Nerve sheathing canal as well as preparation method and application thereof

Abstract

The invention provides a nerve sheathing canal and a preparation method and application thereof, and belongs to the technical field of biomedical material development. According to the nerve sheathing canal provided by the invention, the problem of limited mechanical properties of related materials in the prior art is solved by optimizing the materials and the preparation method. The nerve sheathing canal disclosed by the invention has multiple remarkable advantages that the biocompatibility is excellent, and the nerve sheathing canal is highly compatible with human tissues; the auxiliary agent residue in the processing process is extremely small, so that the biological safety of the product is ensured; the nerve sheathing canal has good flexibility, so that the surgical operation is facilitated, and the surrounding tissues are prevented from being clamped and pressed after the nerve sheathing canal is implanted; due to the addition of graphene, the nerve sheathing canal shows electroactivity, and a new way is provided for nerve tissue repair and function detection. Due to the characteristics, the nerve sheathing canal has a wide application prospect in the field of biomedicine.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical material development, and in particular to a nerve sheath tube and a preparation method and application thereof. Background Art

[0002] Nerve sheath, also known as nerve catheter, is a medical device used to treat nerve damage. It can be used to promote nerve regeneration and reduce the formation of neuromas. It is currently used clinically to treat peripheral nerve injuries. Clinically, the application of nerve sheath is mainly as a protective and auxiliary treatment method after nerve suture, wrapped around the damaged nerve to promote nerve tissue repair and functional recovery.

[0003] The manufacturing process of nerve sheaths has an important impact on their performance. Commonly used manufacturing methods include electrospinning and 3D printing technology, which can add a conductive layer to the nerve sheaths to improve their conductive properties. However, these methods usually use polymer materials instead of natural biological materials.

[0004] Chinese patent CN111028983A discloses a conductive composite material, which includes a composite of natural polymer collagen and reduced graphene oxide; the natural polymer collagen is made of collagen slurry with a mass volume concentration of 3%-10%, and the mass ratio of the reduced graphene oxide to the natural polymer collagen is 0.5%-20%. The conductive composite material provided by the invention improves the shortcomings of existing nerve repair materials such as non-conductivity and weak suturing ability, making it closer to an ideal nerve repair catheter.

[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 the present invention is to provide a nerve sheath tube and a preparation method and application thereof, which can take into account excellent biocompatibility and mechanical properties.

[0007] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions: The present invention provides a method for preparing a nerve sheath tube, comprising the following steps: The collagen, chitosan and graphene are mixed with a solvent, and finely ground and dispersed to obtain a paste-like material; The paste material is transferred into a mold, and subjected to freezing treatment and freeze drying treatment in sequence to obtain a freeze-dried product; The freeze-dried product was demoulded and subjected to vacuum heat treatment to obtain a nerve sheath tube.

[0008] Preferably, the collagen is type I collagen.

[0009] Preferably, the solvent is acetic acid solution; The concentration of the acetic acid solution is 0.3 mol / L to 0.8 mol / L.

[0010] Preferably, the mass ratio of the collagen, chitosan and graphene is 4-20:0.1-10:0.1-30.

[0011] Preferably, the volume ratio of the collagen mass to the solvent is 5g~10g:80 mL~120mL.

[0012] Preferably, the fine grinding and dispersing process is achieved by using a three-roller grinder.

[0013] Preferably, the discharge gap of the fine grinding and dispersion treatment is 10 μm to 30 μm.

[0014] Preferably, the freezing temperature is -50°C to -30°C; And / or, the freezing treatment time is 10h~32h; And / or, the temperature of the freeze-drying treatment is -10°C to 10°C; And / or, the freeze-drying treatment time is 12h~36h; And / or, the temperature of the vacuum heat treatment is 95°C to 115°C; 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~36h.

[0015] The present invention also provides a nerve sheath tube prepared by the preparation method.

[0016] The present invention also provides the use of the above-mentioned nerve sheath tube in the preparation of nerve damage repair products, drug delivery systems, biosensors or neural interface related products.

[0017] Beneficial effects of the present invention: The present invention proposes a method for preparing a nerve sheath tube, which uses collagen as a matrix component, and because of its high similarity to human tissue components, ensures that the prepared nerve sheath tube has excellent biocompatibility. In addition, the present invention adopts freeze-drying technology for preparation, which significantly reduces the possibility of reagent residues used in the manufacturing process, thereby improving the safety of the product.

[0018] In order to overcome the deficiency of collagen freeze-dried products in mechanical strength, the present invention particularly adds chitosan. The addition of chitosan not only enhances the mechanical properties of the nerve sheath, but also maintains its toughness, which makes the nerve sheath easier for doctors to operate and shape during surgery.

[0019] The present invention improves the electrical activity of the nerve sheath by introducing graphene powder prepared by physical methods. The graphene powder does not contain reagent residues that may be produced during the chemical preparation process, so the composition is single and safer. The addition of graphene not only enhances the electrical conductivity of the nerve sheath, but also provides new possibilities for tissue repair and functional detection of damaged nerves, making the nerve sheath more advantageous in clinical applications.

[0020] In summary, the nerve sheath tube of the present invention has many significant advantages: first, it has excellent biocompatibility and is highly compatible with human tissue; second, the residual additives in the processing process are extremely small, ensuring the safety of the product; third, the nerve sheath tube has good flexibility, which is convenient for surgical operation and shaping; finally, the addition of graphene gives the nerve sheath tube unique electrical activity, providing a new way for the repair and functional detection of nerve damage. These characteristics make the nerve sheath tube of the present invention have broad application prospects in the biomedical field. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 The following are photos comparing the appearance of different sheath tubes, wherein A: the sheath tube prepared in comparative example 1; B: the sheath tube prepared in comparative example 2; C: the sheath tube prepared in example 1; and D: the sheath tube prepared in example 2.

