KR102644219B1 - Biodegradable hydrogel nerve conduit combined with triboelectric generator for maximizing regeneration of renal cutting nerve - Google Patents

Abstract

The present invention provides a conduit body connecting both sides of a severed nerve inside a living body; a triboelectric generator electrically connected to the severed nerve through the conduit body and transmitting an electrical signal generated by application of ultrasonic waves to the severed nerve; and an encapsulation layer covering the triboelectric generator element, wherein the conduit body, the triboelectric generator element, and the encapsulation layer are made of a biodegradable material.
The present invention is: Project identification number: 20176104, Project number: 20176104, Ministry name: Ministry of SMEs and Startups, Project management (professional) organization name: Small and Medium Business Technology Information Promotion Agency, Research project name: Entrepreneurship-centered university, Start-up company in the leap stage, Research project name: Ultrasound-based friction Implantable peripheral nerve analgesia electrical stimulation device using 'electromedicine technology using electric power generator' / SONOSTIM, Project performing organization name: Energy Mining, Research period: 2023-05-01 ~ 2023-12-31 This is a research product.

Description

Biodegradable hydrogel nerve conduit combined with triboelectric generator for maximizing regeneration of renal cutting nerve}

The present invention relates to nerve conduits.

If a nerve is severed due to an accident or surgery, surgery is performed to suture both sides of the severed nerve.

If the gap between the two sides of the severed nerve is less than 5 mm, it can be easily treated by suturing both sides of the severed nerve or connecting both sides of the severed nerve with a guide conduit.

However, if the gap between the two sides of the severed nerve is more than 5 mm, treatment by suturing both sides of the severed nerve or connecting both sides of the severed nerve with a guide conduit is not possible.

Therefore, if the gap between the two sides of the severed nerve is 5 mm or more, treatment can be done using autograft and guide conduit. However, autograft may cause damage to the nerve harvesting site and has the problem of not being able to be used multiple times. For reference, autograft involves harvesting nerves from other parts of the body that are of little use or not needed and transplanting them directly to both sides of the severed nerve.

Accordingly, recently, as an alternative to autograft, technology has been developed to promote regeneration of the severed nerve by connecting both sides of the severed nerve with a conductive hydrogel.

However, connecting both sides of the severed nerve with a conductive hydrogel had the problem of poorer regeneration of the severed nerve than autograft and failure to solve biostability.

Domestic Registered Patent Publication No. 10-1860230 (May 15, 2018)

The present invention was created to solve the above-mentioned problems, and the purpose of the present invention is to provide a nerve conduit that can promote regeneration of the severed nerve by transmitting electrical signals to the severed nerve.

The problems to be solved by the present invention are not limited to the problems mentioned above, and other problems not mentioned can be clearly understood by those skilled in the art from the description below.

A nerve conduit according to an embodiment of the present invention includes a conduit body connecting both sides of a severed nerve inside a living body; a triboelectric generator electrically connected to the severed nerve through the conduit body and transmitting an electrical signal generated by application of ultrasonic waves to the severed nerve; and an encapsulation layer covering the triboelectric generator element, wherein the conduit body, the triboelectric generator element, and the encapsulation layer are made of a biodegradable material.

In addition, the encapsulation layer includes one of PLGA [poly(lactic-co-glycolic acid)] and PHBV [Poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid)], and the encapsulation layer Cracks may occur due to the application of ultrasonic waves of a standard intensity or higher.

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In addition, the triboelectric generator includes: a friction layer provided on the conduit body and vibrating by application of the ultrasonic waves; and an electrode layer provided on the inner surface of the encapsulation layer and electrically connected to the conduit body, generating triboelectricity through friction with the friction layer.

Additionally, the friction layer may include any one of PLGA [poly(lactic-co-glycolic acid)], PVA (polyvinylalcohol), and PEG (polyehthylene glycol).

Additionally, the electrode layer may include either Mg or Mo.

In addition, it may further include a spacer that separates the friction layer and the electrode layer from each other.

Additionally, proteinase K, which accelerates biodegradation by body fluids, may be stored between the conduit body and the encapsulation layer.

Additionally, the conduit body may contain stem cells for transplantation.

