Vascular implantable brain-computer interface polymeric membrane material based on magnetosome targeted delivery as well as preparation method and application of vascular implantable brain-computer interface polymeric membrane material

Abstract

The invention relates to a vascular implantable brain-computer interface polymeric membrane material based on magnetosome targeted delivery as well as a preparation method and application of the vascular implantable brain-computer interface polymeric membrane material. The polymeric membrane material comprises a flexible polymeric basement membrane, a biocompatible coating and amination modified magnetosomes loaded on the surface of the coating, the basement membrane is composed of a blend of polycaprolactone and gelatin, and graphene nanosheets are dispersed in the basement membrane; the biocompatible coating is a compound of chitosan and hyaluronic acid; and the magnetosome is loaded on the surface of the coating through electrostatic interaction after amination treatment. The preparation method comprises the following steps: forming a basement membrane, constructing a biocompatible coating, and modifying and compounding the magnetosome. The vascular implantable brain-computer interface polymeric membrane material based on magnetosome targeted delivery can be used in a vascular implantable brain-computer interface targeted delivery system, delivery is carried out through a degradable packaging carrier in a vascular intervention mode, and targeted positioning of a brain target area is achieved under the action of an external magnetic field.

Description

Technical Field

[0001] This invention relates to the field of biomedical engineering technology, and more specifically, to a polymer membrane material for vascular implantable brain-computer interface based on magnetosome targeted delivery, its preparation method, and its application. Background Technology

[0002] Brain-computer interface (BCI) technology, as an important means of enabling signal interaction between the brain and external devices, has broad application prospects in fields such as neurorehabilitation, assistive control, intelligent prostheses, and brain function research. Existing BCI devices are mainly divided into two categories: invasive and non-invasive. Invasive BCIs typically use rigid microelectrode arrays, silicon-based probes, and other structures, requiring craniotomy to directly implant electrodes into the cerebral cortex or deeper tissues to obtain neural signals with high spatiotemporal resolution. This type of surgery inevitably comes with a high risk of infection, tissue damage, and postoperative inflammatory reactions. Due to the mismatch between the implanted materials and the mechanical properties of brain tissue, it is also easy to cause insufficient fit between the device and neural tissue, resulting in significant neural rejection and affecting the stability and reliability of long-term signal acquisition. In contrast, non-invasive BCI methods (such as scalp electrode EEG and transcranial magnetic stimulation TMS) do not require surgery to enter the tissue and have higher safety. However, because the signal needs to penetrate multiple layers of structures such as the skull and meninges, it leads to severe signal attenuation, low targeting accuracy, and limited spatial resolution, making it difficult to meet the needs of precise localization and high-quality signal acquisition of specific brain regions.

[0003] In recent years, some studies have attempted to replace traditional rigid electrodes with flexible polymer materials to improve adhesion and biocompatibility with tissue surfaces. However, such implantation methods still generally rely on craniotomy or other invasive procedures to locate the material on the brain surface, making true minimally invasiveness difficult to achieve. Furthermore, while existing flexible materials can acquire neural signals, they often lack effective in vivo targeted delivery capabilities. In addition, although some research in related fields has proposed using nanoparticles, chemical carriers, or drug delivery systems to achieve in vivo localization via blood vessels, these approaches generally have significant limitations in terms of targeting accuracy, biocompatibility, material stability, and tissue adhesion. Traditional nanocarriers are easily affected by blood flow in the vascular system and are difficult to retain in specific brain regions; moreover, most carriers are only used for drug release and are unsuitable as structural materials for brain-computer interfaces. Some polymer materials can achieve a certain degree of tissue adhesion, but their carrier function is singular, unable to combine conductivity, flexibility, and localization capabilities, and thus cannot meet the multifunctional requirements of brain-computer interface devices.

[0004] In summary, existing brain-computer interface technologies generally face the following key issues: Highly invasive implantation methods: Most methods still require craniotomy, posing significant surgical risks; Insufficient targeting precision: Existing non-invasive systems struggle to achieve high-precision localization of specific brain regions; Poor biocompatibility and long-term stability: Inadequate material-tissue matching can easily lead to rejection or poor adhesion; Limited material functionality: Existing flexible materials struggle to simultaneously possess electrical signal conduction, targeted delivery, and tissue adhesion properties.

[0005] Due to the aforementioned shortcomings, there is currently a lack of a material system that can achieve minimally invasive implantation, high-precision targeting of specific brain regions, good biocompatibility, and can be used for brain-computer interface signal transduction. This field urgently needs new materials and delivery strategies to overcome the limitations of existing technologies in terms of safety, accuracy, and functional integration. Summary of the Invention

[0006] One of the technical problems to be solved by the present invention is to provide a polymer membrane material for vascular implantable brain-computer interface based on magnetosome targeted delivery, so as to solve the problems of highly invasive implantation method, lack of effective targeting ability, poor material-brain tissue adhesion, insufficient biocompatibility and unstable signal acquisition in the prior art.

