CN113180885A

CN113180885A - Optic nerve interface and its preparing method

Info

Publication number: CN113180885A
Application number: CN202110356350.1A
Authority: CN
Inventors: 周婵; 黄勇; 马群忠; 吕金凤; 王介平
Original assignee: Chongqing Academy of Animal Sciences
Current assignee: Chongqing Academy of Animal Sciences
Priority date: 2021-04-01
Filing date: 2021-04-01
Publication date: 2021-07-30

Abstract

The invention relates to the field of biological nerves, in particular to an optic nerve interface and a preparation method thereof. The invention adopts silk fiber and metal material to make a nerve interface which can be connected with optic nerve, the optic nerve axon grows along the gap and can be connected with a lead wire made of metal material through the interface, thereby the optic nerve and the implanted type instrument are connected into reality, and the vision of the patient with visual disorder caused by retinopathy can be recovered. The implanted optic nerve interface researched by the invention has good biocompatibility, is not degraded in vivo for a long time, establishes a one-to-one corresponding relation between the conducting wire and each optic nerve fiber, acquires more direct and accurate signals, and can recover vision of a patient with visual disorder caused by retinopathy.

Description

Optic nerve interface and its preparing method

Technical Field

The invention relates to the field of biological nerves, in particular to an optic nerve interface and a preparation method thereof.

Background

The optical system, retina, optic nerve and visual center of vision are formed, and the lesion of any link can cause visual disturbance. There are many clinical treatments for the pathological changes of the optical system. Visual disturbances caused by retinopathy, optic nerve and central vision disorders are troublesome, with those caused by retinopathy being the most common.

There are many approaches to dealing with the visual disturbance caused by retinopathy. These concepts mainly include two broad categories, one of which is to facilitate retinal repair from a purely medical perspective, and the other of which is to assist the patient in forming vision from the perspective of medical instruments. There are two main strategies in the study of assisting patients with medical devices to establish vision, namely implantable and non-implantable devices. The implanted instrument has good effect but higher difficulty; non-implantable devices circumvent some medical difficulties, but the effect is less than ideal.

The difficulty of implantable devices is that the retina and the visual center are composed of hundreds of millions of cells, and the structures are very complex and basically difficult to reach by manpower. The structure of the optic nerve consists of approximately 5000 nerve fibers, and it is relatively easy to restore the vision of a visually impaired patient starting from the optic nerve. Therefore, it is very important to explore a superior material capable of replacing nerves and a corresponding connection mode, and how to connect the nerves with an implanted instrument becomes a problem to be solved urgently.

Disclosure of Invention

The invention provides an optic nerve interface and a preparation method thereof for solving the problems, and the optic nerve interface is developed by using the good biocompatibility of silk fiber.

One of the objectives of the present invention is to provide an optic nerve interface, which has the following specific technical scheme:

an optic nerve interface, which comprises a conduit, monofilaments and a lead, wherein the conduit is in a tubular shape formed by weaving the monofilaments, the monofilaments piled up in a bundle shape are contained in the conduit, and the lead is positioned in a gap formed between the monofilaments; the nerve end connected with the catheter is provided with a cavity, and the guide wire is made of metal materials.

Preferably, the monofilament is a monofilament in natural cocoon silk fiber, and is made of raw silk through degumming treatment, and the diameter of the monofilament is 15-28 μm.

Preferably, the monofilament diameter is 18 μm.

Preferably, the inner diameter of the catheter is the same as the outer diameter of the optic nerve.

Preferably, the number of filaments and the number of slits contained in the catheter are equal to n, which is the total number of nerve fibers in the optic nerve ± 500.

Preferably, the wire is made of metal with good ductility and excellent conductivity, such as gold, platinum or silver, by step-by-step stretching, and the diameter of the wire is 5-10 μm.

Preferably, the wire is made of gold material and has a diameter of 8 μm.

Preferably, the length of the cavity is 2-20 mm.

