Artificial cochlea super-hydrophilic gel electrode coating material with anti-fibrosis and self-repairing functions and preparation method thereof

Abstract

The invention discloses an artificial cochlea super-hydrophilic gel electrode coating material with anti-fibrosis and self-repairing functions and a preparation method of the artificial cochlea super-hydrophilic gel electrode coating material, and the preparation process comprises the following steps: 1) preparing Res nano-emulsion by adopting nano-emulsification, mixing the Res nano-emulsion with a GelMA solution, and preparing Res (at) GelMA microgel through microfluidic and UV curing; 2) respectively preparing a Res (at) GelMA / CSMA mixed solution and an ODex solution, and mixing the Res (at) GelMA / CSMA mixed solution and the ODex solution to obtain a hydrogel premixed solution; (3) putting the artificial cochlea electrode into a light-transmitting mold, then pouring the hydrogel premixed liquid into the mold, and after UV curing and demolding, constructing an electrode gel precoating on the periphery of the artificial cochlea electrode; and 4) in a reactor, chemically grafting PGS on the surface of the electrode gel pre-coating, and washing, irradiating and sterilizing to obtain the electrode coating material. The artificial cochlea electrode with the novel coating has the advantages of being anti-inflammatory, anti-fibrosis, self-repairing and low in electrode implantation force.

Description

Technical Field

[0001] The present invention belongs to the field of cochlear implants and hydrogel preparation, and specifically relates to a cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repairing functions and a preparation method thereof. Background Art

[0002] Cochlear implants, an assistive hearing technology, are still the main way to improve the hearing of patients with sensorineural hearing loss. However, after electrode implantation, due to surgical trauma and foreign body implantation, a local acute inflammatory reaction occurs in the cochlea, a large number of inflammatory cells migrate out, inflammatory factors are released, and reactive oxygen free radicals are generated, causing apoptosis and dysfunction of residual hair cells in the cochlea, further loss of residual hearing, and postoperative hearing threshold shift. At the same time, the accompanying inflammatory repair and tissue remodeling process causes a large amount of repair fibrin and collagen tissue to adhere around the electrode. The formation of fibrotic tissue will hinder the conduction of electrode electrical signals to auditory neurons, affecting the postoperative hearing recovery effect. At the same time, surgery can easily cause blood components (including fibrinogen, fibroblasts, platelets, etc.) to enter the cochlea and adhere to the electrode surface, playing an important role in initiating the fibrosis process in the cochlea. Therefore, how to effectively regulate the homeostasis of the inner ear microenvironment after surgery and inhibit the deposition of extracellular matrix on the electrode surface has a decisive prognostic value for improving patients' hearing.

[0003] As a natural polyphenol compound, Res has excellent anti-inflammatory, antioxidant and immunomodulatory effects, but its hydrophobic properties, low bioavailability and other shortcomings seriously hinder its clinical application. Microgels are micron-sized gel microspheres constructed from biological hydrogels. They can achieve efficient drug loading through physical assembly and slowly release the loaded drugs during the biodegradation process, maintaining local therapeutic concentrations while reducing systemic toxicity. The present invention uses GelMA as a raw material to prepare gel microspheres using microfluidic technology, which are used as a drug-carrying platform to achieve local long-term drug delivery of Res in the cochlea.

[0004] CSMA is a bioactive polymer made from chitosan functionalized with methacrylic anhydride. It exhibits photocrosslinking properties and excellent biocompatibility, making it a suitable biomaterial platform for effectively loading cells or bioactive components. Furthermore, the high density of amino groups on the CSMA molecular chain imparts chemical programmability, enabling optimization and upgrading of hydrogel performance through specific functional modification. In this study, CSMA was used as one of the raw materials for the cochlear implant electrode coating matrix. This method can not only encapsulate Res-loaded GelMA microgels to construct a dual drug release platform, but also serve as a chemically modifiable electrode coating to impart specialized properties to the electrodes.

[0005] Cochlear implant electrodes are surgically inserted into the patient's cochlea. During the operation, they are inevitably subjected to complex mechanical stresses, which lead to the destruction of the continuity and integrity of the electrode hydrogel coating. Dynamic reversible Schiff base bonds give the hydrogel coating excellent self-repair performance through the reversible breakage-recombination mechanism of intermolecular imine bonds. The present invention innovatively introduces ODex to modify CSMA, and uses its aldehyde group and the abundant amino groups in CSMA to construct dynamic Schiff base bonds, giving the electrode coating micro-damage self-repair function, effectively overcoming the defect of brittle fracture of traditional covalently cross-linked hydrogels.

[0006] Zwitterionic SBMA, through the dynamic charge balance of the zwitterionic groups in its molecular structure, can form a highly hydrated interface layer on the surface of materials, effectively hindering the nonspecific adhesion of cells, bacteria, and proteins to the surface. Due to its excellent biological inertness and chemical stability, it has been widely used as a material for constructing biomedical antifouling interfaces. To achieve SBMA coating on cochlear implant electrodes, a precision electronic implant, this invention uses PGS, a copolymer of SBMA and GMA, as a raw material. The epoxy groups of GMA are used to carry out nucleophilic attack on the amino groups on the surface of CSMA, thereby achieving SBMA grafting on the hydrogel coating surface.

[0007] Based on this, the present invention prepared a new cochlear implant electrode coating with ODex-CSMA self-healing hydrogel as the matrix, loaded with PFD@GelMA microgel, and grafted with zwitterionic polymer PGS on the surface. The coating has excellent properties such as gel self-healing, dual drug controlled release, and surface anti-adhesion. After the electrode is implanted into the cochlea, it exerts local anti-inflammatory and anti-fibrosis effects. Summary of the Invention

[0008] The purpose of the present invention is to provide a cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repair functions and a preparation method thereof to address the problems of local inflammation and fibrosis formation in the cochlea after cochlear implant electrodes are implanted.

[0009] The technical solution adopted in the present invention is as follows:

[0010] A method for preparing a cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repairing functions, the preparation process is as follows:

[0011] 1) Preparation of Res@GelMA microgels: Res nanoemulsion was prepared using nanoemulsification technology, which was then mixed with methacrylated gelatin (GelMA) solution. Res@GelMA microgels were then prepared using microfluidics and UV curing technology.

[0012] 2) preparing a hydrogel premix: preparing a Res@GelMA / methacrylated chitosan mixed solution and an oxidized dextran solution, respectively, and mixing the two to obtain a hydrogel premix;

[0013] 3) Preparing an electrode pre-coating layer: placing the cochlear implant electrode in a light-transmitting mold, and then pouring the hydrogel premix prepared in step 2) into the mold. After UV curing and demolding, an electrode gel pre-coating layer is formed around the cochlear implant electrode.

