阅读说明：本技术 一种助修复可降解自发电场的神经支架 (Help to restore nerve support of degradable self-generating field ) 是由 李扬德 王佳力 刘芳菲 于 2021-01-14 设计创作，主要内容包括：本发明公开了一种助修复可降解自发电场的神经支架,呈中空结构的管状结构,包括可降解的导管外层、导管中间层和导管内层,所述导管中间层位于所述导管外层与所述导管内层之间,所述导管外层具有多个通孔,所述导管中间层和所述导管内层之间设有可降解的正极和负极,正极和负极之间有一定距离,所述正极和所述负极为两种金属活泼性不同金属材质,且负极较正极活泼。正极和负极利用人体内部的体液环境作为电解质溶液形成闭合回路,活波性强的金属作为负极,活波性弱的金属作为正极,与体液形成原电池,发生有序的电子转移过程,产生电流,自发产生电刺激,促进神经元分化、神经突起生长及血旺细胞释放神经营养因子。(The invention discloses a nerve support for assisting in repairing a degradable self-generating field, which is of a tubular structure with a hollow structure and comprises a degradable conduit outer layer, a conduit middle layer and a conduit inner layer, wherein the conduit middle layer is positioned between the conduit outer layer and the conduit inner layer, the conduit outer layer is provided with a plurality of through holes, a degradable anode and a degradable cathode are arranged between the conduit middle layer and the conduit inner layer, a certain distance is reserved between the anode and the cathode, the anode and the cathode are made of two metal materials with different metal reactivities, and the cathode is more reactive than the anode. The positive electrode and the negative electrode form a closed loop by taking a body fluid environment inside a human body as an electrolyte solution, the metal with strong wave activity as the negative electrode and the metal with weak wave activity as the positive electrode form a primary battery with body fluid, and the primary battery and the body fluid generate an ordered electron transfer process to generate current and spontaneously generate electric stimulation to promote neuron differentiation, neurite growth and blood-activating cells to release neurotrophic factors.)

1. The utility model provides a help to restore nerve support from power generation field of degradable, its characterized in that is hollow structure's tubular structure, including degradable pipe skin, pipe intermediate level and pipe inlayer, the pipe intermediate level is located the pipe skin with between the pipe inlayer, the pipe skin has a plurality of through-holes, the pipe intermediate level with be equipped with degradable anodal and negative pole between the pipe inlayer, the pipe intermediate level with at least one of the pipe inlayer has electric conductivity, anodal with there is the certain distance between the negative pole, anodal with the negative pole is the different metal material of two kinds of metal liveliness, just the negative pole is comparatively anodal liveliness.

2. The nerve scaffold for assisting in repairing a degradable self-generating field according to claim 1, wherein the positive electrode is a sheet structure formed of Zn, Fe or an alloy thereof; the negative electrode is a sheet structure formed by Mg, Ca or an alloy thereof.

3. The nerve scaffold for assisting in repairing a degradable self-generating field according to claim 2, wherein the thickness of the positive electrode and the thickness of the negative electrode are smaller than the thickness of the inner layer of the catheter.

4. The nerve scaffold for assisting in repairing a degradable self-generating farm according to claim 2, wherein the thickness of the negative electrode is 3 to 5 μm, and the thickness of the positive electrode is 1 to 3 μm.

5. The repair-assisting nerve scaffold capable of degrading self-generating power field according to claim 1, wherein the positive electrode is a rod-like structure formed of Zn, Fe or ZnFe alloy; the negative electrode is a rod-shaped structure formed by Mg, Ca or an alloy thereof.

6. The nerve scaffold for assisting in repairing a degradable self-generating field according to claim 5, wherein a plurality of Mg rods, Ca rods or MgCa alloy rods are arranged at intervals along the axial direction of the tube axis of the tubular structure at one end between the catheter intermediate layer and the catheter inner layer, and a plurality of Zn rods, Fe rods or ZnFe alloy rods are arranged at intervals along the axial direction of the tube axis of the tubular structure at the other end between the catheter intermediate layer and the catheter inner layer.

