and 1912B). As shown in Figures 19 to 21, all the nanofiber yarns may be bundled together. By converging the folded bundle 1904, the folded bundle 1904 is pulled through the tube 1916, 19. As shown in FIG. 19, the needle or can be bound in a number of ways, including but not limited to using a hook 1908 .

[0087] As described above, the exemplary hollow tube nerve scaffold 1916 receives bundles of nanofiber yarns 1904. The cross section of the tube may be cylindrical, elliptical or polygonal, and may be configured to receive the The fiber bundles provide spacing between fibers to promote nerve regeneration while It expands to fill tube 1916.

[0088] FIG. 20 illustrates an exemplary tube having a bundle of nanofiber yarns 1904 disposed therein (1228). FIG. 12 is a perspective view of bundle 1904. When bundle 1904 is placed (1228) in tube 1916, bundle 19 The central portion of bundle 1904 is enclosed within the tube, while the two ends of bundle 1904 remain outside the tube 2004. FIG. 21 shows a cross-sectional view of a tube 1916 that encapsulates a bundle of nanofiber yarns 1904. The nanofiber yarns are shown aligned and lodged within tube 1916.

[0089] As shown in FIGS. 22-25, a bundle of nanofiber yarns 1904 is disposed within a tube 1916. 2204A and 2204B, the two ends of the bundle 1904 are aligned on either side of the tube (1228). The nanofiber is then cut to fill the cross section of the tube with the newly freed end (shown at B). The fiber bundle expands (1232). Figures 23 and 25 show nanoparticles uniformly distributed throughout the tube. FIG. 19 is a cross-sectional view of a tube 1916 that encapsulates the fiber.

[0090] [Carbon nanofiber nerve scaffolds] As noted above, some nerve scaffold tubes (e.g., tube 304) are biologically compatible. The implant is made from a polymer and / or a bioabsorbable material (e.g., silicone). Therefore, even polymers selected for flexibility and compliance may be incompatible with the neural scaffold device. Stiff enough to cause discomfort to the patient when used in a chair (e.g., polymer tubes are In some cases, tubes made of non-bioabsorbable materials may be difficult to remove from the nerve. Surgical removal may be necessary after regeneration. This additional surgery can be an inconvenience to the patient, cost, and Alternatively, bioabsorbable materials can be used for the tube. However, these materials can be expensive.

[0091] The embodiments described herein are flexible, compliant, biologically compatible and and / or a bioabsorbable tube is made of commercially available bioabsorbable suture material and carbon nanofiber sheet. As described above, the bioabsorbable suture material and the carbon nanotube can be used. A nerve scaffold containing bundles of carbon nanofibers was formed in a nerve scaffold tube made from a nanofiber sheet. An exemplary structure of the scaffold is shown in FIG.

[0092] The exemplary embodiment of a carbon nanofiber nerve scaffold 2600 shown in FIG. The absorbent helix 2604, a bundle of carbon nanofiber yarns 2608, and a cylindrical cartridge. and a nanofiber sheet 2612.

[0093] In some embodiments, the bioabsorbable helix 2604 is in the form of a bundle of nanofiber yarns 2608. The bioabsorbable spiral 2604 may, for example, gradually break down after insertion into the body. Forming the material from a thread or thread of surgical filament (e.g., suture material) that can be disintegrated. Examples of bioabsorbable helix 2604 include polyamide, a material used in surgical sutures. Ligollic acid, polylactic acid, polycaprolactone, collagen, and their polymers As will be appreciated in light of this disclosure, the present invention may be practiced with a variety of different configurations, including, but not limited to, fibers and / or yarns. As can be seen, in some instances, the helix 2604 determines the shape and diameter of the scaffold 2600 as a whole. Scaffolding 26 that can provide a morphology that maintains the structure and thereby inhibits neural regrowth Prevents (or inhibits) the collapse or shrinkage of the 00 cross section.

