Self-adhesive hydrogel photoelectrodes, arrays, devices, applications, and methods of evaluation

Abstract

This invention discloses a self-adhesive hydrogel photoelectrode, array, device, application, and evaluation method. The self-adhesive hydrogel photoelectrode comprises a self-adhesive hydrogel optical fiber and at least one flexible fiber electrode. The optical fiber has a core-skin structure; the skin is composed of adhesive polymers such as polyvinyl alcohol, polyacrylic acid, and polydopamine, while the core is a transparent hydrogel. The flexible fiber electrode comprises conductive materials such as graphene oxide, carbon nanotubes, and polypyrrole. The flexible fiber electrode is directly integrated onto the surface of the optical fiber through the adhesion of the fiber skin, forming a heterogeneous structural unit integrating optical transmission and electrical conduction. This technology relies on a dynamic interface bonding mechanism to achieve stable and reconfigurable heterogeneous integration in a humid environment. The device simultaneously possesses low optical loss, high conductivity, strong tissue adhesion, and excellent biocompatibility, making it suitable for implantable neural modulation and signal acquisition, in vitro testing, and interface reliability assessment.

Description

Technical Field

[0001] This invention belongs to the field of flexible bioelectronics and optoelectronic sensing technology, specifically relating to a self-adhesive hydrogel photoelectrode, array, device, application, and evaluation method. Background Technology

[0002] In neuroscience research and intervention for nervous system diseases, optogenetics combined with electrophysiological recordings has become a powerful tool for analyzing neural circuits. However, existing technologies mainly rely on the binding or integration of rigid optical fibers with metal microelectrodes, which has the following inherent drawbacks: 1) Mismatch in mechanical properties: rigid implants can lead to chronic tissue damage and inflammatory responses, forming glial scars and affecting the long-term stability of signals; 2) Fixed interfaces: once fabricated, the number of channels and spatial configuration cannot be adjusted, lacking flexibility; 3) Complex integration processes: the fabrication of multi-channel arrays relies on expensive micro-nano fabrication techniques, and heterogeneous interfaces are prone to failure in the humid environment of the body.

[0003] In recent years, the development of flexible electronics and conductive hydrogels has provided new ideas for addressing the aforementioned problems. However, existing flexible photoelectrodes still face challenges: simple hydrogel electrodes have insufficient conductivity; the interfacial bonding between conductive polymers and optical fibers is weak, making them prone to peeling off in dynamic physiological environments; and there is a lack of integration strategies that can maintain strong and reversible adhesion in humid environments. Therefore, it is urgent to develop a novel photoelectrode system that combines excellent biocompatibility, stable interfacial integration, flexible design of the number of electrical channels, and ease of assembly. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art and provide a self-adhesive hydrogel photoelectrode, array, device, application, and evaluation method.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] This application provides a self-adhesive hydrogel photoelectrode, comprising:

[0007] A self-adhesive hydrogel optical fiber has a core-skin structure, wherein the skin is composed of a three-dimensional cross-linked network containing at least two of the following components: polyvinyl alcohol, polyacrylic acid, polydopamine, chitosan, and gelatin, and the core is composed of a light-transmitting hydrogel.

[0008] At least one flexible fiber electrode, said electrode comprising at least one conductive material selected from graphene oxide, carbon nanotubes, polypyrrole, and poly3,4-ethylenedioxythiophene;

[0009] The flexible fiber electrode is integrated onto the surface of the self-adhesive hydrogel fiber through the adhesion of the self-adhesive hydrogel fiber sheath, forming a heterogeneous structural unit that integrates optical transmission and electrical conduction.

[0010] Optionally, the diameter of the self-adhesive hydrogel optical fiber is 150~200μm, its optical transmission loss in the visible to near-infrared band is less than 0.5dB / cm, and its interfacial adhesion strength in a humid environment is not less than 1.5N / cm; the diameter of the flexible fiber electrode is 20~50μm, and its volume conductivity is not less than 10S / cm.

[0011] Optionally, the preparation method of the self-adhesive hydrogel photoelectrode includes the following steps:

[0012] S1. Preparation of self-adhesive hydrogel optical fiber: Using coaxial microfluidic spinning technology, the skin precursor liquid and the core precursor liquid are injected into the coaxial channel respectively, and then cross-linked and cured in situ to obtain a self-adhesive hydrogel optical fiber with a skin-core structure.

[0013] S2. Preparation of flexible fiber electrodes: Flexible fiber electrodes based on carbon nanomaterials or conductive polymers are prepared by wet spinning, template polymerization or electrochemical deposition methods.

[0014] S3. Controllable Integration: Under humid conditions, the flexible fiber electrode obtained in step S2 is brought into contact with the self-adhesive hydrogel fiber obtained in step S1. Utilizing the self-adhesive properties of the skin material, stable integration of the two is achieved through multiple hydrogen bonds and dynamic physicochemical interactions at the interface. The integration angle, contact length, and integration position of the flexible fiber electrode and the self-adhesive hydrogel fiber can be adjusted according to requirements.

[0015] Secondly, this application provides a photoelectrode fiber array, comprising: a plurality of the above-described self-adhesive hydrogel photoelectrodes;

[0016] In this structure, multiple self-adhesive hydrogel optical electrodes are interconnected and fixed through the adhesion interface between their respective self-adhesive hydrogel optical fibers, and / or through the adhesion interface between the flexible fiber electrode and the self-adhesive hydrogel optical fiber of another functional unit, forming an integrated network structure with multiple electrical channels.

[0017] Optionally, the fabrication method of the photoelectrode fiber array includes the following steps:

[0018] P1. Provides multiple of the above-mentioned self-adhesive hydrogel photoelectrodes;

[0019] P2. In a humid environment, operate the multiple functional units to bring them into contact with each other at a predetermined spatial position;

[0020] P3. By utilizing the interfacial adhesion properties of the self-adhesive hydrogel fiber optic sheath, the functional units in contact with each other can be dynamically bonded at the interface to self-assemble into a stable optical electrode fiber array with a preset configuration.

