CN115591025A - Nerve regulation device, preparation method and application thereof - Google Patents
Nerve regulation device, preparation method and application thereof Download PDFInfo
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- CN115591025A CN115591025A CN202211397878.4A CN202211397878A CN115591025A CN 115591025 A CN115591025 A CN 115591025A CN 202211397878 A CN202211397878 A CN 202211397878A CN 115591025 A CN115591025 A CN 115591025A
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- vinylidene fluoride
- neuromodulation device
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Abstract
The present application provides a neuromodulation device comprising: the substrate can convert external field energy into electricity, and stimulate the living cells growing on the surface of the substrate to respond and release neurotransmitter molecules. In addition, the application also provides a preparation method of the nerve regulation and control device.
Description
Technical Field
The application relates to the technical field of biomedicine, in particular to a nerve regulation device, a preparation method and application thereof.
Background
The neural regulation and control technology has a key significance for the development of the emerging fields of neuroscience, brain-computer interface and the like. In the existing nerve regulation and control technology, electrical stimulation is mainly applied to neurons in a target area through an implanted electrode device, so that the neurons are induced to generate action potentials to be excited, and the aim of nerve regulation and control is fulfilled. Although such nerve regulation electrode devices based on electrical stimulation exhibit good effects in the fields of deep brain stimulation treatment of nervous system diseases and the like, the existing devices are limited by the working principle and still face a lot of disadvantages in terms of safety and effectiveness of nerve regulation. In particular, existing neuromodulation devices based on electrode stimulation not only have a large difference in modulus from neural tissue, but also often involve complex wiring, integration, and packaging, and risk of tissue damage, bleeding, inflammation, exposure to infection, and the like, during and after implantation. In addition, the information interaction mode of the existing nerve regulation and control device based on electrode stimulation when the nerve response is excited is also essentially different from the natural information interaction mode based on transmitter molecules among nerve clouds in nerve tissues. Such a difference may cause that the existing device may not obtain sufficient specificity during neuromodulation, and may not avoid erroneous activation of non-target neurons around the implantation site, resulting in unexpected side effects.
Recently, by directly implanting living cells, a living interface formed based on the living cells establishes connection with autologous neurons and realizes bionic information interaction, thereby providing new possibility for neural regulation.
However, such techniques do not program the response of implanted living cells, which presents a significant challenge to controlled neuromodulation.
Disclosure of Invention
In view of the above, there is a need to provide a neuromodulation device and a method for manufacturing the same, which can achieve the modulation of specific neural activities and functions.
In order to solve the above problems, the following technical solutions are adopted in the present application:
among the objects of the present application, there is provided a neuromodulation device comprising: the substrate can convert external field energy into electricity and excite the living cells growing on the surface of the substrate to respond and release neurotransmitter molecules, and the living cells grow on the surface of the substrate and the hydrogel is used for encapsulating the living cells on the surface of the substrate.
In some of these embodiments, the substrate has a thickness of 50-500 μm.
In some of the embodiments, the surface topography of the substrate is a planar or three-dimensional structure comprising at least one of a micro-groove array, a micro-cone array, and a micro-pillar array.
In some of these embodiments, the three-dimensional structures have dimensions ranging from 50nm to 20 μm in width, 50nm to 20 μm in height, and 50nm to 20 μm in pitch.
In some of the embodiments, the substrate is at least one of a piezoelectric material, a photo-deformable material composite piezoelectric material, a photovoltaic material, an up-conversion material composite photovoltaic material, a photo-thermal material composite pyroelectric material, a magneto-thermal material composite pyroelectric material, and a piezoelectric ionic gel.
In some of these embodiments, the piezoelectric material comprises a piezoelectric crystal or piezoelectric ceramic or a polyvinylidene fluoride based ferroelectric polymer or piezoelectric polymer, the piezoelectric crystal comprising a quartz crystal or lithium gallate or lithium germanate or titanium germanate or lithium tantalate; the piezoelectric ceramic comprises barium titanate or lead zirconate titanate or lead meta-niobate or lead barium lithium niobate; the polyvinylidene fluoride ferroelectric polymer comprises poly (vinylidene fluoride) or poly (vinylidene fluoride-trifluoroethylene) [ P (VDF-TrFE) copolymer ] or poly (vinylidene fluoride-chlorofluoroethylene) [ P (VDF-CFE) copolymer ] or poly (vinylidene fluoride-chlorotrifluoroethylene) [ P (VDF-CTFE) copolymer ] or poly (vinylidene fluoride-hexafluoropropylene) [ P (VDF-HFP) copolymer ] or poly (vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) [ P (VDF-TrFE-CFE) terpolymer ] or poly (vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene) [ P (VDF-TrFE-CTFE) terpolymer ] or poly (vinylidene fluoride-trifluoroethylene-hexafluoropropylene) [ P (VDF-TrFE-HFP) terpolymer ]; the piezoelectric polymer comprises odd nylon or polyacrylonitrile or vinylidene cyanide and a copolymer thereof or polyurea or polyphenyl cyanoether or polyvinyl chloride or polyvinyl acetate or polypropylene or polytetrafluoroethylene.
In some embodiments, the photo-deformable material composite piezoelectric material is a combination of any one of the following photo-deformable materials and the piezoelectric material; the photoinduced deformation material comprises at least one of photoinduced heterogeneous material or ferroelectric inorganic photoinduced deformation material, and the photoinduced heterogeneous material comprises at least one of azobenzene and derivatives thereof, spiropyran and derivatives thereof; the ferroelectric inorganic photoinduced deformation material comprises at least one of lead titanate, barium titanate, potassium niobate, lithium tantalate, bismuth-layer-shaped perovskite structure ferroelectric, tungsten bronze type ferroelectric, bismuth ferrite, potassium dihydrogen phosphate, ammonium trinitrate sulfate, rosette and perovskite type organic metal halide ferroelectric.
In some of these embodiments, the photovoltaic material comprises at least one of: polyacetylene, polythiophene, polyaniline, polypyrrole and derivatives and copolymers thereof.
In some embodiments, the up-conversion material composite photovoltaic material is any one of the following up-conversion materials and piezoelectric materials in combination; wherein the up-conversion material comprises at least one of yttrium oxide, yttrium oxysulfide, lanthanum fluoride, sodium yttrium fluoride and sodium gadolinium fluoride.