[0014] 4) Preparation of zwitterionic electrode coatings: In a reactor, a copolymer of glycidyl methacrylate and sulfobetaine methacrylate (p(GMA-co-SBMA)) was chemically grafted onto the surface of an electrode gel pre-coating via an epoxy ring-opening reaction. Following rinsing and irradiation sterilization, a super-hydrophilic gel electrode coating material for a cochlear implant with anti-fibrosis and self-repairing properties was obtained.

[0015] Furthermore, in step 1), the nanoemulsification technology is specifically as follows: the oil phase, emulsifier, co-emulsifier and Res are magnetically stirred to dissolve Res in the initial emulsified system, deionized water is then added to the initial emulsified system, and magnetic stirring is performed again to obtain a final emulsified system, and finally the final emulsified system is homogenized to obtain the Res nanoemulsion.

[0016] Furthermore, the oil phase is one of triacetin, myristic acid or WL1349, with a concentration of 3-7 wt%; the emulsifier is one of polyoxyethylene castor oil EL-60, polyoxyethylene castor oil EL-80 or Tween 80, with a concentration of 5-10 wt%;

[0017] The co-emulsifier is one of PEG400, 1,2-propylene glycol or 1,3-butylene glycol, with a concentration of 1-5wt%; the Res concentration is 15-20wt%, and the rest is water;

[0018] During the magnetic stirring process, the rotation speed is 500-1000 rpm and the time is 10-20 min;

[0019] The homogenization adopts micro jet high pressure homogenization with a pressure of 50-100 MPa.

[0020] Furthermore, in step 1), the microfluidic technology is specifically as follows: GelMA is dissolved in a PBS solution containing a photoinitiator in a water bath at 50-60°C in the dark, and after the solution returns to room temperature, a GelMA solution is obtained, and the Res nanoemulsion and the GelMA solution are mixed in equal volumes to prepare a dispersed phase; a surfactant Span 80 is added to isopropyl myristate as an oil phase; a microfluidic device is used to inject the dispersed phase and the oil phase into the inner tube and outer tube of the microfluidic device respectively, and the dispersed phase is cut by the oil phase to form droplets. The generated droplets enter the ice bath collection unit to form spheres, and are simultaneously irradiated by a UV curing device to achieve in-situ curing to obtain microspheres; the microspheres are washed to obtain Res@GelMA microgels, and the PBS solution is a phosphate buffered saline solution.

[0021] Furthermore, the MA grafting degree of the GelMA is 20-40% and the concentration is 7.5-12.5 wt %;

[0022] The photoinitiator is one of Irgacure and lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), with a concentration of 0.5-1.0 wt%;

[0023] The Span 80 concentration is 3-6 wt%;

[0024] The microfluidic device controls the flow rate ratio of the dispersed phase and the oil phase to be 1:100 to 1:50;

[0025] The UV curing device uses a light source with a wavelength of 350-410 nm and a power of 20-40 mW / cm 2 ;

[0026] The microspheres were washed in the following steps: washing with acetone, 75% ethanol and PBS solution in sequence, with each solution washing for 2-4 times.

[0027] Furthermore, in step 2), the preparation of the hydrogel premix is ​​specifically as follows: dissolving methacrylated chitosan (CSMA) in a PBS solution containing a photoinitiator under light-proof heating conditions, cooling the solution to room temperature to obtain a CSMA solution, and mixing the Res@GelMA microgel prepared in step 1) with the CSMA solution to obtain a CSMA mixed solution containing Res@GelMA;

[0028] Oxidized dextran (ODex) was dissolved in a PBS solution containing a photoinitiator to obtain an ODex solution, and the ODex solution was mixed with a CSMA mixed solution containing Res@GelMA to obtain a hydrogel premix solution.

[0029] Furthermore, the viscosity average molecular weight of CS in the CSMA is 800,000-1,000,000, the deacetylation degree is 70-78%, and the grafting degree of MA is 20-40%;

[0030] The degree of oxidation of the ODex is 30-60%;

[0031] The photoinitiator is one of Irgacure or LAP, with a concentration of 0.2-0.5 wt%; CSMA and ODex are dissolved in the photoinitiator PBS solution at a concentration of 5-10 wt%, and the dissolution temperatures are 50-60° C. and 30-50° C., respectively;

[0032] The concentration of Res@GelMA in the CSMA solution is 4-10 wt%.

[0033] Furthermore, in step 3), the electrode pre-coating layer is prepared as follows: the transparent mold is generally conical, and is specifically divided into a transparent hollow conical mold 1 and a transparent hollow conical mold 2;

[0034] First, a cochlear implant electrode is vertically inserted into a transparent hollow conical mold 1, wherein the tip of the cochlear implant electrode is exposed outside the top of the mold 1, and the bottom of the cochlear implant electrode is provided with an electrode positioning ring, which places the non-cochlear implant part of the cochlear implant electrode outside the bottom of the mold 1. A baffle is provided at the opening at the bottom of the mold 1 for fixing the cochlear implant electrode on the central axis of the mold 1, and the top of the mold 1 is facing downward and the bottom is facing upward, and is placed vertically on a horizontal plane; under light-proof conditions, the hydrogel premix prepared in step 2) is poured into the mold 1, and the gas is completely exhausted so that the hydrogel completely fills the gap between the mold and the electrode; then The top of the transparent hollow conical mold 2 is placed vertically downward on the ground, and the hydrogel premix is ​​filled in the mold 2 under light-proof conditions; the tip of the cochlear implant electrode exposed outside the mold 1 is inserted into the mold 2 from the bottom end of the mold 2 and out from the top end of the mold 2 to be exposed outside the mold 2, and the tip of the cochlear implant electrode is pulled, and one end of the cochlear implant top positioning ring is fixed to the baffle at the bottom end of the mold 1, so that the cochlear implant electrode is fixed on the central axis of the mold 1 and the mold 2; the mold 1 and the mold 2 and the cochlear implant electrode wrapped therein are exposed to a UV light source for hydrogel curing, and then the mold 1 and the mold 2 are demolded to complete the preparation of the electrode gel precoat;

[0035] The materials of mold 1 and mold 2 are transparent quartz glass or PMMA; the baffle is composed of two semicircular hollow thin plates; the inner diameter of the top of mold 1 is consistent with the inner diameter of the bottom of mold 2, and the bottom diameter of mold 1 and mold 2 is larger than the top diameter. The shape of mold 1 and mold 2 is gradually tapered from the root to the tip; the wavelength of the UV light source is 350-410nm, and the power is 20-40mW / cm2 The irradiation time is 30-60s, and the UV light source is placed 3-5cm away from the transparent mold.