[0021] Thirdly, this application provides a multimodal bioelectronic device, comprising:

[0022] At least one of the aforementioned self-adhesive hydrogel optical fibers;

[0023] In addition, at least two different types of functional fibers are integrated onto the same surface of the optical fiber through the adhesion of the skin layer;

[0024] The at least two different types of functional fibers include the flexible fiber electrode described above, and at least one other functional fiber selected from microfluidic fibers and drug-loaded fibers.

[0025] Optionally, the integrated interface between the functional fiber and the self-adhesive hydrogel optical fiber has dynamic characteristics, and the bonding of the interface can be reorganized under physiological environmental disturbances to dissipate stress.

[0026] Thirdly, this application provides the application of the above-mentioned self-adhesive hydrogel photoelectrode, the above-mentioned photoelectrode fiber array, or the above-mentioned multimodal bioelectronic device in the fabrication of implantable biomedical devices.

[0027] Fourthly, this application provides an integrated system for in vitro testing of neural signal transduction, comprising:

[0028] The aforementioned photoelectrode fiber array or the aforementioned multimodal bioelectronic device;

[0029] And, in vitro neural tissue samples or cell culture systems;

[0030] The photoelectrode fiber array or the multimodal bioelectronic device is attached to the surface of the neural tissue sample or cell culture system via its self-adhesive hydrogel optical fiber.

[0031] Fifthly, this application provides a method for evaluating the interface stability of bioelectronic devices, using the aforementioned self-adhesive hydrogel photoelectrode, comprising the following steps:

[0032] The flexible fiber electrode is attached to the surface of the self-adhesive hydrogel fiber, and the integrated flexible fiber electrode is put into operation.

[0033] Apply cyclic mechanical loads or chemical environmental changes to the integrated interface;

[0034] The stability of the electrical signal of the flexible fiber electrode under working conditions is monitored to evaluate the dynamic adaptability and durability of the adhesion interface.

[0035] Compared with the prior art, this application has the following beneficial effects:

[0036] This device integrates flexible fiber electrodes directly onto the surface of a self-adhesive hydrogel optical fiber. By utilizing the inherent strong adhesion properties of the fiber sheath and the multiple dynamic bonding effects at the interface, a stable, robust, and adaptive heterogeneous functional interface is constructed in a humid environment, thereby achieving a flexible fusion of optical transmission and electrical conduction. This structure overcomes the common problems of interface peeling, mechanical mismatch, and fixed channel configuration in traditional rigid and flexible photoelectrodes, laying the foundation for the development of novel implantable photoelectric probes that can stably adhere to biological tissues for a long time and whose electrical channels can be flexibly designed. Attached Figure Description

[0037] Figure 1 This is a schematic diagram of the structure of the self-adhesive hydrogel photoelectrode unit of the present invention.

[0038] Figure 2 This is a schematic diagram of another self-adhesive hydrogel photoelectrode unit provided by the present invention.

[0039] Figure 3 This is a schematic diagram of an in vitro testing integrated system.

[0040] Figure 4 This is a schematic diagram illustrating the testing principle of the interface stability assessment method. Detailed Implementation

[0041] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0042] Furthermore, in this invention, an element referred to as fixed to or disposed on another element can be directly disposed on the other element, or an intermediate element may be present. When an element is considered to be connected to another element, it can be directly connected to the other element, or an intermediate element may be present simultaneously. The terms horizontal, left, right, and similar expressions used herein are for illustrative purposes only and do not represent the only possible implementation.

[0043] The following examples are combined Figures 1-4 This application provides a self-adhesive hydrogel photoelectrode, comprising:

[0044] A self-adhesive hydrogel optical fiber has a core-skin structure, wherein the skin is composed of a three-dimensional cross-linked network containing at least two of the following components: polyvinyl alcohol, polyacrylic acid, polydopamine, chitosan, and gelatin, and the core is composed of a light-transmitting hydrogel.

[0045] At least one flexible fiber electrode, said electrode comprising at least one conductive material selected from graphene oxide, carbon nanotubes, polypyrrole, and poly3,4-ethylenedioxythiophene;

[0046] The flexible fiber electrode is integrated onto the surface of the self-adhesive hydrogel fiber through the adhesion of the self-adhesive hydrogel fiber sheath, forming a heterogeneous structural unit that integrates optical transmission and electrical conduction.

[0047] The three-dimensional cross-linked network of the cortex is synergistically cross-linked with polyvinyl alcohol (PVA), polyacrylic acid (PAA), polydopamine (PDA), and chitosan. PVA provides high elasticity and hydrophilicity, PAA enhances dynamic adhesion to biological tissues through carboxyl groups, PDA improves biocompatibility and promotes interfacial bonding with electrode materials through its catechol structure, and chitosan imparts antibacterial properties to the cortex (inhibition rate against Staphylococcus aureus up to 90%). The synergistic effect of these multiple components allows the cortex to adapt to the curved contours of biological tissues (such as the curvature of joint skin) without significant mechanical irritation. The core layer uses polyethylene glycol diacrylate (PEGDA) and acrylamide translucent hydrogel. Within the wavelength range of 400-800 nm, its transmittance is ≥92%, and its light transmission loss is ≤3% / cm. It can efficiently conduct the blue or green light required for optogenetic stimulation, and the refractive indices of the core and cortex are matched: core n=1.42, cortex n=1.38, reducing light leakage.

[0048] The flexible fiber electrode is composed of graphene oxide / carbon nanotubes / polypyrrole (PO). GO provides high conductivity (≥100 S / cm), CNTs enhance fiber flexibility (≥20% elongation at break), and PPy modification improves electrochemical stability and biocompatibility. With an electrode diameter of only 20-50 μm and a surface roughness ≤10 nm, it reduces mechanical damage to tissues. The electrodes are arranged in a parallel configuration, with the optical fibers aligned around the perimeter, and adhesion occurs only in the skin layer without affecting the core layer.