In some embodiments, the photothermal material composite pyroelectric material comprises any one of a combination of a photothermal material and a pyroelectric material; the photo-thermal material comprises at least one of carbon black, carbon nano tubes, graphene, black phosphorus, polydopamine, gold nano rods and gallium-indium alloy liquid metal; the pyroelectric material comprises at least one of polyvinylidene fluoride ferroelectric polymer and perovskite type ferroelectric ceramic, wherein the polyvinylidene fluoride ferroelectric polymer comprises at least one of poly (vinylidene fluoride), poly (vinylidene fluoride-trifluoroethylene) [ P (VDF-TrFE) copolymer ], poly (vinylidene fluoride-chlorofluoroethylene) [ P (VDF-CFE) copolymer ], poly (vinylidene fluoride-chlorotrifluoroethylene) [ P (VDF-CTFE) copolymer ], poly (vinylidene fluoride-hexafluoropropylene) [ P (VDF-HFP) copolymer ], poly (vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) [ P (VDF-TrFE-CFE) terpolymer ], poly (vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene) [ P (VDF-TrFE-CTFE) terpolymer ] and poly (vinylidene fluoride-trifluoroethylene-hexafluoropropylene) [ P (VDF-TrFE-CTFE) terpolymer ], and the perovskite type ferroelectric ceramic comprises at least one of barium titanate, lead zirconium titanate, lead metaniobate and lead lithium niobate.
In some embodiments, the magnetocaloric material composite pyroelectric material is any one of the following magnetocaloric materials and pyroelectric materials in combination; wherein the magnetocaloric material comprises at least one of Ru ferroboron alloy, ferroferric oxide, iron, cobalt, nickel and gadolinium.
In some embodiments, the piezoelectric ionic gel material comprises at least one of polyacrylic acid and polyacrylamide composite gel, polyacrylic acid and chitosan composite gel, sodium alginate and polyacrylamide composite gel, polyacrylic acid and choline composite gel, sodium alginate and choline composite gel, methacrylic acid acylated gelatin and choline composite gel, methacrylic acid acylated hyaluronic acid and choline composite gel.
In some of these embodiments, the living cell is a cell type that can produce neurotransmitters; including but not limited to at least one of primary neuronal cells, neuroimmune cells, including astrocytes or microglia, neuroendocrine cells, cell lines that produce neurotransmitters, and neuronal cells induced from stem cells.
In some of these embodiments, the hydrogel is at least one of the following materials: alginate, chitosan, gelatin and derivatives thereof, collagen and derivatives thereof, hyaluronic acid and derivatives thereof, extracellular matrix protein and derivatives thereof, silk fibroin and derivatives thereof, agarose, carrageenan, dextran, basement membrane matrix, polycaprolactone, polyethylene glycol and derivatives thereof, propylene glycol and epoxyethyl ether block polymer, and polyvinylpyrrolidone.
In some of these embodiments, the hydrogel layer has a thickness of 50-500 μm.
In some of these embodiments, the neurotransmitter molecules include at least one of cholines, monoamines, amino acids, neuropeptides, purines, and nitric oxide, the cholines include acetylcholine, the monoamines include at least one of norepinephrine or epinephrine or dopamine or 5-HT or histamine, and the amino acids include at least one of glutamate or Y-aminobutyric acid or glycine.
The second objective of the present application provides a method for preparing a neural modulation device, comprising the following steps:
preparing the substrate;
growing the living cells on the surface of the substrate;
pre-crosslinking the hydrogel on the surface of the substrate so as to encapsulate the living cells on the surface of the substrate, thereby obtaining the nerve regulation device.
In some embodiments, the step of preparing the substrate specifically comprises the following steps: and preparing the substrate by adopting a casting method or a spin coating method.
In some embodiments, a planar or three-dimensional structure is formed on the surface of the substrate by photolithography, plasma dry etching or machining, and the three-dimensional structure comprises at least one of a micro-groove array, a micro-cone array and a micro-column array.
In some of these embodiments, the viable cells are seeded at a density of 10 3 –10 6 Cells per square centimeter.
In some embodiments, the crosslinking manner of the crosslinking is at least one of ionic crosslinking and ultraviolet crosslinking.
It is a further object of the present application to provide a use of the neuromodulation device in the treatment of brain-computer interface and neurological device diseases.
This application adopts above-mentioned technical scheme, its beneficial effect as follows:
the present application provides a neuromodulation device comprising: the substrate can convert external field energy into electricity, and stimulate the living cells growing on the surface of the substrate to respond and release neurotransmitter molecules.
In addition, compared with the existing nerve regulation and control device, the preparation method of the nerve regulation and control device does not need a complex preparation process and an integrated packaging technology, greatly reduces the construction difficulty of the device, and is simple in preparation process.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings needed to be used in the description of the embodiments of the present application or the prior art will be briefly described below, and it is obvious that the drawings described below are only some embodiments of the present application, and it is obvious for those skilled in the art that other drawings can be obtained according to the drawings without creative efforts.
Fig. 1 is a schematic structural diagram of a neuromodulation device provided in an embodiment of the present application.
Fig. 2 is a flowchart illustrating steps of applying for the neuromodulation device according to the present embodiment.
Detailed Description
Reference will now be made in detail to the embodiments of the present application, examples of which are illustrated in the accompanying drawings, wherein like reference numerals refer to the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are illustrative and intended to explain the present application and should not be construed as limiting the present application.
In the description of the present application, it is to be understood that the terms "upper", "lower", "horizontal", "inner", "outer", and the like, indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, are only for convenience in describing the present application and simplifying the description, and do not indicate or imply that the referred devices or elements must have a specific orientation, be constructed in a specific orientation, and be operated, and thus, should not be construed as limiting the present application.
Furthermore, the terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of the present application, "a plurality" means two or more unless specifically limited otherwise.
In order to make the objects, technical solutions and advantages of the present application more apparent, the present application is described in further detail below with reference to the accompanying drawings and embodiments.
Referring to fig. 1, a schematic structural diagram of a neuromodulation device according to an embodiment of the present application includes: a substrate 110, living cells 120 growing on the surface of the substrate 110, and a hydrogel 130 for encapsulating the living cells 120 on the surface of the substrate 110, wherein the substrate 110 can convert external field energy into electricity and activate the living cells 120 growing on the surface to respond and release neurotransmitter molecules 140, and the external field energy comprises light or a magnetic field or ultrasound.
In some of these embodiments, the substrate has a thickness of 50-500 μm.
In some of the embodiments, the surface topography of the substrate is a planar or three-dimensional structure comprising at least one of a micro-groove array, a micro-cone array, and a micro-pillar array.
In some of these embodiments, the three-dimensional structures have dimensions ranging from 50nm to 20 μm in width, 50nm to 20 μm in height, and 50nm to 20 μm in pitch.
