Sericin-based self-energized nerve interface for nerve injury regeneration and repair

Abstract

The invention relates to a sericin-based self-energized nerve interface for nerve injury regeneration and repair. The sericin-based self-energized nerve interface comprises a basement membrane; the self-powered system is integrated on the base film and comprises a piezoelectric device part, a capacitor part and an electric energy conversion part, the piezoelectric device part is configured to convert instantaneous mechanical energy generated by muscle movement near nerves into electric energy, and the capacitor part is configured to convert the electric energy into electric energy; the electric energy conversion part is configured to condition the electric energy generated by the piezoelectric device part and then charge the capacitor part, and the container part is configured to store the electric energy converted by the electric energy conversion part; and an electrode system integrated on the base film. According to the interface, multi-point and real-time monitoring of resistance signals can be carried out on different functional areas of the dissected nerve, and electrical stimulation can be applied to corresponding positions, so that correlation and cooperation of monitoring and stimulation in space are realized, long-term real-time monitoring and intervention of the whole nerve treatment cycle are realized, and the treatment efficiency is improved. And efficient regeneration and repair of long-distance nerve injury are facilitated.

Description

Technical Field

[0001] This invention relates to the field of nerve injury regeneration and repair, and specifically to a sericin-based self-powered neural interface for nerve injury regeneration and repair. Background Technology

[0002] Peripheral nerve injury is a common disabling disease in clinical practice, usually caused by trauma, tumor resection, or iatrogenic procedures, leading to the interruption of neural pathways and manifesting as loss of motor and sensory function in the corresponding innervation area. Among them, long-segment peripheral nerve transection injuries (usually referring to defects longer than 2-3 cm) account for about 5% of the total, and their functional restoration has always been a major challenge for the international medical community.

[0003] Artificial nerve transplantation is considered a promising method for repairing long-distance peripheral nerve transections. It stabilizes the nerve stump while guiding proximal nerve growth through growth factors secreted by the distal nerve. However, for long-distance nerve defects, artificial nerve transplantation struggles to create a suitable neural regeneration environment. Therefore, repairing long-distance damaged nerves faces several challenges: firstly, the axonal regeneration microenvironment is severely disrupted, making it difficult to quickly establish Schwann cell cords to guide axonal extension; secondly, the axonal regeneration rate is slow, making it difficult to establish effective functional connections with distal target organs in a timely manner; and thirdly, there is a lack of clinical means to monitor the progress of nerve regeneration in real time, hindering timely adjustments and optimization of treatment plans.

[0004] While existing literature reports implantable peripheral nerve interfaces that can directly contact peripheral nerves for precise detection or provide electrical stimulation, such as the biodegradable peripheral nerve interface and its preparation method disclosed in Chinese patent CN119746270A, which integrates a double-layer recording electrode array and a galvanic cell structure to achieve short-term monitoring and electrical stimulation repair of nerve signals, it is particularly suitable for the early stages of nerve injury (such as early identification and intervention of traumatic neuromas). However, its monitoring and stimulation functions are mainly targeted at the early stage of injury and lack the ability to sustainably track the entire long-term nerve regeneration process. Furthermore, the galvanic cell has a limited power supply time, making it difficult to support real-time monitoring and adaptive electrical stimulation intervention for several weeks or even months. Since the regeneration and repair of long-distance transverse nerve structures is a long-term process that requires long-term real-time tracking and adaptive intervention, there is an urgent need in this field for a neural interface that can perform long-term real-time monitoring and intervention to achieve long-term nerve monitoring and electrical stimulation functions for long-term "physical guidance-real-time monitoring-electrical stimulation intervention" to promote efficient regeneration and repair of long-distance nerve injuries. Summary of the Invention

[0005] This application provides a silk-based neural interface that has undergone damage regeneration and repair to solve the above-mentioned problems.

[0006] In a first aspect, embodiments of this application provide a sericin-based self-energizing neural interface for nerve injury regeneration and repair, comprising: Basement membrane; A self-powered system, integrated on the basement membrane, includes a piezoelectric unit, a capacitor unit, and an energy conversion unit. The piezoelectric unit is configured to convert the instantaneous mechanical energy generated by muscle movement near the nerve into electrical energy. The energy conversion unit is configured to condition the electrical energy generated by the piezoelectric unit and charge the capacitor unit. The container unit is configured to store the electrical energy converted by the energy conversion unit. An electrode system, integrated on the basement membrane, is used to establish electrical contact with different functional areas of the severed nerve, and includes a monitoring electrode section and a stimulation electrode section. The processing system, integrated on the basement membrane and electrically connected to the monitoring electrode, stimulation electrode, and capacitor, is configured to: obtain electrical energy from the capacitor and apply a probe signal to the monitoring electrode to obtain resistance signals from different functional areas of the severed nerve; convert the obtained resistance signals into digital signals and analyze them to determine the regeneration status of the severed nerve; generate a digital therapeutic electrical stimulation command based on the determination result; convert the command into an analog electrical stimulation signal and apply it to the corresponding functional area of ​​the severed nerve through the stimulation electrode to promote nerve regeneration.