[0049] The carboxyl groups of PAA in the cortex form hydrogen bonds with the oxygen-containing groups of GO on the electrode surface, the catechol groups of PDA form covalent bonds with the hydroxyl groups on the CNT surface, and the amino groups of chitosan form electrostatic interactions with the pyrrole rings of PPy. These multiple interfacial interactions result in a bonding strength between the electrode and the optical fiber exceeding 0.6 MPa, preventing detachment even during myocardial beating or limb movement. The overall structure integrates light transmission, electrical conduction, and tissue adhesion (cortex). Its self-adhesive properties allow the photoelectrode to adhere tightly to biological tissue, with an interfacial impedance ≤10 Ω·mm². The flexible design allows it to deform with tissue movement, making it suitable for multimodal biological applications such as simultaneous optogenetic stimulation and electrophysiological recording, and skin surface phototherapy and electrical signal monitoring.

[0050] In one specific embodiment, the self-adhesive hydrogel optical fiber has a diameter of 150~200μm, its optical transmission loss in the visible to near-infrared band is less than 0.5dB / cm, and its interfacial adhesion strength in a humid environment is not less than 1.5N / cm; the flexible fiber electrode has a diameter of 20~50μm, and its volume conductivity is not less than 10S / cm.

[0051] The 150-200μm diameter design of the self-adhesive hydrogel optical fiber is highly compatible with the gaps in biological tissues such as subcutaneous tissue and myocardial layer, minimizing implantation trauma. Its transmission loss in the 635nm red light and 808nm near-infrared light bands is as low as 0.3dB / cm and 0.4dB / cm, respectively. Even under a 180° bend with a curvature radius of 500μm, the loss increment is still less than 0.5dB / cm, ensuring stable transmission of light stimulation signals during dynamic movement. The adhesion strength of more than 1.5N / cm in humid environments comes from the multiple hydrogen bond cross-linking between the dermal chitosan and the extracellular matrix glycosaminoglycans. Even under continuous immersion in body fluids such as blood and sweat, the adhesion retention rate is still higher than 85% within 24 hours, effectively preventing the device from shifting in the body or on the skin surface. The flexible fiber electrode uses bioabsorbable PLGA as a substrate, and its diameter of 20-50 μm allows it to form a parallel structure with the self-adhesive hydrogel fiber, avoiding obstruction of light transmission while ensuring sufficient contact between the electrode and tissue. Its CNT / PPy composite conductive layer has a volume conductivity of up to 15 S / cm, and after 1000 ±90° bends, the conductivity decreases by less than 10%, ensuring the clarity of signals during long-term electrophysiological recording. The two are seamlessly integrated through hydrogen bonding between the cortical PAA and the GO on the electrode surface, with an overall thickness controlled at 200-250 μm. When in contact with the skin, the interfacial pressure is less than 1 kPa, resulting in no noticeable foreign body sensation, making it suitable for long-term wear in skin phototherapy-electro-signal monitoring scenarios. When implanted, the synergistic effect of the fiber and electrode can simultaneously achieve optogenetic stimulation and action potential recording of brain tissue, providing multimodal data support for the precise diagnosis and treatment of diseases such as epilepsy.

[0052] In one specific embodiment, the method for preparing a self-adhesive hydrogel photoelectrode includes the following steps:

[0053] S1. Preparation of self-adhesive hydrogel optical fiber: Using coaxial microfluidic spinning technology, the skin precursor liquid and the core precursor liquid are injected into the coaxial channel respectively, and then cross-linked and cured in situ to obtain a self-adhesive hydrogel optical fiber with a skin-core structure.

[0054] S2. Preparation of flexible fiber electrodes: Flexible fiber electrodes based on carbon nanomaterials or conductive polymers are prepared by wet spinning, template polymerization or electrochemical deposition methods.

[0055] S3. Controllable Integration: Under humid conditions, the flexible fiber electrode obtained in step S2 is brought into contact with the self-adhesive hydrogel fiber obtained in step S1. Utilizing the self-adhesive properties of the skin material, stable integration of the two is achieved through multiple hydrogen bonds and dynamic physicochemical interactions at the interface. The integration angle, contact length, and integration position of the flexible fiber electrode and the self-adhesive hydrogel fiber can be adjusted according to requirements.

[0056] In one specific embodiment, the method for preparing a self-adhesive hydrogel photoelectrode includes the following steps:

[0057] S1. Preparation of self-adhesive hydrogel optical fiber: Coaxial microfluidic spinning technology was used to inject the skin precursor solution and the core precursor solution into the coaxial channel respectively: the outer channel diameter was 1.0 mm and the inner channel diameter was 0.5 mm. The skin precursor solution could be an aqueous solution containing polyvinyl alcohol (PVA, mass fraction 8%), tannic acid (TA, mass fraction 2%) and glutaraldehyde (crosslinking agent, volume fraction 1%). The core precursor solution was a mixture of polyethylene glycol diacrylate (PEGDA, molecular weight 575, mass fraction 20%) and photoinitiator I2959 (mass fraction 0.5%). After in-situ crosslinking and curing (UV wavelength 365 nm, power 10 mW / cm², irradiation for 1.5 minutes), a self-adhesive hydrogel optical fiber with a skin-core structure was obtained. Its diameter was about 1.2 mm, the skin thickness was about 0.35 mm, the core diameter was about 0.5 mm, the tensile fracture strain of the optical fiber could reach 35%, and the optical transmission loss (532 nm laser) was less than 0.5 dB / cm.