[0007] To overcome the shortcomings of the prior art, this invention provides a polymer membrane material for vascular implantable brain-computer interfaces based on magnetosome targeted delivery, comprising: A flexible polymer base membrane, the base membrane comprising a blend of polycaprolactone and gelatin and graphene nanosheets dispersed therein; A biocompatible coating disposed on at least one surface of the flexible polymer base membrane, the coating comprising a complex of chitosan and hyaluronic acid; and Aminated magnetosomes are loaded onto the surface of the biocompatible coating via electrostatic interactions.

[0008] Compared with existing technologies, the vascular implantable brain-computer interface polymer membrane material of this invention has the following advantages: Through the synergistic design of a flexible basement membrane, a graphene conductive reinforcing phase, a biocompatible coating, and aminated magnetic particles, this invention achieves comprehensive improvements in implantation method, targeting accuracy, biointerface stability, and signal acquisition performance. Specifically, the flexible polycaprolactone / gelatin basement membrane (mass ratio 6:4) has a tensile strength of 12-15 MPa and an elongation at break of 250-300%, matching the elastic modulus of brain tissue (10-20 MPa) by more than 90%, far superior to traditional silicon-based materials (tensile strength 30-40 MPa). The conductive network constructed from graphene nanosheets significantly reduces the membrane surface resistance (MPa, elongation at break 5%-8%, matching degree only 30%), enabling reliable neural signal transmission even in an ultrathin structure. The chitosan / hyaluronic acid coating enhances the adhesion and biocompatibility of the material on the brain surface, reducing tissue rejection after implantation. Aminated magnetic bodies (saturation magnetization 55-60 emu / g) are stably loaded on the membrane surface. Under the action of an external magnetic field of 0.5-1 T, the magnetic response migration speed is 0.2-0.3 mm / min, which can overcome the blood flow shear force (the blood flow shear force in brain vessels is about 1-5 dyn / cm²) to achieve precise targeted delivery to the target brain region. This allows the membrane material to be implanted without craniotomy via the vascular pathway. Furthermore, the above-mentioned structures of this invention also have a synergistic effect: the magnetic bodies ensure accurate delivery, the coating improves tissue integration, and the conductive layer ensures the stability of signal acquisition. This effectively solves the problems of traditional brain-computer interfaces, such as high invasiveness, insufficient targeting, unstable adhesion, and unreliable signals.

[0009] In one possible implementation, the mass ratio of polycaprolactone to gelatin in the flexible polymer base film is 6:4, and the amount of graphene nanosheets added is 0.4-0.6 wt% of the total mass of polycaprolactone and gelatin.

[0010] Compared with existing technologies, the above-mentioned technical solution, by controlling the mass ratio of polycaprolactone to gelatin to 6:4, can achieve a more reasonable balance between flexibility and mechanical strength in the basement membrane. Polycaprolactone provides the necessary toughness, while gelatin improves hydrophilicity and processability. Graphene in the range of 0.4-0.6wt% can form a stable microscale conductive network, and the dispersion of graphene sheets creates low-impedance electronic conduction paths inside the membrane without damaging the flexible structure of the basement membrane. This significantly reduces surface resistance and improves the stability of nerve signal acquisition while ensuring extremely thin membrane thickness.

[0011] In one possible implementation, the biocompatible coating contains a chitosan to hyaluronic acid mass ratio of 1:1.

[0012] Compared with existing technologies, the above-mentioned technical solution significantly improves the biointerface stability of the material surface through the composite structure of aminopolysaccharides and anionic polysaccharides. The amino groups of chitosan enhance tissue adhesion, while hyaluronic acid improves hydration and lubrication performance and reduces immune response. When the two are mixed in a 1:1 ratio, they can form a uniform cross-linked network, which further improves the adhesion of the membrane material to the brain tissue surface and reduces post-implantation interfacial inflammation.

[0013] In one possible implementation, the magnetic particles have a particle size of 20-50 nm and a loading of 2-3 wt% of the total mass of the polymer film material.

[0014] Compared with existing technologies, the above technical solution enables the magnetosomes to possess both good magnetic responsiveness and stable interfacial adhesion. Setting the particle size to 20–50 nm ensures that the magnetosomes have a high specific surface area and good biodispersibility. Furthermore, controlling the loading to 2–3 wt% can provide sufficient magnetic responsiveness while maintaining the overall performance of the membrane material, thereby enabling effective directional migration and targeted aggregation under the action of an external magnetic field.

[0015] In one possible implementation, the thickness of the flexible polymer base film is 5-10 μm, and the thickness of the biocompatible coating is 50-150 nm.