In some of the embodiments, the substrate is at least one of a piezoelectric material, a photo-deformable material composite piezoelectric material, a photovoltaic material, an up-conversion material composite photovoltaic material, a photo-thermal material composite pyroelectric material, a magneto-thermal material composite pyroelectric material, and a piezoelectric ionic gel.
In some of these embodiments, the piezoelectric material comprises a piezoelectric crystal or piezoelectric ceramic or polyvinylidene fluoride based ferroelectric polymer or piezoelectric polymer, the piezoelectric crystal comprising a quartz crystal or lithium gallate or lithium germanate or titanium germanate or lithium tantalate; the piezoelectric ceramic comprises barium titanate or lead zirconate titanate or lead meta-niobate or lead barium lithium niobate; the polyvinylidene fluoride ferroelectric polymer comprises poly (vinylidene fluoride) or poly (vinylidene fluoride-trifluoroethylene) [ P (VDF-TrFE) copolymer ] or poly (vinylidene fluoride-chlorofluoroethylene) [ P (VDF-CFE) copolymer ] or poly (vinylidene fluoride-chlorotrifluoroethylene) [ P (VDF-CTFE) copolymer ] or poly (vinylidene fluoride-hexafluoropropylene) [ P (VDF-HFP) copolymer ] or poly (vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) [ P (VDF-TrFE-CFE) terpolymer ] or poly (vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene) [ P (VDF-TrFE-CTFE) terpolymer ] or poly (vinylidene fluoride-trifluoroethylene-hexafluoropropylene) [ P (VDF-TrFE-HFP) terpolymer ]; the piezoelectric polymer comprises odd nylon or polyacrylonitrile or vinylidene cyanide and a copolymer thereof or polyurea or polyphenyl cyanoether or polyvinyl chloride or polyvinyl acetate or polypropylene or polytetrafluoroethylene.
In some embodiments, the photo-deformable material composite piezoelectric material is a combination of any one of the following photo-deformable materials and the piezoelectric material; the photoinduced deformation material comprises at least one of photoinduced heterogeneous material or ferroelectric inorganic photoinduced deformation material, and the photoinduced heterogeneous material comprises at least one of azobenzene and derivatives thereof, spiropyran and derivatives thereof; the ferroelectric inorganic photoinduced deformation material comprises at least one of lead titanate, barium titanate, potassium niobate, lithium tantalate, bismuth-layer-shaped perovskite structure ferroelectric, tungsten bronze type ferroelectric, bismuth ferrite, potassium dihydrogen phosphate, ammonium trinitrate sulfate, rosette and perovskite type organic metal halide ferroelectric.
In some of these embodiments, the photovoltaic material comprises at least one of: polyacetylene, polythiophene, polyaniline, polypyrrole and derivatives and copolymers thereof.
In some embodiments, the upconversion material composite photovoltaic material is any one of the following upconversion materials and piezoelectric materials in combination; wherein the up-conversion material comprises at least one of yttrium oxide, yttrium oxysulfide, lanthanum fluoride, sodium yttrium fluoride and sodium gadolinium fluoride.
In some embodiments, the photothermal material composite pyroelectric material comprises any one combination of photothermal material and pyroelectric material; the photo-thermal material comprises at least one of carbon black, carbon nano tubes, graphene, black phosphorus, polydopamine, gold nano rods and gallium-indium alloy liquid metal; the pyroelectric material comprises at least one of polyvinylidene fluoride ferroelectric polymer and perovskite type ferroelectric ceramic, wherein the polyvinylidene fluoride ferroelectric polymer comprises at least one of poly (vinylidene fluoride), poly (vinylidene fluoride-trifluoroethylene) [ P (VDF-TrFE) copolymer ], poly (vinylidene fluoride-chlorofluoroethylene) [ P (VDF-CFE) copolymer ], poly (vinylidene fluoride-chlorotrifluoroethylene) [ P (VDF-CTFE) copolymer ], poly (vinylidene fluoride-hexafluoropropylene) [ P (VDF-HFP) copolymer ], poly (vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) [ P (VDF-TrFE-CFE) terpolymer ], poly (vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene) [ P (VDF-TrFE-CTFE) terpolymer ] and poly (vinylidene fluoride-trifluoroethylene-hexafluoropropylene) [ P (VDF-TrFE-CTFE) terpolymer ], and the perovskite type ferroelectric ceramic comprises at least one of barium titanate, lead zirconium titanate, lead metaniobate and lead lithium niobate.
In some embodiments, the magnetocaloric material composite pyroelectric material is any one of the following magnetocaloric materials and pyroelectric materials in combination; wherein the magnetocaloric material comprises at least one of Ru ferroboron alloy, ferroferric oxide, iron, cobalt, nickel and gadolinium.
In some of these embodiments, the piezoelectric ionic gel material comprises at least one of polyacrylic acid and polyacrylamide composite gel, polyacrylic acid and chitosan composite gel, sodium alginate and polyacrylamide composite gel, polyacrylic acid and choline composite gel, sodium alginate and choline composite gel, methacrylic acid acylated gelatin and choline composite gel, methacrylic acid acylated hyaluronic acid and choline composite gel.
In some of these embodiments, the living cell is a cell type that can produce neurotransmitters; including but not limited to at least one of primary neuronal cells, neuroimmune cells, including astrocytes or microglia, neuroendocrine cells, cell lines that produce neurotransmitters, and neuronal cells induced from stem cells.
In some of these embodiments, the hydrogel is at least one of the following materials: alginate, chitosan, gelatin and derivatives thereof, collagen and derivatives thereof, hyaluronic acid and derivatives thereof, extracellular matrix protein and derivatives thereof, silk fibroin and derivatives thereof, agarose, carrageenan, dextran, basement membrane matrix, polycaprolactone, polyethylene glycol and derivatives thereof, propylene glycol and epoxyethyl ether block polymer, and polyvinylpyrrolidone.
In some of these embodiments, the hydrogel layer has a thickness of 50-500 μm.
In some of these embodiments, the neurotransmitter molecules include at least one of a choline, a monoamine including at least one of norepinephrine or epinephrine or dopamine or 5-HT or histamine, an amino acid, a neuropeptide, a purine, and nitric oxide, the amino acid including at least one of glutamic acid or Y-aminobutyric acid or glycine.
The nerve regulation and control device induces excitation of target neurons through release of living cell neurotransmitter molecules in the device under outfield mediation, thereby realizing regulation and control of specific nerve activities and functions, not only greatly reducing integration complexity and construction difficulty of the device, but also realizing controllability and specificity of nerve regulation and control through outfield mediation remote control, which are different from the conventional nerve regulation and control device in electrical stimulation and a bionic information interaction mode based on the neurotransmitter molecules, and can be used for treatment of brain-computer interface and nerve device diseases.