[0036] Furthermore, in step 4), the preparation process of the zwitterionic coating is specifically as follows: p(GMA-co-SBMA) or PGS is completely dissolved in PBS under 40-50°C water bath conditions to obtain a PGS solution, and the PGS solution is added into a reactor, wherein the reactor comprises: a cylindrical body with three openings on the top; the three openings are a nitrogen inlet, a nitrogen exhaust port, and an electrode placement port; the nitrogen inlet is ventilated to the bottom of the reactor, the electrode placement port is located at the center of the top of the reactor, and the opening diameter is 5-10 mm; and the electrode placement port is equipped with a rubber stopper, the rubber stopper has an electrode card hole, and the electrode card The hole can just insert the cochlear implant electrode to ensure the airtightness of the electrode placement port; the pre-coated electrode prepared in step 3) is suspended in the reactor through the reactor electrode placement port and completely immersed in the PGS solution, and the electrode placement port of the reactor is sealed; before the reaction starts, nitrogen is introduced into the nitrogen inlet for nitrogen bubbling to remove oxygen from the PGS solution and the reactor; then the remaining two openings are closed and the reaction is carried out at 60-80°C in a closed environment for 2-4 hours; after the reaction system is cooled to room temperature, the electrode is removed, the electrode is rinsed with PBS, and irradiated for sterilization, and a cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repair functions is obtained on the electrode surface;

[0037] The molar ratio of glycidyl methacrylate: sulfobetaine methacrylate (GMA): SBMA monomers in the PGS is 1:6-1:4, and the PGS concentration is 2-3 wt %. The nitrogen bubbling time is 10-20 min, and the air flow rate is 20-30 mL / min. The PBS is rinsed 2-4 times.

[0038] A cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repairing functions is obtained by using any of the above methods.

[0039] Compared with the prior art, the present invention has the following advantages:

[0040] 1) The present invention uses CSMA, ODex, GelMA, Res, PGS, etc. as the main raw materials, and combines nanoemulsification technology, microfluidics technology, in situ ultraviolet curing (UV curing process) and mold continuous casting and other combined processes to prepare a cochlear implant super-hydrophilic gel electrode coating material with anti-inflammatory, anti-fibrosis and self-repairing functions. The above raw material selection and process combination are the first of their kind in the present invention and are innovative.

[0041] 2) The cochlear implant electrode coating of the present invention is a novel composite bioactive material having a composite structure of ODex-CSMA self-healing hydrogel as a matrix, Res@GelMA microgel loaded in the matrix, and PGS zwitterionic polymer grafted on the matrix surface. It has the characteristics of anti-inflammatory, multiple anti-fibrosis, self-repair, low electrode implantation force, etc. Among them, the outer side of the gel coating is a zwitterionic polymer PGS coating with super hydrophilic ability. By virtue of the interaction between PGS and water molecules, a highly hydrated interface layer is constructed on the electrode surface, which can significantly reduce the electrode implantation resistance, thereby reducing the damage to the cochlear tissue structure and normal cells during the electrode implantation process, and can significantly reduce non-specific protein adsorption and cell adhesion on the electrode surface, avoid collagen and fibrin forming fibrotic wrapping around the electrode, and effectively inhibit the fibrosis process in the cochlea after electrode implantation, thereby reducing damage to the tissue and reducing the possibility of fibrosis (first level of anti-fibrosis). The hydrogel matrix is ​​composed of ODex and CSMA. The above two molecules undergo Schiff base reaction through rich amino and aldehyde groups. On the one hand, they can form a gel coating in situ on the surface of the cochlear implant. On the other hand, they can give the electrode coating good self-repair ability by virtue of the dynamic reversibility of the Schiff base reaction, which can avoid the rupture of the gel coating during the electrode implantation surgery. Even if the coating is ruptured during use, the gel coating can still be self-repaired through the Schiff base reaction to maintain the continuity and integrity of the coating, effectively solving the problem of easy damage to the gel coating of the cochlear implant electrode in the past; in addition, the implant surface wrapped with flexible hydrogel can effectively reduce the foreign body reaction caused by the mismatch between the implant and the tissue modulus, and relieve local inflammation and fibrosis (the second anti-fibrosis). The gel matrix is ​​physically compounded with drug-loaded gel microspheres. The Res loaded inside has significant anti-inflammatory and antioxidant functions, which can effectively regulate the inflammatory response and reduce tissue oxidative stress damage. It exerts biological effects during the inflammatory response period after electrode implantation, reducing functional hair cell damage caused by the inflammatory response, effectively protecting residual hearing, and reducing the auditory threshold shift caused by electrode implantation. At the same time, it alleviates the fibrosis process associated with inflammatory damage, reduces extracellular matrix deposition caused by tissue remodeling, and avoids the increase in electrode resistance and performance degradation caused by fibrous tissue wrapping around the electrode (the third anti-fibrosis effect). At the same time, the physical barrier effect of the gel matrix and microspheres constructs a dual sustained-release barrier for Res drug release, which can not only avoid the toxic damage of high-concentration drugs to tissue cells but also maintain the local drug effect for a longer time. In addition, the above-mentioned strategy of loading Res into the cochlear implant gel coating overcomes the problem of systemic drug administration due to the blood-labyrinth barrier, which makes it difficult for drugs to enter the cochlea, and achieves local specific enrichment without increasing systemic toxicity. It also overcomes the clinical translation bottleneck of Res, which is that its hydrophobic nature makes it difficult to maintain drug concentration in body fluids and has low bioavailability.The composite structure innovation of the above materials is designed based on the actual clinical use defects of current cochlear implants. It can achieve local anti-inflammatory and anti-fibrosis purposes through careful selection of raw materials and organic compounding of structures, and make great innovations for further realizing the functional modification and upgrading of cochlear implants, as well as improving patients' hearing quality and usage experience.

[0042] 3) The present invention adopts a combined process system based on the synergistic coupling of multiple technologies. The drug-loaded microgel, namely Res@GelMA microgel, is constructed through nanoemulsification technology, microfluidics technology and UV curing technology. The precise molding of the electrode coating is completed by combining the mold continuous casting technology and UV curing technology. Finally, the surface grafting process is synchronized to implement interface functionalization modification. Each process unit collaboratively solves the key performance parameters such as electrode biocompatibility, local anti-inflammatory properties, surface anti-adhesion, coating self-repairing properties, and low implantation force characteristics. Finally, a high-performance cochlear implant electrode coating that meets the needs of minimizing adverse consequences after implantation is successfully prepared. Specifically, the good dispersion of hydrophobic anti-inflammatory drugs in the GelMA aqueous solution is achieved through nanoemulsification technology, and the uniform preparation of drug-loaded microspheres is achieved by using microfluidics technology. The casting process and UV in-situ curing are combined to achieve the precise molding of the composite gel coating on the surface of the cochlear implant. Finally, the surface super-hydrophilic chemical modification of the gel coating is achieved by using a special mold. The present invention is aimed at the actual use needs of the cochlear implant composite gel coating in this field, plans its various functional indicators, and uses the above-mentioned combined process to achieve the controllable construction of the specific structure of the gel coating and the display of its functions, which is obviously innovative.