[0058] S2. Preparation of Flexible Fiber Electrodes: Flexible fiber electrodes based on carbon nanomaterials or conductive polymers are prepared by wet spinning, template polymerization, or electrochemical deposition. For example, in the preparation of carbon nanotube (CNT) fiber electrodes by wet spinning, multi-walled CNTs (10-20 μm in length and 10-15 nm in diameter) are dispersed in a solution of polyvinylpyrrolidone (PVP, 10% by mass) in N,N-dimethylformamide (DMF) (8% by mass of CNTs). After ultrasonic treatment for 2 hours, a uniform dispersion is formed. The dispersion is then extruded through a spinneret (0.5 mm in diameter) into an ethanol coagulation bath and drawn at a speed of 5 cm / min to obtain a diameter of 150 nm. CNTs / PVP fibers with a diameter of μm were obtained, followed by heat treatment at 300°C for 2 hours under a nitrogen atmosphere to remove PVP. The resulting fibers had an electrical conductivity of approximately 100 S / cm and a tensile strength of 150 MPa. Alternatively, an electrochemical deposition method can be used, where a stainless steel wire (0.2 mm in diameter) can be used as the working electrode. In an aqueous solution containing 0.01 mol / L 3,4-ethylenedioxythiophene (EDOT) and 0.1 mol / L polystyrene sulfonate (PSS), a constant voltage of 1.2 V is applied for deposition for 30 minutes to obtain a flexible fiber electrode with a uniform PEDOT:PSS coating. The surface resistance is approximately 50 Ω / cm, and it can withstand 50% tensile strain without breaking.

[0059] S3. Controllable Integration: Under humid conditions (e.g., in phosphate-buffered saline (PBS) at pH 7.4, at 25°C), the flexible fiber electrode obtained in step S2 is brought into contact with the self-adhesive hydrogel fiber obtained in step S1. Multiple hydrogen bonds are formed between the phenolic hydroxyl groups (-OH) in the skin material (PVA / TA) and the oxygen-containing functional groups on the surface of the flexible fiber electrode (e.g., -COOH of CNTs fibers, -SO3H of PEDOT:PSS). At the same time, the benzene ring in TA and the aromatic structure of the carbon nanomaterial generate π-π stacking interaction, achieving stable integration of the two. The integration angle can be adjusted to 0° or 45° through a micro-manipulation platform, the contact length can be controlled to 1-5 mm by traction of the fiber electrode, and the integration position can be precisely positioned by laser marking on the surface of the fiber. After integration, the sample is placed in PBS and left to stand for 10 minutes to allow the dynamic interaction of the interface to fully balance, ensuring that the two still maintain stable transmission of electrical and optical signals under mechanical deformation such as bending, stretching, or torsion.

[0060] Secondly, this application provides a photoelectrode fiber array, comprising: a plurality of the above-described self-adhesive hydrogel photoelectrodes;

[0061] In this structure, multiple self-adhesive hydrogel optical electrodes are interconnected and fixed through the adhesion interface between their respective self-adhesive hydrogel optical fibers, and / or through the adhesion interface between the flexible fiber electrode and the self-adhesive hydrogel optical fiber of another functional unit, forming an integrated network structure with multiple electrical channels.

[0062] The multiple self-adhesive hydrogel photoelectrodes of the photoelectrode fiber array can be arranged in a preset topology, such as linear, grid-like, or radial. Adjacent photoelectrodes are precisely positioned by laser markings on the fiber surface at 0.5mm intervals, such as 1mm or 2mm intervals, ensuring an array spatial resolution ≤1mm, meeting the multi-site monitoring needs of tissues such as the cerebral cortex and heart. The self-adhesive hydrogel fibers of each photoelectrode form multiple hydrogen bonds with the carboxyl or sulfonic acid groups of another hydrogel through hydroxyl groups, combined with the π-π stacking effect of the benzene ring structure, achieving strong interfacial adhesion with a shear strength ≥10kPa. Even under bending with a radius of curvature ≤5mm, tension with a strain ≤20%, or torsion with an angle ≤60°, the connection interface does not peel or break, the impedance change of each electrical channel is still ≤10%, and the optical transmission efficiency decreases by ≤5%, ensuring the synchronous stability of multi-channel signals. The flexible fiber electrodes can be connected to self-adhesive hydrogel optical fibers of functional units such as temperature sensors and drug release units, forming a composite network integrating electrical signal acquisition, photostimulation, and parameter monitoring. Each electrical channel transmits signals independently, allowing simultaneous targeting of superficial and deep tissue sites to achieve synchronous control of multiple regions and parameters. The array integration process requires no additional adhesives and can be quickly assembled using a micromanipulation platform. Furthermore, the number of photoelectrodes can be flexibly increased or decreased according to application requirements, such as 4 channels or 8 channels, to adapt to the spatial scale requirements of different tissues.

[0063] In one specific embodiment, the method for fabricating an optical electrode fiber array includes the following steps:

[0064] P1. Provides multiple of the above-mentioned self-adhesive hydrogel photoelectrodes;

[0065] P2. In a humid environment, operate the multiple functional units to bring them into contact with each other at a predetermined spatial position;

[0066] P3. By utilizing the interfacial adhesion properties of the self-adhesive hydrogel fiber optic sheath, the functional units in contact with each other can be dynamically bonded at the interface to self-assemble into a stable optical electrode fiber array with a preset configuration.

[0067] The fabrication method of the optical electrode fiber array includes the following steps:

[0068] P1. Provide multiple self-adhesive hydrogel photoelectrodes as described above. The connection end face of each photoelectrode is pre-cut into a flat bevel, and the surface is gently rinsed with phosphate buffered saline (PBS) to remove residual uncrosslinked monomers and impurities, ensuring that the active groups (-OH, -COOH, -SO3H) at the interface are fully exposed and maintaining the wet viscous properties of the hydrogel.

[0069] P2. In a humid environment, the spatial orientation of each photoelectrode is adjusted sequentially through a micro-manipulation platform (positioning accuracy ≤10μm) so that the connection end faces of adjacent photoelectrodes make accurate contact at a predetermined two-dimensional or three-dimensional spatial position. The contact area is controlled at 60%-80% of each end face to avoid insufficient bonding strength due to too small a contact area.

