Nerve sheath tube, method for preparing same, and use thereof

Abstract

The present invention relates to the field of biomedical material development technology, and in particular, to a nerve sheath tube, a method for preparing same, and use thereof. The nerve sheath tube provided herein solves the problem of limited mechanical performance of related materials in the prior art by optimizing the materials and the preparation method. The nerve sheath tube of the present invention has many significant advantages: the nerve sheath tube has excellent biocompatibility and is highly compatible with human tissues; the residue of processing aids during processing is minimal, thereby ensuring the biological safety of the product; the nerve sheath tube has good flexibility, which facilitates surgical operations and avoids compression or other injuries to the surrounding tissues after implantation; and due to the addition of graphene, the nerve sheath tube exhibits electroactivity, thereby providing a new approach for nerve tissue repair and function detection. These properties provide the nerve sheath tube of the present invention with a wide range of application prospects in the biomedical field.

Description

A nerve sheath, its preparation method and application Technical Field

[0001] This invention relates to the field of biomedical material development technology, and in particular to a nerve sheath, its preparation method, and its application. Background Technology

[0002] A nerve sheath, also known as a nerve conduit, is a medical device used to treat nerve injuries. It can promote nerve regeneration and reduce the formation of neuromas, and is currently used clinically primarily for the treatment of peripheral nerve injuries. Clinically, the nerve sheath is mainly used after nerve suturing as a protective and adjunctive treatment method, wrapping around the damaged nerve to promote tissue repair and functional recovery.

[0003] The manufacturing process of nerve sheaths has a significant impact on their performance. Commonly used manufacturing methods include electrospinning and 3D printing, which can add a conductive layer to the nerve sheath to improve its conductivity. However, these methods typically use polymeric materials rather than natural biomaterials.

[0004] Chinese patent CN111028983A discloses a conductive composite material comprising a complex of natural polymeric collagen and reduced graphene oxide. The natural polymeric collagen is made from a collagen slurry with a mass-volume concentration of 3%-10%, and the mass ratio of reduced graphene oxide to the natural polymeric collagen is 0.5%-20%. This invention provides a conductive composite material that overcomes the shortcomings of existing nerve repair materials, such as non-conductivity and weak suturing ability, making it closer to an ideal nerve repair conduit.

[0005] However, the existing technical solutions have defects in mechanical properties, which limits their applicability in practical applications. Summary of the Invention

[0006] The purpose of this invention is to provide a nerve sheath, its preparation method, and its application, which can achieve both excellent biocompatibility and mechanical properties.

[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0008] This invention provides a method for preparing a nerve sheath, comprising the following steps:

[0009] Collagen, chitosan, and graphene are mixed with a solvent and then finely ground and dispersed to obtain a paste-like material.

[0010] The paste-like material is transferred into a mold and subjected to freezing and freeze-drying processes in sequence to obtain a freeze-dried product.

[0011] The freeze-dried product was demolded and subjected to vacuum heat treatment to obtain the nerve sheath.

[0012] Preferably, the collagen is type I collagen.

[0013] Preferably, the solvent is an acetic acid solution;

[0014] The concentration of the acetic acid solution is 0.3 mol / L to 0.8 mol / L.

[0015] Preferably, the mass ratio of collagen, chitosan and graphene is 4-20:0.1-10:0.1-30.

[0016] Preferably, the mass ratio of the collagen to the volume ratio of the solvent is 5g-10g:80mL-120mL.

[0017] Preferably, the fine grinding and dispersion treatment is achieved using a three-roll mill.

[0018] Preferably, the discharge gap of the fine grinding and dispersion treatment is 10μm to 30μm.

[0019] Preferably, the freezing temperature is -50℃ to -30℃;

[0020] And / or, the freezing treatment time is 10h to 32h;

[0021] And / or, the freeze-drying process is performed at a temperature of -10°C to 10°C;

[0022] And / or, the freeze-drying process is carried out for 12 hours to 36 hours;

[0023] And / or, the temperature of the vacuum heat treatment is 95℃~115℃;

[0024] And / or, the pressure of the vacuum heat treatment is -0.99 bar to -0.7 bar;

[0025] And / or, the vacuum heat treatment time is 12h to 36h.

[0026] The present invention also provides a nerve sheath prepared by the above preparation method.

[0027] The present invention also provides the application of the above-mentioned nerve sheath in the preparation of nerve injury repair products, drug delivery systems, biosensors or neural interface related products.