Referring to fig. 2, a flow chart of steps of the method for manufacturing the neuromodulation device provided by the present application includes the following steps S110 to S130, and the implementation manner of each step is described in detail below.
Step S110: preparing the substrate.
In some embodiments, the step of preparing the substrate specifically includes the following steps: and preparing the substrate by adopting a casting method or a spin coating method.
Step S120: growing the living cells on the surface of the substrate.
In some embodiments, a planar or three-dimensional structure is formed on the surface of the substrate by photolithography, plasma dry etching or machining, and the three-dimensional structure comprises at least one of a micro-groove array, a micro-cone array and a micro-column array.
Further, the seeding density of the living cells is 10 3 –10 6 Cells per square centimeter.
Step S130: pre-crosslinking the hydrogel on the surface of the substrate so as to encapsulate the living cells on the surface of the substrate, thereby obtaining the nerve regulation device.
In some embodiments, the crosslinking manner of the crosslinking is at least one of ionic crosslinking and ultraviolet crosslinking.
Compared with the existing nerve regulation device, the nerve regulation device preparation method provided by the application does not need a complex preparation process and an integrated packaging technology, the construction difficulty of the device is greatly reduced, the preparation process is simple, and the prepared nerve regulation device can be used for treating brain-computer interface and nerve device diseases.
The above technical solutions of the present application will be described in detail with reference to specific examples.
Example 1
An active interface-based nerve modulation device is structurally shown in figure 1, and comprises a responsive material substrate, living cells growing on the responsive material substrate in an adhesion mode, and hydrogel for encapsulating the living cells; wherein, the responsive material substrate is made of piezoelectric material, the living cell is a nerve-like cell line cell, and the hydrogel is calcium ion crosslinked sodium alginate.
In the embodiment, the surface appearance of the responsive material substrate is a flat unstructured surface, the thickness is 50 microns, and the responsive material substrate is made of polyvinylidene fluoride capable of generating electricity under the mediation of an ultrasonic external field; the inoculated neural-like cell line cells are highly differentiated PC12 cells; the hydrogel material is calcium ion crosslinked sodium alginate, and the thickness is 50 μm.
The preparation method of the nerve regulation and control device based on the active interface comprises the following steps:
1) Preparing a responsive material substrate;
preparing a polyvinylidene fluoride solution with the concentration of 10w/v% by using dimethyl sulfoxide as a solvent; casting polyvinylidene fluoride solution on the surface of the silicon wafer with a smooth surface, and drying at 80 ℃ to prepare a responsive material substrate with a planar surface appearance; the prepared responsive material substrate was irradiated by a cobalt source at an irradiation dose of 15kGy and an irradiation time of 30 minutes to complete material sterilization.
2) Inoculating living cells;
using cell suspension of highly differentiated PC12 cells obtained by trypsinization, and coating the cell suspension on the surface of the sterilized responsive material substrate with 10 6 Cells were seeded at a seeding density of cells per square centimeter.
3) Hydrogel encapsulation;
after cells are inoculated for at least 24 hours, covering the surface of a responsive material substrate inoculated with living cells with 3w/v% of sodium alginate hydrogel prepolymerization liquid, then dropwise adding 0.3M calcium chloride aqueous solution, and completing encapsulation hydrogel crosslinking through ionic crosslinking to obtain the nerve regulation and control device based on the active interface.
Example 2
An active interface-based nerve modulation device is structurally shown in figure 1, and comprises a responsive material substrate, living cells growing on the responsive material substrate in an adhesion mode, and hydrogel for encapsulating the living cells; wherein, the responsive material substrate is made of a photoinduced deformation material composite piezoelectric material, the living cells are nerve-like cell line cells, and the hydrogel is methacrylic acid acylated gelatin.
In the embodiment, the surface appearance of the responsive material substrate is a micro-groove array structure (the width of the micro-grooves is 50 microns, the height of the micro-grooves is 50 microns, and the distance between the micro-grooves is 50 microns), the thickness of the substrate material is 500 microns, and the substrate material is a polyvinylidene fluoride and azobenzene compound which can generate electricity under the mediation of visible light irradiation; the inoculated neural-like cell line cells are highly differentiated PC12 cells; the hydrogel material is methacrylic acidylated gelatin, and the thickness is 500 μm.
The preparation method of the nerve regulation and control device based on the active interface comprises the following steps:
1) Preparing a responsive material substrate;
using dimethyl sulfoxide as a solvent to prepare a mixed solution with the concentration of polyvinylidene fluoride of 5w/v% and the concentration of azobenzene of 1 w/v%; casting the mixed solution on the surface of a micro-groove array structure (the width of a micro-groove is 20 mu m, the height of the micro-groove is 20 mu m, and the distance of the micro-groove is 20 mu m) template obtained by machining, and drying the mixed solution at 80 ℃ to prepare a responsive material substrate with the surface appearance of the micro-groove array; the prepared responsive material substrate was irradiated by a cobalt source at an irradiation dose of 15kGy and an irradiation time of 30 minutes to complete material sterilization.
2) Inoculating living cells;
using cell suspension of highly differentiated PC12 cells obtained by trypsinization, and coating the surface of the sterilized responsive material substrate with 10 6 Cells were seeded at a seeding density of cells per square centimeter.
3) Hydrogel packaging;
after the cells are inoculated for at least 24 hours, covering the surface of a responsive material substrate inoculated with living cells with 10w/v% of methacrylic acidylated gelatin hydrogel pre-polymerization liquid added with 0.1w/v% of 2959 photo-crosslinking agent, then, carrying out reaction for 10 minutes under the irradiation of an ultraviolet crosslinking instrument, and completing the crosslinking of the encapsulated hydrogel through ultraviolet light crosslinking to obtain the nerve regulation device based on the active interface.
Example 3
An active interface-based nerve modulation device is structurally shown in figure 1, and comprises a responsive material substrate, living cells growing on the responsive material substrate in an adhesion mode, and hydrogel for encapsulating the living cells; the responsive material substrate is made of a photovoltaic material, the living cells are primary neurons, and the hydrogel is calcium ion crosslinked sodium alginate.
In this embodiment, the responsive material substrate has a flat and unstructured surface with a thickness of 50 μm and is made of poly-3 hexylthiophene (P3 HT) capable of generating electricity under the mediation of visible light irradiation; the inoculated neural-like cell line cells are highly differentiated PC12 cells; the hydrogel material is calcium ion crosslinked sodium alginate, and the thickness is 50 μm.