[0070] P3. Utilizing the interfacial adhesion properties of the self-adhesive hydrogel fiber sheath, after contact, it is kept still for 5-10 minutes. During this time, the hydroxyl groups in the hydrogel sheath interact with the carboxyl and sulfonic acid groups of the adjacent photoelectrodes through hydrogen bonds, and at the same time, the benzene ring structure undergoes π-π stacking, gradually forming a dense dynamic bonding network at the interface. After self-assembly, the shear strength of the array is tested using a micro-force tester to ensure that it is ≥10kPa. The array is then verified by bending tester, tensile tester, and torsion tester to ensure that there is no peeling or breakage at the connection interface under bending with a curvature radius ≤5mm, tensile strain ≤20%, or torsion with an angle ≤60°. At the same time, the impedance change of each electrical channel is ≤10% and the decrease in optical transmission efficiency is ≤5% by using an electrochemical workstation and optical power meter. Finally, a stable photoelectrode fiber array with a preset configuration is obtained.

[0071] Thirdly, this application provides a multimodal bioelectronic device, comprising:

[0072] At least one of the aforementioned self-adhesive hydrogel optical fibers;

[0073] In addition, at least two different types of functional fibers are integrated onto the same surface of the optical fiber through the adhesion of the skin layer;

[0074] The at least two different types of functional fibers include the flexible fiber electrode described above, and at least one other functional fiber selected from microfluidic fibers and drug-loaded fibers.

[0075] The functional fibers achieve stable anchoring by forming a dynamic bonding network between the functional groups such as hydroxyl and benzene rings in the self-adhesive hydrogel fiber sheath and the carboxyl, sulfonic acid, or aromatic ring structures on their own surface. Among them, the flexible fiber electrodes can be linearly arrayed along the fiber axis, and their conductive layer is in close contact with the hydrogel sheath to maintain the stability of electrical signal transmission. The microfluidic fibers can be arranged in parallel between the flexible fiber electrodes, and their internal microchannels are connected to the external environment through the porous structure of the hydrogel sheath for precise control of drug delivery or biological fluid sampling. The drug-loaded fibers are fixed to the fiber surface in a parallel manner, and the drug loaded on them can be released in a controlled and slow manner through the swelling-shrinkage characteristics of the hydrogel sheath. During integration, the spatial orientation of the functional fibers is adjusted through micromanipulation to maintain the distance between adjacent functional fibers at 20-50 μm, avoiding electrical signal crosstalk or microfluidic channel blockage. Simultaneously, utilizing the self-adhesive properties of the hydrogel skin, the fibers are left to stand for 8-12 minutes at 25°C and 60% humidity to form a dense interfacial bond with the fiber substrate. The peel strength between the functional fibers and the hydrogel skin is measured using a microforce tester, finding it to be ≥15 kPa. This ensures that the functional fibers do not detach or shift under bending with a radius of curvature ≤3 mm or tensile strain ≤15%. The synergistic effect of the functional fibers and the self-adhesive hydrogel fiber enables the integration of multiple modal functions, including optical transmission, electrical signal detection, drug delivery, and body fluid sampling, providing an integrated solution for precise intervention and monitoring in biomedical research.

[0076] In one specific embodiment, the integrated interface between the functional fiber and the self-adhesive hydrogel optical fiber has dynamic characteristics, and the bonding of the interface can be reorganized under physiological environmental disturbances to dissipate stress.

[0077] When a device is subjected to mechanical disturbances or chemical stimuli in the physiological environment, a reversible break-reconstruction process occurs between the self-adhesive hydrogel skin and the surface of the functional fibers at the interface. The originally tightly bound bonding sites temporarily break due to stress or changes in the chemical environment, and then, driven by the self-healing properties of the hydrogel, new bonding structures are formed. This process converts external stress into energy for bonding reorganization, effectively dissipating concentrated stress and preventing interface peeling or functional fiber displacement caused by stress accumulation. This dynamic characteristic gives the integrated interface self-adaptive capabilities, maintaining a tight bond between the functional fibers and the self-adhesive hydrogel fiber substrate even in long-term implanted dynamic environments. This ensures the long-term stability of key performance indicators such as optical transmission efficiency, electrical signal-to-noise ratio, and drug release rate, providing crucial interface reliability assurance for the clinical translation of multimodal bioelectronic devices.

[0078] Thirdly, this application provides the application of the above-mentioned self-adhesive hydrogel photoelectrode, the above-mentioned photoelectrode fiber array, or the above-mentioned multimodal bioelectronic device in the fabrication of implantable biomedical devices.

[0079] This application provides the application of the aforementioned self-adhesive hydrogel photoelectrode, photoelectrode fiber array, or multimodal bioelectronic device in the fabrication of implantable biomedical devices. Specifically, the self-adhesive hydrogel photoelectrode can serve as a functional carrier for implantable optogenetic therapy devices. Utilizing the stress dissipation characteristics of its dynamic bonding network, it achieves long-term close adhesion to soft tissues such as myocardium and nerves, precisely delivering light signals to correct abnormal electrophysiological activity. The photoelectrode fiber array can be integrated into implantable multi-parameter monitoring devices. Through its highly flexible fiber structure and multi-channel sensing capabilities, it can collect real-time photoresponse and electrophysiological signals from tissues, providing high-resolution data for monitoring post-tumor recurrence and assessing wound healing in diabetes. The multimodal bioelectronic device can be applied to implantable closed-loop treatment systems, integrating photomodulation, electrical stimulation, and targeted drug release functions. For diseases such as Alzheimer's disease and chronic heart failure, it achieves integrated "monitoring-intervention-feedback" treatment, significantly improving the efficacy attenuation problem caused by interface instability in traditional implantable devices and enhancing the long-term clinical application value of the device.

[0080] Fourthly, this application provides an integrated system for in vitro testing of neural signal transduction, comprising:

[0081] The aforementioned photoelectrode fiber array or the aforementioned multimodal bioelectronic device;

[0082] And, in vitro neural tissue samples or cell culture systems;

[0083] The photoelectrode fiber array or the multimodal bioelectronic device is attached to the surface of the neural tissue sample or cell culture system via its self-adhesive hydrogel optical fiber.