[0094] In some examples, the spiral 2604 extends in a first direction (e.g., to the right) of the cylindrical substrate 2704. A first spiral is wrapped around the cylindrical substrate 2704 in the opposite direction, and an opposite ( In some examples, the first helix may be formed by a second helix wound around the first helix (e.g., the left side). While on the substrate 2704, the spiral 2604 may be attached to the structure used to form the spiral 2604. The glass transition temperature (T g ) for example, 50%, 60%, 70%, or 8 0%. In yet another example, the helix 2604 can be heated to 100%. provide the stiffness necessary to maintain spacing between the nanofibers of the bundle 2608 so that the nanofibers can be It may be formed from a braided, knitted or crocheted tubular structure.

[0095] The carbon nanofiber sheet 2612 is made up of nanofiber yarn bundles 2608 and helices 2604. The carbon nanofiber sheet can be wrapped around the structure formed by 2612 helps maintain the shape of the helix 2604 and also helps keep the helix 2604 in nanofiber form. This can help maintain the confinement bias on the yarn bundle 2608. , and more specifically, the relative distance and position of the individual nanofiber yarns in the bundle 2608 with respect to each other. By maintaining the implant in place, nerve regrowth can be promoted as described above.

[0096] Helix 2604 is made of a material designed to slowly dissolve in the body over time. The windings of the helix 2604 are fabricated to be flexible and compliant (e.g., in response to movement). The helix 2604 provides more comfort to the patient than some other polymer tubing because it allows Additionally, the spiral 2604 does not require surgical removal due to its absorbable composition.

[0097] 27A-D show steps in the fabrication of a carbon nanofiber nerve scaffold 2600 in one example. As shown in FIG. 27A, a cylindrical substrate 2704 can be provided, around which a A biocompatible and / or bioabsorbable thread (or fiber) is wound to form a helix 2604. The cylindrical substrate 2704 provides a biocompatible and / or bioabsorbable The thread (or fiber) can be formed into a spiral 2604 configuration as shown in FIG. 26. It can be.

[0098] FIG. 27B shows the winding of the carbon nanofiber sheet 2612 around the spiral 2604. In some examples, the carbon nanofiber sheet 2612 can be permeated with a polymer (e.g., using a solution of a solvent and a biocompatible and / or bioabsorbable polymer, where the solvent is removed after application to the sheet). In any case, as shown in FIG. 27C after application of the sheet 2612, the cylindrical substrate 2704 can be removed. The cylindrical void 2708 formed by the removal of the cylindrical substrate 2 704 is defined by the spiral 2604 and / or one or more of the nanofiber sheets 2612. Next, the void 2708 can be used to accommodate a bundle of nanofiber threads 2608. The bundle of carbon nanofiber threads 2608 disposed inside the spiral 2604 includes any of the aforementioned embodiments and requires no further description. Similarly, the carbon nanofiber sheet 2612 wound around the spiral 2604 and the thread 26

[0099] 08 will be described below. The carbon nanofiber nerve scaffold 2600 can, in one example, be formed by winding it spirally. It can be formed.

[0100] The carbon nanofiber nerve scaffold 2600 can, in one example, be formed by winding it spirally. It can be formed.

[0101] [Nanofiber Forest] As used herein, the term "nanofiber" means a fiber having a diameter of less than 1 μm. The embodiments herein are mainly described as being made from carbon nanotubes but are described as being made from graphene, micron or nanoscale graphite fibers as well. and / or other carbon allotropes such as quartz and nanoscale fibers such as boron nitride. It will be appreciated that other compositions of the ba may be densified using the techniques described below. As used herein, the terms "nanofiber" and "carbon nanotube" refer to Single-walled carbon nanotubes and / or polycarbonates in which carbon atoms are bonded together to form a cylindrical structure In some embodiments, the carbon nanotubes referred to herein include both single-walled and double-walled carbon nanotubes. A carbon nanotube has 4 to 10 walls. "Bas sheet" or simply "sheet" refers to a drawing process (the entireties of which are incorporated herein by reference). The present invention is described in WO 2007 / 015710, the disclosure of which is incorporated herein by reference. Due to the fact that the longitudinal axis of the nanofibers in the sheet is not perpendicular to the main surface of the sheet, rather, they are parallel to the major surface of the sheet (i.e., they are often referred to as "forests" "As-deposited" refers to a sheet of aligned nanofibers (in the form of an as-deposited sheet). This is shown in Figures 30 and 31, respectively.