The preparation method of the nerve regulation and control device based on the active interface comprises the following steps:
1) Preparing a responsive material substrate;
preparing a P3HT solution with the concentration of 30mg/mL by using 1, 2-dichlorobenzene as a solvent; pouring the solution on the surface of a silicon wafer with a smooth surface, and spin-coating at 60 ℃ to prepare a responsive material substrate with a planar shape; the prepared responsive material substrate was irradiated by a cobalt source at an irradiation dose of 15kGy and an irradiation time of 30 minutes to complete material sterilization.
2) Inoculating living cells;
coating the sterilized responsive material substrate in 0.1mg/ml polylysine water solution for 6 hr, digesting and extracting hippocampus neuron cell suspension from fetal rat brain, and coating the surface of the coated responsive material substrate with 10 3 Cells were seeded at a seeding density of cells per square centimeter.
3) Hydrogel packaging;
after the cells are inoculated and cultured for 14 days, covering the surface of a responsive material substrate inoculated with living cells with 3w/v% of sodium alginate hydrogel prepolymerization solution, then dropwise adding 0.3M calcium chloride aqueous solution, and completing encapsulation hydrogel crosslinking through ionic crosslinking to obtain the nerve regulation and control device based on the active interface.
Example 4
An active interface-based neuromodulation device, the structure of which is shown in fig. 1, comprises a responsive material substrate, wherein living cells are adhered to the responsive material substrate for growth, and hydrogel is used for encapsulating the living cells; the responsive material substrate is made of an up-conversion material composite photovoltaic material, living cells are primary neurons, and hydrogel is calcium ion crosslinked sodium alginate.
In this embodiment, the responsive material substrate has a flat and unstructured surface with a thickness of 100 μm and is made of poly-3 hexylthiophene (P3 HT) capable of generating electricity under visible light irradiation; the inoculated neural cell line cells are highly differentiated PC12 cells; the hydrogel material is calcium ion crosslinked sodium alginate, and the thickness is 100 μm.
The preparation method of the nerve regulation and control device based on the active interface comprises the following steps:
1) Preparing a responsive material substrate;
preparing a mixture solution containing 30mg/mL of P3HT and 0.1mg/mL of sodium gadolinium fluoride by using 1, 2-dichlorobenzene as a solvent; pouring the solution on the surface of a silicon wafer with a smooth surface, and spin-coating at 60 ℃ to prepare a responsive material substrate with a planar shape; the prepared responsive material substrate was irradiated by a cobalt source at an irradiation dose of 15kGy and an irradiation time of 30 minutes to complete material sterilization.
2) Inoculating living cells;
coating the sterilized responsive material substrate in polylysine aqueous solution with concentration of 0.1mg/ml for 6 hr, digesting and extracting hippocampus neuron cell suspension from fetal mouse brain, and coating the surface of the coated responsive material substrate with 10 3 Cells were seeded at a seeding density of cells per square centimeter.
3) Hydrogel packaging;
after the cells are inoculated and cultured for 14 days, covering the surface of a responsive material substrate inoculated with living cells with 3w/v% of sodium alginate hydrogel prepolymerization solution, then dropwise adding 0.3M calcium chloride aqueous solution, and completing encapsulation hydrogel crosslinking through ionic crosslinking to obtain the nerve regulation and control device based on the active interface.
Example 5
An active interface-based neuromodulation device, the structure of which is shown in fig. 1, comprises a responsive material substrate, wherein living cells are adhered to the responsive material substrate for growth, and hydrogel is used for encapsulating the living cells; the responsive material substrate is made of a photo-thermal material composite pyroelectric material, living cells are stem cell induced neurons, and hydrogel is calcium ion crosslinked sodium alginate.
In this embodiment, the surface topography of the responsive material substrate is a surface of a micro-cone array, the width of the micro-cone is: 5 μm, high: 5 μm, pitch: 5 μm, substrate thickness of 200 μm, and material of P (VDF-TrFE) copolymer and polydopamine composite capable of generating electricity under the mediation of near infrared light irradiation; (ii) the inoculated dopaminergic neurons differentiated from the fully functional induced stem cells; the hydrogel material is calcium ion crosslinked sodium alginate, and the thickness is 200 μm.
The preparation method of the nerve regulation and control device based on the active interface comprises the following steps:
1) Preparing a responsive material substrate;
preparing a mixed solution containing 10w/v% of polyvinylidene fluoride and 0.1w/v% of polydopamine by using dimethyl sulfoxide as a solvent; casting the mixed solution on the surface of a micro-cone array structure (the width of a micro-cone is 5 mu m, the height is 5 mu m and the distance is 5 mu m) template obtained by plasma dry etching, and drying at 80 ℃ to prepare a responsive material substrate with the surface appearance of the micro-cone array; the prepared responsive material substrate was irradiated by a cobalt source at an irradiation dose of 15kGy and an irradiation time of 30 minutes to complete material sterilization.
2) Inoculating living cells;
using cell suspension of dopaminergic neuron obtained by pancreatin digestion and full-function induced stem cell differentiation, and sterilizing the surface of the substrate made of responsive material, and adding 10 4 Cells were seeded at a seeding density of cells per square centimeter.
3) Hydrogel encapsulation;
after the cells are inoculated for at least 24 hours, covering the surface of a responsive material substrate inoculated with living cells with 3w/v% of sodium alginate hydrogel prepolymerization solution, then dropwise adding 0.3M calcium chloride aqueous solution, and completing encapsulation hydrogel crosslinking through ionic crosslinking to obtain the nerve regulation device based on the active interface.
Example 6
An active interface-based nerve modulation device is structurally shown in figure 1, and comprises a responsive material substrate, living cells growing on the responsive material substrate in an adhesion mode, and hydrogel for encapsulating the living cells; the responsive material substrate is made of a magnetocaloric material and a pyroelectric material, the living cells are nerve immune cells, and the hydrogel is calcium ion crosslinked sodium alginate.
In this embodiment, the surface topography of the responsive material substrate is a surface of a micropillar array, the width of the micropillar: 5 μm, high: 5 μm, pitch: 5 μm, the thickness of the substrate is 50 μm, and the material is a compound of P (VDF-TrFE) copolymer and ferroferric oxide which can generate electricity under the mediation of an alternating magnetic field; the inoculated nerve immune cells are mouse astrocytes; the hydrogel material is calcium ion crosslinked sodium alginate, and the thickness is 50 μm.
The preparation method of the nerve regulation and control device based on the active interface comprises the following steps:
1) Preparing a responsive material substrate;
preparing a mixed solution containing 10w/v% of polyvinylidene fluoride and 5mg/mL ferroferric oxide nanoparticles by using dimethyl sulfoxide as a solvent; casting the mixed solution on the surface of a micro-column array structure (width: 5 mu m, height: 5 mu m and space: 5 mu m) template obtained by photoetching to prepare a responsive material substrate with the surface topography of the micro-column array; the prepared responsive material substrate was irradiated by a cobalt source at an irradiation dose of 15kGy and an irradiation time of 30 minutes to complete material sterilization.