[0043] 4) The cochlear implant electrode coating prepared by the present invention stabilizes the homeostasis of the cochlear environment by regulating the acute inflammatory response in the cochlea after implantation, inhibiting the adhesion of cells and proteins on the electrode surface, and reducing the resistance of electrode implantation. This prevents the decline in cochlear implant performance caused by the formation of fibrosis after surgery. The three methods exhibit a nonlinear superposition effect and irreplaceability, and have a significant synergistic effect. The reduction in electrode implantation resistance first reduces tissue damage in the cochlea, drug release regulates the inflammatory cascade reaction that has already formed in the cochlea, and inhibiting electrode surface adhesion effectively reduces the formation of fibrous tissue in the cochlea. The absence of any module will lead to a vicious cycle of inflammation-fibrosis-performance decline. Only the organic combination of the three can achieve full-cycle regulation of cochlear homeostasis, proving that the composite coating material structure and functional design in the present invention are significantly innovative and practical.

[0044] 5) The electrode coating gel casting mold used in the present invention is a conical shape designed entirely according to the external dimensions of the cochlear implant electrode. It covers the entire length of the electrode and conforms to the electrode's tapering shape from base to tip. This ensures uniform coating thickness along the entire length of the electrode and adapts to the physiological structure of the electrode implant site—the scala tympani of the cochlea, where the space gradually narrows from base to apex. The mold unit consists of three components: mold 1, mold 2, and a baffle. Molds 1 and 2 are open at both ends. Designing two separate molds makes it easier to insert and secure the electrode within the mold, and combined with a continuous casting process, significantly reduces the probability of microbubble formation. To secure the electrode in the center of the mold and ensure consistent coating thickness along its entire length and circumference, the present invention designs the baffle as the proximal electrode fixing point, and the distal opening of mold 2 as the distal electrode fixing point. Mold 1 utilizes the electrode's own positioning ring, combined with the baffle, as the proximal fixing point to secure it. Mold 2 secures the electrode tip to the central opening at the top of mold 2 as the distal fixing point, thereby completely securing the electrode to the central axis of molds 1 and 2. The mold device designed in this invention demonstrates significant engineering advancement and targeted design.

[0045] 6) The present invention specially designs a special cylindrical reactor for the process of grafting PGS on the surface of the pre-coated electrode. Its main structure is a cylindrical structure with three openings. The central opening on the top can be used to fix the cochlear implant electrode, and the card hole on the rubber plug in the hole matches the size of the cochlear implant electrode; the other two openings serve as nitrogen inlet and nitrogen exhaust ports, respectively, to adapt to the nitrogen bubbling operation before the reaction starts, remove the air inside the reaction system, and prevent oxygen in the reaction system from destroying Res, providing a stable experimental environment for the PGS grafting reaction, fully meeting the precise requirements of functional modification of the surface of biomaterials.

[0046] 7) The hydrophobicity of Res limits its solubility in body fluids. This invention increases the Res loading in the gel coating to maintain effective drug concentrations within the cochlea after implantation. Precisely because of Res' hydrophobicity, during the grafting of PGS onto the gel surface, the loss of Res from the gel due to diffusion is minimal, ensuring that the drug-loaded coating carries sufficient drug upon cochlear implantation.

[0047] 8) The present invention further modifies the electrode gel coating by a surface grafting process. The preparation process can be completed under mild conditions, and the unreacted PGS remaining in the coating can be removed by simple rinsing after the grafting is completed. It is suitable for the modification of implantable precision electronic devices such as cochlear implant electrodes that are highly sensitive to harsh environments and have high requirements for biosafety and toxicity.

[0048] 9) The cochlear implant electrode coating preparation technology adopted in the present invention is suitable for electrodes of any specifications, has convenient preparation and technical universality, and can be used as a platform technology for expansion and industrial application. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Figure 1 This is a schematic diagram of the preparation process of a cochlear implant super-hydrophilic gel electrode coating with anti-fibrosis and self-repair functions according to one embodiment of the present invention;

[0050] Figure 2 A schematic diagram of a mold according to an embodiment of the present invention;

[0051] Figure 3 A schematic diagram of a reactor according to an embodiment of the present invention;

[0052] Figure 4 The gel coating extract CCK8 of one embodiment of the present invention DETAILED DESCRIPTION

[0053] The present invention is further described below with reference to specific examples.

[0054] like Figure 2 , which is a schematic diagram of the mold of the present invention. The inner diameters of the bottom and top openings of mold one are 1-1.5 mm and 0.5-1.0 mm, respectively, and the height is 19-22 mm. The baffle is composed of two semicircular hollow thin plates, the inner diameter of the semicircle is 0.7-0.9 mm, and the thickness of the thin plate is 0.05-0.1 mm. The inner diameters of the bottom and top openings of mold two are 0.5-1.0 mm and 0.2-0.4 mm, respectively, and the height is 0.5-1.0 mm. The inner diameter of the top of mold one is consistent with the inner diameter of the bottom of mold two, and the bottom diameters of mold one and mold two are respectively larger than the top diameters.

[0055] like Figure 3 FIG. 1 is a schematic diagram of a reactor according to the present invention, comprising a cylindrical body with three openings at the top, 3-4 cm in height and 3-4 cm in inner diameter. The three openings are a nitrogen inlet, a nitrogen exhaust, and an electrode placement port. The nitrogen inlet vents to the bottom of the reactor. The electrode placement port is located at the center of the reactor top, each with a diameter of 5-10 mm. The electrode placement port is equipped with a rubber stopper having an electrode retaining hole that can precisely insert a cochlear implant electrode to ensure airtightness. The electrode retaining hole has a diameter of 0.8-1.5 mm.

[0056] like Figure 4 It can be seen that the biomaterials used in the present invention are non-cytotoxic and extremely safe, and are suitable for the modification of implantable precision electronic devices such as cochlear implant electrodes that are highly sensitive to harsh environments and have high requirements for biosafety and toxicity.

[0057] Comparative Example:

[0058] Using a cochlear implant electrode without gel coating as a control, a fluorescent serum albumin (FITC-BSA) adhesion experiment was conducted on the electrode surface, and 87% of the electrode surface area was adhered by protein; further macrophage adhesion experiment was conducted on the electrode coating surface, and it was found that 59% of the electrode surface area was adhered by macrophages, and a large number of pseudopodia were visible in the macrophages; the electrode was inserted into a cochlear model, and the maximum implantation force was measured to be 0.118N; the electrode was implanted into a normal guinea pig cochlea, and in vitro cochlear tissue sectioning was performed 2 weeks after implantation, showing the formation of fibrotic tissue in the cochlear scala tympani, accounting for 64% of the scala tympani cross-sectional area.