7. The nerve scaffold for assisting in repairing a degradable self-generating field according to claim 1, wherein the material of the outer layer of the catheter is selected from one of polylactic acid, hydroxyapatite, collagen, nerve growth factor and polylactic-acid-polyglycolic acid copolymer.

8. The nerve scaffold for assisting in repairing a degradable self-generating farm as claimed in claim 1, wherein the thickness of the outer layer of the catheter is greater than the thickness of the middle layer of the catheter.

9. The nerve scaffold for assisting in repairing a degradable self-generating farm according to claim 1, wherein the catheter intermediate layer is a conductive polymer structure; the inner layer of the conduit is of a conductive porous fiber structure.

10. The nerve scaffold for assisting in repairing a degradable self-generating field according to claim 1, wherein the inner layer of the catheter has a fiber structure, and the fiber direction is parallel to the electron flow direction between the positive electrode and the negative electrode.

Technical Field

The invention relates to the technical field of nerve repair, in particular to a nerve scaffold for repairing and degrading a self-generating farm in an assisted manner.

Background

The nervous system is one of the most prominent tissues in the human body, which controls the sensory and motor functions of the human body. Trauma such as compression, stretching, laceration, severing and other factors such as ischemia, tumors, etc. will cause partial or complete damage to the nervous system, resulting in loss of function and other neurological disorders. The repair and functional reconstruction of defective nerves have been one of the difficulties in the medical field.

The current theory and medical practice prove that the neuron axons of peripheral nerves can extend under proper conditions and grow over the damaged area, so as to achieve the purpose of nerve regeneration. With the development of neurosurgery, and in particular, microneurosurgery, repair and regeneration of nerve damage has become possible. There are three major types of nerve repair techniques currently studied and clinically applied: direct anastomosis, nerve transplantation (autologous or allogenic), and nerve conduit repair.

The direct anastomosis is to directly carry out surgical suture on the proximal body end and the distal body end of the severed nerve, which is only limited to short nerve rupture (less than 8mm), because the nerve has no stretching function, the tension generated by the suture can influence the regeneration of the nerve, so the direct anastomosis can not be applied to the long intermittent nerve defect, and the curative effect and the yield are only 50%.

Nerve transplantation results in loss of supply area nerve function, insufficient supply of larger and thicker nerve defects, and secondary surgical problems. The problem of immunosuppression needs to be solved by xenotransplantation. Direct anastomosis and nerve transplantation also present the problem of dislocation of severed sensory and motor nerve fibers. In the field of trauma surgery, nerve injury repair is performed by suturing the nerve end, but peripheral nerves are mixed nerves, so a scientific identification method capable of quickly and accurately identifying sensory nerves and motor nerve fibers at the nerve end is still lacked at present, and even if the delicate microsurgery technology is applied to perform fascial suture, the influence on the curative effect of nerve suture and the recovery of nerve function caused by the misorientation butt joint of the sensory and motor nerve fibers after the nerve end is sutured is difficult to avoid.

For patients with long-defect nerve injuries (e.g. greater than 20mm) or lack of suitable conditions for autologous nerve transplantation, it is necessary to use an autologous nerve transplantation substitute, artificial nerve conduit or nerve scaffold, to promote nerve fiber regeneration. Nerve conduit repair (bridging) is a research hotspot of nerve regeneration repair at present, and is a great hotspot which is concerned by the fields of tissue engineering, materials, biology and medicine. Scholars at home and abroad have proved the feasibility of replacing autograft with nerve conduit to repair nerve defect in recent ten years. Because the nerve has certain regeneration and repair capacity, the nerve is induced by the catheter to bridge the near body end and the far body end of the defective nerve and guide the regeneration direction of the nerve, so that the nerve with shorter defect length can be regenerated and repaired. Researchers use the chitosan material of NT3 to make spinal cord reconstruction tubes to promote spinal cord regeneration and injury repair.