[0016] Compared with existing technologies, the above-mentioned technical solution can take into account the material's flexibility, conductivity, and in vivo operational stability. In this embodiment, the ultrathin basement membrane of 5-10 μm can conform to the micro-curvature of the brain surface and reduce mechanical stimulation; while the coating thickness of 50-150 nm is sufficient to provide complete interface modification without affecting the magnetosome load and overall flexibility, so that the membrane can adhere to the brain tissue surface after implantation in vivo and is not easily displaced by blood flow or cerebrospinal fluid impact.

[0017] Another technical problem to be solved by the present invention is to provide a method for preparing a polymer membrane material for a vascular implantable brain-computer interface based on magnetosome targeted delivery, so as to solve the problems of poor interlayer adhesion, uneven distribution of functional components, insufficient biological interface performance, and difficulty in stable loading of magnetic targeting medium in the preparation of traditional membrane materials in the prior art.

[0018] To overcome the shortcomings of the prior art, the present invention provides a method for preparing the aforementioned polymer membrane material, comprising the following steps: S1: Preparation of flexible polymer base film: Polycaprolactone and gelatin are mixed and dissolved in a solvent, graphene nanosheets are added, and after dispersion, a film is formed by solution casting and dried to obtain a flexible polymer base film; S2: Constructing a biocompatible coating: A composite solution of chitosan and hyaluronic acid is coated on the surface of the flexible polymer base film. The amino groups of chitosan and the carboxyl groups of hyaluronic acid form a cross-linked structure to improve the biocompatibility of the material. After drying, a biocompatible coating is formed. S3: Loading magnetosomes: After the magnetosomes are modified by amination, they are combined with the biocompatible coating treated in step S2, so that the magnetosomes are loaded on the surface of the biocompatible coating.

[0019] In the preparation method of the polymer membrane material for vascular implantable brain-computer interface based on magnetosome targeted delivery of the present invention, in step S1, a polycaprolactone / gelatin base membrane is prepared by solution casting, so that graphene nanosheets are uniformly dispersed and form a continuous conductive path during the film formation process, ensuring that the material obtains stable electrical properties on the basis of flexibility; in step S2, a chitosan and hyaluronic acid composite solution is used to directly form a film on the substrate surface, so that the biocompatible coating is tightly bonded to the substrate structure, avoiding the interlayer delamination or local unevenness problems that are easy to occur in traditional coating processes; further, in step S3, the magnetosomes are aminated to enable them to electrostatically recombine with the carboxyl groups or negatively charged groups on the coating surface, so as to achieve directional and stable loading of the magnetosomes on the membrane surface. The steps described above in this invention are interconnected during the preparation process, forming a multifunctional gradient structure composed of a substrate layer, a coating layer, and magnetic bodies. By controlling the fixation of each functional component in the material at its corresponding level without migration or aggregation, the biocompatibility, conductivity, and targeting responsiveness of the material are significantly improved. The preparation method of this invention enables the obtained membrane material to have stable structural integrity and repeatability, and can be reliably used in vascular interventional targeted delivery scenarios. It successfully solves the problems of easy delamination of membrane structures, difficulty in achieving both functions, instability of the targeting medium, and poor interface performance in the background technology.

[0020] In one possible implementation, in step S1, the solvent is a mixture of dichloromethane and ethanol, and the volume ratio of dichloromethane to ethanol is (3±0.5):1.

[0021] Compared with existing technologies, the above technical solution, by setting the solvent as a mixture of dichloromethane and ethanol, can maintain good solubility of polycaprolactone and gelatin in the system and effectively control the dispersion state of graphene nanosheets in the solution. Dichloromethane has strong dissolving power, which is conducive to the unfolding of polycaprolactone segments, while ethanol can adjust the polarity of the solution, making it easier for gelatin and graphene nanosheets to form a uniform dispersion system. As a result, a uniform and dense base film can be obtained during the casting process, avoiding pores, agglomeration or local thickness unevenness.

[0022] In one possible implementation, in step S2, the coating method is to coat the composite solution by spraying at a pressure of 0.2 ± 0.05 MPa.

[0023] Compared with existing technologies, the above technical solution can achieve uniform deposition of biocompatible coating on the substrate membrane surface, avoiding local accumulation or coating thickness deviation caused by dip coating or scraping. The spraying pressure of 0.2±0.05 MPa can atomize chitosan / hyaluronic acid droplets with a stable particle size, forming a continuous and uniform coating spread. Finally, the coating thickness is controlled, the surface is smooth, and the interlayer bonding is strong.

[0024] In one possible implementation, step S3, the amination modification of the magnetosomes includes: extracting magnetosomes from magnetotactic bacteria, dispersing them to obtain a suspension; adding 3-aminopropyltriethoxysilane to the suspension at a final concentration of 0.05-0.15 wt% for surface modification, so that the surface of the magnetosomes carries amino groups.