[0007] In conjunction with the first aspect, in one embodiment, the processing system includes: Signal processing module: It is configured to convert the resistance signals of different functional regions of the severed nerve acquired by the monitoring electrode into digital signals, and to convert therapeutic electrical stimulation commands into analog electrical stimulation signals; Control module: It is configured to obtain electrical energy from the capacitor section and apply a detection signal to the monitoring electrode section, and analyze the digital signal obtained by the signal processing module to determine the regeneration status of the severed nerve, and generate a digital therapeutic electrical stimulation command based on the determination result, which is then converted into an analog electrical stimulation signal by the signal processing module and applied to the corresponding functional area of ​​the severed nerve through the stimulation electrode section.

[0008] In conjunction with the first aspect, in one embodiment, the basement membrane includes a first basement membrane and a second basement membrane; The self-powered system and the processing system are integrated on the first basement membrane, which is configured to be implanted and fixed to muscle tissue near the severed nerve. The electrode system is integrated onto the second basement membrane, which is configured to be able to roll up and wrap around the severed nerve; The first basement membrane is provided with an interface, which is electrically connected to the signal processing module. The interface is also connected with a wire, one end of which is connected to the interface and the other end of which is connected to the electrode system.

[0009] In conjunction with the first aspect, in one embodiment, the base membrane is a flexible film formed of a biodegradable blend material, the blend material including sericin and polylactic acid-glycolic acid copolymer.

[0010] In conjunction with the first aspect, in one embodiment, the capacitor portion includes a first electrode layer, a second electrode layer, a separator layer disposed between the first electrode layer and the second electrode layer, an electrolyte disposed within the space formed by the electrode layer and the separator layer, and a first encapsulation layer covering the outer side of the entire portion.

[0011] In conjunction with the first aspect, in one embodiment, both the first electrode layer and the second electrode layer are biodegradable sericin-based conductive hydrogels, the diaphragm layer is a cellulose nanofiber membrane, the first encapsulation layer is a sericin film, and the electrolyte is a sodium chloride / polyvinyl alcohol gel.

[0012] In conjunction with the first aspect, in one embodiment, the piezoelectric unit includes a piezoelectric active layer, an upper electrode layer, and a lower electrode layer stacked together, as well as an upper encapsulation layer and a lower encapsulation layer covering the outer sides of the upper electrode layer and the lower electrode layer.

[0013] In conjunction with the first aspect, in one embodiment, the piezoelectric active layer is composed of a biodegradable sericin matrix and zinc oxide nanorods dispersed therein, the upper electrode layer and the lower electrode layer are flexible carbon cloth, and the upper encapsulation layer and the lower encapsulation layer are polylactic acid films.

[0014] In conjunction with the first aspect, in one embodiment, the monitoring electrode, the stimulation electrode, and the wire are all biodegradable conductive gels. The conductive gels include sericin modified with aminated reduced graphene oxide, polyvinyl alcohol, citric acid, and β-cyclodextrin. The monitoring electrode and the stimulation electrode are alternately arranged in a lattice on the basement membrane, and the power conversion part is a diode.

[0015] In conjunction with the first aspect, in one embodiment, a wireless transmission module disposed on the first basement membrane is further included, which is electrically connected to the control module and the capacitor section. The wireless transmission module is configured to send digital signals and judgment results acquired by the control module to an external device, and / or receive control commands from the external device, and transmit the control commands to the control module.

[0016] The beneficial effects of the technical solutions provided in this application include: 1. This invention constructs a complete energy capture and storage unit by integrating a piezoelectric unit, an energy conversion unit, and a capacitor unit. The piezoelectric unit can spontaneously generate electrical energy using the physiological movement of muscles near the nerve, and the capacitor unit stores it to continuously power the electrode system. This design frees the interface from dependence on external power sources, achieving energy self-sufficiency and providing a fundamental guarantee for long-term, continuous nerve monitoring and stimulation. The electrode system integrates functionally independent monitoring and stimulation electrodes, which are arranged alternately in a dot matrix. This allows the interface to perform multi-point, real-time monitoring of resistance signals in different functional areas of the severed nerve and to apply electrical stimulation at corresponding locations. This achieves spatial correlation and synergy between monitoring and stimulation, thereby enabling long-term real-time monitoring and intervention throughout the entire nerve treatment cycle, which is beneficial for promoting efficient regeneration and repair of long-distance nerve injuries.

[0017] 2. The neural interface of the present invention adopts a distributed dual basement membrane structure design, wherein the second basement membrane used to wrap the nerve and its integrated electrode system are made entirely of biodegradable sericin-based materials. This design allows the basement membrane portion that directly contacts the nerve to be naturally absorbed by the body after the regeneration cycle, thus avoiding the risk of needing to remove the nerve twice by surgery, and greatly reducing the risk of chronic inflammation, fibrous encapsulation and nerve compression caused by permanent foreign body retention.

