An electrode array for auditory brain-computer interfaces

Abstract

This invention discloses an electrode array for an auditory brain-computer interface (BCI). The electrode array includes a silicone electrode body, a passively released drug coating, multiple electrode stimulation contacts, and an actively released drug coating. The passively released drug coating is a non-conductive polymer layer carrying anti-inflammatory drugs; the actively released drug coating is a conductive polymer layer carrying neurotrophic factors. This electrode array can sequentially release multiple drugs after implantation. Before the BCI is activated, anti-inflammatory drugs are passively released into the main body of the silicone electrode body to reduce cochlear damage and protect the remaining spiral ganglion. After activation, neurotrophic factors are actively released at the electrode contacts using electro-controlled release technology, creating a high-to-low drug concentration gradient from the electrode stimulation contacts to the spiral ganglion. This achieves a safe, stable, and long-lasting function of guiding directional nerve growth, potentially significantly improving the effectiveness of the auditory BCI.

Description

Technical Field

[0001] This invention relates to the field of electrode array technology, and more particularly to an electrode array for auditory brain-computer interfaces. Background Technology

[0002] According to the latest hearing report from the World Health Organization, approximately 466 million people worldwide suffer from hearing loss, accounting for 6.5% of the global population. It is projected that by 2050, over 700 million people will lose their hearing. Hearing loss has become a global health problem affecting society and the economy. Brain-computer interfaces (BCIs), which create a direct connection between the brain and external devices, are the most effective tools for restoring neural function. In auditory reconstruction, cochlear implants and auditory brainstem implants were among the earliest implantable auditory BCIs researched. They can bypass the damaged inner ear and directly electrically stimulate the upstream auditory nerve. After decades of development, cochlear implants have become the most successful and widely used BCI in clinical practice, and are almost the only treatment for severe sensorineural hearing loss. With the increase in age-related, noise-induced, and drug-induced hearing loss, the demand for auditory BCIs will continue to grow.

[0003] The core challenge of auditory brain-computer interfaces lies in achieving a balance between minimizing damage to the auditory nerve and maximizing the restoration of auditory function. Taking cochlear implants as an example, issues such as trauma to the inner ear during implantation surgery, foreign body reactions caused by the electrode array, and insufficient precision of electrical stimulation remain current research bottlenecks. Most cochlear implant recipients struggle to hear in noisy environments and accurately locate the direction of sounds. The main reasons for these problems are: ① insufficient number and / or limited function of spiral ganglion cells in the inner ear; ② excessive distance between the electrodes inserted into the cochlea and the spiral ganglion cells, resulting in diffuse and inaccurate electrical stimulation from the cochlea, and interference between adjacent electrodes; ③ the fibrous sheath forming around the electrode array after implantation affects the transmission of electrical signals. Clearly, addressing these shortcomings involves improving the function and number of spiral ganglion cells, shortening the distance between the auditory nerve endings and the electrodes (making them as close as possible or even directly connected), and preventing the formation of fibrosis around the electrodes.

[0004] To reduce surgical trauma, minimize local tissue reaction, and mitigate auditory nerve damage, existing protective strategies primarily involve the use of anti-inflammatory drugs (such as corticosteroids) and neurotrophic factors (such as brain-derived neurotrophic factor (BDNF) and neurotrophic factor-3 (NT-3)). However, systemic drug administration has significant side effects and is difficult to deliver to the surgical site, while local administration often requires invasive procedures, increasing the risk of intracranial infection and causing significant patient suffering. Clearly, drug delivery via an electrode array is a promising application, allowing drugs to be delivered directly to the implantation site during surgery and released slowly, avoiding secondary trauma to the implantation site. Studies have shown that the hydrogel coating of cochlear implant electrodes can load BDNF, which is beneficial for protecting the survival of auditory nerve endings (spiral ganglion cells). However, this simple drug delivery method involves uncontrolled passive diffusion, failing to maintain a stable and effective drug concentration, thus hindering therapeutic efficacy. Furthermore, electrode arrays carrying only a single type of drug have serious limitations in practical applications. To protect the auditory nerve, anti-inflammatory drugs are needed in the early postoperative period, followed by the administration of neurotrophic factors after the inflammation subsides. Otherwise, postoperative inflammation can lead to extensive proliferation of fibrous tissue around the implanted electrode array, forming fibrous encapsulation and hindering drug release. Therefore, there is an urgent need for an electrode array that can avoid fibrosis around the electrodes, protect the auditory nerve, and even guide the direction of nerve fibers for auditory brain-computer interfaces. Summary of the Invention