[0025] Compared with existing technologies, the above-mentioned technical solution significantly improves the electrostatic bonding ability between the magnetosomes and the biocompatible coating, making the magnetosomes more stably distributed on the membrane surface. After hydrolysis, 3-aminopropyltriethoxysilane (APTES) forms silanol groups, which can condense with hydroxyl groups on the surface of the magnetosomes and introduce a positively charged amino functional layer, enhancing its electrostatic adsorption with negatively charged groups (hyaluronic acid carboxyl groups). Furthermore, the concentration can be further controlled, making the magnetosome loading controllable, uniformly attached and not easy to fall off, while maintaining magnetic response sensitivity.

[0026] The present invention also provides an application of the aforementioned polymer membrane material in a vascular implantable brain-computer interface targeted delivery system. The vascular implantable brain-computer interface targeted delivery system includes an implant, an encapsulation carrier, and a magnetic field generating device. The implant is made of the aforementioned polymer membrane material. The encapsulation carrier is used to encapsulate the implant and is biodegradable in vivo. The magnetic field generating device is used to apply a guiding magnetic field externally. The system delivers the implant via vascular intervention and the guiding magnetic field controls the targeted positioning of the implant in a target area of ​​the brain.

[0027] Compared with existing technologies, the application of a polymer membrane material of the present invention in a vascular implantable brain-computer interface targeted delivery system has the following advantages: The aminated magnetic bodies loaded on the surface of the polymer membrane material of the present invention generate controllable directional migration force under the action of an external magnetic field, enabling the membrane encapsulated in a biodegradable carrier to overcome blood flow shear interference and aggregate in a specific area; the encapsulation carrier gradually degrades and releases the membrane after reaching the target area, while the biocompatible coating on the surface of the membrane further enhances its adhesion stability on the brain tissue surface; the implant of the present invention can smoothly enter the brain vascular network without craniotomy and accurately locate in the target brain region under the control of an external magnetic field, while maintaining a stable tissue interface, effectively solving the problems of low targeting accuracy of non-craniotomy methods, large trauma of traditional implantation methods, and difficulty in stable implant attachment in the prior art. Attached Figure Description

[0028] Figure 1 This is a cross-sectional view of the polymer membrane material of the present invention; Among them, 1. Aminated magnetic bodies; 2. Biocompatible coating; 3. Flexible polymer base membrane; Figure 2 This is a flowchart illustrating the preparation method of the polymer membrane material of the present invention. Figure 3 This is a schematic diagram illustrating the principle of applying the polymer membrane material of the present invention to a targeted delivery system. Detailed Implementation

[0029] First, those skilled in the art should understand that these embodiments are merely illustrative of the technical principles of the present invention and are not intended to limit the scope of protection of the present invention. Those skilled in the art can make adjustments as needed to adapt to specific application scenarios.

[0030] In the description of the embodiments of the present invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "connected" and "linked" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium. Those skilled in the art can understand the specific meaning of the above terms in the embodiments of the present invention based on the specific circumstances.

[0031] In embodiments of the present invention, unless otherwise explicitly specified and limited, "above" or "below" the second feature can mean that the first feature is in direct contact with the second feature, or that the first feature is in indirect contact with the second feature through an intermediate medium. Furthermore, "above," "on top of," and "over" the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply that the first feature is at a lower horizontal level than the second feature.

[0032] This invention provides a polymer membrane material for vascular implantable brain-computer interfaces based on magnetosome-targeted delivery, such as... Figure 1 As shown, it includes: A flexible polymer base membrane 3, wherein the base membrane comprises a blend of polycaprolactone and gelatin and graphene nanosheets dispersed therein. A biocompatible coating 2 disposed on at least one surface of the flexible polymer base membrane 3, the coating comprising a complex of chitosan and hyaluronic acid; and Aminated magnetosomes 1 are loaded onto the surface of the biocompatible coating 2 via electrostatic interactions.

[0033] As a preferred embodiment, in the flexible polymer base film 3, the mass ratio of polycaprolactone to gelatin is 6:4, and the amount of graphene nanosheets added is 0.4-0.6 wt% of the total mass of polycaprolactone and gelatin.

[0034] As a preferred embodiment, in the biocompatible coating 2, the mass ratio of chitosan to hyaluronic acid is 1:1.

[0035] As a preferred embodiment, the magnetic particles have a particle size of 20-50 nm and a loading amount of 2-3 wt% of the total mass of the polymer membrane material.

[0036] As a preferred embodiment, the thickness of the flexible polymer base film 3 is 5-10 μm, and the thickness of the biocompatible coating 2 is 50-150 nm.

[0037] The present invention also provides a method for preparing the aforementioned polymer membrane material, such as... Figure 2 As shown, it includes the following steps: S1: Preparation of flexible polymer base film: Polycaprolactone and gelatin are mixed and dissolved in a solvent, graphene nanosheets are added (to improve conductivity), dispersed and then formed into a film by solution casting and drying to obtain a flexible polymer base film; S2: Constructing a biocompatible coating: A composite solution of chitosan and hyaluronic acid is coated on the surface of the flexible polymer substrate membrane. The amino groups of chitosan and the carboxyl groups of hyaluronic acid form a cross-linked structure, which improves the biocompatibility of the material and ensures that the film has electrode writability (silver-based microelectrode patterns with a line width of 50-100μm can be prepared on the film surface by inkjet printing technology). After drying, a biocompatible coating is formed. S3: Loading magnetosomes: After the magnetosomes are modified by amination, they are combined with the biocompatible coating treated in step S2, so that the magnetosomes are loaded on the surface of the biocompatible coating.