[0102] The dimensions of carbon nanotubes can vary greatly depending on the production method used. For example, the diameter of the carbon nanotube may be 0.4 nm to 100 nm, and its length may be Carbon nanotubes can also range from 10 μm to over 55.5 cm. It has a very high aspect ratio (ratio of length to diameter) of more than 2,000,000:1. Given the wide range of size possibilities, the properties of carbon nanotubes are highly Many interesting properties of carbon nanotubes have been established. However, to utilize the properties of carbon nanotubes in practical applications, Scalable and controllable production that allows maintaining or enhancing the characteristics of nanotubes A method is needed.

[0103] The unique structure of carbon nanotubes makes them suitable for specific applications. It has specific mechanical, electrical, chemical, thermal and optical properties that make it possible to Nanotubes exhibit excellent electrical conductivity, high mechanical strength, good thermal stability, and are hydrophobic. In addition to these properties, carbon nanotubes can also exhibit useful optical properties. For example, carbon nanotubes can be used to emit or detect light at narrowly selected wavelengths. Carbon nanotubes may also be used in light emitting diodes (LEDs) and photodetectors. It may also prove useful for photon and / or phonon transport.

[0104] In accordance with various embodiments of the subject disclosure, nanofibers (including carbon nanotubes) are The nanotubes (e.g., carbon nanotubes) form what is referred to herein as a "forest." As used herein, nanofibers or The carbon nanotube "forests" are arranged substantially parallel to each other on the substrate. FIG. 28 shows an array of nanofibers on a substrate. An exemplary forest is shown. The substrate may be of any shape, but in some embodiments, the substrate The material has a plane on which the forest is collected. As can be seen in Figure 28, the number of nanometers in the forest is The fibers may be approximately equal in height and / or diameter.

[0105] The nanofiber forests disclosed herein can be relatively dense. The disclosed nanofiber forests have at least 1 billion nanofibers / cm 2 has a density of In some specific embodiments, the nanofiber forests described herein may be 10 0 billion / cm 2 and 30 billion / cm 2 In other examples, the densities of the cellulose esters described herein may be between 0.1 and 0.2. Nanofiber Forest is made up of 90 billion nanofibers per cm 2 The density may range from 0.1 to 1.0. The forest may contain regions of high or low density, with certain regions being devoid of nanofibers. The nanofibers in the forest may also exhibit inter-fiber connections. For example, , adjacent nanofibers in the nanofiber forest are attracted to each other by van der Waals forces. In any case, the density of the nanofibers in the forest is This can be increased by applying the techniques described herein.

[0106] Methods for producing nanofiber forests are described, for example, in US Pat. The present invention is described in WO 2007 / 015710, the entire disclosure of which is incorporated herein by reference. It is listed.