[0018] 3. The self-powered system integrated on the first basement membrane of the present invention is constructed using natural sericin as the main substrate. Sericin has excellent biocompatibility, extremely low immunogenicity and can be completely metabolized and absorbed by the body, which helps to reduce chronic inflammation and fibrous encapsulation caused by long-term implantation and create a more favorable microenvironment for nerve regeneration. Attached Figure Description

[0019] To more clearly illustrate the technical solutions in the embodiments of this application, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0020] Figure 1 This is a schematic diagram of the sericin-based neural interface of the present invention; Figure 2 This is a summary diagram illustrating the steps of the method of using this invention; Figure 3 This is an example diagram illustrating how the self-powered system of the present invention can effectively convert bodily mechanical energy into electrical energy and output it. Figure 4 These are some examples of performance characterization of the conductive gel of the present invention; Figure 5This is an example diagram illustrating the stable electrical performance of the sericin-based neural interface of the present invention; Figure 6 This is an example illustration demonstrating the good biocompatibility of the sericin-based neural interface of the present invention; Figure 7 This diagram illustrates an example of muscle signal and spinal cord modulation in the sciatic nerve via electrical stimulation using a sericin-based nerve interface according to the present invention. Detailed Implementation

[0021] To enable those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present application, and not all embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present application.

[0022] This application provides a sericin-based self-energizing neural interface for nerve injury regeneration and repair, comprising: ① Basement membrane; it is a flexible thin film with good biocompatibility, controllable degradation, and certain mechanical strength and flexibility; The basement membrane is made of a biodegradable blend material. In a preferred embodiment of this example, the blend material includes sericin and polylactic-co-glycolic acid copolymer (PLGA). The mass ratio of sericin to PLGA can be adjusted between 1:9 and 9:1. In this example, it is preferably 1:1. By adjusting the ratio, the flexibility, degradation rate and water permeability of the basement membrane can be controlled.

[0023] The basement membrane preparation method provided in this embodiment is as follows: sericin and PLGA are dissolved together in hexafluoroisopropanol (HFIP) to prepare a solution with a total concentration of 2%-5% (w / v). The membrane is formed on a clean substrate by spin coating. After drying and ethanol annealing (inducing sericin to form a stable β-sheet structure, making it insoluble in water but enzymatically hydrolyzable), a flexible membrane with uniform thickness is finally obtained. It can be rolled into a tube shape to tightly wrap severed nerves of different diameters, or it can be implanted and fixed to muscle tissues (such as gastrocnemius and biceps brachii) with rich blood supply and frequent daily activities near severed nerves by suturing, so as to efficiently collect the mechanical energy generated by muscle movement. In this embodiment, the basement membrane substrate specifically includes a first basement membrane and a second basement membrane; ② A self-powered system, integrated on the first basement membrane, comprising: 201: Piezoelectric unit, configured to convert the instantaneous mechanical energy generated by muscle movement near the nerve into electrical energy. The piezoelectric unit consists of the following layers from bottom to top: lower encapsulation layer, lower electrode layer, piezoelectric active layer, upper electrode layer, and upper encapsulation layer. The piezoelectric active layer is made of a biodegradable composite material. In one specific implementation of this embodiment, a sericin solution modified with aminated reduced graphene oxide (A-rGO) is used as the matrix, zinc oxide nanorods (ZnONRS) are incorporated as the piezoelectric reinforcing phase, and then polyvinyl alcohol (PVA) solution and crosslinking agent (such as glutaraldehyde) are added. After uniform mixing, the mixture is cast into a film and cured. A-rGO improves the conductivity of the matrix and the interfacial bonding with ZnO, while ZnO NRS provides a significant piezoelectric effect. By adjusting the proportion and concentration of sericin, its degradation time can be adjusted to ensure that it can completely cover the entire repair cycle of severed nerves. Electrode layer and encapsulation layer: Both upper and lower electrode layers are made of flexible, porous, and biocompatible carbon cloth to collect charges. The upper and lower encapsulation layers are made of biodegradable polylactic acid (PLA) film to isolate body fluids and protect the internal structure.

[0024] The working principle of the piezoelectric active layer is as follows: When the interface deforms due to muscle movement, pressure is transmitted to the piezoelectric active layer, causing the ZnO NRS crystals in it to be compressed or bent, and the positive and negative charge centers to be relatively displaced, thereby generating an instantaneous potential difference (voltage) between the upper and lower electrode layers. Each time the muscle moves, an electrical pulse is generated.

[0025] 202: Capacitor section: It is configured to store the electrical energy converted by the piezoelectric section. It is a double-layer capacitor structure, including two symmetrical first electrode layers and second electrode layers, with a separator layer in the middle. The whole is wrapped by a first encapsulation layer and injected with gel electrolyte. First electrode layer and second electrode layer: made of biodegradable conductive hydrogel. In a preferred embodiment of this example, the raw materials include methacrylated sericin, aminated reduced graphene oxide, polyethylene glycol diacrylate and four-arm polyethylene glycol succinimide carbonate. During preparation, the above raw materials and photoinitiator are mixed in a specific ratio to form a uniform precursor solution. After being injected into the electrode mold, it is cured by irradiation under a specific wavelength LED light source, thereby forming a composite hydrogel electrode layer with a three-dimensional network structure, which has excellent ionic conductivity, toughness and degradability. By adjusting the proportion and concentration of methacrylated sericin, its degradation time can be adjusted to ensure that it can completely cover the entire resected nerve repair cycle. Membrane layer and electrolyte: The membrane layer is an ultrathin cellulose nanofiber membrane to prevent direct short circuits between the first and second electrode layers; the electrolyte is a sodium chloride (NaCl) / polyvinyl alcohol (PVA) gel, which is rich in freely mobile Na+. + and Cl - ion.