[0028] The beneficial effects of this invention are:

[0029] This invention proposes a method for preparing nerve sheaths. This method utilizes collagen as a matrix component, which, due to its high similarity to human tissue components, ensures excellent biocompatibility of the prepared nerve sheaths. Furthermore, this invention employs freeze-drying technology, which significantly reduces the possibility of reagent residues during manufacturing, thereby improving product safety.

[0030] To overcome the shortcomings of freeze-dried collagen products in terms of mechanical strength, this invention specifically adds chitosan. The addition of chitosan not only enhances the mechanical properties of the nerve sheath but also maintains its toughness, making the nerve sheath easier for doctors to manipulate and shape during surgery.

[0031] This invention enhances the electrical activity of nerve sheaths by introducing graphene powder prepared using a physical method. This graphene powder is free of reagent residues that may arise during chemical preparation, making it simpler and safer. The addition of graphene not only improves the conductivity of nerve sheaths but also provides new possibilities for tissue repair and functional testing of damaged nerves, giving nerve sheaths greater advantages in clinical applications.

[0032] In summary, the nerve sheath of this invention has several significant advantages: First, it exhibits excellent biocompatibility and is highly compatible with human tissues; second, minimal additive residues remain during processing, ensuring product safety; third, the nerve sheath possesses good flexibility, facilitating surgical manipulation and shaping; and finally, the addition of graphene endows the nerve sheath with unique electroactivity, providing a new approach for the repair and functional testing of damaged nerves. These characteristics make the nerve sheath of this invention a promising candidate for widespread application in the biomedical field. Attached Figure Description

[0033] Figure 1 shows a comparison of the appearance of different sheaths, where A: the sheath prepared in Comparative Example 1; B: the sheath prepared in Comparative Example 2; C: the sheath prepared in Example 1; and D: the sheath prepared in Example 2.

[0034] Figure 2 shows a photograph of the sheath's appearance;

[0035] Figure 3 shows the microscopic state of the unmixed graphene.

[0036] Figure 4 shows the microscopic state of the unevenly mixed collagen fibers;

[0037] Figure 5 shows the microscopic state of the slurry after the graphene powder is fully dispersed. Detailed Implementation

[0038] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0039] Example 1

[0040] ① Use dried type I collagen and grind it into fine powder in a grinder for about 30 seconds;

[0041] ② Prepare 100 mL of 0.5 mol / L acetic acid solution;

[0042] ③ Add the solution from ② to 7.5g of powder from ①, 3g of chitosan, and 1g of graphene, and stir until no dry powder falls off;

[0043] ④ Grind the gel-like mixture from ③ using a three-roll mill until a fine paste that can be uniformly discharged from a 20μm gap is formed;

[0044] ⑤ Inject the paste-like slurry from ④ into the assembled mold, freeze at -40℃ for more than 2 hours, then remove the central rod of the mold while keeping it frozen, and freeze-dry at 0℃ for 24 hours;

[0045] ⑥ After freeze-drying, the sponge-like sheath formed is demolded and treated in an environment of 105℃-0.9bar for 24 hours. Then the sheath is cut and trimmed to the required length to obtain the finished product.

[0046] Example 2

[0047] The only difference from Example 1 is that step ③ is changed to:

[0048] ③ Add the solution from ② to 5g of powder from ①, 5g of chitosan, and 3g of graphene, and stir until no dry powder falls off.

[0049] Comparative Example 1

[0050] The only difference from Example 1 is that the amount of raw materials used is replaced by adding only collagen and not chitosan and graphene.

[0051] In step ④, a three-roll mill is not used in the preparation process; instead, ordinary mechanical stirring is used for mixing.

[0052] Comparative Example 2

[0053] The only difference from Example 1 is that a three-roll mill is not used in step ④ of the preparation process; instead, ordinary mechanical stirring is used for mixing.

[0054] Figure 1 shows a comparison photograph of the appearance of the sheaths prepared in the above embodiments and comparative examples.

[0055] Experimental Example

[0056] In this invention, when collagen, chitosan, graphene, and acetic acid solution are mixed uniformly into a paste-like slurry, uneven mixing can easily occur due to the hydrophobicity of graphene and the agglomerative properties of chitosan. This uneven mixing manifests in materials mechanics as stress concentration caused by segregation, leading to a decrease in mechanical properties.