[0005] To overcome the shortcomings of existing technologies, this invention provides an electrode array for auditory brain-computer interfaces, which solves the problems existing in traditional technologies. It can avoid fibrosis around the electrodes, protect the auditory nerve, and achieve safe, stable, and long-term guidance of nerve growth, and is expected to significantly improve the effectiveness of auditory brain-computer interfaces.

[0006] This invention is achieved using the following technical solution:

[0007] An electrode array for an auditory brain-computer interface includes an electrode silicone body, a passively released drug coating covering the outer surface of the electrode silicone body, a plurality of electrode stimulation contacts embedded in the electrode silicone body, and an actively released drug coating coated on the electrode stimulation contacts. The electrode silicone body contains a loop electrode, an electrode wire, a wavy lead, a stimulation lead, and a loop lead. The loop electrode is located at the end of the electrode silicone body. The electrode wire connects the electrode stimulation contacts to the loop electrode. The stimulation lead connects the electrode wire to the electrode stimulation contacts. The loop electrode is connected to the loop lead. The passively released drug coating is a non-conductive polymer layer carrying an anti-inflammatory drug. The actively released drug coating is a conductive polymer layer carrying neurotrophic factors.

[0008] Furthermore, the rear end of the electrode silicone body is gradually narrowed towards the front end.

[0009] Furthermore, the ratio of the maximum diameter to the minimum diameter of the electrode silicone body is 1:(0.6-0.9).

[0010] Furthermore, each of the electrode stimulation contacts is embedded in the electrode silicone body at intervals.

[0011] Furthermore, the number of electrode stimulation contacts is 8-24.

[0012] Furthermore, the front end of the electrode silicone body is provided with a front passive release section, and the active release drug coating on each electrode stimulation contact forms an active release section. The length of the front passive release section is 0.05-0.3 times the length of the active release section.

[0013] Furthermore, the electrode silicone body is provided with a first central passive release section on the side away from the electrode stimulation contact, and a second central passive release section is provided on the side of the electrode silicone body close to the electrode stimulation contact. The second central passive release section is located between each of the electrode stimulation contacts, and a rear passive release section is provided at the rear end of the electrode silicone body.

[0014] Furthermore, the non-conductive polymer layer is one or a combination of two or more of polyethylene, polypropylene, polystyrene, polyvinyl chloride, polycaprolactone, and polytrimethylene carbonate.

[0015] Furthermore, the conductive polymer layer is one or a combination of two or more of polypyrrole, polythiophene, polyacetylene, polyaniline, poly(p-phenylene), polystyrene, polythiophene ethylene, polyfuran ethylene, polyphenylene sulfide, polyphenylene acetylene, and poly(3,4-ethylenedioxythiophene).

[0016] Furthermore, the anti-inflammatory drug is one or a combination of two or more of the following: extracellular vesicles, exosomes, glucocorticoids, nonsteroidal anti-inflammatory drugs, immunosuppressants, and biological agents; the neurotrophic factor is one or a combination of two or more of the following: extracellular vesicles, exosomes, neurotrophic factor-3 (NT-3), brain-derived neurotrophic factor, neurotrophic factor-4 (NT-4), glial cell-derived neurotrophic factor, neurotrophic factor-6 (NT-6), neurotrophic factor-a (NT-a), and pro-angiogenic factors.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0018] The electrode array of this invention has a non-conductive polymer layer carrying anti-inflammatory drugs coated on the silicone electrode body, and a conductive polymer layer carrying neurotrophic factors coated on the electrode stimulation contacts. This allows for the sequential release of multiple drugs after implantation. Before the auditory brain-computer interface is activated, anti-inflammatory drugs are passively released in the main body of the silicone electrode body to reduce cochlear damage and protect the remaining spiral ganglion. After activation, neurotrophic factors are actively released at the electrode contacts using electro-controlled release technology, creating a drug concentration gradient from high to low between the electrode stimulation contacts and the spiral ganglion. This achieves a safe, stable, and long-lasting function of guiding nerve growth, and is expected to significantly improve the effectiveness of the auditory brain-computer interface. Attached Figure Description