[0038] As a preferred embodiment, in step S1, the solvent is a mixture of dichloromethane and ethanol, and the volume ratio of dichloromethane to ethanol is (3±0.5):1.

[0039] As a preferred embodiment, in step S2, the coating method is to coat the composite solution by spraying, and the spraying pressure is 0.2±0.05 MPa.

[0040] As a preferred embodiment, in step S3, the amination modification of the magnetosomes includes: extracting magnetosomes from magnetotactic bacteria, dispersing them to obtain a suspension; adding 3-aminopropyltriethoxysilane to the suspension at a final concentration of 0.05-0.15 wt% for surface modification, so that the surface of the magnetosomes carries amino groups.

[0041] This invention provides an application of the aforementioned polymer membrane material in a vascular implantable brain-computer interface targeted delivery system. The vascular implantable brain-computer interface targeted delivery system includes an implant, an encapsulation carrier, and a magnetic field generating device. The implant is made of the aforementioned polymer membrane material. The encapsulation carrier is used to encapsulate the implant and is biodegradable in vivo. The magnetic field generating device is used to apply a guiding magnetic field externally. The system delivers the implant via vascular intervention and the guiding magnetic field controls the targeted positioning of the implant in a target area of ​​the brain.

[0042] Its specific application process is as follows: Figure 3 As shown, it includes the following steps: A1: The polymer membrane material is cut into circular membranes with a diameter of 2-3 mm (adapted to the inner diameter of blood vessels) as implants, and encapsulated in biodegradable polylactic acid microtubules to form an implant carrier. The inner diameter of the polylactic acid microtubules is 3 mm and the wall thickness is 100 μm. A2: The implantable carrier is delivered to the vicinity of the target blood vessel via a catheter through a femoral artery puncture procedure. The catheter has an inner diameter of 3.5 mm and is made of polytetrafluoroethylene. The implantable carrier is then pushed into the internal carotid artery. A3: A low-frequency guiding magnetic field with a strength of 0.5-1T and a frequency of 50 Hz is applied externally to the scalp corresponding to the target brain region. Utilizing the magnetic response characteristics of the magnetosome, the polylactic acid microtubules are guided to degrade in the target vascular region and release the circular membrane. The circular membrane specifically adsorbs to the vascular endothelium and brain surface tissue through its chitosan-hyaluronic acid composite layer, thereby achieving close adhesion to the target brain region and completing the craniotomy-free implantation.

[0043] The following embodiments, incorporating specific data and operating methods, are provided to further elaborate on the technical solution of the present invention: Example 1: This embodiment provides a polymer membrane material for a vascular implantable brain-computer interface based on magnetosome targeted delivery and its preparation method. The polymer membrane material is prepared by the following steps, and the polymer membrane material includes a flexible polymer base membrane, a biocompatible coating, and an aminated modified magnetosome loaded on the surface of the coating.

[0044] Step S1: Preparation of flexible polymer substrate membrane Weigh 6 g of polycaprolactone (molecular weight 80,000) and 4 g of gelatin (molecular weight 100,000), add them to 50 mL of dichloromethane-ethanol mixed solvent (volume ratio 3:1), and stir at room temperature for 2 h until completely dissolved to obtain a polycaprolactone / gelatin blend solution. Add 0.05 g of graphene nanosheets (5–10 μm in diameter) to this solution and disperse using ultrasound for 15 min (power 300 W) to form a homogeneous suspension. Pour the resulting suspension into a casting mold with an area of ​​10 cm × 10 cm and dry it in a vacuum drying oven at 30 ℃ for 8 h. After drying, peel off the film to obtain a flexible polymer substrate film.

[0045] Step S2: Constructing a biocompatible coating A chitosan-hyaluronic acid composite solution with a mass fraction of 1 wt% was prepared, wherein the mass ratio of chitosan to hyaluronic acid was 1:1, and the solvent was a 0.1 mol / L acetic acid solution. The composite solution was then sprayed onto at least one side of the flexible polymer substrate membrane obtained in step S1 at a spraying pressure of 0.2 MPa. After forming a uniform wet film, the membrane was dried at 37 ℃ for 2 h to obtain a polymer membrane with a chitosan / hyaluronic acid biocompatible coating on its surface.

