RU2564558C1 - Artificial nerve - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: artificial nerve comprises electrically conducting organic polymer. It represents a medium of at least one electrically conducting organic polymer; the above medium has a through porosity with pores filled with sodium and potassium ionic solution, and is wrapped round with at least one layer of polymeric dielectric. At least one end of the artificial nerve is coated with a cation exchange membrane.

EFFECT: enabling the artificial nerve receiving and transmitting electric pulses received from an active nerve directly, and making them affined in the setting of short response time and resistance, adequate elasticity and durability of the artificial nerve.

8 cl, 1 tbl, 2 ex

Description

The invention relates to the field of electrically conductive materials, namely to artificial nerves based on polymers. The invention can be used in neurosurgery and prosthetics in the manufacture of bionic limbs or as an independent implant, as well as in robotics, in particular in the production of high-precision manipulators.

A facial nerve prosthesis is known in which the signal collection module collects the electromyographic signals of the muscles of the face from the healthy side of the face, the signals are sent to the control element and the processing module to complete the analysis, processing and conversion of the signals. Electrostimulation on the muscles of the affected side is realized by microstimulation of the electrodes in such a way that it causes contraction of the muscles of the face (CN 101185788 A, A61B 5/0488, 05/28/2008).

The disadvantage of this prosthesis of the facial nerve is that its work depends on the work of the muscles of the face with a healthy facial nerve, that is, if such a nerve is absent, its use is impossible.

Known medical artificial graft of a nerve trunk, including a sheath or sheath with a building fiber inserted into it, the sheath contains many micropores, and the sheath and / or building fiber contain silk fibroin (EP 1938774 A1, A61F 2/04, 02.07.2008).

The disadvantage of the described transplant is that it can only serve to restore damaged areas of the nerves and is not able to transmit a signal to the executive organ.

Known conductive polymer composite, consisting of polycaprolactone fumarate and polypyrrole (electrically conductive polymer), designed for nerve regeneration. When a current was passed through a nerve in the presence of the said composite, restoration of the nerve fiber in the direction of the applied current was observed (US 2013331869 A1, A61F 2/04, 12/12/2013).

The limitation in the use of the described composite lies in the fact that it cannot be used as missing sections of a nerve that receive or transmit a signal to organs.

The objective of the invention is the creation of a harmless flexible wear-resistant polymer electrical wire, which can be an analogue of the nerve fiber.

The technical result of the proposed invention is to enable the artificial nerve to receive and transmit electrical impulses received directly from the living nerve, and to provide affinity between them with reduced response time and resistance, as well as with sufficient elasticity and strength of the artificial nerve.

The technical result is achieved due to the fact that the proposed artificial nerve, which is a medium of at least one organic conductive polymer, which has a through porosity with pores filled with a solution of sodium and potassium ions, and which is entwined with at least one layer of a polymer dielectric, at least one end of the artificial nerve has a cation exchange membrane.

The electrically conductive polymer may be selected from the group: polypyrrole, polyazulene, polythiophene, poly-α-naphthylamine and a mixture thereof. These substances have high biocompatibility with nerve tissue, and they also have the ability to heal nerves.

The polymer dielectric can be selected from the group: polyethylene, polystyrene, a mixture of polystyrene and its copolymer, polytetrafluoroethylene, polyamide and a mixture thereof. These substances are characterized by high temperature and chemical resistance.

As a cation exchange membrane, you can use the MK-40 brand membrane or nafion-117 brand membrane, which have high chemical resistance. The MK-40 membrane is the most affordable, and the nafion-117 membrane is characterized by increased resistance to swelling when in contact with water.

The potassium and sodium solution may be, for example, a solution of KCl and NaCl.

To enhance the transmitted impulse, the artificial nerve may additionally contain polyvinylidene fluoride nanofibres.

If the artificial nerve should play the role of the sensitive, a matrix of piezoelectrics should be attached to its end.

The matrix of piezoelectrics can be a matrix of nanofibres of polyvinylidene fluoride, which are sufficiently strong and susceptible to contact.

For a long time there was the problem of creating an artificial analogue of nerve fiber - a biocompatible electrically conductive material that could be stitched with a nerve. However, most conductors are metals and other inorganic substances that are very distant in chemical affinity for nerve tissue. A similar problem can be solved using organic electrically conductive polymers, preferably polypyrrole, polyazulene, polythiophene, poly-α-naphthylamine or a mixture thereof. The listed polymers, being harmless, possessing high temperature and chemical resistance, among other things, are able not only to cross-link with nerves, but when passing current through a nerve, they contribute to the restoration of nerve fiber, which was established experimentally. In the most pronounced form, polypyrrole exhibits this property.