In addition, it may further include a bonding layer provided on the inner surface of the conduit body and bonded to at least one side of the severed nerve.

Additionally, the bonding layer may be a mixture of biodegradable material with any one of a catechol functional group, a gallol functional group, and plant-derived polyphenol.

Other specific details of the invention are included in the detailed description and drawings.

The nerve conduit according to one embodiment of the present invention has the effect of promoting regeneration of the severed nerve by transmitting electrical signals to the severed nerve.

In addition, the nerve conduit according to an embodiment of the present invention minimizes the loss of electrical signals generated from the triboelectric generator element, as the optimal impedance of the electrical signal generated from the triboelectric generator element is similar to the impedance of the severed nerve. Thus, it can be delivered to a severed nerve.

In addition, the nerve conduit according to one embodiment of the present invention has the effect of accelerating biodegradation within the living body by causing cracks when ultrasonic waves of a certain intensity or higher are applied.

The effects of the present invention are not limited to the effects mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the description below.

Figure 1 is a perspective view showing a nerve conduit according to an embodiment of the present invention.
Figure 2 is an exploded perspective view showing a nerve conduit according to an embodiment of the present invention.
Figure 3 is a cross-sectional view showing a nerve conduit according to an embodiment of the present invention.
Figure 4 is a cross-sectional view showing a state in which a crack occurs in a nerve conduit according to an embodiment of the present invention when ultrasound waves of a certain intensity or higher are applied.
Figure 5 is a graph showing the RMS power of the triboelectric generator according to the impedance of the conduit body of the nerve conduit according to an embodiment of the present invention.
Figure 6 is a graph showing the impedance of the triboelectric generator according to the size of the electrode layer of the nerve conduit according to an embodiment of the present invention.
Figure 7 is a graph showing the impedance of the triboelectric generator according to the operating frequency of the triboelectric generator of the nerve conduit according to an embodiment of the present invention.
Figure 8 is a perspective view showing a nerve conduit according to another embodiment of the present invention.

The advantages and features of the present invention and methods for achieving them will become clear by referring to the embodiments described in detail below along with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below and may be implemented in various different forms. The present embodiments are merely provided to ensure that the disclosure of the present invention is complete and to provide a general understanding of the technical field to which the present invention pertains. It is provided to fully inform the skilled person of the scope of the present invention, and the present invention is only defined by the scope of the claims.

The terminology used herein is for describing embodiments and is not intended to limit the invention. As used herein, singular forms also include plural forms, unless specifically stated otherwise in the context. As used in the specification, “comprises” and/or “comprising” does not exclude the presence or addition of one or more other elements in addition to the mentioned elements. Like reference numerals refer to like elements throughout the specification, and “and/or” includes each and every combination of one or more of the referenced elements.

Unless otherwise defined, all terms (including technical and scientific terms) used in this specification may be used with meanings commonly understood by those skilled in the art to which the present invention pertains. Additionally, terms defined in commonly used dictionaries are not interpreted ideally or excessively unless clearly specifically defined.

Hereinafter, embodiments of the present invention will be described in detail with reference to the attached drawings.

Figure 1 is a perspective view showing a nerve conduit according to an embodiment of the present invention, Figure 2 is an exploded perspective view showing a nerve conduit according to an embodiment of the present invention, and Figure 3 is a nerve conduit according to an embodiment of the present invention. is a cross-sectional view showing a state, and Figure 4 is a cross-sectional view showing a state in which a crack occurs in a nerve conduit according to an embodiment of the present invention due to the application of ultrasound waves of a certain intensity or higher.

As shown in Figures 1 to 3, the nerve conduit according to an embodiment of the present invention may include a conduit body 100, a triboelectric generator 200, and an encapsulation layer 300. Here, the conduit body 100, the triboelectric power plant element 200, and the encapsulation layer 300 may be made of biodegradable materials.

As an example, the conduit body 100 and the triboelectric power plant element 200 may be made of a biodegradable material that has a faster biodegradation rate than the encapsulation layer 300.

The conduit body 100 serves to connect both sides of the severed nerve 10 inside the living body.

