An adaptive diameter-reducing nerve cuff for use in a severed nerve injury and a method of making

Abstract

The application discloses a self-adapting diameter-reducing nerve sleeve applied to a nerve injury of a disconnecting type and a preparation method of the nerve sleeve. The inner diameter of the nerve sleeve is larger than the outer diameter of a nerve to be repaired. The nerve sleeve is a tube with a consistent diameter. The nerve sleeve can be self-adaptively shrunk under the body temperature or a safe stimulation to the human body, so that the nerve sleeve is in close contact with the nerve in the nerve sleeve. The main body of the nerve sleeve is a phase-change shrinkable hydrogel. An adhesive coating is arranged on the inner layer of the nerve sleeve. In order to improve the shrinkage efficiency, the nerve sleeve contains a photo-thermal effect material, such as a carbon nanotube. In the preparation, a hydrogel precursor solution is prepared first, then is cast into a mold, is shaped through calcium ion cross-linking and / or ultraviolet cross-linking, and is demolded after shaping. The adhesive coating is arranged after demolding. The application of the nerve sleeve can reduce the difficulty of nerve butt joint. The 360-degree self-adapting shrinkage can greatly reduce the contact difficulty of the nerve sleeve and the nerve. In addition, the contact effectiveness is ensured, and the operation time is saved.

Description

Technical Field

[0001] This invention belongs to the field of neural bridging device technology, specifically an adaptive diameter-reducing nerve cannula for use in severed nerve injuries and its preparation method. Background Technology

[0002] Nerve transection injury refers to the complete or partial rupture of nerve fibers, nerve membranes, or even the entire nerve due to trauma, surgery, traction, compression, or other reasons. This results in the interruption of axonal continuity, disintegration of myelin sheath, and complete or partial loss of nerve conduction.

[0003] Currently, common repair methods include end-to-end nerve anastomosis, nerve transplantation (autologous / allogeneic nerve), nerve transfer, and nerve conduit repair. Regardless of the method, all require nerve reconnection and subsequent suturing, which inevitably damages the nerve and affects subsequent treatment outcomes. Furthermore, nerve suturing is performed under a microscope, demanding extremely high surgical skill, resulting in prolonged surgery time, increased anesthesia risks for patients, and higher surgical costs. Summary of the Invention

[0004] The suturing process increases the difficulty of the surgery. Furthermore, when using a nerve cannula, in addition to suturing, different sizes of nerve cannulas are needed to ensure effective nerve repositioning, as the nerve must be tightly attached to the cannula. The need for dimensional consistency also makes nerve insertion into the cannula difficult. This application addresses these issues by disclosing a nerve cannula that is larger than the nerve to be repaired, suitable for most patients with severed nerve injuries. This nerve cannula can adaptively shrink under body temperature and light stimulation, ensuring close contact between the cannula and the nerve. It also slowly degrades during nerve repair, avoiding the difficulties and risks associated with cannula removal.

[0005] The specific technical solution is as follows: An adaptive shrinking nerve cannula for use in severed nerve injuries, wherein the inner diameter of the nerve cannula is larger than the outer diameter of the nerve to be repaired, the nerve cannula is a tubular structure with a uniform diameter, and the nerve cannula can adaptively shrink under body temperature or stimulation that is safe for the human body, so that the nerve cannula can be in close contact with the nerve inside the nerve cannula.

[0006] Furthermore, the neural cannula is biodegradable, and its degradation cycle matches the rate of nerve regeneration. During use, the two severed nerve segments are inserted into the nerve cannula from both sides under micromanipulation, ensuring contact and stable positioning within the cannula. Continuous physical (light) stimulation then causes the nerve cannula to shrink until it is in close contact with the two nerve segments, achieving end-to-end anastomosis and fixation. This adaptive shrinkage mechanism achieves a tight connection between the nerve and the cannula, thus realizing nerve connection. During the bridging and nerve regeneration process, the biodegradable material of the nerve cannula is gradually degraded and absorbed within the body, ensuring nerve repair while simultaneously undergoing its own degradation, eliminating the need for a second surgery. The degradation cycle is designed to match the rate of nerve regeneration, providing sufficient physical support for nerve repair before naturally disappearing without any foreign body residue. Furthermore, because of the adaptive shrinkage mechanism, surgeons do not need to perform precise pre-forming or select multiple cannula sizes. The procedure only requires ensuring that the adaptively shrinking nerve cannula can shrink to a minimum size equal to or smaller than the outer diameter of the nerve to be repaired. During the procedure, because the nerve cannula is larger than the nerve to be repaired, inserting the nerve into the cannula is relatively easy. After fitting, physical stimulation automatically reduces the cannula's diameter, tightly and evenly wrapping it around the nerve sheath of different diameters, achieving perfect "adaptive fitting" and solving the problem of diameter mismatch. The entire process requires no microsurgical sutures, significantly shortening the operation time and reducing anesthesia risks. The biodegradable material degrades gradually according to a preset cycle after providing support, highly matching the rhythm of nerve regeneration, ensuring structural integrity during repair while avoiding long-term foreign body stimulation.