[0084] This integrated system emits light signals of specific wavelengths through a highly flexible fiber structure of photoelectrode fiber arrays, enabling precise optogenetic stimulation of isolated neural tissue samples or cell culture systems. Simultaneously, its multi-channel sensing capabilities allow for real-time acquisition of electrophysiological parameters such as the conduction rate, amplitude, and waveform changes of neural signals after stimulation. By employing multimodal bioelectronic devices, it can further integrate photomodulation, electrostimulation, and targeted drug release functions, simulating in vivo disease states in an in vitro environment. By simultaneously monitoring photoresponse signals, electrophysiological signals, and tissue metabolic indicators after drug action, the system can analyze the synergistic effects of multimodal intervention on neural signal transmission. The system can also connect to a high-precision signal amplifier and data acquisition terminal to convert the acquired raw signals into quantifiable digital data. Algorithms can then be used to analyze the spatiotemporal characteristics of neural signal transmission, providing in vitro model validation for parameter optimization and efficacy evaluation of implantable optogenetic therapy devices or multimodal bioelectronic devices, overcoming the limitations of traditional in vivo experiments, which involve long cycles and complex variables. Furthermore, the dynamic bonding network of self-adhesive hydrogel optical fibers can achieve non-damaging and tight adhesion to isolated neural tissues or cell culture systems, avoiding sample damage caused by mechanical traction, ensuring the stability and repeatability of signal acquisition during testing, and improving the reliability of in vitro test results.

[0085] Fifthly, this application provides a method for evaluating the interface stability of bioelectronic devices, using the aforementioned self-adhesive hydrogel photoelectrode, comprising the following steps:

[0086] The flexible fiber electrode is attached to the surface of the self-adhesive hydrogel fiber, and the integrated flexible fiber electrode is put into operation.

[0087] Apply cyclic mechanical loads or chemical environmental changes to the integrated interface;

[0088] The stability of the electrical signal of the flexible fiber electrode under working conditions is monitored to evaluate the dynamic adaptability and durability of the adhesion interface.

[0089] The cyclic mechanical load can employ stretch-release cycles, compression cycles, or bending cycles to simulate the dynamic mechanical stimulation experienced by biological tissue movement or implanted devices. Changes in the chemical environment can be achieved by adjusting the buffer pH (e.g., switching from physiological pH 7.4 to pathological acidic pH 5.0 or alkaline pH 8.5), increasing ion concentration (e.g., raising NaCl concentration from physiological 0.9% to pathological hypertonic 5%), or introducing biological fluid components such as serum or protein adsorption from cell culture media to simulate chemical corrosion and interfacial interactions under physiological or pathological conditions in vivo. During monitoring, in addition to recording real-time electrical signals of the flexible fiber electrode, such as impedance, current, and voltage, electrochemical impedance spectroscopy (EIS) can be simultaneously acquired to analyze changes in interfacial charge transfer resistance, steady-state current-voltage (IV) curves to assess electrode reactivity, and signal-to-noise ratio (SNR) to reflect signal transmission quality. By calculating the impedance change rate, a value exceeding 10% is considered the interface failure threshold; current density fluctuations exceeding ±5% indicate a decrease in stability or SNR attenuation; and an SNR reduction to below 70% of the initial value is considered interface performance degradation. This allows for a quantitative assessment of the dynamic adaptability of the adhesion interface. Furthermore, the microstructure of the hydrogel-substrate interface can be observed before and after the experiment using scanning electron microscopy (SEM), or interface roughness changes can be detected using atomic force microscopy (AFM). This helps verify the physical mechanisms of electrical signal changes, such as the presence of hydrogel desorption, electrode surface corrosion, or interface microcracks, further enhancing the reliability and scientific validity of the evaluation results.

[0090] Example 1: Preparation and Characterization of Self-Adhesive Hydrogel Photoelectrode

[0091] 1. Fabrication of self-adhesive hydrogel optical fibers

[0092] Preparation of the pretreatment solution for the cortex: Polyvinyl alcohol (PVA, Mw 89,000-98,000) was dissolved in deionized water (8 wt%), and polyacrylic acid (PAA, Mw 250,000, 1:1 mass ratio with PVA) was added and stirred thoroughly. Dopamine hydrochloride (DA, 2 mg / mL) and genipin (as a crosslinking agent, 0.2 wt%) were then added. The mixture was degassed in an ice bath for later use. This formulation utilizes the hydrogen bonding network of PVA-PAA, the electrostatic interaction between the carboxyl groups of PAA and histamine, and the catechol groups of dopamine to provide wet adhesion and antioxidant properties.

[0093] Core layer precursor solution preparation: Dissolve N-isopropylacrylamide (NIPAM) and acrylamide (AAm) monomers (molar ratio 7:3) in deionized water, and add photoinitiator (Irgacure2959, 0.5 wt%) and crosslinking agent (N,N'-methylenebisacrylamide, MABAA, 0.5% molar fraction).

[0094] The spinning process was carried out using a coaxial injection pump: the sheath precursor solution was injected into the outer channel with an inner diameter of 300 μm, and the core precursor solution was injected into the inner channel with an inner diameter of 150 μm; subsequently, under irradiation with 365 nm ultraviolet light at an intensity of 10 mW / cm², the spinning solution was cured in a receiving bath containing a saturated borax solution that promotes PVA crosslinking. After drawing and collection, a continuous optical fiber with a final diameter of approximately 180 μm was obtained.

[0095] Performance testing:

[0096] Optical loss: Using a helium-neon laser (632.8nm) and an optical power meter, the input and output power of a 10cm long optical fiber were measured, and the loss was calculated to be 0.32dB / cm.

[0097] Adhesion strength: A 5mm long optical fiber was attached to moist pigskin tissue, and a 90° peel test was performed using a universal testing machine at a speed of 0.5mm / s. The average interfacial adhesion strength was measured to be 1.8N / cm.

[0098] 2. Fabrication of flexible fiber electrodes

[0099] Preparation of spinning solution: Carbon nanotubes (CNTs) and graphene oxide (GO) are dispersed in an aqueous solution containing polypyrrole (PPy) monomer (0.1M) and dopant (sodium p-toluenesulfonate, 0.05M) at a mass ratio of 1:2, and ultrasonic treatment is performed to form a uniform dispersion.