As an example, the conduit body 100 has a ring shape and may have an inner diameter corresponding to the outer diameter of the cut nerve 10. Accordingly, both sides of the cut nerve 10 can be inserted into both sides of the conduit body 100, respectively.

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The conductive hydrogel included in the conduit body 100 may serve to electrically connect both sides of the severed nerve 10. In addition, the conductive hydrogel included in the conduit body 100 has similar mechanical properties to nerves, which can minimize nerve fatigue, and is permeable, making it easy for substances that promote nerve regeneration, such as ion cells, to penetrate. In addition, when both sides of the severed nerve 10 are electrically connected through the conductive hydrogel contained in the conduit body 100, the severed nerve 10 is cut by a fine electromotive force (e.g., 100 mv or less) itself. Regeneration of the damaged nerve 10 can be activated. However, when regeneration of the severed nerve 10 is activated by the minute electromotive force of the severed nerve 10 itself, regeneration of the severed nerve 10 is not promoted.

As an example, the conductive hydrogel included in the conduit body 100 may be any one of GelMa, Chitosan, Collagen, and PVA, and salt may be added to improve conductivity.

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As an example, the conduit body 100 may further include PLGA (poly(lactic-co-glycolic acid)). Accordingly, cracks may occur in the conduit body 100 when ultrasonic waves of a standard intensity or higher are applied. At this time, as biological fluid penetrates into the inside of the conduit main body 100 through the cracks that occur in the conduit main body 100, biodegradation of the conduit main body 100 may progress. Accordingly, by setting the point of application of ultrasonic waves of a standard intensity or higher to the friction layer 210, it is possible to determine the point in time at which biodegradation of the friction layer 210 progresses. Here, the reference intensity of ultrasound may be 3W/cm ² .

Furthermore, proteinase K may be stored between the conduit body 100 and the encapsulation layer 300. In this way, when proteinase K is stored between the conduit main body 100 and the encapsulation layer 300, it is absorbed by biological fluids that have penetrated into the inside of the conduit main body 100 through cracks in the conduit main body 100. Proteinase K is dissolved, and the dissolved proteinase K can act as an enzyme that accelerates the biodegradation of nerve conduits.

As an example, the conduit body 100 may include stem cells for transplantation. In this way, when stem cells for transplantation are transplanted into the conduit body 100, an electrical signal is transmitted from the triboelectric generator element 200 to the severed nerve 10 through the conduit main body 100, and the severed nerve ( When the regeneration of 10) is promoted, the therapeutic effect of stem cells is added, and the regeneration of the severed nerve 10 can be further promoted. These stem cells for transplantation may be transplanted into the inner surface of the conduit body 100.

The triboelectric generator element 200 is electrically connected to the severed nerve 10 through the conduit body 100 and can transmit an electrical signal generated by application of ultrasonic waves to the severed nerve 10. As a result, the electric signal transmitted from the triboelectric generator 200 to the severed nerve 10 can promote regeneration of the severed nerve 10. For reference, the triboelectric generator 200 can transmit triboelectricity generated based on friction by applying ultrasonic waves to the severed nerve 10, and this triboelectricity may be an electrical signal.

As an example, ultrasonic waves applied to the triboelectric power plant element 200 may be generated from the ultrasonic generator device 20. The ultrasonic generator device 20 can set the intensity of ultrasonic waves applied to the triboelectric power generation element 200, and set the point of time at which the ultrasonic waves are applied to the triboelectric power generation element 200.

As another example, the triboelectric power plant element 200 may have a curved plate shape with a radius corresponding to the radius of the conduit body 100.

As another example, the triboelectric power plant element 200 may have a ring shape with a shape corresponding to the circumference of the conduit body 100.

The triboelectric power plant element 200 may include a friction layer 210, an electrode layer 220, and a spacer 230.

The friction layer 210 is provided on the conduit body 100 and can vibrate by applying ultrasonic waves.

As an example, the friction layer 210 may include any one of poly(lactic-co-glycolic acid) [PLGA], polyvinylalcohol (PVA), and polyehthylene glycol (PEG).

The electrode layer 220 is provided on the inner surface of the encapsulation layer 300 and can generate triboelectricity through friction with the friction layer 210. This triboelectricity may be identical to an electrical signal.