[0019] Figure 1 This is a schematic diagram of the electrode array for an auditory brain-computer interface according to the present invention;

[0020] Figure 2 for Figure 1 A partial cross-section of the electrode silicone body of the electrode array shown;

[0021] Figure 3 for Figure 1 The cross-section of the electrode array shown at the electrode stimulation contact point;

[0022] Figure 4 for Figure 1 Scanning electron microscope (SEM) images of the passive release end of the electrode array before and after drug loading;

[0023] Figure 5 for Figure 1 Scanning electron microscope (SEM) images of the active release end of the electrode array before and after drug loading;

[0024] Figure 6 for Figure 1 The anti-inflammatory effect of dexamethasone loaded onto the passive release end of the electrode array shown;

[0025] Figure 7 for Figure 1 The electrode array shown demonstrates the nerve growth-promoting effect of actively releasing terminal mesenchymal stem cell extracellular vesicles.

[0026] In the diagram: 1. Silicone electrode body; 2. Electrode stimulation contact; 3. Passive drug release coating; 4. Active drug release coating; 5. Electrode wire; 6. Wavy lead wire; 7. Loop electrode; 8. Stimulation lead wire; 9. Loop lead wire; 10. Ganglion; 11. Nerve fiber. Detailed Implementation

[0027] The present invention will now be further described in conjunction with specific embodiments. It should be noted that, without conflict, the various embodiments or technical features described below can be arbitrarily combined to form new embodiments.

[0028] like Figures 1-3 The diagram shows an electrode array according to a preferred embodiment of the present invention, used for an auditory brain-computer interface. Specifically, the electrode array includes an electrode silicone body 1, a passive drug-releasing coating 3 covering the outer surface of the electrode silicone body 1, multiple electrode stimulation contacts 2 embedded in the electrode silicone body 1, and an active drug-releasing coating 4 coated on the electrode stimulation contacts 2. The electrode silicone body 1 is provided with a loop electrode 7, an electrode wire 5, a wavy lead 6, a stimulation lead 8, and a loop lead 9. The loop electrode 7 is located at the end of the electrode silicone body 1. The electrode wire 5 connects the electrode stimulation contacts 2 and the loop electrode 7. The stimulation lead 8 connects the electrode wire 5 and the electrode stimulation contacts 2. The loop electrode 7 is connected to the loop lead 9. The passive drug-releasing coating 3 is a non-conductive polymer layer carrying an anti-inflammatory drug. The active drug-releasing coating 4 is a conductive polymer layer carrying neurotrophic factors.

[0029] like Figure 1 As shown, before the auditory brain-computer interface is activated, anti-inflammatory drugs are gradually and passively released through the passive drug-release coating 3 on the electrode silicone body 1 to reduce cochlear damage and protect the remaining spiral ganglion. After activation, using electro-controlled release technology, under the action of the electrode stimulation contact 2, neurotrophic factors are actively released from the drug-release coating 4 to create a connection between the electrode stimulation contact 2 and the spiral ganglion (e.g., Figure 1 The drug concentration gradient from high to low (transmission between the middle ganglion 10 and nerve fiber 11) enables safe, stable, and long-lasting guidance of directional nerve growth, which is expected to significantly improve the effectiveness of auditory brain-computer interfaces. Multiple drugs can be sequentially delivered at specific release times and sites in the inner ear to promote the directional growth and repair of auditory nerve endings (spiral ganglion cells).