[0026] Encapsulation layer: uses a sericin film to ensure overall biodegradability.

[0027] 203: Power conversion unit, which consists of a miniature full-wave rectifier bridge composed of four diodes. Its input terminal is connected to the upper and lower electrode layers of the piezoelectric unit via wires, and its output terminal is connected to the first electrode layer (positive) and the second electrode layer (negative) of the capacitor unit via wires. It is used to convert the unstable AC pulse power generated by the piezoelectric unit into DC power suitable for storage in the capacitor unit.

[0028] The working principle of the capacitor section is as follows: Charging process: When the voltage generated by the piezoelectric unit is converted by the energy conversion unit and applied to the first and second electrode layers of the capacitor unit, the ions (Na+) in the electrolyte... + and Cl - They migrate to the electrode surfaces with opposite charges and adhere tightly to the electrode / electrolyte interface, forming two charge layers (i.e., "electric double layer"), where electrical energy is stored electrostatically. Discharge process: When the electrode is connected to the external stimulation electrode circuit, the adsorbed ions detach from the electrode surface and return to the electrolyte, and the stored electrostatic energy is released to form a current output. This process can be carried out quickly and repeatedly.

[0029] like Figure 3 , Figure 3 An example diagram is provided showing how a self-powered system can effectively convert the body's mechanical energy into electrical energy and output it: Point A in the diagram represents the self-powered system converting the force of swallowing into electrical energy, with the vertical axis representing the output voltage. Point B in the diagram represents the self-powered system converting the force of bending the finger into electrical energy; the vertical axis represents the output voltage. Point C in the diagram represents the self-powered system converting the force of wrist flexion into electrical energy, with the vertical axis representing the output voltage. In the figure, point D represents the self-powered system converting the force of the leg and chest muscles of the SD rat into electrical energy, and the vertical axis represents the output voltage. Point E in the diagram indicates that the self-powered system converts the force of a hand strike into electrical energy. The diagram shows the LED lights before, during, and after the strike. The middle image illustrates the principle of generating electrical energy by pressing and releasing the power supply. The right image shows the output voltage and output current.

[0030] ③ The electrode system, which is integrated on the second basement membrane, is used to establish electrical contact with different functional areas of the severed nerve, including but not limited to the proximal stump, the distal stump, and the regeneration bridging area. The electrodes are arranged alternately on the basement membrane in a dot matrix. When the second basement membrane wraps around the nerve, the dot matrix can cover and distinguish the above-mentioned areas corresponding to nerve regeneration, thereby realizing spatial positioning monitoring and stimulation. Specifically: Both the monitoring electrode and the stimulation electrode are biodegradable conductive gels. Functional partitioning is achieved through circuit design. In one specific embodiment, the conductive gel is made of the following components: amination-reduced graphene oxide (A-rGO) modified sericin, polyvinyl alcohol (PVA), citric acid (CA), and β-cyclodextrin (β-CD). Among them, CA and β-CD form inclusion complexes through supramolecular interactions, which together with PVA and sericin construct a stable gel network. During the preparation process, glutaraldehyde is added for chemical cross-linking. After molding, it is immersed in calcium chloride solution to introduce ionic cross-linking, and finally a conductive gel with high conductivity, high adhesion, toughness, and biodegradability is obtained. By adjusting the proportion and concentration of sericin, its degradation time can be adjusted to ensure that it can completely cover the entire detached nerve repair cycle. Electrode system working principle: Monitoring electrode section: The electrical impedance of nerve tissue is closely related to its structural integrity, edema, scarring and axon regeneration density. When the detection signal is applied to different functional areas of the severed nerve through the monitoring electrode section, the monitoring electrode section can simultaneously collect the feedback signal of the nerve tissue, that is, the resistance signal. By acquiring the resistance signal, the nerve regeneration status of the corresponding functional area can be determined. Stimulation electrode section: When the applied therapeutic electrical stimulation flows through the stimulation electrode section across the epineurium of the target area, the applied exogenous electric field and current can produce multiple biological effects, such as driving the flow of ions within the nerve axon and directly promoting its directional growth and extension. Specifically, the electrodynamic and growth-accelerating effects on axons include: A. It guides the growth cone to move in a directional manner, enabling it to more accurately traverse the injury gap and reduce the risk of neuroma formation; it promotes cytoskeleton rearrangement, induces asymmetric polymerization of microtubules and actin within the growth cone, and physically propels the axon to extend forward; B. It regulates the local cellular microenvironment of the damaged area, promotes the migration and proliferation of Schwann cells and the secretion of neurotrophic factors, forms the Büngner zone, guides axons to pass smoothly through the damaged area, and creates favorable conditions for regeneration. C. Before nerve function is restored, regular electrical stimulation of muscles innervated by distal nerves can simulate nerve signals, thereby effectively preventing muscle atrophy and fibrosis. like Figure 4 As shown, Figure 4 This section showcases some of the performance characteristics of the conductive gel: Figure 4 Point A in the middle indicates that the conductive gel exhibits good conductivity stability over a long period of time by adjusting different proportions. Figure 4 The B in the middle indicates that the conductive gel has good conductivity when connected to a power source at different stretching ratios (0%-100%), and can light up an LED bulb; Figure 4 The C in the figure indicates that the conductive gel has good adhesion to different substrates, and the shear force on pigskin is 8.7 N / m.