[0046] Step S3: Loading and modifying magnetosomes with amination First, amination-modified magnetic bodies are prepared: 1) Cultivate magnetotactic spirochetes AMB-1 to the logarithmic growth phase (OD). 600=0.8), collect bacterial cells by centrifugation at 5000 rpm for 10 min, and wash 3 times with 0.01 mol / L PBS buffer (pH 7.4); 2) Add lysozyme (final concentration 1 mg / mL) to the bacterial cells, incubate at 37 ℃ for 2 h, then sonicate (500 W power, 20 min time), and centrifuge at 12000 rpm for 20 min to collect the precipitate and obtain coarse magnetic bodies; 3) Wash the coarse magnetosomes three times with 0.1 mol / L hydrochloric acid solution to remove impurities, and then adjust the pH to 7.4 with PBS buffer to obtain a magnetosome suspension; 4) Add 3-aminopropyltriethoxysilane (APTES) to the magnetosome suspension to a final concentration of 0.1 wt%. After stirring and reacting at 30 °C for 4 h, collect the modified magnetosomes by centrifugation at 10,000 rpm for 15 min and resuspend them in PBS for later use, thereby obtaining a magnetosome suspension with amino groups on the surface.

[0047] The polymer membrane obtained in step S2 was then placed in the above-mentioned aminated magnetosome suspension, and the magnetosome loading was controlled to be 2 wt% of the polymer membrane mass. The membrane was then shaken and incubated at 37 ℃ for 1 h, so that the positively charged aminated magnetosomes self-assembled and were loaded onto the surface of the chitosan / hyaluronic acid biocompatible coating through electrostatic interaction. After incubation, the membrane was centrifuged at 8000 rpm for 10 min to remove the free magnetosomes, and the vascular implantable brain-computer interface polymer membrane material with surface-loaded aminated modified magnetosomes was obtained.

[0048] The polymer membrane material prepared by the method in this embodiment has the following structural parameters: the flexible polymer base membrane has a thickness of approximately 8 μm and is made by blending polycaprolactone and gelatin in a mass ratio of 6:4, wherein the amount of graphene nanosheets added accounts for 0.5 wt% of the total mass of polycaprolactone and gelatin; the biocompatible coating has a thickness of approximately 100 nm and is composed of chitosan and hyaluronic acid in a mass ratio of 1:1; the loading of aminated magnetosomes is approximately 2 wt% of the total mass of the material, and their particle size is 20-50 nm; this material combines flexibility, conductivity, high biocompatibility, and magnetic field-responsive targeting capability. Its performance parameters, as tested, are as follows: tensile strength 13.2 MPa, elongation at break 275%, surface resistivity 90 Ω, magnetosome saturation magnetization 58 emu / g, brain cell adhesion rate of 88% after 72 hours, and targeting error of 0.4 mm under external magnetic field guidance.

[0049] Example 2 This embodiment provides an application of a polymer membrane material for vascular implantable brain-computer interface based on magnetosome targeted delivery. The application includes its use in a vascular implantable brain-computer interface targeted delivery system. The polymer membrane material is prepared according to steps S1–S3 of Embodiment 1.

[0050] The magnetic microbody-polymer membrane composite material prepared in Example 1 was cut into circular membranes with a diameter of 2 mm, and the membranes were encapsulated in polylactic acid microtubes, which served as biodegradable encapsulation carriers. Adult male SD rats weighing 250–300 g were selected as experimental animals, and polylactic acid microtubes containing the composite membranes were implanted via femoral artery puncture. The microtubes were then pushed to the internal carotid artery of the rats using a catheter with an inner diameter of 3.5 mm.

[0051] A low-frequency magnetic field with an intensity of 0.8 T and a frequency of 50 Hz was applied to the scalp region corresponding to the motor cortex of the rat brain for 30 min. Through the response of the magnetosome to the applied magnetic field, polylactic acid microtubules were guided to gradually degrade and release a composite membrane in the target vascular region. Real-time observation by MRI imaging showed that the polylactic acid microtubules reached the target vascular region within 15-20 min under the guidance of the magnetic field and were completely degraded within 48-72 h. The aggregation rate of the composite membrane in the target brain region reached more than 95%.

[0052] On the 7th day post-surgery, the rats were euthanized and their brain tissue was dissected. The composite membrane was found to be tightly attached to the corresponding area of ​​the motor cortex, with no obvious local tissue swelling or rejection. Electrical signal testing using microelectrodes placed on the surface of the composite membrane revealed a signal acquisition sensitivity of 48-52 μV, a signal-to-noise ratio of 36-38 dB, and a signal fluctuation amplitude of ≤±3 μV over 7 days of continuous acquisition. In contrast, traditional invasive silicon-based electrodes have a signal-to-noise ratio of 26-28 dB and a signal fluctuation amplitude of ±8-10 μV, demonstrating a 2.5-3 times improvement in signal stability compared to this invention.

[0053] Several comparative examples are provided below to further illustrate the technical effects of the present invention: Comparative Example 1: This comparative example provides a method for preparing a membrane material, which differs from Example 1 in that graphene nanosheets are not added to the polycaprolactone / gelatin solution in step S1.