As an example, the electrode layer 220 may include either Mg or Mo.

As another example, the electrode layer 220 is connected to the conduit body 100 through the electrode lead line 221, so that triboelectricity generated in the electrode layer 220 is transmitted to the conduit body 100 through the electrode lead line 221. It can be passed on.

The electrode lead line 221 may extend from the electrode layer 220 to the conduit body 100 and be connected to the conduit body 100. Accordingly, as the electrode layer 220 is connected to the conduit body 100 through the electrode lead line 221, a separate wire is not needed.

The spacer 230 serves to separate the friction layer 210 and the electrode layer 220 from each other. The reason why the spacer 230 separates the friction layer 210 and the electrode layer 220 is that the friction layer 210 and the electrode layer 220 are attached due to friction between the friction layer 210 and the electrode layer 220. This is to prevent it from being separated after being separated.

As an example, the spacer 230 is provided around the friction layer 210 and has a thicker thickness than the friction layer 210, so it serves to separate the friction layer 210 and the electrode layer 220 from each other. You can.

As an example, the optimal impedance of the triboelectric power plant element 200 varies depending on the ultrasonic frequency applied to the triboelectric power plant element 200 and the size of the electrode layer 220, but is generally 30 to 300 kΩ. . The optimal impedance of this triboelectric generator element 200 is similar to the impedance of a nerve, and the optimal impedance of the triboelectric generator element 200 is formed to be similar to the impedance of the conduit body 100, so that the triboelectric generator element ( The loss of the electrical signal transmitted from 200) to the severed nerve 10 through the conduit body 100 can be minimized, and the optimal electrical signal can be transmitted from the triboelectric generator 200 to the conduit body 100. there is. Therefore, the nerve conduit according to an embodiment of the present invention has an optimal impedance of the electrical signal generated from the triboelectric generator element 200, as the optimal impedance of the electric signal is similar to the impedance of the severed nerve 10. It is possible to minimize the loss of electrical signals occurring in and transmit them to the severed nerve (10).

The encapsulation layer 300 serves to cover the triboelectric power plant element 200.

As shown in FIG. 4, the encapsulation layer 300 is made of either PLGA [poly(lactic-co-glycolic acid)] and PHBV [Poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid)]. Including, cracks may occur due to the application of ultrasonic waves of a standard intensity or higher. At this time, when a crack occurs in the encapsulation layer 300, the electrode layer 220 coupled to the encapsulation layer 300 also mechanically cracks, and the encapsulation layer 300 and the electrode layer 220 ), biodegradation of the encapsulation layer 300 and the electrode layer 220 may progress as the biological fluid penetrates into the inside. Accordingly, it is possible to determine the point in time at which biodegradation of the encapsulation layer 300 progresses by setting the point in time at which ultrasonic waves higher than the standard intensity are applied to the encapsulation layer 300. Here, the standard intensity of ultrasonic waves may be 3W/cm ² , and cracks may occur in the encapsulation layer 300 when ultrasonic waves of 3W/cm ² or more are applied. For reference, until ultrasonic waves of a standard intensity or higher are applied to the encapsulation layer 300, the encapsulation layer 300 may serve to protect the triboelectric generator 200 from bodily fluids inside a living body.

Furthermore, proteinase K may be stored between the conduit body 100 and the encapsulation layer 300. In this way, when proteinase K is stored between the conduit body 100 and the encapsulation layer 300, the encapsulation layer 300 is damaged through cracks that occur in the encapsulation layer 300 and the electrode layer 220. Proteinase K is dissolved by the body fluid that penetrates into the inside of the body, and the dissolved proteinase K can act as an enzyme that accelerates the biodegradation of the nerve conduit.

For example, in the severed nerve 10, the cell membrane acts as a dielectric, so the severed nerve 10 can be modeled as an electric circuit in which a plurality of capacitors and resistors are connected. Therefore, as the frequency of the ultrasonic waves applied to the severed nerve 10 increases, the reactance of the capacitor decreases, so the electrical signal can be better transmitted to the severed nerve 10. Furthermore, the ultrasonic waves applied to the triboelectric power plant element 200 may be in a high frequency range of 20 kHz or higher. By applying ultrasonic waves in this high-frequency region to the triboelectric generator element 200, the efficiency of the triboelectric generator element 200 transmitting electrical signals to the severed nerve 10 will be improved compared to the case where ultrasonic waves in the low-frequency region are applied. You can.