[0059] Example 1:

[0060] 1.5 g of triacetin, 2.0 g of polyoxyethylene castor oil EL-60, and 0.8 g of PEG400 were mixed separately and magnetically stirred at 500 rpm to mix thoroughly. 4.5 g of Res was added and stirred until completely dissolved. Deionized water was added to make the volume 25 ml and stirring was continued for 10 min. The mixture was homogenized three times using a 22 kPa microjet high-pressure homogenizer to obtain a uniform Res nanoemulsion.

[0061] 2) Under light-proof conditions, 0.5 g of GelMA with a grafting degree of 30% was fully dissolved in 5 ml of 0.25 wt% LAP solution in a 60°C water bath to prepare a GelMA solution. When the solution returned to room temperature, 5 ml of the Res nanoemulsion prepared in step 1) was fully mixed with it to prepare a dispersed phase containing 5%

[0062] Span 80 isopropyl myristate was used as the oil phase. The inner diameters of the inner and outer tubes of the microfluidic device were 110 μm and 210 μm, respectively. The flow rate ratio of the dispersed phase to the oil phase was controlled at 1:80. The microgel particles were reversibly cross-linked and solidified after entering the ice bath collection unit. A 405 nm wavelength UV light source with a wavelength of 30 mW / cm 2 The microgel particles were irradiated for 60 s to completely solidify them, and then washed three times with acetone, 75% ethanol solution and PBS solution, respectively, to obtain stably cross-linked Res@GelMA microgels.

[0063] 3) Under light-shielded conditions, 0.25 g of CSMA (CSMA having a viscosity-average molecular weight of 1,000,000, a degree of deacetylation of 75%, and a degree of MA grafting of 30%) was dissolved in 5 ml of a 0.25 wt% LAP solution to obtain a CSMA solution. Subsequently, 0.4 g of Res@GelMA prepared in step 2) was added to the CSMA solution and mixed thoroughly. Simultaneously, 0.25 g of 50% ODex (ODex) was fully dissolved in 5 ml of a 0.25 wt% LAP solution in a 37°C water bath to prepare an ODex solution for later use.

[0064] 4) Place the cochlear implant electrode into a transparent hollow conical mold 1, keeping the electrode in the central axis position of the mold 1 to avoid bending of the electrode; Under light-proof conditions, fully mix the Res@GelMA / CSMA mixed solution prepared in step 3) with the ODex solution, and immediately pour it into molds 1 and 2. When the solution completely fills the gap between the molds, immediately merge the two molds so that the coating pre-solution completely covers the electrode surface. Use a 405nm wavelength light source, 30mW / cm 2 The electrode was irradiated for 60 seconds, with the UV light source placed 3 cm from the mold. After curing, the mold was removed to obtain the electrode gel pre-coating. Molds 1 and 2 were made of transparent quartz glass. The inner diameters of the bottom and top openings of Mold 1 were 1.35 mm and 0.75 mm, respectively, and the height was 21 mm. The baffles were composed of two semicircular hollow plates with an inner diameter of 0.8 mm and a thickness of 0.1 mm. Mold 2 had inner diameters of 0.75 mm and 0.3 mm, respectively, and a height of 0.7 mm.

[0065] 5) Dissolve 1.0 g of PGS in 50 ml of PBS in a 50°C water bath and pour the entire solution into a cylindrical reactor. The reactor has a 4 cm high, 4 cm inner diameter, and three openings at the top: a nitrogen inlet, a nitrogen exhaust, and an electrode placement port. The nitrogen inlet vents to the bottom of the reactor. The electrode placement port is located at the center of the reactor top and has an opening diameter of 8 mm. The electrode placement port is equipped with a rubber stopper with a 1 mm diameter hole for inserting a cochlear implant electrode. The electrode gel pre-coating obtained in step 4) is placed in a reactor and suspended in the PGS solution, and the electrode is completely immersed in the solution. The electrode placement port is sealed and purged with nitrogen for 15 minutes at a flow rate of 20 mL / min. Then, the nitrogen inlet and nitrogen outlet are completely sealed with a sealing film. The reaction is carried out at 80°C for 3 hours. After the reaction is completed, the coating surface is rinsed 3 times with PBS to remove unreacted PGS, thereby obtaining a cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repair functions.

[0066] 6) An extract of the gel coating was prepared, and 293T cells were cultured with the extract. After 3 days of culture, a CCK8 experiment was performed, and the cell survival rate was approximately 97%; the gel coating was subjected to a self-healing test, and the cut gel could achieve self-healing within 15 minutes; a serum albumin (BSA) non-specific protein adhesion experiment was performed on the surface of the prepared electrode coating, and the amount of non-specific protein adhesion on the electrode surface was reduced by 93% compared with the control example; a macrophage adhesion experiment was further performed on the electrode coating surface, and the amount of macrophage adhesion on the coated electrode surface was reduced by 91% compared with the control example, and the macrophages appeared round, indicating that the coated electrode can effectively reduce macrophage adhesion and avoid macrophage activation; the electrode was inserted into the cochlear model, and the maximum implantation force was measured to be 0.055N, which was lower than that of the control example; the electrode was implanted into the cochlea of ​​a normal guinea pig, and in vitro cochlear tissue sections were performed 2 weeks after implantation. Compared with the control example, the fibrosis area of ​​the cochlea of ​​the guinea pig implanted with the coated electrode was reduced by 80%, indicating that the electrode coating can significantly reduce the formation of fibrosis after electrode implantation.

[0067] Example 2

[0068] 1.5 g of triacetin, 2.0 g of polyoxyethylene castor oil EL-60, and 0.8 g of PEG400 were mixed separately and magnetically stirred at 500 rpm to mix thoroughly. 4.5 g of Res was added and stirred until completely dissolved. Deionized water was added to make the volume 25 ml and stirring was continued for 10 min. The mixture was homogenized three times using a 22 kPa microjet high-pressure homogenizer to obtain a uniform Res nanoemulsion.