Therefore, the nerve conduit repair is a promising nerve regeneration repair technology, and the nerve regeneration repair with short defect length can be realized by bridging the near body end and the far body end of the defect nerve through the conduit induction and guiding the regeneration direction of the nerve. However, the nerve conduit and the scaffold material far fail to meet clinical requirements and expectations of patients, and become bottlenecks that restrict implementation and development of nerve conduit repair technology, and how to perfect design of the nerve conduit and the scaffold material and improve and promote nerve repair and regeneration is a difficult point and a hotspot of current research, and research personnel and medical personnel are urgently needed to solve the problem.

Since the important function of nerve fibers is to transmit nerve impulses, the conduction process of nerve impulses is an electrochemical process, which is an electrochemical change that occurs sequentially on nerve fibers. If a material which can promote the conduction of nerve electrical signals is implanted between the defective nerve fibers or the spinal cord, the regeneration of the nerve fibers is promoted. At present, an artificial nerve conduit is generally implanted, and then the nerve/muscle is electrically stimulated through skin to promote nerve regeneration and repair, or an implanted electrical stimulation device is adopted, however, the former carries out accurate skin electrical stimulation at a loss part to increase the infection risk, the latter has high requirements on processing of miniaturized equipment, and the large-area application is difficult to realize considering the factors of electric leakage and non-degradability.

Therefore, there is a need to develop a neural scaffold for assisting in repairing degradable self-generating farms to solve the above-mentioned drawbacks.

Disclosure of Invention

Aiming at the defects in the prior art, the invention aims to provide a nerve scaffold for assisting in repairing a degradable self-generating farm.

In order to achieve the purpose, the invention discloses a nerve scaffold for assisting in repairing a degradable self-generating field, which is a tubular structure with a hollow structure and comprises a degradable conduit outer layer, a conduit middle layer and a conduit inner layer, wherein the conduit middle layer is positioned between the conduit outer layer and the conduit inner layer, the conduit outer layer is provided with a plurality of through holes, a degradable anode and a degradable cathode are arranged between the conduit middle layer and the conduit inner layer, at least one of the conduit middle layer and the conduit inner layer has conductivity, a certain distance is reserved between the anode and the cathode, the anode and the cathode are made of two metal materials with different metal reactivities, and the cathode is more reactive than the anode.

Compared with the prior art, when the nerve scaffold for the assisted-repairing degradable self-generating field is implanted into a damaged part, the positive electrode and the negative electrode form a closed loop by using a body fluid environment inside a human body as an electrolyte solution, the metal with strong activity wave is used as the negative electrode, the metal with weak activity wave is used as the positive electrode, and forms a primary battery with the body fluid, so that an ordered electron transfer process is generated, current is generated, electric stimulation is generated spontaneously, and neuron differentiation, neurite growth and blood-activating cell release of neurotrophic factors are promoted. The problem that the current conductive nerve conduit needs to be externally added with electrical stimulation through a metal electrode and the electrical stimulation is not accurate enough is solved, the nerve regeneration speed can be effectively improved, meanwhile, the pain and inconvenience of a patient are reduced, and the infection risk is reduced.

Preferably, the positive electrode has a sheet structure formed of Zn, Fe, or an alloy thereof.

Preferably, the thickness of the positive electrode and the thickness of the negative electrode are both smaller than the thickness of the inner layer of the conduit.

Preferably, the thickness of the positive electrode is 1 to 3 μm.

Preferably, the negative electrode is a sheet structure formed of Mg, Ca, or an alloy thereof.

Preferably, the thickness of the negative electrode is 3 to 5 μm.

Preferably, the positive electrode is a rod-shaped structure formed by Zn, Fe or ZnFe alloy; the negative electrode is a rod-shaped structure formed by Mg, Ca or an alloy thereof.

Preferably, a plurality of Mg rods, Ca rods or MgCa alloy rods are arranged at intervals along the axial direction of the tube axis of the tubular structure at one end between the intermediate layer of the guide tube and the inner layer of the guide tube, and Zn rods, Fe rods or ZnFe alloy rods are arranged at intervals along the axial direction of the tube axis of the tubular structure at the other end between the intermediate layer of the guide tube and the inner layer of the guide tube.