[0107] A variety of methods can be used to generate the nanofiber precursor forest, for example: In some embodiments, the nanofibers are grown in a high temperature furnace, as shown diagrammatically in FIG. In some embodiments, the catalyst may be deposited on a substrate and placed in the reactor, and then The substrate may be exposed to a fuel compound fed into the reactor. The substrate can withstand temperatures above 100° C. and can be an inert material. The material may include stainless steel or aluminum disposed on a silicon (Si) wafer, but may also include other Ceramic substrates (e.g., alumina, zirconia, SiO2, glass ceramics) are The precursor forest nanofibers may be used instead of the carbon nanotube. In one example, a carbon-based compound such as acetylene may be used as the fuel compound. After being introduced into the vessel, the fuel compound(s) may then begin to accumulate on the catalyst and migrate from the substrate. They may grow upward and assemble to form a forest of nanofibers. The reactor also includes a gas inlet through which the fuel compound(s) and carrier gas can be supplied to the reactor, and a gas inlet through which the fuel compound(s) and carrier gas can be supplied to the reactor. and a gas outlet through which the spent fuel compound and carrier gas can be released from the reactor. Examples of carrier gases include hydrogen, argon, and helium. These gases, particularly Hydrogen may also be introduced into the reactor to promote the growth of the nanofiber forest. Additionally, dopants that are to be incorporated into the nanofibers may be added to the gas stream.

[0108] The process used to produce a multi-layered nanofiber forest involves splitting each nanofiber into A fiber forest is formed on a substrate and then contacted with a first nanofiber forest. The second nanofiber forest grows by the addition of the first nanofiber. A nanofiber forest is formed on a substrate, and a catalyst is deposited on the first nanofiber forest. Then, additional fuel compound is introduced into the reactor and placed on the first nanofiber forest. Many of these include promoting the growth of a secondary nanofiber forest from a catalyst placed in the nanofiber matrix. It can be formed by any suitable method. The growth method, type of catalyst, and catalyst Depending on the location of the nanofiber layer, the second nanofiber layer may be grown on top of the first nanofiber layer, and by directly growing on the substrate after refreshing the catalyst with, for example, hydrogen gas. , which grows under the first nanofiber layer. In any case, the second nanofiber forest The nanofibers in the first nanofiber forest can be aligned nearly end-to-end. However, there is a readily detectable interface between the first and second forests. The layer nanofiber forest may include any number of forests. For example, a multi-layer precursor A forest may contain 2, 3, 4, 5, or more forests.

[0109] [Nanofiber sheet] In addition to being arranged in a forest configuration, the nanofibers of the present application may also be arranged in a sheet configuration. As used herein, the terms "nanofiber sheet," "nanotube sheet," or The term "sheet" refers to a nanofiber array in which the nanofibers are aligned end-to-end in a plane. An example diagram of a nanofiber sheet with dimensions labeled is shown in Figure 30. In some embodiments, the sheet has a length and / or width that is more than 100 times the thickness of the sheet. In some embodiments, the length, width, or both are less than 1 / 2 the average thickness of the sheet. 0 3 , 10 6 , or 10 9 The nanofiber sheet has a thickness of, for example, about 5 nm to It can have a thickness of 30 μm and any length and width suitable for the intended application. In some embodiments, the nanofiber sheet has a length of 1 cm to 10 meters and a width of 1 cm These lengths are provided for illustrative purposes only. The length and width of the nanofiber sheet are The constraints are imposed by the configuration of the manufacturing equipment, not by the physical or chemical properties of the The process can produce sheets of any length. These sheets are wound into rolls during production. It can be attached.

[0110] As can be seen in FIG. 30, the axis along which the nanofibers are aligned end-to-end is the nanofiber alignment axis. In some embodiments, the direction of nanofiber alignment is referred to as the row direction. The nanofibers may be continuous throughout the entire fiber. The nanofibers are not necessarily perfectly parallel to each other. Instead, the direction of nanofiber alignment is determined based on the average or typical direction of nanofiber alignment. It is understood to be a measure.

[0111] The nanofiber sheet can be prepared by any type of suitable process capable of producing the sheet. In some exemplary embodiments, the nanofiber sheet may be assembled using , may be drawn from a nanofiber forest. An example of a nanofiber sheet that has been applied is shown in FIG.