[0031] The specific integration method is as follows: On the side of the self-powered system, electrode system, and base membrane that are to be bonded, a water-soluble polyvinyl alcohol (PVA) film is pre-coated as a temporary adhesive layer. Then, the self-powered system and electrode system are placed in a predetermined area of ​​the base membrane and temporarily fixed using the adhesiveness of PVA. Subsequently, a small amount of water mist is sprayed onto the surface of the integrated self-powered system and electrode system or they are briefly exposed to moisture. The moisture dissolves the PVA sacrificial layer. Since the back of the self-powered system and electrode system is in direct contact with the surface of the base membrane, a strong and permanent bond is formed between them after the water molecules evaporate, thanks to the inherent micro-adhesion of the sericin base membrane surface and the molecular forces between materials. Then, a biodegradable conductive material (such as A-rGO / serice composite ink) is used to connect the circuits of the piezoelectric part, capacitor part, and electrode system according to the design, thereby completing the integrated design.

[0032] In summary, the neural interface of this embodiment is divided into two parts by a first basement membrane and a second basement membrane. The second basement membrane, which is used to encapsulate the nerve, and its integrated electrode system are entirely composed of biodegradable sericin-based materials. This design allows the basement membrane portion that directly contacts the nerve to be naturally absorbed by the body after the regeneration cycle. On the one hand, this avoids the risk of needing to remove the nerve twice by surgery, and on the other hand, it greatly reduces the risk of chronic inflammation, fibrous encapsulation, and nerve compression caused by permanent foreign body retention. The self-powered system integrated on the first basement membrane is functionalized using natural sericin as the main substrate. Sericin has excellent biocompatibility, extremely low immunogenicity, and the characteristic of being completely metabolized and absorbed by the body. This helps to reduce chronic inflammation and fibrous encapsulation caused by long-term implantation and creates a more favorable microenvironment for nerve regeneration.

[0033] ④ In order to facilitate the processing of feedback signals from nerve tissue collected by the monitoring electrodes and generate precise therapeutic electrical stimulation accordingly, the silk-based neural interface of this embodiment also integrates a processing system on the basement membrane, which mainly includes a control module and a signal processing module. The control module and the signal processing module are connected by wires and are respectively electrically connected to the capacitor section by wires. Control module: It is preferably a microcontroller, which integrates a programmable power management circuit and a central processing unit. The power management circuit can accurately schedule and distribute electrical energy from the capacitor section according to a set strategy based on the system working mode (monitoring, analysis or stimulation). The central processing unit is used to generate detection signals, analyze and compare the uploaded digital signals with thresholds to determine the regeneration status of the severed nerve, and generate therapeutic electrical stimulation commands containing specific parameters (including but not limited to target point, waveform, frequency, intensity and pulse width) based on the judgment results. The signal processing module, preferably a mixed-signal processing chip integrating an analog front-end, can convert the resistance signal from the monitoring electrode into a digital signal through an internal analog-to-digital converter, and can also convert the digital stimulation command from the control module into an analog electrical stimulation signal (such as a constant current or constant voltage pulse with a specific frequency, intensity, and pulse width) and output it to the stimulation electrode through an internal digital-to-analog converter. In this embodiment, a programmable gain amplifier and an anti-aliasing filter are also preferably integrated to amplify and filter the input signal. Under the command of the control module, the signal processing module can generate a detection signal through its internally integrated detection circuit, or it can use its internally integrated stimulation drive circuit (such as a constant current output stage based on an H-bridge) to convert the therapeutic electrical stimulation command from the control module into a precise, low-power analog control waveform using electrical energy obtained in real time from the capacitor section. This waveform is then amplified and synthesized into an analog electrical stimulation signal with specific therapeutic parameters (such as a constant current or constant voltage pulse with specific frequency, intensity, and pulse width). Specifically: The control module instructs the signal processing module to generate a detection signal (in this embodiment, the detection signal is preferably a constant current excitation signal, specifically a weak current with a constant amplitude and a specific frequency, such as a sinusoidal or square wave current with a frequency of 1kHz to 100kHz and a constant amplitude of 10μA to 100μA). This detection signal is applied to the monitoring electrode through a wire and coupled into the target nerve functional area (such as the proximal stump, regeneration bridging area, or distal stump) in a low-impedance manner through its conductive gel interface. According to Ohm's law, the current flowing through the nerve tissue in this area will generate a feedback voltage drop at its two ends that is proportional to the tissue impedance. This voltage is the original analog resistance signal that characterizes the real-time state of the nerve tissue. After being collected by the monitoring electrode, it is transmitted back to the signal processing module, which converts it into a digital signal that can be analyzed and judged before processing and analysis. The processing and analysis process is as follows: The control module has one or more preset resistance thresholds. These thresholds are pre-set based on typical electrical characteristics of different stages of neural regeneration constructed from preclinical experimental data. Each threshold represents a corresponding neural regeneration state (including but not limited to: normal regeneration, tissue edema, fibrosis tendency, risk of regeneration arrest, etc.). Different neural regeneration states represent different therapeutic electrical stimulation intensities, frequencies, pulse widths, etc. In a specific example of this embodiment: In a specific example of this embodiment, when the digital signal of a certain functional area is detected to exceed a first set threshold (preferably 2.5 kΩ in this embodiment), the control module determines that there is a risk of regeneration stagnation in that area. Immediately, the control module generates a corresponding therapeutic electrical stimulation command (preferably 20 Hz frequency, 1 mA current intensity, and 0.1 ms pulse width in this embodiment) and instructs its power management circuit to dispatch the corresponding electrical energy from the capacitor section to the stimulation drive circuit of the signal processing module. After receiving the command and energy, the signal processing module generates the final analog electrical stimulation signal through the coordinated work of its digital-to-analog converter and the stimulation drive circuit. The signal is then output through a wire to the stimulation electrode section of the corresponding area and applied to the nerve tissue. During the stimulation application, the monitoring electrode section and the signal processing module continuously monitor and convert the digital resistance signal of the area synchronously and feed back the latest digital signal to the control module, forming a real-time closed loop. When the control module determines that the digital signal has fallen back to below the safe threshold (e.g., 1.5 kΩ), it indicates that the situation has improved, and then instructs the signal processing module to stop outputting.