2) Inoculating living cells;
using cell suspension of mouse astrocyte obtained by trypsinization, and sterilizing the surface of the responsive material substrate with 10% of the amount of the cell suspension 4 Cells were seeded at a seeding density of cells per square centimeter.
3) Hydrogel packaging;
after cells are inoculated for at least 24 hours, covering the surface of a responsive material substrate inoculated with living cells with 3w/v% of sodium alginate hydrogel prepolymerization liquid, then dropwise adding 0.3M calcium chloride aqueous solution, and completing encapsulation hydrogel crosslinking through ionic crosslinking to obtain the nerve regulation and control device based on the active interface.
Example 7
An active interface-based nerve modulation device is structurally shown in figure 1, and comprises a responsive material substrate, living cells growing on the responsive material substrate in an adhesion mode, and hydrogel for encapsulating the living cells; wherein, the responsive material substrate is made of piezoelectric ion gel material, the living cell is neuroendocrine cell, and the hydrogel is calcium ion cross-linked sodium alginate.
In this embodiment, the surface topography of the responsive material substrate is a surface of a micropillar array, the width of the micropillar: 50nm, high: 50nm, pitch: 50nm, the thickness of the substrate is 50 μm, and the material is a compound of polymethacrylic acid and choline capable of generating electricity under ultrasonic mediation; the inoculated neuroendocrine cells are mouse alveolar neuroendocrine cells; the hydrogel material is calcium ion crosslinked sodium alginate, and the thickness is 50 μm.
The preparation method of the nerve regulation and control device based on the active interface comprises the following steps:
1) Preparing a responsive material substrate;
preparing an aqueous solution containing 10w/v% of methacrylic acid, 3w/v% of choline chloride and 0.1w/v% of 2959 photoinitiator; casting the mixed solution on the surface of a micro-column array structure (width: 50nm, height: 50nm and spacing: 50 nm) template obtained by photoetching, and reacting for 10 minutes under the irradiation of an ultraviolet cross-linking instrument to prepare a responsive material substrate with the surface topography of the micro-column array; the prepared responsive material substrate was irradiated by a cobalt source at an irradiation dose of 15kGy and an irradiation time of 30 minutes to complete material sterilization.
2) Inoculating living cells;
cell suspension of mouse alveolar neuroendocrine cells obtained by trypsinization was applied to the surface of a sterilized responsive material substrate at a rate of 10 4 Cells were seeded at a seeding density of cells per square centimeter.
3) Hydrogel packaging;
after cells are inoculated for at least 24 hours, covering the surface of a responsive material substrate inoculated with living cells with 3w/v% of sodium alginate hydrogel prepolymerization solution, then dropwise adding 0.3M calcium chloride aqueous solution, and completing encapsulation hydrogel crosslinking through ionic crosslinking to obtain the nerve regulation and control device based on the active interface
It is to be understood that various features of the above-described embodiments may be combined in any combination, and for the sake of brevity, all possible combinations of features in the above-described embodiments may not be described in detail, but rather, all combinations of features may be considered to fall within the scope of the present disclosure unless there is a conflict between such combinations.
The foregoing is considered as illustrative only of the preferred embodiments of the invention and is presented only in the detailed description of the principles of the invention. Any modifications, equivalents, and improvements made within the spirit and principles of the present application and other embodiments of the present application that one skilled in the art may recognize without inventive faculty are intended to be included within the scope of the present application.
Claims (22)
1. A neuromodulation device, comprising: the substrate can convert external field energy into electricity and excite the living cells growing on the surface of the substrate to respond and release neurotransmitter molecules, and the living cells grow on the surface of the substrate and the hydrogel is used for encapsulating the living cells on the surface of the substrate.
2. The neuromodulation device of claim 1 wherein the substrate has a thickness of 50-500 μ ι η.
3. The neuromodulation device of claim 1 wherein the surface topography of the substrate is a planar or three-dimensional structure comprising at least one of a micro-groove array, a micro-cone array, and a micro-pillar array.
4. The active interface-based neuromodulation device of claim 1 wherein the three-dimensional structure has a dimension width of 50nm to 20 μ ι η, a height of 50nm to 20 μ ι η, and a spacing of 50nm to 20 μ ι η.
5. The neuromodulation device as in claim 1,2, 3 or 4, wherein the substrate is at least one of a piezoelectric material, a photo-deformable material composite piezoelectric material, a photovoltaic material, an up-conversion material composite photovoltaic material, a photo-thermal material composite pyroelectric material, a magneto-thermal material composite pyroelectric material, and a piezoelectric ionic gel.
6. The neuromodulation device as in claim 5, wherein the piezoelectric material comprises a piezoelectric crystal or a piezoelectric ceramic or a ferroelectric polymer of the polyvinylidene fluoride family or a piezoelectric polymer, the piezoelectric crystal comprising quartz crystal or lithium gallate or lithium germanate or titanium germanate or lithium tantalate; the piezoelectric ceramics comprise barium titanate or lead zirconate titanate or lead meta niobate or lead barium lithium niobate; the polyvinylidene fluoride ferroelectric polymer comprises poly (vinylidene fluoride) or poly (vinylidene fluoride-trifluoroethylene) [ P (VDF-TrFE) copolymer ] or poly (vinylidene fluoride-chlorofluoroethylene) [ P (VDF-CFE) copolymer ] or poly (vinylidene fluoride-chlorotrifluoroethylene) [ P (VDF-CTFE) copolymer ] or poly (vinylidene fluoride-hexafluoropropylene) [ P (VDF-HFP) copolymer ] or poly (vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) [ P (VDF-TrFE-CFE) terpolymer ] or poly (vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene) [ P (VDF-TrFE-CTFE) terpolymer ] or poly (vinylidene fluoride-trifluoroethylene-hexafluoropropylene) [ P (VDF-TrFE-HFP) terpolymer ]; the piezoelectric polymer comprises odd nylon or polyacrylonitrile or vinylidene cyanide and copolymer thereof or polyurea or polyphenyl cyanoether or polyvinyl chloride or polyvinyl acetate or polypropylene or polytetrafluoroethylene.