Figure 5 is a graph showing the RMS power of the triboelectric generator element 200 according to the impedance of the conduit body 100 of the nerve conduit according to an embodiment of the present invention, and Figure 6 is a graph showing the RMS power of the nerve conduit according to an embodiment of the present invention. It is a graph showing the impedance of the triboelectric generator element 200 according to the size of the electrode layer 220 of the conduit, and FIG. 7 shows the impedance of the triboelectric generator element 200 of the nerve conduit according to an embodiment of the present invention. This is a graph showing the impedance of the triboelectric power plant element 200. For reference, FIGS. 5 to 7 are measurements taken when the size of the electrode layer 220 of the triboelectric power plant element 200 is 0.5 x 1.0 cm ² and the operating frequency is 20 kHz.

Referring to FIG. 5, it can be seen that when the impedance of the conduit body 100 is 10000 ohm corresponding to the nerve impedance, the RMS power of the triboelectric generator 200 is 20 μW.

Referring to Figures 6 and 7, it can be seen that the impedance of the triboelectric power plant element 200 is inversely proportional to the size of the electrode layer 220 and the intensity of the operating frequency. Therefore, the size of the electrode layer 220 of the triboelectric generator 200 and the strength of the operating frequency are adjusted so that the impedance of the triboelectric generator 200 corresponds to the impedance of the severed nerve 10, thereby generating triboelectricity. The impedance of the power generator 200 can be custom designed and applied to the severed nerve 10.

Hereinafter, the operation of the nerve conduit according to an embodiment of the present invention will be described. The following process can be performed by the user or the robot arm. Additionally, the operation of the nerve conduit according to one embodiment of the present invention can be applied to the operation of the nerve conduit according to another embodiment of the present invention.

First, the conduit body 100 is connected to both sides of the severed nerve 10 inside the living body.

Next, ultrasonic waves are applied to the triboelectric power plant element 200. At this time, the triboelectric generator element 200 may transmit an electrical signal generated by application of ultrasonic waves to the severed nerve 10. As a result, an electrical signal is transmitted to the severed nerve 10, thereby promoting regeneration of the severed nerve 10. Here, the ultrasonic waves applied to the triboelectric power plant element 200 may be generated from the ultrasonic generator device 20.

Next, when rapid biodegradation of the nerve conduit is required, ultrasonic waves of a standard intensity or higher are applied to the triboelectric generator 200. As a result, cracks occur in the encapsulation layer 300, and the electrode layer 220 coupled to the encapsulation layer 300 also mechanically cracks, causing the encapsulation layer 300 and the electrode layer ( As biological fluid penetrates into the inside of 220), biodegradation of the encapsulation layer 300 and the electrode layer 220 may progress. Furthermore, proteinase K stored between the conduit body 100 and the encapsulation layer 300 is absorbed into the body fluid of a living body that has penetrated into the inside of the encapsulation layer 300 through a crack in the encapsulation layer 300. It dissolves and can act as an enzyme that accelerates the biodegradation of nerve conduits.

Hereinafter, the manufacturing process of a nerve conduit according to an embodiment of the present invention will be described.

First, a conduit body 100 having an inner diameter corresponding to the outer diameter of the cut nerve 10 is manufactured.

Next, the friction layer 210 is attached to the outer surface of the conduit body 100. Here, the friction layer 210 may be dip coated or brush coated and may have a film form.

Next, a spacer 230 is attached around the friction layer 210. At this time, a bonding agent may be applied to the spacer 230.

Afterwards, the electrode layer 220 is coated or deposited on the inner surface of the encapsulation layer 300.

Finally, the encapsulation layer 300 is attached to the conduit body 100.

Figure 8 is a perspective view showing a nerve conduit according to another embodiment of the present invention.