[0007] Furthermore, the length of the nerve cannula ranges from 5 to 20 mm; the inner diameter is set from 1 to 10 mm; and the minimum inner diameter that the nerve cannula can adaptively shrink is 0.7 to 8 mm; the shrinkage range is 0.3 to 2 mm. This size setting can ensure the repair of severed nerves ranging from as thin as 0.7 mm to as thick as 8 mm. The shrinkage range of 0.3 to 2 mm reduces the requirements for size setting and simplifies the selection of nerve cannulas during specific repairs.

[0008] Furthermore, a nerve cannula with an inner diameter of 1 mm is provided, and a nerve cannula model is provided at 0.5 mm intervals; this design can meet the repair needs of most severed nerve injuries by providing a limited number of models.

[0009] Furthermore, an adhesive coating is provided on the inner side of the nerve cannula. This adhesive coating ensures stability of the end-to-end position after adaptive cannula shrinkage, minimizing the risk of postoperative nerve dislodgement. The adhesive coating uses a polyacrylic acid coating, which is made by adding a deionized aqueous solution of 20% acrylic acid (by volume) and 1% α-ketoglutaric acid (by mass) into the cannula. Due to the water absorption of the hydrogel, the solution is adsorbed onto the surface. After irradiation with 365nm ultraviolet light, the acrylic monomers polymerize to form polyacrylic acid (PAA). The carboxyl groups of PAA can form a dense hydrogen bond network with these groups on the tissue surface, thus providing tissue adhesion.

[0010] Furthermore, the main body of the nerve cannula is a phase change shrinking hydrogel, which undergoes a sol-gel phase transition triggered by body temperature, achieving in-situ molding and dynamic shrinkage; preferably, the phase change shrinking hydrogel is a phase change hydrogel containing PF127.

[0011] Furthermore, the neural cannula, primarily composed of phase-change shrinkage hydrogel, contains calcium ions (Ca²⁺). + The substances that undergo cross-linking reactions with calcium ions ensure the biodegradability of the nerve cannula.

[0012] Furthermore, the nerve cannula contains a uniformly distributed photothermal material, enabling it to rapidly shrink under near-infrared light irradiation.

[0013] Furthermore, the photothermal material is carbon nanotubes (CNTs).

[0014] Furthermore, CNTs can be modified or combined with other photothermal materials, such as nano-iron oxide (Fe3O4), carbon quantum dots, graphene quantum dots, and graphene oxide quantum dots, to improve the nerve healing efficiency brought about by photothermal effects and conductivity. Alternatively, CNT / Fe3O4 composite nanomaterials (magnetic targeting and photothermal synergy) can be used in conjunction with in vitro magnetic repair devices to improve the recovery speed through exogenous stimulation of nerve repair.

[0015] Furthermore, the light wave is near-infrared; this type of light can penetrate deep into tissues, precisely activating the local photothermal effect generated by carbon nanotubes, causing the phase change shrinking hydrogel to rapidly undergo a sol-gel transition and initiate a shrinkage process under physiological conditions. This wavelength does not damage human tissue, and the carbon nanotubes are highly sensitive to near-infrared radiation, enabling the sheath to adaptively shrink within minutes, achieving rapid and tight coverage of the nerve stump.

[0016] Furthermore, the phase transition temperature of the nerve sheath is 35-38℃. This is specifically controlled by adjusting the mass concentration of the phase transition hydrogel in the nerve sheath. The phase transition shrinkage hydrogel is specifically PF127 hydrogel, and the mass concentration of the PF127 hydrogel precursor solution can be adjusted within the range of 10% to 20%.

[0017] The present invention also discloses a method for preparing a nerve cannula based on PF127.

[0018] 1) Prepare a PF127 hydrogel precursor solution with a phase transition temperature of 35-38℃; add calcium ions (Ca²⁺) to the hydrogel precursor solution. + Substances that undergo cross-linking reactions, such as sodium alginate, carboxymethyl chitosan, or hyaluronic acid, which are polysaccharides containing carboxyl groups.

[0019] 2) The hydrogel precursor solution is injected into the mold. The mold includes a receiving tube of the same size and a support rod of the same size. The support rod is sleeved in the center of the receiving tube. There is an annular cavity between the receiving tube and the support rod. The annular cavity is used to inject the hydrogel precursor solution.

[0020] 3) Add calcium ions to crosslink.

[0021] 4) Demolding produces a neural cannula with adaptive shrinkage.

[0022] Furthermore, an adhesive coating is added to the inner layer of the demolded nerve cannula.

[0023] Furthermore, photothermal materials, such as carbon nanotubes, nano-iron oxide, or their composites, are added to the hydrogel precursor solution in step 1. This method can enhance the thermal shrinkage effect of the prepared neural cannula after photostimulation.