[0022] Figure 2 This is a photo of the sheath appearance; Figure 3 This is a microscopic image of graphene that is not mixed; Figure 4 This is a microscopic picture of unmixed collagen fibers; Figure 5 This is a microscopic image of the slurry after graphene powder is fully dispersed. DETAILED DESCRIPTION

[0023] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0024] Example 1 ①Use dry type I collagen and grind it into fine powder using a grinder for about 30 seconds; ②Prepare 100mL of 0.5mol / L acetic acid solution; ③ Add the solution in ② to 7.5g of the powder in ①, 3g of chitosan, and 1g of graphene, and stir until no dry powder falls off; ④ Grind the colloid mixed in ③ with a three-roller grinder until a fine paste is formed that can be evenly discharged from a 20μm gap; ⑤ Inject the paste slurry in ④ into the assembled mold, freeze it at -40℃ for more than 2h, then remove the center rod of the mold while keeping it frozen, and freeze-dry it at 0℃ for 24h; ⑥ After freeze-drying is completed, the sponge-like sheath is removed from the mold and treated in an environment of 105°C -0.9 bar for 24 hours. The sheath is then cut and trimmed to the required length to obtain a finished product.

[0025] Example 2 The only difference from Example 1 is that step ③ is changed to: ③ Add the solution in ② to 5g of the powder in ①, 5g of chitosan and 3g of graphene, and stir until no dry powder falls off.

[0026] Comparative Example 1 The only difference from Example 1 is that the amount of raw materials is replaced by: only collagen is added, and chitosan and graphene are not added; In step ④, a three-roller grinder is not used during the preparation process, and ordinary mechanical stirring and mixing is used instead.

[0027] Comparative Example 2 The only difference from Example 1 is that a three-roller grinder is not used in the preparation process of step ④, but is replaced by ordinary mechanical stirring and mixing.

[0028] Figure 1 The following are comparison photos of the appearance of the sheath tubes prepared in the above embodiment and comparative example.

[0029] Experimental example In the present invention, when collagen + chitosan + graphene + acetic acid solution are mixed evenly into a paste-like slurry, uneven mixing is likely to occur due to the hydrophobicity of graphene and the agglomeration of chitosan. Uneven mixing manifests itself in material mechanics as stress concentration caused by segregation, resulting in decreased mechanical properties.

[0030] The appearance photo of the sheath provided by the present invention is as follows Figure 2 As shown, the right side of the figure is a sheath formed by fully mixing the raw materials, mechanically stirring and mixing for a long time, and then freeze-drying. It can be seen that both black spots formed by graphene agglomeration and white spots formed by insufficient dispersion of collagen fibers are visible to the naked eye; while the sheath on the left side is formed by mixing the raw materials with a three-roller grinder and then freeze-drying. There are no obvious black spots or white spots and the uniformity is good.

[0031] Product performance testing: Observed under a microscope, the unmixed graphene results are as follows Figure 3 As shown, the results of unmixed collagen fibers are as follows Figure 4 As shown, the slurry state of graphene powder after it is fully dispersed is as follows Figure 5As shown, in the slurry obtained by ordinary mechanical stirring and mixing, graphene powder particles connected into sheets and collagen fibers that are agglomerated and overlapped can be observed; while the slurry mixed by a three-roller grinder can make the graphene powder fully dispersed without agglomeration, and the collagen fibers are not agglomerated and entangled, reaching a uniform state.

[0032] The tensile strength of the sheath with an inner diameter of 5 mm was tested, and the results are shown in Table 1 below: Table 1 Tensile strength test results

[0033] From the above table 1, we can know that: The slurry mixed by the three-roller mill can fully disperse the graphene powder without agglomeration, and the collagen fibers are not agglomerated and entangled, reaching a uniform state. This significantly improves the mechanical properties of the nerve sheath, especially the tensile strength, which is crucial for maintaining the structural stability of the sheath during nerve repair surgery.

[0034] In clinical applications, the tensile strength of the nerve sheath directly affects its performance after implantation. If the tensile strength is insufficient, the sheath may be deformed or broken due to external forces during or after implantation, which will seriously affect the nerve repair effect. Therefore, improving the tensile strength of the nerve sheath by optimizing the mixing process is a major advantage of the present invention in practical applications.

[0035] The present invention ensures the excellent properties of the nerve sheath by precisely controlling the ratio of collagen, chitosan and graphene and adopting freeze-drying technology.

[0036] In summary, the nerve sheath provided by the present invention has excellent performance in biocompatibility, electrical activity, mechanical properties, etc., and provides a new solution for clinical nerve repair. Through the nerve sheath of the present invention, it is expected to achieve better treatment effects in the field of nerve injury repair and improve the quality of life of patients.

[0037] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

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

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

3. The preparation method according to claim 1, characterized in that: The solvent is 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 the 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:80 mL~120mL.

6. The preparation method according to claim 1, characterized in that: The fine grinding and dispersing process is achieved by using a three-roller grinder.

7. The preparation method according to claim 6, characterized in that: The discharge gap of the fine grinding and dispersing process is 10 μm to 30 μm.

8. The preparation method according to claim 1, characterized in that: The temperature of the freezing treatment is -50°C to -30°C; And / or, the freezing treatment time is 10h~32h; And / or, the temperature of the freeze-drying treatment is -10°C to 10°C; And / or, the freeze-drying treatment time is 12h~36h; And / or, the temperature of the vacuum heat treatment is 95°C to 115°C; 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~36h.

9. A neural sheath tube obtained by the preparation method according to any one of claims 1 to 8.

10. Use of the nerve sheath tube according to claim 9 in the preparation of nerve damage repair products, drug delivery systems, biosensors or neural interface related products.

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