[0034] It should be noted that the above-mentioned threshold setting, stimulation parameters, and neural regeneration state mapping relationship are only one example to illustrate the principle. In practical applications, the threshold setting, stimulation frequency, and neural regeneration state mapping relationship can be redefined and adjusted through experimental optimization or clinical experience according to different neural injury models, individual differences, and treatment stages. The protection scope of this embodiment covers all implementation schemes based on the closed-loop logic of "resistance signal monitoring → threshold judgment → state judgment → stimulation triggering".

[0035] In addition, the core circuit units and technical solutions adopted by the control module and signal processing module to realize their complete functional chain (including signal detection, analog-to-digital / digital-to-analog conversion, logic judgment, stimulus driving, etc.) are all well-known technologies and mature devices in the field of electronic technology.

[0036] The sericin-based self-energizing neural interface for nerve injury regeneration and repair in this embodiment also includes: ⑤ The wireless transmission module, which is mounted on the first basement membrane, is electrically connected to the control module and the capacitor section via wires. Specifically: Wireless transmission module: It is preferably a miniature Bluetooth or near-field communication chip, used to realize data interaction between the neural interface and external devices. Specifically, the module can transmit the digital signals processed by the control module, the judged neural regeneration status, and the data to an external smartphone or dedicated monitor to achieve remote real-time monitoring; at the same time, it can also receive control commands from external devices (such as adjusting stimulation parameters and updating judgment thresholds) and transmit the commands to the control module to realize remote personalized treatment adjustment.

[0037] This neural interface constructs a complete energy capture and storage unit through a piezoelectric part and a capacitor part on the first basilar membrane. The piezoelectric part can spontaneously generate electrical energy using the physiological movement of muscles near the nerve, and after being converted by the energy conversion part, it is stored by the capacitor part to continuously power the electrode system. This design frees the interface from dependence on external power sources, achieving energy self-sufficiency and providing a fundamental guarantee for long-term, continuous nerve monitoring and stimulation. By integrating functionally independent monitoring electrode parts and stimulation electrode parts, and arranging them alternately in a dot matrix, the interface can perform multi-point, real-time monitoring of resistance signals in different functional areas of the severed nerve. Through the control module and signal processing module, electrical stimulation can be applied at the corresponding locations, thereby realizing the spatial correlation and synergy between monitoring and stimulation. This enables long-term real-time monitoring and intervention throughout the entire nerve treatment cycle, which is conducive to promoting efficient regeneration and repair of long-distance nerve injuries.