[0112] As can be seen in Figure 31, nanofibers are pulled laterally from the nanofiber forest. The nanofibers may then be aligned end-to-end to form a nanofiber sheet. In embodiments where the fibers are derived from a nanofiber forest, the dimensions of the forest can be controlled. For example, the nanofiber sheet may be formed by subjecting the nanofiber sheet to a specific dimension. The width of the sheet may be approximately equal to the width of the nanofiber forest from which the sheet was drawn. The length of the sheet can be determined, for example, by the end of the drawing process when the desired sheet length is achieved. can be controlled by terminating

[0113] Nanofiber sheets have many properties that can be used for various applications. The fiber sheets have the following characteristics: tunable opacity, high mechanical strength and flexibility, thermal and electrical conductivity. The highly ordered nanofibers within the sheet may be conductive and may also exhibit hydrophobic properties. Considering the array, the nanofiber sheet can be very thin. The sheets are on the order of about 10 nm thick (measured within normal measurement tolerances) and are nearly quadratic. In other examples, the thickness of the nanofiber sheet can reach 200 nm or 300 nm. Thus, the nanofiber sheet adds minimal additional thickness to the component. This may be added.

[0114] Similar to the nanofiber forest, the nanofibers in the nanofiber sheet are The nanofibers are functionalized by adding chemical groups or elements to their surface. The nanofiber sheet may be used in combination with other nanofibers to provide different chemical activity than the nanofibers alone. Functionalization can be performed on already functionalized nanofibers or on nanofibers that have not yet been functionalized. Functionalization can also be performed on uncoated nanofibers. Using any of the techniques described herein, including but not limited to grouping techniques. This can be done.

[0115] The nanofiber sheets extracted from the nanofiber forest should also have high purity. In some cases, more than 90%, more than 95%, or even 9% of the nanofiber sheet is More than 9% of the weight percent is attributable to nanofibers. Similarly, the nanofiber sheet , more than 90%, more than 95%, more than 99%, or more than 99.9% carbon weight It may contain amounts.

[0116] [Other Considerations] The foregoing description of the embodiments of the present disclosure has been presented for purposes of illustration and is intended to be exhaustive; It is not intended to limit the invention or to limit the claims to the precise form disclosed. It will be appreciated that many modifications and variations are possible in light of the present disclosure.

[0117] The language used herein has been selected primarily for purposes of readability and instruction. However, the words may not be selected to describe or limit the subject matter of the present invention. Therefore, the scope of the present disclosure is not limited to this Detailed Description, but to the present specification. It is intended that the present application be limited by any claims arising in any application based thereon. Accordingly, the disclosure of the present embodiments is to be construed as falling within the scope of the present invention as set forth in the following claims. These are intended to be illustrative, not limiting.

Claims

1. a cylindrical helix constructed from surgical suture material, said cylindrical helix defining an interior chamber; a bundle of aligned carbon nanofiber yarns within the inner chamber of the cylindrical helix; a carbon nanofiber sheet wrapped around a surface of the cylindrical spiral opposite the internal chamber; 1. A carbon nanofiber nerve scaffold comprising:

2. The carbon nanofiber neural scaffold of claim 1, wherein the aligned carbon nanofiber yarns are spaced 5 μm to 15 μm apart from each other.

3. The carbon nanofiber nerve scaffold of claim 1 , wherein the carbon nanofiber sheet comprises a bioabsorbable polymer infiltrate.

4. 10. The carbon nanofiber neural scaffold of claim 1, wherein the cylindrical helix comprises a first helix wound in a first direction and a second helix wound in a second direction opposite the first helix.

5. 10. The carbon nanofiber nerve scaffold of claim 1, wherein the cylindrical spiral is formed from a crocheted tubular structure.

6. 10. The carbon nanofiber nerve scaffold of claim 1, wherein the cylindrical helix is ​​formed from a knitted tubular structure.

7. The carbon nanofiber nerve scaffold of claim 1 , wherein the surgical suture material is bioabsorbable.

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