[0024] Furthermore, a photocrosslinking agent and a photoinitiator are added to the hydrogel precursor solution in step 1 to form a photocrosslinking polymerization system. After step 3, light treatment is performed to initiate in-situ polymerization using ultraviolet or visible light, enhancing the crosslinking density and mechanical stability of the hydrogel network, thereby improving the structural maintenance ability of the neural cannula in the physiological environment. The photocrosslinking agent is the ultraviolet photocrosslinking agent PF127Di (acrylamide PF127); the photoinitiator is LAP; LAP is a phenyl-2,4,6-trimethylbenzoyl lithium phosphinate photoinitiator, belonging to type I photoinitiators. LAP is a water-soluble, cell-compatible blue light photoinitiator that can rapidly initiate the curing of photosensitive hydrogel materials under blue light (wavelength 405nm).

[0025] Furthermore, a solution containing calcium ions is added after light treatment to facilitate cross-linking. This double cross-linking enhances the in vivo stability of the nerve cannula.

[0026] Furthermore, the main component of the hydrogel precursor solution is PF127; and it reacts with calcium ions (Ca²⁺). + The substance that undergoes the cross-linking reaction is sodium alginate; The preparation principle of the heat-shrinkable hydrogel: Sodium alginate is added to the PF127 solution, utilizing the calcium ion cross-linking formed by sodium alginate and calcium chloride solution for shaping. PF127 transforms from a sol to a gel as the temperature rises above its phase transition point, simultaneously undergoing volume shrinkage. This process can be precisely triggered by the local thermal effect induced by near-infrared light, achieving rapid morphological changes and airtight encapsulation around the nerve stump. The mass concentration of PF127 can be adjusted within the range of 10%–20%, with higher concentrations resulting in more pronounced volume changes and lower shrinkage (phase transition) temperatures. By adjusting the PF127 concentration, the phase transition temperature can be precisely controlled within the 35–38°C range, ensuring a rapid response under near-infrared photothermal effects. Carbon nanotubes, acting as a photothermal conversion agent, are uniformly dispersed in the hydrogel system, significantly improving photothermal conversion efficiency and rapidly raising the local temperature above the phase transition point, triggering the sol-gel transition and synchronous shrinkage. This process achieves immediate encapsulation and microenvironment sealing of the nerve stump, effectively preventing fibrous tissue invasion and promoting directional axonal regeneration.

[0027] The biodegradable principle of the nerve cannula: Neither PF127 nor sodium alginate can be degraded into small molecules in the human body. However, due to the physical / ionic cross-linking properties of the composite hydrogel, the cross-linking structure of sodium alginate and PF127 is destroyed when calcium ions are slowly removed from the body, and their monomers are slowly metabolized out of the body.

[0028] Furthermore, the mass concentration of PF127 can be adjusted in the range of 10% to 20%. The higher the concentration, the more obvious the volume change and the lower the shrinkage (phase transition) temperature.

[0029] Furthermore, the mass concentration of sodium alginate (SA) can be adjusted within the range of 0.5% to 2%. The higher the concentration, the stronger the ionic crosslinking, resulting in better sleeve toughness and a reduction in the shrinkage (phase transition) temperature of PF127. However, the higher the crosslinking strength, the more stable the structure, and the less obvious the thermal shrinkage effect of PF127. Therefore, it is necessary to adjust the concentration to balance the sleeve toughness and the effect of photothermal shrinkage.

[0030] Furthermore, the mass concentration of PF127Di can be adjusted within the range of 1% to 10%. The higher the concentration, the better the sleeve toughness and forming rate, which can effectively assist the forming of the sleeve in the mold and assist in demolding.

[0031] Furthermore, the mass concentration of CNTs can be adjusted within the range of 0.5% to 2%. The higher the concentration, the lower the toughness and forming rate of the sleeve, but the more obvious the photothermal effect. This concentration can help the sleeve shrink rapidly under infrared light, thereby improving the shrinkage efficiency.

[0032] Technical effect 1. By fabricating a biodegradable nerve cannula with an inner diameter larger than the diameter of the severed nerve and featuring self-adaptive shrinkage, the nerve docking speed can be accelerated. Due to its larger diameter, it can meet most nerve docking requirements, eliminating the need to develop too many different types of nerve cannulas; the self-adaptive shrinkage ensures close contact between the nerve and the nerve cannula, fixing the position after end-to-end anastomosis.

[0033] 2. By placing a photothermal material within the nerve cannula and applying an adhesive coating to the inner wall, microsurgical suturing is simplified to three simple steps: nerve-to-cannula connection, infrared light illumination, and automatic adhesion after adaptive cannula shrinkage. This eliminates the need for traditional sutures, and the illumination and adhesion steps are completed within 5-10 minutes. Furthermore, these steps require less experience from the surgeon, reducing workload and the learning curve, enabling more surgeons in various hospitals to master and perform high-quality nerve repair surgery. Simultaneously, the reduced surgical time significantly decreases the exposure time of nerve tissue during surgery, lowering the risk of infection and complications.

[0034] 3. Achieve precise adaptive anastomosis: The adaptive contraction efficiency ensures that the cannula and the nerve epidermis achieve a tight 360° fit without dead angles, realizing low-tension and high-precision anastomosis.