[0069] 2) Under light-proof conditions, 0.5 g of GelMA with a grafting degree of 30% was fully dissolved in 5 ml of 0.25 wt% LAP solution in a 60°C water bath to prepare a GelMA solution. When the solution returned to room temperature, 5 ml of the Res nanoemulsion prepared in step 1) was fully mixed with it to prepare a dispersed phase containing 5%

[0070] Span 80 isopropyl myristate was used as the oil phase. The inner diameters of the inner and outer tubes of the microfluidic device were 110 μm and 210 μm, respectively. The flow rate ratio of the dispersed phase to the oil phase was controlled at 1:80. The microgel particles were reversibly cross-linked and solidified after entering the ice bath collection unit. A 405 nm wavelength UV light source with a wavelength of 30 mW / cm 2 The microgel particles were irradiated for 60 s to completely solidify them, and then washed three times with acetone, 75% ethanol solution and PBS solution, respectively, to obtain stably cross-linked Res@GelMA microgels.

[0071] 3) Under light-shielded conditions, 0.25 g of CSMA (CSMA having a viscosity-average molecular weight of 1,000,000, a degree of deacetylation of 75%, and a degree of MA grafting of 30%) was dissolved in 5 ml of a 0.25 wt% LAP solution to obtain a CSMA solution. Subsequently, 0.4 g of Res@GelMA prepared in step 2) was added to the CSMA solution and mixed thoroughly. Simultaneously, 0.25 g of ODex (30% oxidation degree) was fully dissolved in 5 ml of a 0.25 wt% LAP solution in a 37°C water bath to prepare an ODex solution for later use.

[0072] 4) Place the cochlear implant electrode into a transparent hollow conical mold 1, keeping the electrode in the center axis position of the mold to avoid bending of the electrode; under light-proof conditions, fully mix the Res@GelMA / CSMA mixed solution prepared in step 3) with the ODex solution, and immediately pour it into molds 1 and 2. When the solution completely fills the gap between the molds, immediately merge the two molds so that the coating pre-solution completely covers the electrode surface. Use a 405nm wavelength light source, 30mW / cm 2 The electrode was irradiated for 60 seconds, with the UV light source placed 3 cm from the mold. After curing, the mold was removed to obtain the electrode gel pre-coating. Molds 1 and 2 were made of transparent quartz glass. The inner diameters of the bottom and top openings of Mold 1 were 1.35 mm and 0.75 mm, respectively, and the height was 21 mm. The baffles were composed of two semicircular hollow plates with an inner diameter of 0.8 mm and a thickness of 0.1 mm. Mold 2 had inner diameters of 0.75 mm and 0.3 mm, respectively, and a height of 0.7 mm.

[0073] 5) Dissolve 1.0 g of PGS in 50 ml of PBS solution in a 50°C water bath and pour the entire solution into a cylindrical reactor. The reactor has a cylindrical body with three openings at the top, 4 cm in height and 4 cm in inner diameter. The three openings are a nitrogen inlet, a nitrogen outlet, and an electrode placement port. The nitrogen inlet vents to the bottom of the reactor. The electrode placement port is located at the center of the reactor top and has an opening diameter of 8 mm. The electrode placement port is equipped with a rubber stopper with an electrode clip hole for inserting a cochlear implant electrode. The electrode clip hole has a diameter of 1 mm. The electrode gel precoat obtained in step 4) is placed in the reactor and suspended in the PGS solution, with the electrode completely immersed in the solution. The electrode placement port is sealed and purged with nitrogen for 15 minutes at a flow rate of 20 mL / min. The nitrogen inlet and nitrogen outlet are then completely sealed with a sealing film. The reaction is carried out at 80°C for 3 hours. After the reaction is completed, the coating surface is rinsed three times with PBS to remove unreacted PGS, thereby obtaining the cochlear implant electrode coating material.

[0074] 6) Compared with Example 1, Example 2 used ODex with a lower degree of oxidation, and the other preparation conditions were the same.

[0075] An extract of the gel coating was prepared, and 293T cells were cultured with the extract. A CCK8 experiment was performed after culturing for 3 days, and the cell survival rate was approximately 97%. The gel coating was subjected to a self-healing test. The self-healing time after gel cutting was prolonged compared with Example 1, and self-healing was required to be achieved after 30 minutes. A serum albumin (BSA) non-specific protein adhesion experiment was performed on the surface of the prepared electrode coating. Compared with the control example, the amount of non-specific protein adhesion on the electrode surface was reduced by 91%. A macrophage adhesion experiment was further performed on the surface of the electrode coating. Compared with the control example, the amount of macrophage adhesion on the coated electrode surface was reduced by 92%, and the macrophages appeared round, indicating that the coated electrode can effectively reduce macrophage adhesion and avoid macrophage activation. The electrode was inserted into the cochlear model, and the maximum implantation force measured was lower than that of the control example, at 0.058 N. The electrode was implanted into the cochlea of ​​a normal guinea pig, and in vitro cochlear tissue sections were performed 2 weeks after implantation. Compared with the control example, the fibrosis area of ​​the cochlea of ​​the guinea pig implanted with the coated electrode was reduced by 60%.

[0076] Example 3:

[0077] 1.5 g of triacetin, 2.0 g of polyoxyethylene castor oil EL-60, and 0.8 g of PEG400 were mixed separately and magnetically stirred at 500 rpm to mix thoroughly. 4.5 g of Res was added and stirred until completely dissolved. Deionized water was added to make the volume 25 ml and stirring was continued for 10 min. The mixture was homogenized three times using a 22 kPa microjet high-pressure homogenizer to obtain a uniform Res nanoemulsion.

[0078] 2) Under light-proof conditions, 0.5 g of GelMA with a grafting degree of 30% was fully dissolved in 5 ml of 0.25 wt% LAP solution in a 60°C water bath to prepare a GelMA solution. When the solution returned to room temperature, 5 ml of the Res nanoemulsion prepared in step 1) was fully mixed with it to prepare a dispersed phase containing 5%

[0079] Span 80 isopropyl myristate was used as the oil phase. The inner diameters of the inner and outer tubes of the microfluidic device were 110 μm and 210 μm, respectively. The flow rate ratio of the dispersed phase to the oil phase was controlled at 1:80. The microgel particles were reversibly cross-linked and solidified after entering the ice bath collection unit. A 405 nm wavelength UV light source with a wavelength of 30 mW / cm 2 The microgel particles were irradiated for 60 s to completely solidify them, and then washed three times with acetone, 75% ethanol solution and PBS solution, respectively, to obtain stably cross-linked Res@GelMA microgels.

[0080] 3) Under light-shielded conditions, 0.25 g of CSMA (CSMA having a viscosity-average molecular weight of 1,000,000, a degree of deacetylation of 75%, and a degree of MA grafting of 30%) was dissolved in 5 ml of a 0.25 wt% LAP solution to obtain a CSMA solution. Subsequently, 0.4 g of Res@GelMA prepared in step 2) was added to the CSMA solution and mixed thoroughly. Simultaneously, 0.25 g of ODex was fully dissolved in 5 ml of a 0.25 wt% LAP solution in a 37°C water bath to prepare an ODex solution for later use.