[0057] The appearance of the sheath provided by the present invention is shown in Figure 2. The right side of the figure shows the sheath formed by freeze-drying after the raw materials are fully mixed and mechanically stirred for a long time. It can be seen that whether it is the black spots formed by graphene agglomeration or the white spots formed by insufficient dispersion of collagen fibers, they are visible to the naked eye. The sheath formed by freeze-drying the raw materials mixed by a three-roll mill on the left side has no obvious black spots or white spots and has better uniformity.

[0058] Product performance testing:

[0059] Under a microscope, the results of the unequally mixed graphene are shown in Figure 3, the results of the unequally mixed collagen fibers are shown in Figure 4, and the results of the slurry after the graphene powder is fully dispersed are shown in Figure 5. The slurry obtained by ordinary mechanical stirring can show graphene powder particles that are connected in sheets and collagen fibers that are agglomerated and overlapped together; while the slurry mixed by the three-roll mill can fully disperse the graphene powder without agglomeration and the collagen fibers are not agglomerated and entangled, achieving a uniform state.

[0060] The tensile strength of the sheath with an inner diameter of 5 mm was tested, and the results are shown in Table 1 below:

[0061] Table 1 Tensile strength test results

[0062] As can be seen from the contents of Table 1 above:

[0063] The slurry, after being mixed using a three-roll mill, allows the graphene powder to be fully dispersed without agglomeration, and the collagen fibers also remain undisturbed, achieving a uniform state. This significantly improves the mechanical properties of the nerve sheath, especially its tensile strength, which is crucial for maintaining the structural stability of the sheath during nerve repair surgery.

[0064] In clinical applications, the tensile strength of the nerve sheath directly affects its post-implantation performance. Insufficient tensile strength can lead to deformation or breakage of the sheath during or after implantation due to external forces, severely impacting nerve repair outcomes. Therefore, optimizing the mixing process to improve the tensile strength of the nerve sheath is a significant advantage of this invention in practical applications.

[0065] This invention ensures the superior properties of nerve sheaths by precisely controlling the ratio of collagen, chitosan, and graphene, and by employing freeze-drying technology.

[0066] In summary, the nerve sheath provided by this invention exhibits excellent performance in terms of biocompatibility, electroactivity, and mechanical properties, offering a novel solution for clinical nerve repair. With the nerve sheath of this invention, better therapeutic effects can be expected in the field of nerve injury repair, improving patients' quality of life.

[0067] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing a nerve sheath, characterized in that, Includes the following steps: Collagen, chitosan, and graphene are mixed with a solvent and then finely ground and dispersed to obtain a paste-like material. The paste-like material is transferred into a mold and subjected to freezing and freeze-drying processes in sequence to obtain a freeze-dried product. The freeze-dried product was demolded and subjected to vacuum heat treatment to obtain the nerve sheath.

2. The preparation method according to claim 1, characterized in that, The collagen is type I collagen.

3. The production method according to claim 1, characterized by, The solvent is an acetic acid solution; The concentration of the acetic acid solution is 0.3 mol / L to 0.8 mol / L.

4. The preparation method according to claim 1, characterized in that, The mass ratio of collagen, chitosan and graphene is 4–20:0.1–10:0.1–30.

5. The preparation method according to claim 1, characterized in that, The mass ratio of the collagen to the volume of the solvent is 5g-10g:80mL-120mL.

6. The preparation method according to claim 1, characterized in that, The fine grinding and dispersion process is achieved using a three-roll mill.

7. The production method according to claim 6, wherein The discharge gap of the fine grinding and dispersion treatment is 10μm to 30μm.

8. The method of claim 1, wherein, The freezing temperature is -50℃ to -30℃; And / or, the freezing treatment time is 10h to 32h; And / or, the freeze-drying process is performed at a temperature of -10°C to 10°C; And / or, the freeze-drying process is carried out for 12 hours to 36 hours; And / or, the temperature of the vacuum heat treatment is 95℃~115℃; And / or, the pressure of the vacuum heat treatment is -0.99 bar to -0.7 bar; And / or, the vacuum heat treatment time is 12h to 36h.

9. A nerve sheath prepared by any one of claims 1 to 8.

10. The use of the nerve sheath of claim 9 in the preparation of nerve injury repair products, drug delivery systems, biosensors, or neural interface-related products.

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