[0035] 4. The cannula itself acts as a guiding catheter, effectively preventing the invasion of surrounding connective tissue and guiding Schwann cells to migrate in an orderly manner and axons to grow in a directional manner. Attached Figure Description

[0036] Figure 1 This is a schematic diagram of the fabrication process of the nerve cannula of the present invention; Figure 2 This is a schematic diagram of the PFeC generation process. Figure 3 A schematic diagram of a nerve cannula mold and a nerve cannula structure; Figure 4 A cross-sectional view of the mold assembly for injecting the hydrogel precursor solution; Figure 5 This is a flowchart illustrating the step-by-step demolding process of the mold. Figure 6 A schematic diagram of a severed nerve sleeved into a nerve cannula with a 1mm gap inside the nerve cannula; Figure 7 This is a schematic diagram of the experimental procedure for nerve cannula in rats; Figure 8 A schematic diagram of the process for magnetic targeting recovery after the use of a nerve cannula with PFeC; Figure 9 This is a schematic diagram illustrating the contraction process of the nerve cannula stimulated by near-infrared light. Figure 10A schematic diagram showing the nerve cannula being placed in the surgical area of ​​a rat and the severed nerve extending into the nerve cannula; Figure 11 For reference in Examples 2.1-2.3 Figure 10 A bar chart comparing the shrinkage time of various nerve cannulas after setting them up in different ways. Figure 12 These are renderings of different types of nerve cannula repair methods.

[0037] Explanation of main figure symbols 1. Support rod; 2. Receptacle tube; 3. Nerve cannula; 41. First occlusion tube; 42. Second occlusion tube. Detailed Implementation

[0038] To make the objectives, technical solutions, and advantages of this application clearer, the technical solutions of this application will be clearly and completely described below in conjunction with specific embodiments and corresponding drawings. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of them. Based on the embodiments in this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0039] Glossary: PF127: Pluronic F-127, Polosham 407 CNT: Carbon Nanotubes Dopamine (DA): Dopamine (DA) DAimmobilization: Dopamine fixation Fe³ + / Fe² + : ferric ions / ferrous ions crystallization PDA: Polydopamine PFeC: (A polymer of carbon nanotubes, polydopamine, and iron ions shown in the diagram) Fe3O4: Iron(II,III) oxide Diameter-adaptive seamless connector Alternating magnetic field: alternating magnetic field anisotropic PFeC generates electricity: anisotropic PFeC generates electricity Nerverepair: Neural Repair Casting: casting Magnetic orientation: UV+Ca² + Ultraviolet rays + calcium ions acrylicacid(AAc) + acrylicacid-NHS (AAC-NHS): Acrylic acid (AAc) + succinimide acrylate (AAC-NHS) polyAAc-co-AAc-NHS(PAA) adhesive layer: Polyacrylic acid-copolymer-acrylic acid-succinimide (PAA) adhesive layer Example 1: An Adaptive Nerve Cannula with Reduced Diameter An adaptive shrinking nerve cannula 3 for use in severed nerve injuries is disclosed. The inner diameter of the nerve cannula 3 is larger than the outer diameter of the nerve to be repaired. The nerve cannula 3 is a tube with a uniform diameter and can adaptively shrink under body temperature or stimulation safe for the human body, ensuring close contact between the nerve cannula 3 and the nerve within. The nerve cannula 3 is biodegradable, and its degradation cycle matches the nerve regeneration rate. The main body of the nerve cannula 3 is a phase change shrinking hydrogel, specifically a PF127-containing hydrogel. The phase change temperature of the nerve cannula 3 is 35-38℃, specifically controlled by adjusting the mass concentration of the phase change hydrogel. The specific phase change shrinking hydrogel is PF127 hydrogel, and the mass concentration of the PF127 hydrogel precursor solution can be adjusted within the range of 10% to 20%. Of course, other phase change shrinking hydrogels with a phase change temperature of 35-38℃ can also be selected in practice.

[0040] A more preferred embodiment is that the length of the nerve cannula 3 ranges from 5 to 20 mm; the inner diameter of the nerve cannula 3 is set to 1 to 10 mm; and the minimum inner diameter of the nerve cannula 3 that can adaptively shrink is 0.7 to 8 mm; the shrinkage range is 0.3 to 2 mm. This size setting can ensure the repair of severed nerves ranging from as thin as 0.7 mm to as thick as 8 mm. The shrinkage range of 0.3 to 2 mm reduces the requirements for size setting and reduces the difficulty of selecting the nerve cannula 3 during specific repairs.

[0041] A more preferred embodiment is to provide a nerve cannula 3 with an inner diameter of 1 mm, and to provide a different type of nerve cannula 3 at intervals of 0.5 mm; this arrangement can meet the repair needs of most severed nerve injuries by providing a limited number of different types.

[0042] The nerve cannula 3 contains calcium ions (Ca²⁺). +The cross-linking reaction occurs between the substance and calcium ions. The substance that cross-links with calcium ions can be a carboxyl-containing polysaccharide such as sodium alginate, carboxymethyl chitosan, or hyaluronic acid; sodium alginate is preferred. In vivo, calcium ions are slowly eliminated, the cross-linking structure of sodium alginate and PF127 is destroyed and degraded, and the monomers of sodium alginate and PF127 are slowly metabolized and excreted from the body.