The current impulse in the living nerve passes immediately in both directions, that is, from the brain to the axon, which transfers the impulse to the working organ, and vice versa - from the axon to the brain, while the impulse is transmitted in both directions throughout the volume of the nerve fiber. First of all, this occurs due to the movement of charges in the fiber volume in both directions: electrons serve as a negative charge, and sodium ions as a positive charge, and the total ion current is determined immediately by three phenomena: the movement of sodium ions, the opposite movement of potassium ions and current leakage spent on the work of the host authorities. To ensure the ability of the artificial nerve to ion exchange with the present, it must have through porosity, and the pores must be filled with a solution of sodium and potassium ions, for example, in the form of a solution of NaCl and KCl, while a cation exchange membrane that allows ions to pass through must be applied to the stitched end of the artificial nerve alkali metals.

In the future, before performing artificial innervation, it will be necessary to mechanically make a recess at the end of the artificial nerve. When stapling, the end of the living nerve is placed in this recess so that both the fiber and the sheath of the latter are in contact with the electrically conductive polymer, but at the same time that the pores of the polymer are completely covered by the membrane. In this case, the fiber and sheath are fused with the polymer. Moreover, the use of polymers of polyazulene, polythiophene, poly-α-naphthylamine, and to a greater extent polypyrrole, leads to healing and accelerated proliferation of nerve tissue.

As a membrane, you can use a MK-40 chemically stable membrane, which is a composite of KU-2 ion-exchange resin and polyethylene, a nafion-117 homogeneous membrane, which is a copolymer of tetrafluoroethylene and perfluorinated sulfonated vinyl ether, as well as many other cation-exchange membranes, which should be select, based on their chemical resistance, price and pore size.

When a neuron or its process, an axon, is excited, Na ⁺ ions rush into the aforementioned neuron. In contrast to the flow of Na ⁺ ions from the cell, a compensating flow of K ⁺ ions diffuses through the membrane, which is somewhat delayed. A similar phenomenon can be observed when ions pass through an artificial cation-exchange membrane, which is associated with a difference in the sizes of potassium and sodium ions (potassium ion radius is 133 pm, sodium is 97 pm), while such characteristics as electronegativity and electrode potential slightly differ.

This process leads to the appearance of a negative charge on the outer surface of the cell membrane. The inner surface of the membrane acquires a positive charge, which provokes the appearance of an action potential.

In the case of stitching the living nerve with the proposed artificial analog, the nucleation of the action potential takes place not on the border “living nerve (or artificial nerve) - the receiving organ”, but on the border “living nerve - artificial nerve”, since the latter will serve in this case as an intermediate receiving organ, which will subsequently transmit an impulse to the final receiving organ. It is difficult to judge the shortcomings of such a device, however, it is obvious that such a difference will have a negative effect if an additional loss of current occurs during the artificial nerve in view of its properties.

To exclude a strong loss of current, said artificial nerve must be completely or partially entwined with at least one layer of polymer dielectric. Leave bare areas only in places of contact with the receiving authority. The following compounds are recommended to be used as dielectrics in view of the presence of a number of advantages described below:

- polytetrafluoroethylene, which has exceptional chemical resistance to acids, alkalis and oxidizing agents and has very wide operating temperature limits (from -270 to + 260 ° C), does not dissolve in organic solvents, is not wetted by water;

- polyamide, which is characterized by high strength, wear resistance, chemical resistance in various oils, dilute acids and alkalis;

- polyethylene, which is characterized by resistance to aggressive environments (except oxidizing agents) and moisture resistance, but it is typical for it to swell in the environment of hydrocarbons and their halogen derivatives. Polyethylene can be used in temperatures ranging from -20 to + 100 ° C. Its heat resistance can be increased by radiation;

- polystyrene, which is resistant to weak solutions of acids, alkalis and aliphatic hydrocarbons, has high mechanical strength, flexibility and elasticity.

It is worth noting that the production of films of pure polystyrene with a thickness of less than 100 μm is very difficult, but if you use it in a mixture with copolymer (s), the industry practices the manufacture of such films with a thickness of about 20 μm, which is quite comparable with the size of nerve fibers. As the copolymer, for example, styrene-butadiene-styrene or polytetrafluoroethylene can be used.