[0030] In one embodiment, the rear end of the electrode silicone body 1 gradually narrows (shrinks) towards the front end to adapt to the internal structure of the cochlea. Preferably, the ratio of the maximum diameter to the minimum diameter of the electrode silicone body 1 is 1:(0.6-0.9), such as 1:0.6, 1:0.7, 1:0.68, 1:0.9, etc. Each of the electrode stimulation contacts 2 is spaced apart and embedded within the electrode silicone body 1. The number of electrode stimulation contacts 2 is 8-24, such as 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, etc., to facilitate setting different numbers of stimulation contacts according to the patient's condition. In other embodiments, the front end of the electrode silicone body 1 is further provided with a front-end passive release section, and the active release drug coating 4 on each electrode stimulation contact 2 forms an active release section. The length of the front-end passive release section is 0.05-0.3 times the length of the active release section, such as 0.05, 0.08, 0.1, 0.15, 0.2, 0.25, 0.3, etc. Figure 1 and Figure 3 As shown, the electrode silicone body 1 is provided with a first central passive release section on the side away from the electrode stimulation contact 2, and a second central passive release section on the side of the electrode silicone body 1 close to the electrode stimulation contact 2. The second central passive release section is located between each of the electrode stimulation contacts 2. The rear end of the electrode silicone body 1 is provided with a rear passive release section. That is, the entire electrode silicone body 1 can release anti-inflammatory drugs with the cochlear contact part before the auditory brain-computer interface is turned on.

[0031] Optionally, the passively released drug coating 3 is a non-conductive polymer layer carrying an anti-inflammatory drug. The non-conductive polymer layer is one or a combination of two or more of polyethylene (PE), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC), polycaprolactone (PLL), and polytrimethylene carbonate (PTMC). That is, the anti-inflammatory drug is loaded in the non-conductive polymer layer. For example, the anti-inflammatory drug can form an anti-inflammatory drug layer in the non-conductive polymer layer through intermolecular forces, hydrogen bonds, covalent bonds, miscibility, or different volatility. The anti-inflammatory drug is released before the auditory brain-computer interface is activated, so that it acts on the part in contact with the cochlea. The specific release method depends on the specific relationship between the polymer coating and the drug, which will not be elaborated here. In this embodiment, the anti-inflammatory drug may be one or a combination of two or more of the following: extracellular vesicles, exosomes, glucocorticoids, nonsteroidal anti-inflammatory drugs (such as aspirin), immunosuppressants (such as cyclosporine), and biological agents (such as anti-tumor necrosis factor (TNF) drugs and anti-interleukin (IL) drugs). Optionally, the loading amount of the anti-inflammatory drug in the non-conductive polymer layer is 0.1-10 wt%, such as 0.1 wt%, 0.5 wt%, 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, etc.

[0032] The actively released drug coating 4 is a conductive polymer layer carrying neurotrophic factors. The conductive polymer layer is one or a combination of two or more of the following: polypyrrole, polythiophene, polyacetylene, polyaniline, poly(p-phenylene), polystyrene, polythiophene ethylene, polyfuran ethylene, polyphenylene sulfide, polyphenylene acetylene, and poly(3,4-ethylenedioxythiophene). That is, the neurotrophic factors are loaded within the conductive polymer layer. For example, the neurotrophic factors can be chemically or electrochemically doped to form a neurotrophic factor layer within the conductive polymer layer. After the auditory brain-computer interface is activated, electro-controlled release technology is used to release the neurotrophic factors outside the electrode array, creating a high-to-low concentration gradient between the electrodes and ganglia (or a low-to-high concentration release, depending on the need). The specific release method depends on the relationship between the specific polymer coating and the drug, and will not be elaborated further here. In this embodiment, the neurotrophic factor can be one or a combination of two or more of the following neurotrophic drugs: extracellular vesicles, exosomes, neurotrophic factor-3 (NT-3), brain-derived neurotrophic factor (BDNF), neurotrophic factor-4 (NT-4), glial cell-derived neurotrophic factor (GDNF), neurotrophic factor-6 (NT-6), neurotrophic factor-a (NT-a), and angiogenesis factors. The drug is loaded into the reaction solution during the preparation of the conductive polymer, and then released via a reverse reaction during electrode discharge. Optionally, the loading amount of neurotrophic factor in the conductive polymer layer is 0.1-10 wt%, such as 0.1 wt%, 0.5 wt%, 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, etc.