Preferably, the cavity has a length of 20 mm.

Preferably, the outer surface of the lead is wrapped by an organic polymer, and the organic polymer has the performance of electric insulation, difficult degradation in vivo and good biocompatibility.

The second purpose of the present invention is to provide a method for preparing the neural interface, which comprises the following specific technical scheme:

a method for preparing an optic nerve interface, comprising the following steps:

(1) weaving the monofilaments to obtain the catheter;

(2) stacking monofilaments within the conduit;

(3) adding metal wires into the piled monofilament gaps;

(4) the nerve end connected with the catheter is provided with a cavity.

Furthermore, the number of monofilaments and the number of slits contained in the catheter are the same, and are both n, which is the total number of nerve fibers in the optic nerve +/-500.

Preferably, 5000 monofilaments are contained in the catheter, the number of the gaps is 5000, and the number of the wires is 5000.

Further, the monofilament is made of raw silk by degumming and has a diameter of 15-28 μm.

The metal wire with the diameter of about 5-10 mu m is preset in the optic nerve interface, so that the information communication between the nerve fiber message and external equipment can be ensured.

The invention has the advantages that: the implanted optic nerve interface researched by the invention adopts the silk fiber which has good biocompatibility and is not degraded in vivo for a long time to develop the nerve interface, and the acquired signals are more direct, accurate and complete. Compared with the neural interface for recovering the visual disorder, the implanted type optic nerve interface researched by the invention establishes a one-to-one corresponding relation with each optic nerve fiber, so that the vision of the patient with the visual disorder caused by retinopathy can be recovered.

Drawings

FIG. 1 is a flow chart of the preparation of the neural interface of the present invention

FIG. 2 is a diagram of an application scenario of the neural interface of the present invention

FIG. 3 is the NF200 immunofluorescence chromosome observation chart of rat optic nerve cross section

FIG. 4 is a transmission electron microscope photograph of the cross section of the mouse optic nerve in the example

FIG. 5 is a graph showing the growth of rat sciatic nerve fibers in the gap formed by silk fibers in the example

In the figure, 1-lead, 2-monofilament, 3-conduit, 4-nerve fiber, 5-optic nerve, 6-signal conversion device, 7-wireless signal transmitter, 8-brain-machine interface and wireless signal receiver, 9-microchannel.

Detailed Description

The present invention will be described in further detail with reference to the following examples and drawings, it being understood that the present invention is not limited to the particular examples described herein, but is capable of modification in various forms and details, and can be modified within the spirit and scope of the invention.

Fig. 2 is a research object of the present invention, even if the vision-impaired patient restores vision by implanting a brain-machine interface, which is a technical problem that the brain-machine interface needs to overcome, in cooperation with an external device, the present invention adopts silk fibers with good biocompatibility and no degradation in vivo for a long time to develop a nerve interface, and uses metals to make conducting wires, such as yellow, silver, copper and other conducting metals.

DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION

(1) Study of rat optic nerve Structure

Rat optic nerves were taken, transected, and observed with a transmission electron microscope. The nerve fibers were counted and analyzed for shape, diameter and arrangement.

(2) Preparation of silk monofilament fiber

Boiling the cooked silk with dilute alkali, and removing sericin to obtain monofilament fiber for later use.

(3) Preparation of metal wire from gold

A series of pores with gradient diameters are preset on a metal plate, the minimum pore diameter is 8 mu m, gold wires are gradually stretched and extruded in the pores, and the metal wires with the diameter of 8 mu m are finally prepared by utilizing the excellent ductility of the gold. The wires are treated with an organic polymer and coated with a layer of insulating material on the outer surface for use.