[0043] A more preferred embodiment is that the nerve cannula 3 contains a uniformly distributed photothermal material, namely carbon nanotubes (CNTs). The carbon nanotubes are uniformly dispersed within a PF127 hydrogel network, generating a controllable thermal effect under near-infrared light irradiation. This triggers localized heating of the hydrogel and accelerates the sol-gel phase transition, achieving contraction. This process is rapid, spatially selective, and effectively avoids thermal damage to surrounding tissues. The carbon nanotubes also possess electrical conductivity, which accelerates nerve healing.

[0044] A more preferred implementation is that CNTs can be modified or combined with other photothermal materials, such as nano-iron oxide (Fe3O4), carbon quantum dots, graphene quantum dots, and graphene oxide quantum dots, to improve the nerve healing efficiency brought about by photothermal effect and conductivity. Alternatively, CNT / Fe3O4 composite nanomaterials (magnetic targeting and photothermal synergy) can be used in conjunction with external magnetic recovery devices to improve the recovery speed through exogenous stimulation of nerve repair.

[0045] A more preferred embodiment is that an adhesive coating is also provided on the inner side of the nerve cannula 3. This adhesive coating ensures the stability of the end-to-end position of the adaptive shrinkage cannula, minimizing the risk of postoperative nerve dislodgement. The adhesive coating uses a polyacrylic acid coating. A deionized aqueous solution of 20% acrylic acid (by volume) and 1% α-ketoglutaric acid (by mass) is added to the cannula and placed in place. Due to the water absorption of the hydrogel, the solution is adsorbed onto the surface. After irradiation with 365nm ultraviolet light, the acrylic monomers polymerize to form polyacrylic acid (PAA). The carboxyl groups of PAA can form a dense hydrogen bond network with these groups on the tissue surface, thus providing tissue adhesion. The adhesive coating can be a bioactive material that can specifically react with the components of the epineurium to form a strong biological adhesion. The bioactive adhesive coating contains neuroadhesion peptides and matrix-mimicking components, which can further mediate the anchoring and extension of epineurium cells on the basis of physical adhesion, enhancing interfacial stability. The coating slowly releases neurotrophic factors in the early stages of degradation, continuously promoting... The process involves axonal regeneration and myelin formation. The entire repair process achieves synergistic advancement of physical support, biological integration, and functional reconstruction, ultimately restoring both neural structure and function. The specific component settings for the adhesive coating are as follows: 1. The volume concentration of acrylic acid can be adjusted within the range of 10%–20%. Higher concentrations result in higher viscosity and better adhesion. 2. The mass concentration of α-ketoglutarate can be adjusted within the range of 0.5%–2%. 3. A combination of 1%–5% succinimide-modified acrylic acid (AAs-NHS) and acrylic acid can be used. NHS can react with the amino groups of proteins on the tissue surface to form covalent bonds, enhancing adhesion. 4. A combination of 1%–5% thiol-modified polyacrylic acid (PAAs-SH) and acrylic acid can be used. SH can react with the thiol groups of proteins on the tissue surface to form disulfide bonds, enhancing adhesion.

[0046] The method of using the nerve cannula 3 is as follows: The two ends of the severed nerve are inserted into the nerve cannula 3 from both ends, maintaining a distance of 1-3 mm between the two nerve segments, preferably 1-2 mm. After placement, clamps or other instruments are used to maintain the position of the two severed nerve segments, effectively exposing the nerve cannula 3. For nerve cannulas 3 without photothermal material, a heat lamp is used for insulation, and the diameter is adaptively reduced using phase change temperature until it fits tightly against the nerve. For nerve cannulas 3 with photothermal material, near-infrared light is used for irradiation, utilizing the photothermal effect to rapidly reduce the diameter. The entire reduction process is simple and requires no suturing.

[0047] Example 2: Method for preparing a nerve cannula with PF127 as the main component First, let's introduce PF127, Pluronic F-127, also known as Poloxamer 407. It is a very unique polymer with a chemical structure of PEO-PPO-PEO triblock copolymer. Its molecular chain has a hydrophobic polypropylene glycol segment in the middle and hydrophilic polyethylene glycol segments at both ends. As the temperature increases, the hydrophobicity of the PPO segments increases, causing them to dehydrate and aggregate to form micelles. These micelles then accumulate to form physical cross-linking points. Macroscopically, its aqueous solution is a flowing liquid at low temperatures. However, when the temperature rises to near body temperature, the solution transforms into a transparent semi-solid gel. Essentially, this is a phase transition process, which is completely reversible. Cooling it down will restore it to a liquid state, a process known as thermally reversible gelation.

[0048] The preparation principle of heat-shrinkable hydrogel: Sodium alginate is added to PF127 solution, and calcium ions formed by sodium alginate and calcium chloride solution are used for cross-linking and shaping.

[0049] Example 2.1 A method for preparing a heat-shrinkable nerve cannula using only PF127 refer to Figure 1 1) Prepare a hydrogel precursor solution by dissolving 20% ​​(w / v) PF127 and 1% sodium alginate in deionized water.