[0038] In addition, this embodiment also provides a method for using the above-mentioned silk-based neural interface, including the following steps: S1. Installation Interface: The second basement membrane is rolled up and wrapped around the severed nerve, so that the electrode system comes into contact with the epineurium of the severed nerve. The first basement membrane is implanted and fixed to the muscle tissue (such as the gastrocnemius and biceps brachii) near the severed nerve with rich blood supply and frequent daily activities by means of suturing, so that the piezoelectric part is mechanically coupled with the muscle fascia, ensuring that the regular contraction and relaxation of the muscle can efficiently and continuously drive the deformation of the piezoelectric material during physiological activities or rehabilitation training, thereby providing a sufficient and stable biomechanical energy supply for the entire system. S2, Energy Harvesting: The mechanical energy generated by muscle movement is collected by the piezoelectric unit and converted into electrical energy, which is then converted into DC electrical energy by a miniature full-wave rectifier bridge and stored in the capacitor unit. S3. Signal Monitoring and Processing: The control module instructs the signal processing module to generate a sinusoidal or square wave current (detection signal) with a frequency of 1kHz to 100kHz and a constant amplitude of 10μA to 100μA. This current is applied to the monitoring electrode through a wire and flows into the nerve functional area it contacts via the conductive gel interface of the monitoring electrode. According to Ohm's law, the current flowing through the tissue in this area will generate a voltage drop across its two ends. This voltage drop is collected and transmitted back by the same monitoring electrode, thereby realizing the real-time acquisition of the resistance signals of different functional areas of the severed nerve. After being collected by the monitoring electrode, the signals are transmitted back to the signal processing module, which converts them into digital signals that can be analyzed and judged for further processing and analysis. The control module compares and analyzes the digital signal with its internally stored resistance thresholds. These thresholds are pre-set based on the typical electrical characteristics of different stages of nerve regeneration constructed from preclinical experimental data. Each threshold represents a corresponding nerve regeneration state (including but not limited to: normal regeneration, tissue edema, fibrosis tendency, risk of regeneration arrest, etc.). Different nerve regeneration states represent different therapeutic electrical stimulation intensities, frequencies, pulse widths, etc. Through this comparison, the control module completes the intelligent judgment of the nerve regeneration state. S4. Stimulus and Control: Once the control module determines that the neural state of a certain functional area (such as the regeneration bridging area) needs intervention (e.g., there is a risk of regeneration arrest), the control module will immediately generate corresponding therapeutic electrical stimulation commands (including but not limited to parameters such as frequency, intensity, and pulse width), and instruct its power management circuit to dispatch the corresponding electrical energy from the capacitor section to the stimulation drive circuit of the signal processing module. After receiving the command and energy, the signal processing module, through the coordinated work of its digital-to-analog converter and the stimulation drive circuit, generates the final analog electrical stimulation signal and outputs it through the wire to the stimulation electrode section of the corresponding area and applies it to the nerve tissue. During stimulation, the control module continuously executes step S3 to monitor the resistance change of the target area. When the resistance signal is detected to improve to a preset safe range, the control module will automatically stop or adjust the stimulation of the area, thus forming an adaptive treatment closed loop of "resistance signal monitoring → threshold judgment → state judgment → stimulation triggering".

[0039] Please see Figure 5 , Figure 5 The data characterize the stable electrical properties of the sericin-based neural interface of this application; like Figure 5 As shown, Figure 5 The output energy density of the sericin-based neural interface in this application is 26 μWh cm⁻², as indicated by point A in the middle. Figure 5 The B-value in the middle section characterizes the ability of the silk-based neural interface of this application to maintain capacitive characteristics and stable electrical performance under multiple charge-discharge cycles; Figure 5 The C-shape characterizes the fact that the sericin-based neural interface of this application can maintain stable electrical output performance even under adverse conditions (such as bending at 90 degrees and 150 degrees); Please see Figure 6 , Figure 6 Data characterize that the sericin-based neural interface of this application has good cell compatibility in SD rats; Please see Figure 7 , Figure 7 An example diagram characterizing the muscle signals and spinal cord modulation of the sciatic nerve by the sericin-based neural interface of this application. like Figure 7 As shown, Figure 7 The diagram at point A illustrates how the sciatic nerve can be stimulated by the sericin-based neural interface of this application to achieve bidirectional neural modulation: 1. The descending gastrocnemius / tibialis anterior muscle signals are recruited, and after reaching the stimulation threshold, the muscles will tremble. Each tremor will produce a pulse-like voltage signal output; 2. The descending spinal cord will express c-Fos protein in the pain sensory area (indicating successful stimulation). Figure 7 The image at point B represents the electrocardiographic output signal of the gastrocnemius muscle monitored by the sericin-based nerve interface of this application stimulating the sciatic nerve at different frequencies. Figure 7 The diagram at point C shows the division of different sensory regions of the spinal cord; Figure 7 The D in the middle indicates that the unstimulated sciatic nerve group does not express c-Fos in the pain sensory area, while the stimulated sciatic nerve group expresses c-Fos in the pain sensory area. This shows that the sericin-based neural interface can successfully induce c-Fos expression in the spinal cord when the sciatic nerve is stimulated, which indirectly proves the effectiveness of the sericin-based neural interface of this application.

[0040] In the description of this application, it should be noted that the terms "upper," "lower," etc., indicating the orientation or positional relationship are based on the orientation or positional relationship shown in the accompanying drawings, and are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this application. Unless otherwise expressly specified and limited, the terms "installed," "connected," and "linked" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication between two elements. For those skilled in the art, the specific meaning of the above terms in this application can be understood according to the specific circumstances.

[0041] It should be noted that in this application, relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.

[0042] The above description is merely a specific embodiment of this application, enabling those skilled in the art to understand or implement this application. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of this application. Therefore, this application is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features claimed herein.