(4) Preparation of optic nerve interface

Weaving a conduit with the inner diameter of 700 mu m by using monofilament fibers; placing about 5000 monofilaments in the catheter, wherein the monofilament fibers are piled up into a bundle, about 5000 gaps are formed among the monofilaments, and each gap can just accommodate 1 optic nerve fiber to grow in the gap; one side (2 mm from the end) of each slit is preset with 1 wire (total of about 5000 wires, diameter about 8 μm) to prepare the optic nerve interface, as shown in fig. 1, wherein the 2mm space reserved in each slit is for optic nerve fiber ingrowth until the wire is connected. After the optic nerve is transected, the section is inserted into a cavity reserved in the catheter, and the axons of the optic nerve grow along the gaps until the axons are connected with the guide wire, so that the aim that each optic nerve fiber is connected with one guide wire is fulfilled.

The prepared neural interface is shown in figure 1 and comprises a tubular catheter woven by monofilaments, the monofilaments and a lead, wherein the monofilaments which are piled up into bundles are contained in the catheter, and the lead is positioned in a gap formed between the monofilaments and is made of a metal material; the nerve end connected with the catheter is provided with a cavity. The monofilament is made of silk fibroin and has a diameter of 18 μm; the inner diameter of the conduit is 700 mu m; the catheter contains 5000 monofilaments, the number of the gaps is 5000, and the number of the wires is 5000. The wire is made of gold material and has a diameter of 8 μm. The length of the cavity is 2 mm. The outer surface of the lead is wrapped with organic polymer to play a role of insulation.

(5) Biocompatible detection of optic nerve interface

The optic nerve of the rat is cut off, and the optic nerve interfaces are respectively implanted at the broken ends of the optic nerve facing to the eyeball side and the brain side. And (3) obtaining materials at a series of time points, performing morphological observation, transcriptome analysis and bioelectricity detection, taking the materials as a basis for judging the biocompatibility of the optic nerve interface, and adjusting the preparation scheme of the optic nerve interface on the basis of the basis.

It can be seen from fig. 3-5 that rat sciatic nerve fibers grow well in the gap formed by the silk fibers, thereby verifying the feasibility of the invention for preparing the nerve interface by using the silk fibers, and explaining that the diameters of specific guide lines and guide pipes, the size of the reserved gap and the like are the prerequisite guarantees, after all, the optic nerve is simpler than other nerves, and if the nerve interface is applied to other nerves, specific parameters of the guide pipes, the guide lines, the monofilament gaps and the cavities (reserved growth spaces) need to be further explored.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.

Claims

1. An optic nerve interface, characterized in that, the nerve interface comprises a conduit, monofilaments and a lead, the conduit is in a tubular shape formed by weaving the monofilaments, the monofilaments piled up in a bundle shape are contained in the conduit, and the lead is positioned in a gap formed between the monofilaments; the nerve end connected with the catheter is provided with a cavity, and the guide wire is made of metal materials.

2. The neural interface of claim 1, wherein the monofilaments are monofilaments of natural silk fibres having a diameter of 15-28 μm.

3. The neural interface of claim 1, wherein the inner diameter of the conduit is the same as the outer diameter of the optic nerve.

4. The neural interface of claim 1, wherein the number of monofilaments and the number of slits contained within the conduit are the same.

5. The neural interface of claim 1, wherein the leads are made of gold material and have a diameter of 5-10 μm.

6. The neural interface of claim 1, wherein the cavity is 2-20mm in length.

7. The neural interface as claimed in claim 1, wherein the outer surface of the lead is coated with an organic polymer, and the organic polymer has an electrical insulating effect, is difficult to degrade in vivo, and has good biocompatibility.

8. A method for preparing an optic nerve interface, comprising the following steps:

(1) weaving the monofilaments to obtain the catheter;

(2) stacking monofilaments within the conduit;

(3) adding metal wires into the piled monofilament gaps;

(4) the nerve end connected with the catheter is provided with a cavity.

9. The method of claim 8, wherein the number of filaments and the number of slits contained in the conduit are the same.

10. The method of claim 8, wherein the monofilaments are made of silk fibroin and have a diameter of 18 μm; the lead is made of gold material and has a diameter of 5-10 μm.