[0050] 2) The hydrogel precursor solution is injected into the mold; the mold includes an internal support rod 1 and an external receiving tube 2. The entire receiving tube 2 is a tube structure with a constant inner diameter, and the support rod 1 is a cylindrical structure with a constant diameter. The inner and outer shapes of the receiving tube 2 are similar to the outer shape of the support rod 1. After the receiving tube 2 and the support rod 1 are combined, an annular cavity is formed between the receiving tube 2 and the support rod 1. The annular cavity is used to inject the hydrogel precursor solution. The mold also includes a sealing and maintaining structure that seals both ends of the annular cavity and maintains the position of the receiving tube 2 and the support rod 1 in the combined state. The sealing and maintaining structure is an elastic flexible tube, including two sealing tubes. The inner diameter of the first sealing tube 41 is the same as the outer diameter of the receiving tube 2, and the inner diameter of the second sealing tube 42 is the same as the diameter of the support rod 1. A sealing and maintaining structure is provided at each end. In a more preferred embodiment, the length of the support rod 1 is longer than that of the receiving tube 2 to ensure sufficient operating position when the receiving tube 2 is separated from the support rod 1 with the nerve sheath 3.

[0051] 3) First, perform preliminary shaping at a temperature of 32-37 degrees Celsius for 30-60 minutes. Then, control the relative position change of the support rod 1 and the receiving tube 2 so that the receiving tube 2 is separated from the preliminary shaped nerve cannula 3 and support rod 1. Then, soak the separated nerve cannula 3 and support rod 1 in 2% calcium chloride crosslinking agent for crosslinking for 10 minutes.

[0052] 4) Separate the nerve cannula 3 from the support rod 1 to complete the demolding operation and prepare an adaptively narrowed nerve cannula 3 for repairing severed nerves.

[0053] 5) Apply an adhesive coating to the inside of the heat-shrinkable sleeve after demolding and cure it using ultraviolet light. The adhesive coating uses a polyacrylic acid coating, employing a deionized aqueous solution of 20% v / v acrylic acid and 1% w / v α-ketoglutaric acid. After being added to the sleeve and left to stand, the hydrogel's hygroscopic properties will cause the solution to be adsorbed onto the surface. After irradiation with 365nm ultraviolet light, the acrylic monomers will polymerize to form polyacrylic acid (PAA). The carboxyl groups of PAA can form a dense hydrogen bond network with these groups on the tissue surface, thus providing tissue adhesion. It is unclear whether bioactive materials need to be added to the adhesive coating.

[0054] When using, refer to Figure 4 Remove the nerve cannula 3 from the low-temperature environment, then insert the two ends of the severed nerve into the two ends of the cannula respectively, keeping the position of the nerve and the nerve cannula 3 unchanged. Then, as the body temperature rises, the temperature of the nerve cannula 3 reaches the temperature of phase transition tube shrinkage, and wait for or provide an external heat source to shrink the nerve cannula 3 into close contact with the nerve.

[0055] refer to Figure 5 First, a rat model was constructed. Then, the severed nerve was bridged to the nerve sheath 3. The nerve sheath without added heat-effect agent was kept warm and its shrinkage controlled by the rat's body temperature and a heat lamp. This method of preparation of the nerve sheath 3 is more convenient and faster, with a shorter cross-linking time. However, the shrinkage is slow when irradiated by a surgical heat lamp, which is relevant to the above method. Figure 8 and 9 Currently, through rat simulation experiments, the simulation experiments are mainly carried out using a rat model with the same nerve transection constructed. The number of rats is 6, and the overall retraction time of the nerve cannula 3 is in the range of 20-30 minutes. The average time for the 6 rats is 25.6 minutes, with an error of 4.1 minutes.

[0056] Although the surgery time is still relatively long, it is still an adaptive tube shrinking procedure that avoids the suturing step and reduces the reliance on doctors.

[0057] Example 2.2 A method for preparing a nerve cannula with an added photocrosslinking step. refer to Figure 1 ;1) Prepare a hydrogel precursor solution by dissolving 15% (w / v) PF127, 5% PF127Di (acryloylated PF127, crosslinked using UV), 0.25% LAP (photoinitiator) and 1% sodium alginate in deionized water.

[0058] 2) The hydrogel precursor solution was injected into the mold. Compared with the mold in Example 2.1, the mold was made of transparent material, specifically polytetrafluoroethylene material.

[0059] 3) First, perform preliminary shaping at a temperature of 32-37 degrees Celsius for 30-60 minutes, then use 365nm ultraviolet light for shaping. Then, control the relative position change of the support rod 1 and the receiving tube 2 so that the receiving tube 2 is separated from the pre-shaped nerve cannula 3 and support rod 1. Then, soak the separated nerve cannula and support rod 1 in 2% calcium chloride crosslinking agent for secondary crosslinking for 10 minutes.

[0060] 4) Separate the nerve cannula 3 from the support rod 1 to complete the demolding operation and prepare an adaptively narrowed nerve cannula 3 for repairing amputation injuries.

[0061] 5) Spray an adhesive coating inside the heat shrink sleeve after demolding and cure it with ultraviolet light.

[0062] The shape of the nerve cannula 3 prepared in this embodiment is the same as that of the nerve cannula 3 in Example 2.1, and the method of use is also the same.