[0081] 4) Place the cochlear implant electrode into a transparent hollow conical mold 1, keeping the electrode in the central axis position of the mold 1 to avoid bending of the electrode; Under light-proof conditions, fully mix the Res@GelMA / CSMA mixed solution prepared in step 3) with the ODex solution, and immediately pour it into molds 1 and 2. When the solution completely fills the gap between the molds, immediately merge the two molds so that the coating pre-solution completely covers the electrode surface. Use a 405nm wavelength light source, 30mW / cm 2 The electrode was irradiated for 60 seconds, with the UV light source placed 3 cm from the mold. After curing, the mold was removed to obtain the electrode gel pre-coating. Molds 1 and 2 were made of transparent quartz glass. The inner diameters of the bottom and top openings of Mold 1 were 1.35 mm and 0.75 mm, respectively, and the height was 21 mm. The baffles were composed of two semicircular hollow plates with an inner diameter of 0.8 mm and a thickness of 0.1 mm. Mold 2 had inner diameters of 0.75 mm and 0.3 mm, respectively, and a height of 0.7 mm.

[0082] 5) Dissolve 0.2g of PGS in 50ml of PBS solution in a 50°C water bath and pour the entire solution into a cylindrical reactor. The reactor has a cylindrical body with three openings at the top, 4cm in height and 4cm in inner diameter. The three openings are a nitrogen inlet, a nitrogen outlet, and an electrode placement port. The nitrogen inlet vents to the bottom of the reactor. The electrode placement port is located at the center of the reactor top and has an opening diameter of 8mm. The electrode placement port is equipped with a rubber stopper with an electrode clip hole for inserting a cochlear implant electrode. The electrode clip hole diameter is 1mm. The electrode gel pre-coating obtained in step 4) is placed in the reactor and suspended in the PGS solution, with the electrode completely immersed in the solution. The electrode placement port is sealed and purged with nitrogen for 15 minutes at a flow rate of 20mL / min. The nitrogen inlet and nitrogen outlet are completely sealed with a sealing film. The reaction is carried out at 80°C for 3 hours. After the reaction is completed, the coating surface is rinsed three times with PBS to remove unreacted PGS, thereby obtaining a cochlear implant electrode coating material.

[0083] 6) Compared with Example 1, Example 3 reduces the PGS concentration, and the other conditions are the same. The extract of the gel coating was prepared, and 293T cells were cultured with the extract. After 3 days of culture, a CCK8 experiment was performed, and the cell survival rate was about 98%; the gel coating was subjected to a self-healing test, and the cut gel could achieve self-healing within 15 minutes; a serum albumin (BSA) non-specific protein adhesion experiment was performed on the surface of the prepared electrode coating, and the uncoated electrode was used as a control. The results showed that the amount of non-specific protein adhesion on the electrode surface was reduced by 74%. Compared with Example 1, the ability of the coating to inhibit non-specific protein adhesion decreased, indicating that sufficient PGS can effectively increase the anti-protein adhesion ability of the hydrogel coating; the macrophage adhesion experiment was further performed on the electrode coating surface. Compared with the uncoated electrode, the amount of macrophage adhesion on the coated electrode surface was reduced by 72%, and the uncoated electrode surface Macrophages showed more pseudopodia, while macrophages adhered to the surface of the coated electrode appeared in a similar round shape, indicating that the coated electrode can effectively reduce the adhesion of macrophages and avoid macrophage activation. It also shows that a sufficient dose of PGS will effectively reduce cell adhesion on the hydrogel surface; the electrode was inserted into the cochlear model, and the maximum implantation force was measured to be smaller than that of the control group, but higher than that of Example 1, which was 0.091N, indicating that a sufficient dose of PGS can significantly reduce the resistance to electrode implantation; the electrode was implanted into the cochlea of ​​a normal guinea pig, and in vitro cochlear tissue sections were taken 2 weeks after implantation. Compared with the uncoated electrode, the fibrosis area of ​​the guinea pig cochlea implanted with the coated electrode was reduced by 63%, indicating that the electrode coating can significantly reduce the formation of fibrosis after electrode implantation, and sufficient PGS surface grafting will more effectively reduce fibrosis around the implanted electrode.

Claims

1. A method for preparing a cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repair functions, characterized in that: The preparation process is as follows: 1) Preparation of Res@GelMA microgels: Res nanoemulsion was prepared using nanoemulsification technology, which was then mixed with methacrylated gelatin (GelMA) solution. Res@GelMA microgels were then prepared using microfluidics and UV curing technology. 2) preparing a hydrogel premix: preparing a Res@GelMA / methacrylated chitosan mixed solution and an oxidized dextran solution, respectively, and mixing the two to obtain a hydrogel premix; 3) Preparing an electrode pre-coating layer: placing the cochlear implant electrode in a light-transmitting mold, and then pouring the hydrogel premix prepared in step 2) into the mold. After UV curing and demolding, an electrode gel pre-coating layer is formed around the cochlear implant electrode. 4) Preparation of zwitterionic electrode coatings: In a reactor, a copolymer of glycidyl methacrylate and sulfobetaine methacrylate (p(GMA-co-SBMA)) was chemically grafted onto the surface of an electrode gel pre-coating via an epoxy ring-opening reaction. Following rinsing and irradiation sterilization, a super-hydrophilic gel electrode coating material for a cochlear implant with anti-fibrosis and self-repairing properties was obtained.

2. The method for preparing a cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repairing functions according to claim 1, characterized in that: In step 1), the nanoemulsification technology specifically comprises: magnetically stirring the oil phase, emulsifier, co-emulsifier and Res to dissolve Res in the initial emulsified system, then adding deionized water to the initial emulsified system, and magnetically stirring again to obtain a final emulsified system, and finally homogenizing the final emulsified system to obtain the Res nanoemulsion.

3. The method for preparing a cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repairing functions according to claim 2, characterized in that: The oil phase is one of triacetin, myristic acid or WL1349, with a concentration of 3-7 wt%; the emulsifier is one of polyoxyethylene castor oil EL-60, polyoxyethylene castor oil EL-80 or Tween 80, with a concentration of 5-10 wt%; The co-emulsifier is one of PEG400, 1,2-propylene glycol or 1,3-butylene glycol, with a concentration of 1-5wt%; Res concentration is 15-20wt%, the rest is water; During the magnetic stirring process, the rotation speed is 500-1000 rpm and the time is 10-20 min; The homogenization adopts micro jet high pressure homogenization with a pressure of 50-100 MPa.