[0033] The specific fabrication steps for this electrode array are as follows:

[0034] (1) Fabrication of a neural stimulation electrode array:

[0035] Electrode stimulation contacts 2 are prepared using platinum-iridium alloy as the main material;

[0036] Electrode wire 5, wavy lead wire 6, and stimulation lead wire 8 are made of copper wire or other conductive wire; electrode stimulation contact 2 is sequentially soldered to electrode wire 5, wavy lead wire 6, and stimulation lead wire 8.

[0037] The loop electrode 7 and loop lead 9 are made of copper wire or other conductive wire; the loop electrode 7 and the loop lead 9 are welded together; the electrode silicone body 1, i.e., the nerve stimulation electrode array, is formed by silicone injection molding.

[0038] (2) Preparation of the drug coating on electrode silicone body 1:

[0039] Weigh an appropriate amount of polytrimethylene carbonate (PTMC, molecular weight can be 10k-500k) (or polyethylene, polypropylene, polystyrene, polyvinyl chloride, polycaprolactone, or a combination thereof), dissolve it in an appropriate amount of dichloromethane (DCM), and stir thoroughly (the mass fraction of PTMC / DCM can be 1%-20%). After it is fully dissolved, add an appropriate amount of anti-inflammatory drug. Taking dexamethasone as an example, weigh an appropriate amount of dexamethasone and add it to the above mixed solution, stirring vigorously until the dexamethasone particles are evenly dispersed (the mass fraction of dexamethasone / (PTMC / DCM) mixed solution can be 1%-10%), and obtain the drug coating solution for later use.

[0040] The nerve stimulation electrode array prepared in step (1) is completely immersed in the above-mentioned drug coating solution for 1-60 seconds. Then, the electrode coated with the drug coating is slowly removed, and the electrode is gently shaken to distribute the coating solution evenly and wait for the solvent to evaporate. After the coating solution dries, the coating on the electrode stimulation contact 2 is removed under a microscope using a special instrument. The exposed electrode stimulation contact 2 is rinsed with deionized water and dried for later use.

[0041] (3) Preparation of an electrically controlled drug release coating for electrode stimulation contact 2:

[0042] Electro-controlled drug-release coatings for electrode stimulation contacts 2 were prepared using a three-electrode electrochemical reaction method. The nerve stimulation electrode treated in step (2) was used as the working electrode, a calomel electrode as the reference electrode, and a platinum sheet as the counter electrode. The electrolyte solution was a mixed solution of dissolved hydrochloric acid (1-55 mol / L) and aniline (0.5-2 mol / L), doped with neurotrophic drugs and / or angiogenesis-promoting drugs to promote nerve repair. The polymerization reaction was controlled using a constant voltage method at 0.5V-2V. After the reaction was complete, the nerve stimulation electrode array was rinsed with deionized water and dried for later use. The prepared structure is shown below. Figures 4-7

[0043] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0044] 1. Previous transelectrode drug delivery methods often focused on delivering a single drug, such as anti-inflammatory drugs or neurotrophic drugs, which failed to effectively guide the elongation of the auditory nerve. This invention can selectively deliver two or more drugs at different sites.

[0045] 2. Previous methods for promoting nerve growth, such as viral injection, plasmid transfection, and nanoparticle drug delivery, all require invasive cochlear injection, which can damage the cochlear microstructure. This invention delivers drugs directly through the cochlear implant electrode, thus avoiding damage.

[0046] 3. Existing methods for delivering neurotrophic factors via cochlear implant electrodes, such as hydrogel-loaded drugs, cannot avoid foreign body reactions around the electrodes. Severe foreign body reactions can cause fibrous tissue to surround the electrodes, preventing drug release. This invention loads anti-inflammatory and anti-fibrotic drugs onto the silicone body of the electrodes and electrically controls the release of neurotrophic factors at the two electrode stimulation contacts. This allows for the delivery of neurotrophic factors while preventing fibrous tissue from encapsulating the electrodes.