7. The neuromodulation device as in claim 5 or 6, wherein the photo-deformable material composite piezoelectric material is a combination of any of the following photo-deformable materials and the piezoelectric material; the photoinduced deformation material comprises at least one of photoinduced heterogeneous material or ferroelectric inorganic photoinduced deformation material, and the photoinduced heterogeneous material comprises at least one of azobenzene and derivatives thereof, spiropyran and derivatives thereof; the ferroelectric inorganic photoinduced deformation material comprises at least one of lead titanate, barium titanate, potassium niobate, lithium tantalate, bismuth-layer-shaped perovskite structure ferroelectric, tungsten bronze type ferroelectric, bismuth ferrite, potassium dihydrogen phosphate, ammonium trinitrate sulfate, rosette and perovskite type organic metal halide ferroelectric.
8. The neuromodulation device as in claim 5, wherein the photovoltaic material comprises at least one of: polyacetylene, polythiophene, polyaniline, polypyrrole and derivatives and copolymers thereof.
9. The neuromodulation device as in claim 5 or 6, wherein the up-conversion material composite photovoltaic material is any one of the following up-conversion materials and the piezoelectric material in combination; wherein the up-conversion material comprises at least one of yttrium oxide, yttrium oxysulfide, lanthanum fluoride, sodium yttrium fluoride and sodium gadolinium fluoride.
10. The neuromodulation device as in claim 5, wherein the photothermal material and the pyroelectric composite material comprise any one of a photothermal material and a pyroelectric material in combination; the photo-thermal material comprises at least one of carbon black, carbon nano tubes, graphene, black phosphorus, polydopamine, gold nano rods and gallium-indium alloy liquid metal; the pyroelectric material comprises at least one of polyvinylidene fluoride ferroelectric polymer and perovskite type ferroelectric ceramic, wherein the polyvinylidene fluoride ferroelectric polymer comprises at least one of poly (vinylidene fluoride), poly (vinylidene fluoride-trifluoroethylene) [ P (VDF-TrFE) copolymer ], poly (vinylidene fluoride-chlorofluoroethylene) [ P (VDF-CFE) copolymer ], poly (vinylidene fluoride-chlorotrifluoroethylene) [ P (VDF-CTFE) copolymer ], poly (vinylidene fluoride-hexafluoropropylene) [ P (VDF-HFP) copolymer ], poly (vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) [ P (VDF-TrFE-CFE) terpolymer ], poly (vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene) [ P (VDF-TrFE-CTFE) terpolymer ] and poly (vinylidene fluoride-trifluoroethylene-hexafluoropropylene) [ P (VDF-TrFE-CTFE) terpolymer ], and the perovskite type ferroelectric ceramic comprises at least one of barium titanate, lead zirconium titanate, lead metaniobate and lead lithium niobate.
11. The neuromodulation device as in claim 5 or 10, wherein the magnetocaloric material and the pyroelectric material are combined together, wherein the magnetocaloric material and the pyroelectric material are any one of the following materials; wherein the magnetocaloric material comprises at least one of Ru ferroboron alloy, ferroferric oxide, iron, cobalt, nickel and gadolinium.
12. The neuromodulation device as in claim 5, wherein the piezoelectric ionic gel material comprises at least one of a polyacrylic acid and polyacrylamide composite gel, a polyacrylic acid and chitosan composite gel, a sodium alginate and polyacrylamide composite gel, a polyacrylic acid and choline composite gel, a sodium alginate and choline composite gel, a methacrylic acid acylated gelatin and choline composite gel, a methacrylic acid acylated hyaluronic acid and choline composite gel.
13. The neuromodulation device as in claim 1, wherein the living cell is a neurotransmitter-producing cell type; including but not limited to at least one of primary neuronal cells, neuroimmune cells, including astrocytes or microglia, neuroendocrine cells, cell lines that produce neurotransmitters, and neuronal cells induced from stem cells.
14. The neuromodulation device as in claim 1, wherein the hydrogel is at least one of the following materials: alginate, chitosan, gelatin and derivatives thereof, collagen and derivatives thereof, hyaluronic acid and derivatives thereof, extracellular matrix protein and derivatives thereof, silk fibroin and derivatives thereof, agarose, carrageenan, dextran, basement membrane matrix, polycaprolactone, polyethylene glycol and derivatives thereof, propylene glycol and epoxyethyl ether block polymer, and polyvinylpyrrolidone.
15. The neuromodulation device of claim 1 wherein the hydrogel layer has a thickness of 50-500 μ ι η.
16. The neuromodulation device as in claim 1, wherein the neurotransmitter molecules comprise at least one of cholines, monoamines, amino acids, neuropeptides, purines, and nitric oxide, wherein the cholines comprise acetylcholine, the monoamines comprise at least one of norepinephrine or epinephrine or dopamine or 5-HT or histamine, and the amino acids comprise at least one of glutamate or Y-aminobutyric acid or glycine.
17. A method of making the neuromodulation device of claim 1, comprising the steps of:
preparing the substrate;
growing the living cells on the surface of the substrate;
pre-crosslinking the hydrogel on the surface of the substrate so as to encapsulate the living cells on the surface of the substrate, thereby obtaining the nerve regulation device.
18. The method for preparing a neuromodulation device as claimed in claim 17, wherein the step of preparing the substrate specifically comprises the steps of: and preparing the substrate by adopting a casting method or a spin coating method.
19. The method of claim 17, wherein the planar or three-dimensional structure is formed on the surface of the substrate by photolithography, dry plasma etching or machining, and the three-dimensional structure comprises at least one of a micro-groove array, a micro-cone array and a micro-column array.
20. The method of making a neuromodulation device as in claim 17,the seeding density of the living cells is 10 3 –10 6 Cells per square centimeter.
21. The method of claim 17, wherein the crosslinking is performed by at least one of ionic crosslinking and ultraviolet crosslinking.