Preferably, the material of the outer layer of the catheter is selected from one of polylactic acid, hydroxyapatite, collagen, nerve growth factor and polylactic-co-glycolic acid.

Preferably, the thickness of the outer layer of the conduit is greater than the thickness of the middle layer of the conduit.

Preferably, the conduit intermediate layer is a conductive polymer structure; the inner layer of the conduit is of a conductive porous fiber structure.

Preferably, the inner layer of the conduit is of a fiber structure, and the fiber direction is parallel to the electron flow direction between the anode and the cathode.

Preferably, the inner layer of the conduit is in a porous fiber structure.

Preferably, the thickness of the inner layer of the conduit is 20-40 μm.

Preferably, the inner layer of the catheter is polycaprolactone porous fiber.

Drawings

FIG. 1 is a schematic structural diagram of a nerve scaffold for assisting in repairing a degradable self-generating farm according to the present invention.

Fig. 2 is a sectional view of the nerve scaffold for repairing the degradable self-generating farm shown in fig. 1.

Fig. 3 is a schematic structural diagram of another embodiment of the nerve scaffold for assisting in repairing the degradable self-generating farm shown in fig. 1.

Fig. 4 is a schematic exploded view of the nerve scaffold of the assisted repair degradable self-generating farm shown in fig. 3.

Description of the symbols:

the self-generating power plant repairing assisting and degradable nerve scaffold 100 comprises a catheter outer layer 10, through holes 11, a catheter middle layer 30, a catheter inner layer 50, a positive electrode 70 and a negative electrode 90.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Referring to fig. 1-2, the repair-assisting degradable self-generating farm nerve scaffold 100 of the present application is a tubular structure with a hollow structure, and includes a degradable catheter outer layer 10, a catheter intermediate layer 30 and a catheter inner layer 50, that is, the catheter outer layer 10, the catheter intermediate layer 30 and the catheter inner layer 50 are all biodegradable, the catheter intermediate layer 30 is located between the catheter outer layer 10 and the catheter inner layer 50, the catheter outer layer 10 has a plurality of through holes 11, the catheter outer layer 10 is filled with the through holes 11 in an array, a degradable positive electrode 70 and a degradable negative electrode 90 are disposed between the catheter intermediate layer 30 and the catheter inner layer 50, at least one of the catheter intermediate layer 30 and the catheter inner layer 50 has electrical conductivity, a certain distance is provided between the positive electrode 70 and the negative electrode 90, the positive electrode 70 and the negative electrode 90 are made of two metal materials with different metal reactivities, and the negative electrode.

Referring to fig. 2-4, the positive electrode 70 is a sheet structure formed of Zn, Fe or alloys thereof. The negative electrode 90 has a sheet structure formed of Mg, Ca, or an alloy thereof. On one hand, Zn, Fe or alloy thereof, Mg, Ca or alloy thereof is completely biodegradable in human body, does not produce harm to human body, and does not need secondary operation; on the other hand, Mg and Ca are more prone to losing electrons than Zn and Fe active waves, under the condition that body fluid is used as electrolyte solution, the positive electrode 70 and the negative electrode 90 form a closed loop to generate current, meanwhile, the electrode potentials of Zn and Fe are-0.7618V and-0.447V respectively, the electrode potentials of Mg and Ca are-2.372V and-2.868V respectively, and voltage generated in the system can stimulate nerves to generate self-repairing. Preferably, the positive electrode 70 has a Zn sheet structure and the negative electrode 90 has a Mg sheet structure. It is understood that the positive electrode 70 is disposed at one end between the conduit intermediate layer 30 and the conduit inner layer 50, and the negative electrode 90 is disposed at the other end between the conduit intermediate layer 30 and the conduit inner layer 50. In another embodiment, the positive electrode 70 is a rod-like structure formed of Zn, Fe, or ZnFe alloy; the negative electrode 90 has a rod-like structure of Mg, Ca, or an alloy thereof. Preferably, referring to FIG. 4, Mg rods, Ca rods, or MgCa alloy rods are used at one end of the tubular structure between the intermediate layer 30 of the guide tube and the inner layer 50 of the guide tube at intervals along the axial direction K of the tube axis (as shown in FIG. 1), and Zn rods, Fe rods, or ZnFe alloy rods are used at the other end of the tubular structure between the intermediate layer 30 of the guide tube and the inner layer 50 of the guide tube at intervals along the axial direction K of the tube axis.