The proposed artificial nerve entwined with the indicated polymer dielectrics, in view of the presence of the latter properties such as temperature and chemical stability, can be used in aggressive environments, for example, in mechanical engineering and robotics, as an element of the transmission of a current pulse in ultraprecise manipulators.

First of all, the proposed artificial nerve is intended for its use both as a conductive element of the bionic limbs, and as an independent implant replacing the living nerve.

If it is used in a bionic limb, the desired reaction (speed and trajectory) of a given limb to a current impulse entering through an artificial nerve can be provided, for example, by correctly adjusting the neurocomputer interface (adjusting the response of limb elements to a particular input signal) or by selecting material with the desired properties (artificial muscles) into which the impulse enters.

Regarding the possibility of using an artificial nerve as an independent implant, the following should be noted.

In a living organism, neuromuscular transmission is more complex than the transmission of momentum in bionic limbs, a process accompanied by biochemical reactions in the nerve endings. An important role in neuromuscular transmission is played by substances such as neurotransmitters, which are essentially mediators in the transmission of momentum.

However, it is known that living, but denervated muscles can contract automatically as a result of the action of current pulses (Kozlovskaya L.E., Volotovskaya A.V. Electrodiagnostics / teaching aid for doctors, Minsk, BelMAPO, 2010, p. 8, paragraph 3).

It is also known that after a complete degeneration reaction, the muscle ceases to respond to the faradic current and only responds to the galvanic current (http: //www.n-bolezni.ru/top_diagn/2_1_3.html, as well as Kozlovskaya L.E., Volotovskaya A.V. Electrodiagnostics / teaching aid for doctors, Minsk BelMAPO, 2010, p. 11, paragraph 7), while during direct muscle irritation with this type of current, it reacts with a sluggish contraction (Kozlovskaya LE, Volotovskaya AV Electrodiagnosis / teaching aid for doctors, Minsk, BelMAPO, 2010, p. 8, paragraph 3).

Based on the foregoing, it can be concluded that neurotransmitters are extremely desirable biochemical correctors of pulse transmission, but if the pulse is a constant electric current of low voltage and low power (galvanic current), the transmission of this pulse can occur without their participation.

After receiving an electrical impulse from a living nerve by the movement of sodium ions and the opposite movement of potassium ions, a galvanic current is formed in the proposed nerve. In this case, the muscle response is enhanced due to the fact that the proposed nerve is connected directly to the muscle fibers. If the excitation of muscle fibers by galvanic current is carried out, for example, using myostimulants through the skin, fat deposits, etc., then due to the electrical resistance of the latter, the muscles will react very weakly.

In the event that the living nerve died long ago, there is a possibility of complete loss by the muscles of electroexcitation and their necrosis. To prevent this throughout the illness, it is strongly recommended that they be stimulated, such as electrophoresis, massage, myostimulation, etc.

In the case of a complete or partial reaction of degeneration, as follows from the foregoing, the proposed bionic nerve is able to provide, though sluggish and inferior, but movement of living muscles.

Moreover, this drawback can be partially compensated if the artificial nerve contains nanofibers of the organic polymer polyvinylidene fluoride, which can be obtained in the process of so-called electrospinning. This substance has been found to have piezoelectric properties, and it has many advantages over inorganic substances that generate current: it is not brittle, and also has a greater affinity for polypyrrole, polyazulene, polythiophene and poly-α-naphthylamine, of which more degrees may consist of a polymeric artificial nerve.

The use of polyvinylidene fluoride nanofiber will compensate for the defective excitation of muscles by the artificial nerve. When the initial brain signal through the nerve reaches the executive motor organ, the movement of the latter will lead to the movement of the artificial nerve, in which the polyvinylidene fluoride nanofibers begin to deform, amplifying the incoming signal.

The described improvement is recommended if the artificial nerve serves as a motor nerve. If it serves as a sensitive one, then a matrix of piezoelectrics should be attached to its end, which should receive the signal, that is, “feeling”, in the role of which, for example, elements from piezoelectric ceramics made of lead zirconate titanate PbZrO ₃ can serve - PbTiO ₃ , or elements consisting of Bi ₁₂ GeO ₂₈ or Bi ₁₂ SiO ₂₀ , however, due to its high strength and sensitivity, it is preferable to use polyvinylidene fluoride nanofibres.

When implementing such a scheme, the movement of piezoelectrics will lead to the creation of a signal-feeling going to the brain.