[0100] Wet spinning and post-treatment: The above dispersion was injected into a spinning apparatus with ferric chloride (FeCl3, 0.1M) as the coagulation bath for wet spinning to obtain nascent fibers. The fibers were then reduced in hydroiodic acid vapor and stretched and annealed to obtain the final flexible fiber electrode with a diameter of approximately 35 μm.

[0101] Performance testing: Its volumetric conductivity was measured to be 18 S / cm using the four-probe method.

[0102] 3. Controllable integration

[0103] The prepared optical fibers and electrodes were immersed in deionized water or a low-ionic-strength buffer solution. Under a microscope, the fiber electrode was held with precision tweezers and gently brought into contact with the side of the self-adhesive hydrogel optical fiber at a perpendicular angle, maintaining a contact length of approximately 2 mm, and left to stand for 30 seconds. Due to the strong adhesion of the fiber sheath and the multiple hydrogen bonds between the oxygen-containing functional groups on the electrode surface and the sheath, a stable bond was rapidly formed. Experiments showed that by adjusting the contact angle (0° or 45°), length (0.5-5 mm), and position, precise and robust integration of the electrode at different sites on the optical fiber could be achieved.

[0104] It should be noted that the low ionic strength buffer solution mentioned above can be a 5 mM Tris-HCl buffer solution with a pH of 7.4. Using a low ionic concentration medium for integration can effectively reduce the shielding effect of high concentration ions on hydrogen bonds, ensuring that the functional groups on the cortex and electrode surface are in full contact and form a stable dynamic bonding network, thereby maintaining the integrity of the interface in the subsequent physiological environment.

[0105] Example 2: Construction and Performance of Opto-Electrode Fiber Arrays

[0106] This embodiment explains how to assemble an array from basic units.

[0107] Assembly process: Four self-adhesive hydrogel photoelectrode units prepared according to the method of Example 1 are provided. These units are manually manipulated in PBS solution. For example, an optical fiber can be configured with the electrodes adhered to the fiber surface in a 4x4 array to form a photoelectrode fiber array.

[0108] Interface stability verification: The assembled photoelectrode fiber array was immersed in simulated cerebrospinal fluid at 37°C and subjected to a reciprocating bending test at a frequency of 1 Hz with a curvature radius of 5 mm. After 10,000 bending cycles, the impedance of each electrode channel was measured, and the change was found to be less than 15% of the initial value, indicating that the adhesion interface maintains excellent stability under dynamic mechanical load.

[0109] Functional verification of the channels: The photoelectrode fiber array was implanted into an isolated mouse cerebral cortex slice. By applying a 473nm blue light pulse through the core of a single fiber, stable and clear local field potential signals and action potentials could be recorded simultaneously from four integrated electrodes, with a signal-to-noise ratio (SNR) > 8, demonstrating the independence and functionality of each electrical channel.

[0110] Example 3: Construction of Multimodal Bioelectronic Devices

[0111] This embodiment demonstrates the scalability of the platform.

[0112] Device Construction: A self-adhesive hydrogel optical fiber prepared in Example 1 was used. First, a flexible fiber electrode was integrated onto its surface according to the method in Example 1. Then, a gelatin microfluidic fiber loaded with the anti-inflammatory drug dexamethasone (prepared by microfluidic method, approximately 50 μm in diameter) was prepared. In PBS, the microfluidic fiber was attached parallel to the other side of the same optical fiber surface. After standing, the microfluidic fiber was firmly adhered to the fiber sheath through hydrogen bonding between its gelatin shell and the fiber sheath.

[0113] Multimodal functional demonstration: The device was implanted subcutaneously in rats. Optical fibers were used to transmit near-infrared light for local photothermal therapy, while integrated electrodes monitored the electrophysiological activity of local tissues. Simultaneously, dexamethasone was slowly released via microfluidic fibers to alleviate potential photothermal-induced inflammatory responses. Experimental data showed that, compared to the control group with only photoelectrodes, the expression level of the inflammatory factor (TNF-α) was reduced by approximately 60% one week after implantation, confirming its synergistic therapeutic advantage.

[0114] Example 4: Application of an integrated system for in vitro testing

[0115] This embodiment provides a specific application scenario.

[0116] System setup: The photoelectrode fiber array constructed in Example 2 was implanted into the CA1 region of the hippocampus.

[0117] Test procedure: Neurons expressing Channelrhodopsin-2 were optically stimulated through designated optical fibers in the array, while field excitatory postsynaptic potentials (fEPSPs) induced on the Schaffer collateral pathway were recorded using all four electrode channels.

[0118] Results: The system successfully achieved simultaneous recording of spatially specific optical stimulation and multi-point electrical signals of neural pathways. The recorded fEPSP waveforms were clear, and long-term potentiation (LTP) was stably observed. This system provides a reliable platform for high-throughput screening of neuromodulation strategies or drugs under controlled conditions.

[0119] Example 5: Method for evaluating interface stability

[0120] This embodiment provides implementation details and data for the method.

[0121] Evaluation setup: A self-adhesive hydrogel photoelectrode unit was attached to a periodically stretchable silicone substrate (modulus ~100 kPa, simulating brain tissue). The two ends of the electrode were connected to an electrochemical workstation to monitor its AC impedance at 1 kHz.

[0122] Test process:

[0123] Mechanical disturbance: The tensile test table was started to induce a 10% periodic strain in the substrate (frequency 1 Hz). Impedance was continuously monitored for 8 hours (approximately 28,800 cycles).

[0124] Chemical disturbance: Under continuous small-amplitude vibration (simulating physiological tremor), the environmental solution is switched from PBS to an acidic solution (pH=5.0) or a solution containing a high concentration of protein (1% BSA) for 2 hours, and then switched back to PBS.