[0054] The specific operation is as follows: Following the method in step S1 of Example 1, 6 g of polycaprolactone and 4 g of gelatin were dissolved in a 3:1 dichloromethane-ethanol mixed solvent and stirred for 2 h. Without adding graphene nanosheets, the mixture was directly cast and dried to obtain a flexible substrate film. Subsequently, the coating was constructed and magnetic bodies were loaded according to steps S2 and S3 of Example 1 to obtain a graphene-free composite film material.

[0055] Test results show that the surface resistance of the basement membrane is 540-560 Ω, the electrode signal acquisition sensitivity is only 8-10 μV, the signal-to-noise ratio is 12-15 dB, and the output voltage fluctuation range is ±15-20 μV, which cannot meet the requirements of EEG signal transmission.

[0056] Comparative Example 2: This comparative example provides a membrane material that differs from Example 1 in that: no magnetic bobbin loading treatment is performed in step S3, and the resulting membrane surface does not contain aminated magnetic bobbins.

[0057] The specific operation is as follows: After preparing the flexible polymer base membrane and its biocompatible coating in accordance with steps S1 and S2 of Example 1, the material was not immersed in the magnetic granule suspension, but was directly dried and used as a comparative sample.

[0058] When this material was used in vascular delivery experiments, after injection via the femoral artery, the composite membrane failed to migrate directionally under an applied magnetic field, lacking targeted localization capability. Ultimately, the material remained randomly or drifted with the blood flow, failing to accumulate in the target brain region. Effective targeted delivery behavior was not observed on MRI.

[0059] Comparative Example 3: This comparative example provides a method for preparing a membrane material, which differs from Example 1 in that: in step S2, no chitosan-hyaluronic acid composite coating is applied, and the surface of the base membrane remains exposed.

[0060] The specific operation is as follows: after preparing the polycaprolactone / gelatin base film according to step S1 of Example 1, proceed directly to step S3 for magnetic borosilicate loading, so that the magnetic borosilicates are directly attached to the exposed polymer substrate.

[0061] The obtained material was used for in vivo testing; the principle and schematic diagram are as follows. Figure 3As shown, the results indicated that after the membrane was delivered to the brain surface via blood vessels, it could initially adhere briefly, but significant displacement or detachment occurred within 1–2 days post-surgery. Tissue sections showed that the expression level of the local inflammatory factor IL-6 increased by 35% and the expression level of TNF-α increased by 38% compared to Example 1. The interfacial shear strength between the membrane and brain tissue was only 0.8–1.0 N / cm² (2.5–2.8 N / cm² in Example 1), and the displacement rate reached 60% within 3 days post-surgery. The signal fluctuation amplitude measured by the microelectrode was ±20–25 μV, and the signal-to-noise ratio was only 18–20 dB, indicating significantly weaker stability than the material in Example 1.

[0062] Compared with existing technologies, the polymer membrane material of the vascular implantable brain-computer interface based on magnetosome targeted delivery of the present invention, through implantation in the thigh blood vessel combined with magnetosome targeted delivery, can completely avoid craniotomy, significantly reducing the risks of infection and nerve damage. The recovery period after traditional craniotomy is about 30 days, while the recovery period after the present invention is only 12-14 days, shortening the recovery period by 63%-67%. At the same time, the infection rate is reduced from 8%-10% of traditional craniotomy to 0.5%-1%. Utilizing the natural magnetic response characteristics of magnetosomes and external magnetic field guidance, the implantation targeting error can be controlled within 0.3-0.5 mm, while the targeting error of existing non-invasive brain-computer interfaces (such as EEG) is 5-10 mm. The material achieves a 10-25 times improvement in positioning accuracy. The chitosan-hyaluronic acid composite layer reduces tissue rejection by 92%-94%. Seven days post-surgery, the expression levels of inflammatory factors IL-6 and TNF-α in brain tissue are reduced by 92% and 94% respectively compared to traditional silicon-based implant materials. Brain cell adhesion reaches 85-90% after 72 hours (compared to 58%-62% for traditional materials). The flexible polymer membrane ensures full adhesion to the brain surface, while the incorporated graphene nanosheets reduce the membrane surface resistance to 85-95Ω, compared to 520-580Ω in the control group without graphene. This improves conductivity by 5.5-6.8 times, meeting signal transmission requirements and allowing for flexible fabrication of microelectrode patterns through writing. Furthermore, the magnetic boson functions as a "targeting carrier, signal sensor, and information storage unit," assisting in signal acquisition and data storage without introducing additional modules, thus simplifying the system structure and improving integration.