4. The method for preparing a cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repairing functions according to claim 1, characterized in that: In step 1), the microfluidic technology is specifically as follows: GelMA is dissolved in a PBS solution containing a photoinitiator in a water bath at 50-60° C. in the dark, and after the solution returns to room temperature, a GelMA solution is obtained, and the Res nanoemulsion and the GelMA solution are mixed in equal volumes to prepare a dispersed phase; isopropyl myristate and a surfactant Span 80 are added as the oil phase; A microfluidic device was used to inject the dispersed phase and oil phase into the inner and outer tubes of the microfluidic device, respectively. The dispersed phase was cut by the oil phase to form droplets. The generated droplets entered an ice bath collection unit to form spheres. At the same time, they were irradiated by a UV curing device to achieve in-situ curing to obtain microspheres. The microspheres were washed to obtain Res@GelMA microgels.

5. The method for preparing a cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repairing functions according to claim 4, characterized in that: The MA grafting degree of the GelMA is 20-40%, and the concentration is 7.5-12.5wt%; The photoinitiator is one of Irgacure and lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), with a concentration of 0.5-1.0 wt%; The Span 80 concentration is 3-6 wt%; The microfluidic device controls the flow rate ratio of the dispersed phase and the oil phase to be 1:100 to 1:50; The UV curing device uses a light source with a wavelength of 350-410 nm and a power of 20-40 mW / cm 2 ; The microspheres were washed in the following steps: washing with acetone, 75% ethanol and PBS solution in sequence, with each solution washing for 2-4 times.

6. The method for preparing a cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repairing functions according to claim 1, characterized in that: In step 2), the preparation of the hydrogel premix is ​​specifically as follows: dissolving methacrylated chitosan (CSMA) in a PBS solution containing a photoinitiator under light-proof heating conditions, cooling the solution to room temperature to obtain a CSMA solution, and mixing the Res@GelMA microgel prepared in step 1) with the CSMA solution to obtain a CSMA mixed solution containing Res@GelMA; Oxidized dextran (ODex) was dissolved in a PBS solution containing a photoinitiator to obtain an ODex solution, and the ODex solution was mixed with a CSMA mixed solution containing Res@GelMA to obtain a hydrogel premix solution.

7. The method for preparing a cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repairing functions according to claim 6, characterized in that: The viscosity average molecular weight of CS in the CSMA is 800,000-1,000,000, the deacetylation degree is 70-78%, and the grafting degree of MA is 20-40%. The degree of oxidation of the ODex is 30-60%; The photoinitiator is one of Irgacure or LAP, with a concentration of 0.2-0.5 wt%; CSMA and ODex are dissolved in the photoinitiator PBS solution at a concentration of 5-10 wt%, and the dissolution temperatures are 50-60° C. and 30-50° C., respectively; The concentration of Res@GelMA in the CSMA solution is 4-10 wt%.

8. The method for preparing a cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repairing functions according to claim 1, characterized in that: In step 3), the electrode pre-coating layer is prepared as follows: the transparent mold is generally conical, and is specifically divided into a transparent hollow conical mold 1 and a transparent hollow conical mold 2; First, a cochlear implant electrode is vertically inserted into a transparent hollow conical mold 1, wherein the tip of the cochlear implant electrode is exposed outside the top of the mold 1, and the bottom of the cochlear implant electrode is provided with an electrode positioning ring, which places the non-cochlear implant part of the cochlear implant electrode outside the bottom of the mold 1. A baffle is provided at the opening at the bottom of the mold 1 for fixing the cochlear implant electrode on the central axis of the mold 1, and the top of the mold 1 is facing downward and the bottom is facing upward, and is placed vertically on a horizontal plane; under light-proof conditions, the hydrogel premix prepared in step 2) is poured into the mold 1, and the gas is completely exhausted so that the hydrogel completely fills the gap between the mold and the electrode; then The top of the transparent hollow conical mold 2 is placed vertically downward on the ground, and the hydrogel premix is ​​filled in the mold 2 under light-proof conditions; the tip of the cochlear implant electrode exposed outside the mold 1 is inserted into the mold 2 from the bottom end of the mold 2 and out from the top end of the mold 2 to be exposed outside the mold 2, and the tip of the cochlear implant electrode is pulled, and one end of the cochlear implant top positioning ring is fixed to the baffle at the bottom end of the mold 1, so that the cochlear implant electrode is fixed on the central axis of the mold 1 and the mold 2; the mold 1 and the mold 2 and the cochlear implant electrode wrapped therein are exposed to a UV light source for hydrogel curing, and then the mold 1 and the mold 2 are demolded to complete the preparation of the electrode gel precoat; The materials of mold 1 and mold 2 are transparent quartz glass or PMMA; the baffle is composed of two semicircular hollow thin plates; the inner diameter of the top of mold 1 is consistent with the inner diameter of the bottom of mold 2, and the bottom diameter of mold 1 and mold 2 is larger than the top diameter; the wavelength of the UV light source is 350-410nm, and the power is 20-40mW / cm 2 The irradiation time is 30-60s, and the UV light source is placed 3-5cm away from the transparent mold.

9. The method for preparing a cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repairing functions according to claim 1, characterized in that: In step 4), the preparation process of the zwitterionic coating is specifically as follows: p(GMA-co-SBMA) or PGS is completely dissolved in PBS under 40-50°C water bath conditions to obtain a PGS solution, and the PGS solution is added into a reactor, wherein the reactor comprises: a cylindrical body with three openings on the top; the three openings are a nitrogen inlet, a nitrogen exhaust port, and an electrode placement port; the nitrogen inlet is ventilated to the bottom of the reactor, and the electrode placement port is located at the center of the top of the reactor; and the electrode placement port is equipped with a rubber stopper, and the rubber stopper has an electrode card hole, and the electrode card The hole can just insert the cochlear implant electrode; the pre-coated electrode prepared in step 3) is suspended in the reactor through the electrode placement port of the reactor and completely immersed in the PGS solution, and the electrode placement port of the reactor is sealed; before the reaction starts, nitrogen is introduced into the nitrogen inlet for nitrogen bubbling to remove oxygen from the PGS solution and the reactor; then the three openings are closed and the reaction is carried out in a closed environment at 60-80°C for 2-4 hours; after the reaction system is cooled to room temperature, the electrode is removed, the electrode is rinsed with PBS, and irradiated for sterilization, and a cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repairing functions is obtained on the electrode surface; The molar ratio of glycidyl methacrylate: sulfobetaine methacrylate (GMA:SBMA) monomers in the PGS is 1:6-1:4, and the PGS concentration is 2-3wt%. The nitrogen bubbling time is 10-20 minutes, and the air flow rate is 20-30 mL / min. The PBS is used to rinse the electrode 2-4 times.

10. A cochlear implant super-hydrophilic gel electrode coating material with anti-fibrosis and self-repairing functions, characterized in that: The method according to any one of claims 1 to 9 is used to obtain the

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