22. Use of the neuromodulation device of claim 17 for the treatment of brain-computer interface and neurological device diseases.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116459389A (en) * | 2023-05-04 | 2023-07-21 | 深圳先进技术研究院 | Bionic visual repair material, repair film, preparation method of repair film and repair device |
Citations (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4892538A (en) * | 1987-11-17 | 1990-01-09 | Brown University Research Foundation | In vivo delivery of neurotransmitters by implanted, encapsulated cells |
| CN1161744A (en) * | 1994-09-23 | 1997-10-08 | 纽罗斯菲里斯控股有限公司 | In vitro models of CNS function and dysfunction |
| AU2002321050A1 (en) * | 2001-06-05 | 2002-12-16 | Rosemarie Daig | Cell populations for detecting neuronal targets and potential active ingredients |
| CA2495132A1 (en) * | 2002-08-09 | 2004-02-19 | Ottawa Health Research Institute | Bio-synthetic matrix and uses thereof |
| US20060034807A1 (en) * | 2002-08-09 | 2006-02-16 | Ottawa Health Research Institute | Innervated artificial tissues and uses thereof |
| CN1871340A (en) * | 2003-09-03 | 2006-11-29 | 利莱恩斯生命科学有限公司 | In vitro generation of gabaergic neurons from embryonic stem cells and their use in the treatment of neurological disorders |
| CN1894401A (en) * | 2003-03-12 | 2007-01-10 | 睿良思生命科学私人有限公司 | Derivation of terminally differentiated dopaminergic neurons from human embryonic stem cells |
| CN1946381A (en) * | 2003-11-13 | 2007-04-11 | 利兰·斯坦福青年大学托管委员会 | Artificial synapse chip |
| CN102181396A (en) * | 2011-03-24 | 2011-09-14 | 中国人民解放军第三军医大学第三附属医院 | Method for inducing neural stem cells to be directionally differentiated into sensory neurons in vitro |
| CN103215226A (en) * | 2012-12-16 | 2013-07-24 | 中国医学科学院医学生物学研究所 | Method for co-culturing with nerve stem cell to inducing rASCs to be DA Neuron by Lmx1a mediation |
| CN103245724A (en) * | 2013-05-21 | 2013-08-14 | 东南大学 | Nerve cell discharge performance detection method under variable concentration medicine action |
| CN109414526A (en) * | 2016-05-17 | 2019-03-01 | 德累斯顿协会莱布尼茨聚合物研究所 | The method for being used to form the functional network of human neuronal cell and Deiter's cells |
| CN110702650A (en) * | 2019-09-26 | 2020-01-17 | 南京大学 | Synchronous monitoring method for chemical signals and electric signals of neural cell network |
| US20210268268A1 (en) * | 2018-07-20 | 2021-09-02 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Conformable neural interface device with hydrogel adhesion and methods of using the same |
| CN113413488A (en) * | 2021-06-09 | 2021-09-21 | 济南大学 | Preparation method of degradable piezoelectric fiber scaffold and product thereof |
| CN113621144A (en) * | 2021-06-11 | 2021-11-09 | 四川大学 | Magnetoelectric response bionic hydrogel and magnetoelectric response bionic hydrogel capable of adjusting cell electricity microenvironment and preparation method thereof |
| CN114561357A (en) * | 2022-01-17 | 2022-05-31 | 济南大学 | Method for accelerating differentiation of neural stem cells to neurons based on radio signals generated by electromagnetic induction |
-
2022
- 2022-11-09 CN CN202211397878.4A patent/CN115591025B/en active Active
Patent Citations (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4892538A (en) * | 1987-11-17 | 1990-01-09 | Brown University Research Foundation | In vivo delivery of neurotransmitters by implanted, encapsulated cells |
| CN1161744A (en) * | 1994-09-23 | 1997-10-08 | 纽罗斯菲里斯控股有限公司 | In vitro models of CNS function and dysfunction |
| AU2002321050A1 (en) * | 2001-06-05 | 2002-12-16 | Rosemarie Daig | Cell populations for detecting neuronal targets and potential active ingredients |
| CA2495132A1 (en) * | 2002-08-09 | 2004-02-19 | Ottawa Health Research Institute | Bio-synthetic matrix and uses thereof |
| US20060034807A1 (en) * | 2002-08-09 | 2006-02-16 | Ottawa Health Research Institute | Innervated artificial tissues and uses thereof |
| CN1894401A (en) * | 2003-03-12 | 2007-01-10 | 睿良思生命科学私人有限公司 | Derivation of terminally differentiated dopaminergic neurons from human embryonic stem cells |
| CN1871340A (en) * | 2003-09-03 | 2006-11-29 | 利莱恩斯生命科学有限公司 | In vitro generation of gabaergic neurons from embryonic stem cells and their use in the treatment of neurological disorders |
| CN1946381A (en) * | 2003-11-13 | 2007-04-11 | 利兰·斯坦福青年大学托管委员会 | Artificial synapse chip |
| CN102181396A (en) * | 2011-03-24 | 2011-09-14 | 中国人民解放军第三军医大学第三附属医院 | Method for inducing neural stem cells to be directionally differentiated into sensory neurons in vitro |
| CN103215226A (en) * | 2012-12-16 | 2013-07-24 | 中国医学科学院医学生物学研究所 | Method for co-culturing with nerve stem cell to inducing rASCs to be DA Neuron by Lmx1a mediation |
| CN103245724A (en) * | 2013-05-21 | 2013-08-14 | 东南大学 | Nerve cell discharge performance detection method under variable concentration medicine action |
| CN109414526A (en) * | 2016-05-17 | 2019-03-01 | 德累斯顿协会莱布尼茨聚合物研究所 | The method for being used to form the functional network of human neuronal cell and Deiter's cells |
| US20190247546A1 (en) * | 2016-05-17 | 2019-08-15 | Leibniz-Institut Für Polymerforschung Dresden E.V. | Method for forming a functional network of human neuronal and glial cells |
| US20210268268A1 (en) * | 2018-07-20 | 2021-09-02 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Conformable neural interface device with hydrogel adhesion and methods of using the same |
| CN110702650A (en) * | 2019-09-26 | 2020-01-17 | 南京大学 | Synchronous monitoring method for chemical signals and electric signals of neural cell network |
| CN113413488A (en) * | 2021-06-09 | 2021-09-21 | 济南大学 | Preparation method of degradable piezoelectric fiber scaffold and product thereof |
| CN113621144A (en) * | 2021-06-11 | 2021-11-09 | 四川大学 | Magnetoelectric response bionic hydrogel and magnetoelectric response bionic hydrogel capable of adjusting cell electricity microenvironment and preparation method thereof |
| CN114561357A (en) * | 2022-01-17 | 2022-05-31 | 济南大学 | Method for accelerating differentiation of neural stem cells to neurons based on radio signals generated by electromagnetic induction |
Non-Patent Citations (3)
| Title |
|---|
| MING YANG ET AL: "Polypyrrole/sulfonated multi-walled carbon nanotubes conductive hydrogel for electrochemical sensing of living cells", CHEMICAL ENGINEERING JOURNAL, pages 1 - 9 * |
| XUEMIN DU ET AL: "Bioinspired microcone-array-based living biointerfaces: enhancing the anti-inflammatory effect and neuronal network formation", MICROSYSTEMS & NANOENGINEERING, pages 1 - 8 * |
| 吴烨堃: "医用水凝胶神经接口研究进展", 卫生研究, pages 342 - 346 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116459389A (en) * | 2023-05-04 | 2023-07-21 | 深圳先进技术研究院 | Bionic visual repair material, repair film, preparation method of repair film and repair device |
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