[0047] 4. Existing methods of drug delivery via cochlear implant electrodes simply encapsulate the drug in biomaterials, resulting in uncontrolled, passive drug release. This invention employs an electro-controlled release method, which actively releases neurotrophic factors only after the cochlear implant is activated, creating a drug concentration gradient from high to low from the electrode contact point to the nerve. This guides the auditory nerve to grow to the cochlear implant electrode stimulation contact point 2, reducing the nerve-interface distance.

[0048] The above embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-substantial changes and substitutions made by those skilled in the art based on the present invention shall fall within the scope of protection claimed by the present invention.

Claims

1. An electrode array for an auditory brain-computer interface, characterized in that, The device includes an electrode silicone body, a passive drug-releasing coating covering the outer surface of the electrode silicone body, multiple electrode stimulation contacts embedded in the electrode silicone body, and an active drug-releasing coating coated on the electrode stimulation contacts. The electrode silicone body contains a loop electrode, an electrode wire, a wavy lead, a stimulation lead, and a loop lead. The loop electrode is located at the end of the electrode silicone body. The electrode wire connects the electrode stimulation contacts to the loop electrode. The stimulation lead connects the electrode wire to the electrode stimulation contacts. The loop electrode is connected to the loop lead. The passive drug-releasing coating is a non-conductive polymer layer carrying an anti-inflammatory drug. The active drug-releasing coating is a conductive polymer layer carrying neurotrophic factors. The front end of the electrode silicone body also has a front passive release section. The active drug-releasing coating on each electrode stimulation contact forms an active release section, the length of which is 0.05-0.3 times the length of the active release section. The electrode stimulation contacts are spaced apart within the electrode silicone body.

2. The electrode array for an auditory brain-computer interface according to claim 1, characterized in that, The electrode silicone body is designed to gradually narrow from the rear end to the front end.

3. The electrode array for an auditory brain-computer interface according to claim 2, characterized in that, The ratio of the maximum diameter to the minimum diameter of the electrode silicone body is 1:(0.6-0.9).

4. The electrode array for an auditory brain-computer interface according to claim 1, characterized in that, The number of electrode stimulation contacts is 8-24.

5. The electrode array for an auditory brain-computer interface according to claim 1, characterized in that, The electrode silicone body is provided with a first central passive release section on the side away from the electrode stimulation contact, and a second central passive release section is provided on the side of the electrode silicone body close to the electrode stimulation contact. The second central passive release section is located between each of the electrode stimulation contacts, and a rear passive release section is provided at the rear end of the electrode silicone body.

6. The electrode array for an auditory brain-computer interface according to claim 1, characterized in that, The non-conductive polymer layer is one or a combination of two or more of polyethylene, polypropylene, polystyrene, polyvinyl chloride, polycaprolactone, and polytrimethylene carbonate.

7. The electrode array for an auditory brain-computer interface according to claim 1, characterized in that, The conductive polymer layer is one or a combination of two or more of the following: polypyrrole, polythiophene, polyacetylene, polyaniline, poly(p-phenylene), polystyrene, polyfuran ethylene, polyphenylene sulfide, and polyphenylene acetylene.

8. The electrode array for an auditory brain-computer interface according to claim 1, characterized in that, The conductive polymer layer is one or a combination of two or more of polypyrrole, polyacetylene, polyaniline, poly(p-phenylene), polystyrene, polythiophene ethylene, polyfuran ethylene, polyphenylene sulfide, polyphenylene acetylene, and poly(3,4-ethylenedioxythiophene).

9. The electrode array for an auditory brain-computer interface according to claim 1, characterized in that, The anti-inflammatory drug is one or a combination of two or more of the following: extracellular vesicles, exosomes, glucocorticoids, nonsteroidal anti-inflammatory drugs, and immunosuppressants; the neurotrophic factor is one or a combination of two or more of the following: extracellular vesicles, exosomes, neurotrophic factor-3 (NT-3), brain-derived neurotrophic factor, neurotrophic factor-4 (NT-4), glial cell-derived neurotrophic factor, neurotrophic factor-6 (NT-6), neurotrophic factor-a (NT-a), and pro-angiogenic factors.

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