Claims

1. A sericin-based self-powered neural interface for nerve injury regeneration and repair, characterized in that, include: Basement membrane; A self-powered system, integrated on the basement membrane, includes a piezoelectric unit, a capacitor unit, and an energy conversion unit. The piezoelectric unit is configured to convert the instantaneous mechanical energy generated by muscle movement near the nerve into electrical energy. The energy conversion unit is configured to condition the electrical energy generated by the piezoelectric unit and charge the capacitor unit. The container unit is configured to store the electrical energy converted by the energy conversion unit. An electrode system, integrated on the basement membrane, is used to establish electrical contact with different functional areas of the severed nerve, and includes a monitoring electrode section and a stimulation electrode section. The processing system, integrated on the basement membrane and electrically connected to the monitoring electrode, stimulation electrode, and capacitor, is configured to: obtain electrical energy from the capacitor and apply a probe signal to the monitoring electrode to obtain resistance signals from different functional areas of the severed nerve; convert the obtained resistance signals into digital signals and analyze them to determine the regeneration status of the severed nerve; generate a digital therapeutic electrical stimulation command based on the determination result; convert the command into an analog electrical stimulation signal and apply it to the corresponding functional area of ​​the severed nerve through the stimulation electrode to promote nerve regeneration.

2. The sericin-based self-energizing neural interface for nerve injury regeneration and repair according to claim 1, characterized in that, The processing system includes: Signal processing module: It is configured to convert the resistance signals of different functional areas of the severed nerve acquired by the monitoring electrode into digital signals, and to convert therapeutic electrical stimulation commands into analog electrical stimulation signals; Control module: It is configured to obtain electrical energy from the capacitor section and apply a detection signal to the monitoring electrode section, and analyze the digital signal obtained by the signal processing module to determine the regeneration status of the severed nerve, and generate a digital therapeutic electrical stimulation command based on the determination result, which is then converted into an analog electrical stimulation signal by the signal processing module and applied to the corresponding functional area of ​​the severed nerve through the stimulation electrode section.

3. The sericin-based self-energizing neural interface for nerve injury regeneration and repair according to claim 2, characterized in that, The basement membrane includes a first basement membrane and a second basement membrane; The self-powered system and the processing system are integrated on the first basement membrane, which is configured to be implanted and fixed to muscle tissue near the severed nerve. The electrode system is integrated onto the second basement membrane, which is configured to be able to roll up and wrap around the severed nerve; The first basement membrane is provided with an interface, which is electrically connected to the signal processing module. The interface is also connected with a wire, one end of which is connected to the interface and the other end of which is connected to the electrode system.

4. The sericin-based self-energizing neural interface for nerve injury regeneration and repair according to claim 1, characterized in that, The base membrane is a flexible film formed from a biodegradable blend of materials, including sericin and polylactic acid-glycolic acid copolymer.

5. The sericin-based self-energizing neural interface for nerve injury regeneration and repair according to claim 1, characterized in that, The capacitor section includes a first electrode layer, a second electrode layer, a separator layer disposed between the first electrode layer and the second electrode layer, an electrolyte disposed in the space formed by the electrode layer and the separator layer, and a first encapsulation layer covering the outside of the whole.

6. The sericin-based self-energizing neural interface for nerve injury regeneration and repair according to claim 5, characterized in that, The first electrode layer and the second electrode layer are both biodegradable sericin-based conductive hydrogels, the membrane layer is a cellulose nanofiber membrane, the first encapsulation layer is a sericin film, and the electrolyte is a sodium chloride / polyvinyl alcohol gel.

7. The sericin-based self-energizing neural interface for nerve injury regeneration and repair according to claim 1, characterized in that, The piezoelectric element includes a piezoelectric active layer, an upper electrode layer, and a lower electrode layer stacked together, as well as an upper encapsulation layer and a lower encapsulation layer covering the outside of the upper electrode layer and the lower electrode layer.

8. The sericin-based self-energizing neural interface for nerve injury regeneration and repair according to claim 7, characterized in that, The piezoelectric active layer is composed of a biodegradable sericin-based composite material, which includes a sericin matrix modified with aminated reduced graphene oxide and zinc oxide nanorods dispersed therein. The upper and lower electrode layers are flexible carbon cloth, and the upper and lower encapsulation layers are polylactic acid films.

9. The sericin-based self-energizing neural interface for nerve injury regeneration and repair according to claim 3, characterized in that, The monitoring electrode, the stimulation electrode, and the wire are all biodegradable conductive gels. The conductive gels include sericin modified with amino-reduced graphene oxide, polyvinyl alcohol, citric acid, and β-cyclodextrin. The monitoring electrode and the stimulation electrode are arranged alternately in a lattice on the basement membrane. The power conversion part is a diode.

10. The sericin-based self-energizing neural interface for nerve injury regeneration and repair according to claim 3, characterized in that, It also includes a wireless transmission module disposed on the first basement membrane, which is electrically connected to the control module and the capacitor section. The wireless transmission module is configured to send digital signals and judgment results acquired by the control module to an external device, and / or receive control commands from an external device, and transmit the control commands to the control module.

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