[0125] Evaluation results:

[0126] Mechanical durability: During the entire mechanical cycle test, the fluctuation range of the electrode impedance is less than ±10%, and it can quickly recover to within ±5% of the initial value after the test, indicating that the interface has good fatigue resistance and dynamic stability.

[0127] Chemical adaptability: In acidic or protein solutions, a reversible, transient increase in impedance (<20%) was observed, which largely recovered once the environment returned to normal. This confirms that interfaces based on dynamic bonds can adapt to changes in the chemical environment and undergo recombination, rather than being permanently destroyed.

[0128] Evaluation conclusion: This method can effectively quantify the dynamic adaptability and durability of the adhesion interface, providing a key evaluation basis for the reliability of devices in long-term applications.

[0129] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from its spirit or essential characteristics. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, all variations falling within the meaning and scope of equivalents of the claims are intended to be included within the present invention. No reference numerals in the claims should be construed as limiting the scope of the claims.

[0130] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A self-adhesive hydrogel photoelectrode characterized by, include: A self-adhesive hydrogel optical fiber has a core-skin structure, wherein the skin is composed of a three-dimensional cross-linked network containing at least two of the following components: polyvinyl alcohol, polyacrylic acid, polydopamine, chitosan, and gelatin, and the core is composed of a light-transmitting hydrogel. At least one flexible fiber electrode, said electrode comprising at least one conductive material selected from graphene oxide, carbon nanotubes, polypyrrole, and poly3,4-ethylenedioxythiophene; The flexible fiber electrode is integrated onto the surface of the self-adhesive hydrogel fiber through the adhesion of the self-adhesive hydrogel fiber sheath, forming a heterogeneous structural unit that integrates optical transmission and electrical conduction.

2. The self-adhesive hydrogel photoelectrode according to claim 1, wherein The self-adhesive hydrogel optical fiber has a diameter of 150~200μm, and its optical transmission loss in the visible to near-infrared band is less than 0.5dB / cm, and its interfacial adhesion strength in a humid environment is not less than 1.5N / cm; the flexible fiber electrode has a diameter of 20~50μm, and its volume conductivity is not less than 10S / cm.

3. The self-adhesive hydrogel photoelectrode according to claim 1 or 2, characterized in that, The preparation method of the self-adhesive hydrogel photoelectrode includes the following steps: S1. Preparation of self-adhesive hydrogel optical fiber: Using coaxial microfluidic spinning technology, the skin precursor liquid and the core precursor liquid are injected into the coaxial channel respectively, and then cross-linked and cured in situ to obtain a self-adhesive hydrogel optical fiber with a skin-core structure. S2. Preparation of flexible fiber electrodes: Flexible fiber electrodes based on carbon nanomaterials or conductive polymers are prepared by wet spinning, template polymerization or electrochemical deposition methods. S3. Controllable Integration: Under humid conditions, the flexible fiber electrode obtained in step S2 is brought into contact with the self-adhesive hydrogel fiber obtained in step S1. Utilizing the self-adhesive properties of the skin material, stable integration of the two is achieved through multiple hydrogen bonds and dynamic physicochemical interactions at the interface. The integration angle, contact length, and integration position of the flexible fiber electrode and the self-adhesive hydrogel fiber can be adjusted according to requirements.

4. A photoelectric fiber array, characterized in that, include: The self-adhesive hydrogel photoelectrode according to claim 1 or 2; In this structure, multiple self-adhesive hydrogel optical electrodes are interconnected and fixed through the adhesion interface between their respective self-adhesive hydrogel optical fibers, and / or through the adhesion interface between the flexible fiber electrode and the self-adhesive hydrogel optical fiber of another functional unit, forming an integrated network structure with multiple electrical channels.

5. The photoelectrode fiber array according to claim 4, characterized in that, Methods for fabricating optical electrode fiber arrays Includes the following steps: P1. Provides a plurality of self-adhesive hydrogel photoelectrodes as described in claim 1 or 2; P2. In a humid environment, operate the multiple functional units to bring them into contact with each other at a predetermined spatial position; P3. By utilizing the interfacial adhesion properties of the self-adhesive hydrogel fiber optic sheath, the functional units in contact with each other can be dynamically bonded at the interface to self-assemble into a stable optical electrode fiber array with a preset configuration.

6. A multimodal bioelectronic device, characterized in that, include: At least one self-adhesive hydrogel optical fiber as described in claim 1; In addition, at least two different types of functional fibers are integrated onto the same surface of the optical fiber through the adhesion of the skin layer; The at least two different types of functional fibers include the flexible fiber electrode of claim 1, and at least one other functional fiber selected from microfluidic fibers and drug-loaded fibers.

7. The multimodal bioelectronic device according to claim 6, characterized in that, The integrated interface between the functional fiber and the self-adhesive hydrogel optical fiber has dynamic characteristics, and the bonding of the interface can be reorganized under physiological environmental disturbances to dissipate stress.

8. The application of a self-adhesive hydrogel photoelectrode as described in claim 1 or 2, a photoelectrode fiber array as described in claim 4, or a multimodal bioelectronic device as described in claim 6 in the fabrication of implantable biomedical devices.

9. An integrated system for in vitro testing of neural signal transduction, characterized in that, include: The photoelectrode fiber array of claim 4 or the multimodal bioelectronic device of claim 6; And, in vitro neural tissue samples or cell culture systems; The photoelectrode fiber array or the multimodal bioelectronic device is attached to the surface of the neural tissue sample or cell culture system via its self-adhesive hydrogel optical fiber.

10. A method for evaluating the interface stability of bioelectronic devices, characterized in that, Using the self-adhesive hydrogel photoelectrode according to claim 1 or 2 includes the following steps: The flexible fiber electrode is attached to the surface of the self-adhesive hydrogel fiber, and the integrated flexible fiber electrode is put into operation. Apply cyclic mechanical loads or chemical environmental changes to the integrated interface; The stability of the electrical signal of the flexible fiber electrode under working conditions is monitored to evaluate the dynamic adaptability and durability of the adhesion interface.

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