In the event that the executive organ is of artificial origin (artificial muscle, neurocomputer interface), as noted above, the problem of "sluggish movement" of the muscles disappears, because the response of artificial organs can be set by adjusting the neurocomputer interface or by selecting material of artificial muscles of a given size.

Examples of carrying out the invention

Example 1

An artificial nerve was made 10 cm long and 1.5 mm thick (excluding dielectric). First, polythiophene, poly-α-naphthylamine and a blowing agent were mixed in the following ratio of components, wt.%:

polythiophene twenty poly-α-naphthylamine 74 blowing agent 6

As a blowing agent used porphore brand DF-3. The resulting mixture was gradually heated to a temperature of 240 ° C, that is, to a temperature sufficient to decompose the porophore, kept for 4 minutes - until the through pore formation process was completed, cooled to a temperature of 150 ° C and began to pass through a die with a diameter of 1.5 mm . After the spinneret, the obtained thread was cooled to a temperature of 60 ° C, cut to the desired size and soaked in a solution heated to 60 ° C for 5 minutes containing 9 wt.% NaCl and 9 wt.% KCl. Then the thread was twisted around a dielectric layer consisting of polytetrafluoroethylene, 25 μm thick, cooled to room temperature, a MF-4SK cation exchange membrane was applied to the ends, and these ends were placed in a solution containing 9 wt.% NaCl and 9 wt.% KCl.

A layer of polytetrafluoroethylene was partially removed from the nerve.

Passing a current of 4 modes by means of contact between the needle electrodes and the sections exposed from the dielectric shell, the response time, resistance, and pulse conduction velocity were determined. By passing current through the contact of the needle electrodes with integral sections of the filament, the resistivity of the dielectric sheath was calculated.

Researches on elasticity, tensile and compression strength were also conducted.

The measured characteristics of the artificial nerve are presented in table 1.

After measurements, a cation exchange membrane was removed from one end of the nerve.

The second part of the experiment was that under anesthesia the frog began to replace the lower part of the muscular nerve of the hind left paw. The frog was placed in an alcohol solution containing benzocaine for 20 minutes. After its immobility, which indicated the onset of anesthesia, the surgeon was asked to replace the lower part of the muscular nerve of the hind left paw in such a way that the implantable nerve passes in the same way as the real one, so that the parts of the nerve exposed from the dielectric come into contact with the muscles.

After removing a part of the muscle nerve at the end of its artificial analogue, a depression was made by mechanical means, the activated end of the living nerve was inserted into the depression in such a way that both the fiber and the sheath of the nerve were in contact with the electrically conductive polymer, but at the same time that the polymer pores were completely covered by the membrane. Then, epineural sutures were applied along the compatible edges using KL-3 medical polyurethane adhesive.

A few hours after the operation, the frog could sluggishly and with a weak amplitude make movements with the operated foot. A few days later, it was possible to draw a conclusion about the implant engraftment.

When jumping, the frog often turned to the left. This testified to the fact that the left paw in the part of the replaced nerve worked inferiorly - the nerve signal excited muscles weakly, and also, in all likelihood, the brain's information about the trajectory of movement was distorted. But nevertheless, since all aspects of the technical result were achieved and the left paw in terms of the replaced nerve nevertheless worked, we can conclude that the proposed artificial nerve is working.

Example 2

An artificial nerve was made 25 cm long and 2.5 mm thick (excluding dielectric). The artificial nerve was an analogue of the cat’s caudal nerve.

Initially, polypyrrole, polythiophene and blowing agent were mixed in the following ratio of components, wt.%:

polypyrrole 60 polythiophene 33 blowing agent 7

The blowing agent used was the porophore n-toluenesulfonylsemicarbazide (PTSS). The resulting mixture was gradually heated to a temperature of 260 ° C, that is, to a temperature sufficient to decompose the porophore, kept for 4 minutes - until the through pore formation process was completed, and cooled to a temperature of 150 ° C. Then polyvinylidene fluoride nanofibers were added to it in an amount of 9 wt. % and began to pass through a die with a diameter of 2.5 mm. After the spinneret, the obtained thread was cooled to a temperature of 60 ° C, trimmed to the desired size and soaked in a solution heated to 60 ° C for 5 minutes containing 7 wt.% NaCl and 7 wt.% KCl. Then the thread was wrapped around a dielectric layer consisting of polystyrene and styrene-butadiene-styrene, 20 μm thick, cooled to room temperature, a MK-40 brand cation-exchange membrane was applied to the ends, and these ends were placed in a solution containing 7 wt.% NaCl and 7 wt.% KCl.