[0063] The neural sheath 3 prepared in this embodiment, by adding a photocurable material, is cured under ultraviolet light. Because it uses a double cross-linking system, its toughness is better than that of Example 2.1. However, because no material with photothermal effect is added, the neural sheath 3 shrinks slowly after nerve docking under heat lamp irradiation. Figure 8 and Figure 9 Currently, through rat simulation experiments, the simulation experiments are mainly carried out using a rat model with the same nerve transection constructed. The number of rats is 6, and the overall shrinkage time of the nerve cannula 3 is in the range of 20-30 minutes. The average time for the 6 rats is 24.6 minutes, with an error of 4.8 minutes.

[0064] Of course, the nerve cannula 3 prepared by this method has the advantage of being self-adaptive to shrinking, except that it takes a long time to shrink. This avoids the need for suturing and reduces the dependence on doctors.

[0065] Example 2.3 A method for preparing a neural cannula by adding a photocrosslinking step and incorporating a photoeffect substance into a hydrogel precursor solution. refer to Figure 1 and Figure 2 ;1) A hydrogel precursor solution was prepared by dissolving 15% (w / v) PF127, 5% PF127Di (acryloylated PF127, crosslinked using ultraviolet light), 0.25% LAP (photoinitiator), 1% sodium alginate and carbon nanotubes (CNT) in deionized water.

[0066] 2) The hydrogel precursor solution was injected into the mold, which was made of a transparent material compared to the mold in Example 2.1.

[0067] 3) First, perform preliminary shaping at a temperature of 32-37 degrees Celsius for 30-60 minutes, then use 365nm ultraviolet light for shaping. Then, control the relative position change of the support rod 1 and the receiving tube 2 so that the receiving tube 2 is separated from the pre-shaped nerve cannula 3 and support rod 1. Then, soak the separated nerve cannula and support rod 1 in 2% calcium chloride crosslinking agent for secondary crosslinking for 10 minutes.

[0068] 4) Separate the nerve cannula 3 from the support rod 1 to complete the demolding operation and prepare an adaptively narrowed nerve cannula 3 for repairing amputation injuries.

[0069] 5) Spray an adhesive coating inside the heat shrink sleeve after demolding and cure it with ultraviolet light.

[0070] The shape of the nerve cannula 3 prepared in this embodiment is the same as that of the nerve cannula 3 in Example 2.1. When using either type of cannula, refer to... Figure 7 The shrinkage process differs; after inserting the same or different nerves into the nerve cannula 3, illumination is performed using the 808 wavelength. Under illumination, the CNTs generate collective electron oscillations, thus efficiently absorbing light and rapidly generating heat. Combined with the thermal phase change contraction of PF127, the cannula can rapidly shrink in volume under illumination. (See reference...) Figure 5 First, a rat model was constructed. Then, the severed nerve was bridged with nerve sheath 3. The nerve sheath, infused with a thermogenic agent, was controlled to shrink using the rat's body temperature and near-infrared light irradiation, as per reference. Figure 8 and Figure 9 Currently, through rat simulation experiments, the simulation experiments are mainly carried out using a rat model with the same nerve transection constructed. The number of rats is 6, and the overall retraction time of the nerve cannula 3 is in the range of 5-8 minutes; the average time for the 6 rats is 6.4 minutes, with an error of 2 minutes.

[0071] A more preferred embodiment; see reference Figure 2 and Figure 6 Furthermore, dopamine and divalent and trivalent iron ions can be chelated on the outer side of the CNT. When using the nerve cannula 3 in this embodiment, in addition to light-induced cannulation, magnetic targeted stimulation can be applied to the sutured nerve to accelerate nerve repair. An exogenous magnetic field can generate a directional current in the CNT / Fe / PDA complex, promoting the directional growth of nerve axons and Schwann cells. (See references for further details.) MagneticField‐AssistedConductiveNerveGuidanc eConduitEnablingPeripheralNerveRegenerationwithWirelessElectricalStimulation- Liu-2025-AdvancedFunctionalMaterials-WileyOnlineLibrary. Alternatively, graphene can be used to replace carbon nanotubes. Graphene has a similar function to carbon nanotubes (CNTs) in this paper, acting as a conductor, while iron oxide is responsible for generating charges under the influence of a magnetic field.

[0072] Example 3: Effects of using the adaptive diameter-reducing nerve cannula The rat experimental results of repairing severed nerves using the nerve cannulas 3 prepared by the methods of Examples 2.2 and 2.3 and the direct suturing method are mainly compared by comparing the specific staining of nerve axons and myelin sheaths with the target muscle reinnervation.

[0073] S100 (S100 protein immunofluorescence staining) and NF200 (Neurofilament 200 immunofluorescence staining) are specific stainings for nerve axons and myelin sheaths; the stronger the signal, the better the recovery.

[0074] Masson staining of the gastrocnemius muscle is used to observe the results of nerve regeneration and the re-innervation of the target muscle; the integrity of the muscle fibers reflects the recovery effect.