As shown in FIG. 8, the nerve conduit according to another embodiment of the present invention may further include a bonding layer 400, unlike one embodiment.

The bonding layer 400 may be provided on the inner surface of the conduit body 100 and bonded to at least one side of the cut nerve 10. Therefore, in this embodiment, as the conduit body 100 and the severed nerve 10 are joined, the procedure of suturing the conduit body 100 and the severed nerve 10 with a suture can be omitted.

As an example, the bonding layer 400 may be a biodegradable material mixed with one of a catechol functional group, a gallol functional group, and plant-derived polyphenol. Here, the biodegradable material may be a naturally derived biodegradable material such as Chitosan or collagen, or a synthetic biodegradable material such as GelMa, PVA, or PEG. Additionally, the plant-derived polyphenol may be tannic acid.

According to the present invention, the nerve conduit according to an embodiment of the present invention has the effect of promoting regeneration of the severed nerve 10 by transmitting electrical signals to the severed nerve 10.

In addition, in the nerve conduit according to an embodiment of the present invention, the optimal impedance of the electric signal generated from the triboelectric generator element 200 is similar to the impedance of the severed nerve 10, so that the triboelectric generator element 200 It is possible to minimize the loss of electrical signals occurring in and transmit them to the severed nerve (10).

In addition, the nerve conduit according to one embodiment of the present invention has the effect of accelerating biodegradation within the living body by causing cracks when ultrasonic waves of a certain intensity or higher are applied.

Above, embodiments of the present invention have been described with reference to the attached drawings, but those skilled in the art will understand that the present invention can be implemented in other specific forms without changing its technical idea or essential features. You will be able to understand it. Therefore, the embodiments described above should be understood in all respects as illustrative and not restrictive.

10: Severed nerve
20: Ultrasonic generator
100: conduit body
200: Triboelectric power plant element
210: friction layer
220: electrode layer
221: electrode lead line
230: spacer
300: Encapsulation layer
400: joint layer

Claims (11)

A conduit body connecting both sides of a severed nerve inside a living body;
A triboelectric generator electrically connected to the severed nerve through the conduit body and transmitting an electrical signal generated by application of ultrasonic waves to the severed nerve;
an encapsulation layer covering the triboelectric generator; and
It includes a bonding layer provided on the inner surface of the conduit body and bonded to at least one side of the severed nerve,
The conduit body, the triboelectric generating element, and the encapsulation layer are made of biodegradable materials,
The impedance of the triboelectric generator is 30 kΩ to 300 kΩ, similar to the impedance of a nerve,
The impedance of the triboelectric generator and the impedance of the conduit body are similar to each other,
The bonding layer is a biodegradable material mixed with one of a catechol functional group, a gallol functional group, and a plant-derived polyphenol,
The biodegradable material is a naturally derived biodegradable material or a synthetic biodegradable material,
The naturally derived biodegradable material is Chitosan or collagen,
The synthetic biodegradable material is any one of GelMa, PVA and PEG, nerve conduit.
According to paragraph 1,
The encapsulation layer includes one of PLGA [poly(lactic-co-glycolic acid)] and PHBV [Poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid)],
The encapsulation layer is a nerve conduit in which cracks occur when ultrasonic waves of a reference intensity or higher are applied.
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The triboelectric power plant,
a friction layer provided on the conduit body and vibrating by application of the ultrasonic waves; and
A nerve conduit comprising an electrode layer provided on an inner surface of the encapsulation layer and electrically connected to the conduit body, generating triboelectricity through friction with the friction layer.
According to clause 4,
The friction layer is a nerve conduit containing any one of PLGA [poly(lactic-co-glycolic acid)], PVA (polyvinylalcohol), and PEG (polyehthylene glycol).
According to paragraph 4,
Nerve conduit, wherein the electrode layer contains either Mg or Mo.
According to paragraph 4,
Nerve conduit further comprising a spacer spaced apart from the friction layer and the electrode layer.
According to paragraph 4,
A nerve conduit in which proteinase K, which accelerates biodegradation by body fluids, is stored between the conduit body and the encapsulation layer.
According to paragraph 1,
A nerve conduit, wherein the conduit body contains stem cells for transplantation.
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