A layer of polystyrene and styrene-butadiene-styrene was partially removed from the nerve.

Passing a current of 4 modes by means of contact between the needle electrodes and the sections exposed from the dielectric shell, the response time, resistance, and pulse conduction velocity were determined. By passing current through the contact of the needle electrodes with integral sections of the filament, the resistivity of the dielectric sheath was calculated.

The measured characteristics of the artificial nerve are presented in table 1.

After measurements, a cation exchange membrane was removed from one end of the nerve.

The second part of the experiment was that under general anesthesia, the cat began to innervate, due to a long-standing injury, which lost the ability to move its tail. The surgeon was asked to perform artificial innervation in such a way that the implantable nerve passes in the same way as the real caudal nerve of the cat should pass, and so that the parts of the nerve exposed from the dielectric are in contact with the muscles.

First, a recess was made mechanically at the end of the artificial nerve, an activated end of the living nerve was placed in the recess in such a way that both the fiber and the sheath of the nerve were in contact with the electrically conductive polymer, but the pores of the polymer were completely covered by the membrane. Then, epineural sutures were placed along the compatible edges.

After two days after the operation, the cat could make slow tail movements with a weak amplitude. A few days later, it was possible to draw a conclusion about the implant engraftment. Due to the chemical inertness and biocompatibility of the components, its effect on the body can be compared with the effect of a dental filling.

As noted above, it is obvious that due to the lack of biochemical reactions associated with neurotransmitters released in the nerve endings, despite the implementation of the mechanism of galvanic current formation in artificial nerves with the participation of sodium and potassium ions, akin to the mechanism of current formation in living nerves, and despite to amplify the current signal using polyvinylidene fluoride nanofibers, the proposed artificial nerve cannot guarantee the restoration of such complex functions, such as, for example, restoration of human ability and write, sew, make quick rectilinear motion, and perform other physiologically complex operations. However, from the description of the present invention, it is obvious that at the same time it is able to restore such simple functions as a quick tail swing, twitching of a foot, raising a hand, step with a foot, and so on. And due to the fact that most of the movements of a living organism are such, we can conclude that the proposed nerve is largely able to replace the real one.

Moreover, it is also worth noting the fact that the nervous system of many species has an amazing ability to successfully restore synaptic connections that were broken as a result of trauma (http://nervonet.ru/?cat=5&paged=2). But since at this stage there is no material evidence that the proposed invention can contribute to the restoration of the synapse and biochemical processes occurring in it and associated with the release of neurotransmitters, this issue is the basis for improving the artificial nerve, further development of this field and new inventions that will be able to fully return to people their feelings and movements.

Due to the fact that the proposed artificial nerve has a reduced response time and resistance, as well as sufficient elasticity and strength, and at the same time it is able to receive and transmit pulses of the living nerve, having an affinity with it, the invention can be used to innervate paralyzed or lost sensory parts body, as well as when creating prostheses, including bionic limbs. The proposed invention can also find application in mechanical engineering and robotics, in particular in the design of high-precision manipulators.

Claims (8)

1. An artificial nerve, which is a medium of at least one organic electrically conductive polymer, which has through porosity with pores filled with a solution of sodium and potassium ions, and which is entwined with at least one layer of a polymer dielectric, at least at one end of the artificial nerve applied cation exchange membrane. 2. The artificial nerve according to claim 1, characterized in that the electrically conductive polymer is selected from the group: polypyrrole, polyazulene, polythiophene, poly-α-naphthylamine and their mixture. 3. The artificial nerve according to claim 1, characterized in that the polymer dielectric is selected from the group: polyethylene, polystyrene, a mixture of polystyrene and its copolymer, polytetrafluoroethylene, polyamide and a mixture thereof. 4. The artificial nerve according to claim 1, characterized in that a MK-40 brand membrane or a nafion-117 brand membrane is used as a cation exchange membrane. 5. The artificial nerve according to claim 1, characterized in that the potassium and sodium solution is a solution of KCl and NaCl. 6. The artificial nerve according to claim 1, characterized in that it further comprises a polyvinylidene fluoride nanofiber. 7. The artificial nerve according to claim 1, characterized in that a matrix of piezoelectrics is attached to its end. 8. The artificial nerve according to claim 7, characterized in that the matrix of piezoelectrics is a matrix of polyvinylidene fluoride nanofibres.