Referring to fig. 1-2, the thickness of the positive electrode 70 and the thickness of the negative electrode 90 are both smaller than the thickness of the inner layer 50 of the catheter. Specifically, the thickness of the positive electrode 70 is 1 to 3 μm, such as but not limited to 1 μm, 2 μm, 3 μm. The thickness of the negative electrode 90 is 3 to 5 μm, and may be, for example, but not limited to, 3 μm, 4 μm, 5 μm. The thickness of the inner layer 50 of the conduit is 20-40 μm, and may be, but is not limited to, 20 μm, 25 μm, 30 μm, 35 μm, 40 μm. Further, the thickness of the catheter outer layer 10 is greater than the thickness of the catheter intermediate layer 30. Specifically, the thickness of the outer layer 10 of the catheter is 320-360 μm, such as but not limited to 320 μm, 330 μm, 340 μm, 350 μm, 360 μm. The thickness of the conduit intermediate layer 30 is 290-320 μm, such as but not limited to 290 μm, 300 μm, 310 μm, 320 μm.

Referring to fig. 1-2, the outer layer 10 of the catheter is made of one material selected from polylactic acid, hydroxyapatite, collagen, nerve growth factor and polylactic-co-glycolic acid. The outer layer 10 of the catheter is used as the outer layer of the nerve scaffold 100, a plurality of through holes 11 are formed in the outer layer to carry out nutrition conveying channels, and meanwhile, the material is adopted to realize complete biodegradation, so that the catheter has biocompatibility and can also play a supporting role. The catheter intermediate layer 30 is made of a conductive polymer, preferably a porous polymer material, to allow body fluid to permeate through, for example, the catheter intermediate layer 30 is made of polylactic acid-polytrimethylene carbonate, which is not only biocompatible and completely biodegradable, but also has good toughness. The inner layer 50 of the catheter is in a fibrous structure for attachment of neurons. Preferably, an electrically conductive porous fibrous structure is employed to allow body fluids to penetrate. The fibrous structure of the inner layer 50 of the catheter may improve the biocompatibility of the nerve scaffold 100. Further, the fiber direction of the fiber structure is parallel to the tube axis of the tubular structure, that is, the electron flow direction between the positive electrode 70 and the negative electrode 90 is parallel to the fiber direction of the fiber structure, that is, the tube axis direction K direction, which increases the adhesion of the number of nerve cells and increases the length of neurites. Specifically, the catheter inner layer 50 may be, but is not limited to, a polycaprolactone porous fiber. It is sufficient that either of the conduit intermediate layer 30 and the conduit inner layer 50 has a conductive property and is used for electron transfer, and it is preferable that the conduit intermediate layer 30 uses a conductive polymer layer as a transfer layer of electrons, but not limited thereto.

Compared with the prior art, when the nerve scaffold 100 for the assisted-repairing degradable self-generating field is implanted into a damaged part, the anode 70 and the cathode 90 form a closed loop by using a body fluid environment inside a human body as an electrolyte solution, the metal with strong activity wave property serves as the cathode 90, the metal with weak activity wave property serves as the anode 70, and forms a primary battery with the body fluid, an ordered electron transfer process is generated, current is generated, electrical stimulation is generated spontaneously, neuron differentiation, neurite growth and blood-activating cell release neurotrophic factors are promoted. The problem that the current conductive nerve conduit needs to be externally added with electrical stimulation through a metal electrode and the electrical stimulation is not accurate enough is solved, the nerve regeneration speed can be effectively improved, meanwhile, the pain and inconvenience of a patient are reduced, and the infection risk is reduced.

The above disclosure is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the scope of the present invention, therefore, the present invention is not limited by the appended claims.