[0075] refer to Figure 12 It can be seen that the nerve repair effect of the adaptive shrinking nerve cannula 3 in Example 2.3 with added CNT material is closest to that of the undamaged sham surgery group. Moreover, the nerve repair effect of the adaptive shrinking nerve cannula 3 in Example 2.2 is significantly better than that of direct suturing.

Claims

1. An adaptive diameter-reducing nerve cannula for use in severed nerve injuries, characterized in that, The inner diameter of the nerve cannula is larger than the outer diameter of the nerve to be repaired. The nerve cannula is a tube with a uniform diameter. The nerve cannula can adaptively shrink under body temperature or stimulation that is safe for the human body, so that the nerve cannula can make close contact with the nerve inside the nerve cannula. The main body of the nerve cannula is a phase change shrinking hydrogel.

2. The nerve cannula according to claim 1, characterized in that, The length of the nerve cannula ranges from 5 to 20 mm; the inner diameter of the nerve cannula is set from 1 to 10 mm; and the minimum inner diameter of the nerve cannula that can adaptively shrink is 0.7 to 8 mm; the shrinkage range is 0.3 to 2 mm.

3. The nerve cannula according to claim 2, characterized in that, A nerve cannula with an inner diameter of 1 mm is provided, and a different type of nerve cannula is provided at intervals of 0.5 mm.

4. The nerve cannula according to claim 1, characterized in that, The nerve cannula is biodegradable, and its degradation cycle matches the rate of nerve regeneration. The nerve cannula, primarily composed of phase change shrinkage hydrogel, contains substances that undergo cross-linking reactions with calcium ions and calcium ions themselves, ensuring the cannula's biodegradability. Preferably, the phase change shrinkage hydrogel precursor solution is a PF127 precursor solution.

5. The nerve cannula according to claim 1, characterized in that, An adhesive coating is also provided on the inner side of the nerve cannula; Preferably, the adhesive coating is a polyacrylic acid coating; Preferably, the inner wall of the sleeve is coated with a deionized aqueous solution of 20% V / V acrylic acid and 1% W / V α-ketoglutaric acid.

6. The nerve cannula according to claim 1, characterized in that, The nerve cannula comprises a uniformly distributed photothermal material, enabling it to rapidly shrink under near-infrared irradiation. Preferably, the photothermal material is carbon nanotubes; Preferably, CNTs can be used in place of or in combination with other photothermal materials, such as nano-iron oxide, carbon quantum dots, graphene quantum dots, and graphene oxide quantum dots. Alternatively, the photothermal effect material is a CNT / Fe3O4 composite nanomaterial.

7. A method for preparing a nerve cannula, characterized in that, 1) Prepare a phase change hydrogel precursor solution with a phase change temperature of 35-38℃; add a substance that can undergo a cross-linking reaction with calcium ions to the hydrogel precursor solution; 2) The hydrogel precursor solution is injected into the mold. The mold includes an internal support rod 1 and an external receiving tube. The entire receiving tube is a tube structure with a constant inner diameter, and the support rod is a cylindrical structure with a constant diameter. The inner and outer shapes of the receiving tube are similar to the outer shape of the support rod. After the receiving tube and the support rod are combined, an annular cavity is formed between the receiving tube and the support rod. The annular cavity is used to inject the hydrogel precursor solution. 3) Control the relative position change of the support rod and the receiving tube to separate the receiving tube from the initially shaped nerve cannula and support rod, and then soak the separated nerve cannula and support rod in calcium chloride crosslinking agent for crosslinking. 4) Separate the nerve cannula from the support rod to complete the demolding operation, and manufacture an adaptive diameter-reducing nerve cannula that can be applied to severed nerve injuries; Preferably, an adhesive coating is added to the inner wall of the demolded nerve cannula.

8. The method according to claim 7, characterized in that, Photothermal material is added to the hydrogel precursor solution in step 1, preferably carbon nanotubes, nano-iron oxide, or a composite thereof.

9. The preparation method according to claim 7, characterized in that, In step 1, a photocrosslinking agent and a photoinitiator are added to the hydrogel precursor solution to form a photocrosslinking polymerization system. After the preliminary shaping step in step 3, ultraviolet crosslinking is performed. Then, the relative positions of the support rod and the receiving tube are controlled to separate the receiving tube from the preliminary shaped nerve cannula and the support rod. Finally, the separated nerve cannula and the support rod are immersed in calcium chloride crosslinking agent for secondary crosslinking. In-situ polymerization is initiated by ultraviolet or visible light to enhance the crosslinking density and mechanical stability of the hydrogel network.

10. The preparation method according to claim 7, characterized in that, The mold also includes a sealing and maintaining structure that seals both ends of the annular cavity and maintains the position of the receiving tube and the support rod in the combined state; the sealing and maintaining structure is an elastic flexible tube, including two sealing tubes, the inner diameter of the first sealing tube is the same as the outer diameter of the receiving tube, and the inner diameter of the second sealing tube is the same as the diameter of the support rod, with a sealing and maintaining structure at each end. Preferably, the length of the support rod is longer than that of the receiving tube, so as to ensure sufficient operating space when the receiving tube is separated from the support rod with the nerve sheath; Preferably, both the mold's receiving tube and support rod are made of transparent polytetrafluoroethylene material.

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