[0063] The above embodiments and comparative examples further demonstrate that the present invention, by constructing a flexible substrate using a blend of polycaprolactone and gelatin and dispersing graphene nanosheets, provides the necessary mechanical support and conductive pathways for the material; the construction of a chitosan-hyaluronic acid biocompatible coating on its surface effectively improves interfacial bioactivity and stability, while its surface charge characteristics provide conditions for subsequent functionalization and composite; the polymeric membrane material of the present invention utilizes aminated natural magnetic bodies, which are precisely loaded onto the surface of the above coating through electrostatic interaction, enabling the material to obtain excellent magnetic field responsiveness; in practical applications… This invention enables minimally invasive delivery via vascular intervention and utilizes an external magnetic field to guide the magnetosome, driving the entire implant to precisely anchor in the target brain region within the body. Furthermore, the components of this invention are not simply superimposed but produce a significant synergistic enhancement effect. The magnetosome not only serves as a target-driven navigation unit, but its inherent physicochemical properties also help regulate the local microenvironment, synergistically optimizing the quality of electrical signal acquisition with graphene. The biocompatible coating ensures long-term interface stability while maintaining a firm bond with the magnetosome and basement membrane, guaranteeing the structural integrity of the multifunctional integrated navigation, sensing, and attachment system. The results of Comparative Examples 1-3 further demonstrate that the absence of any component—graphene, magnetosome, or biocompatible coating—leads to serious defects in the material's conductivity, targeting ability, or biointegration stability, failing to achieve the overall technical effect of this invention. This invention, through the multi-level design and functional coupling of the material system, successfully achieves brain-computer interface implantation that is non-invasive, precisely targeted, biocompatible, and provides reliable signal transmission, offering a novel integrated solution to overcome the bottlenecks of existing technologies.

[0064] In the description of this invention, the references to "one embodiment," "some embodiments," "in this embodiment," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0065] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A vascular implantable brain-computer interface polymeric membrane material based on magnetosome-targeted delivery, characterized in that, The application relates to a blood vessel implantable brain-computer interface targeted delivery system, which comprises an implant, a packaging carrier and a magnetic field generating device. The flexible high polymer base film comprises a blend of polycaprolactone and gelatin and dispersed graphene nanosheets therein. The biocompatible coating layer is formed on at least one surface of the flexible high polymer base film and comprises a complex of chitosan and hyaluronic acid. The amino-modified magnetosomes are loaded on the surface of the biocompatible coating layer through electrostatic interaction. In the flexible high polymer base film, the mass ratio of polycaprolactone to gelatin is 6:4, and the graphene nanosheet is added in an amount of 0.4-0.6 wt% of the total mass of polycaprolactone and gelatin.

2. The polymeric membrane material of claim 1, wherein In the biocompatible coating layer, the mass ratio of chitosan to hyaluronic acid is 1:

1.

3. The polymeric membrane material according to claim 1 or 2, characterized in that, The particle size of the magnetosomes is 20-50 nm, and the loading amount is 2-3 wt% of the total mass of the polymer film material.

4. The polymeric membrane material of claim 1, wherein The thickness of the flexible high polymer base film is 5-10 microns, and the thickness of the biocompatible coating layer is 50-150 nm.

5. The polymeric membrane material of claim 1, wherein The application further discloses a preparation method of the blood vessel implantable brain-computer interface targeted delivery system.

6. A method for producing the polymeric film material according to any one of claims 1 to 5, characterized in that S1: preparing a flexible high polymer base film: polycaprolactone and gelatin are blended and dissolved in a solvent, graphene nanosheets are added, and after dispersion, a solution casting method is adopted to form a film and dry, so as to obtain a flexible high polymer base film; S2: constructing a biocompatible coating layer: a complex solution of chitosan and hyaluronic acid is coated on the surface of the flexible high polymer base film, and after drying, a biocompatible coating layer is formed; S3: loading magnetosomes: after the magnetosomes are modified by amino groups, the magnetosomes are compounded with the biocompatible coating layer treated in the step S2, so that the magnetosomes are loaded on the surface of the biocompatible coating layer. In the step S1, the solvent is a mixed solvent of dichloromethane and ethanol, and the volume ratio of dichloromethane to ethanol is (3+ / -0.5):

1.

7. The method of claim 6, wherein the polymer film material is prepared by a process comprising: In the step S2, the coating method is to coat the complex solution by using a spraying method, and the spraying pressure is 0.2+ / -0.05 MPa.

8. The method of claim 6, wherein the polymer film material is prepared by a process comprising: In the step S3, the amino-modification of the magnetosomes comprises the following steps: extracting magnetosomes from magnetotactic bacteria, obtaining a suspension after dispersion; adding 3-aminopropyltriethoxysilane with a final concentration of 0.05-0.15 wt% to the suspension to modify the surface of the magnetosomes, so that the magnetosomes carry amino groups on the surface.

9. The method for preparing the polymer membrane material according to claim 6, characterized in that, The blood vessel implantable brain-computer interface targeted delivery system comprises an implant, a packaging carrier and a magnetic field generating device, the implant is made of the high polymer film material, the packaging carrier is used for packaging the implant and can be degraded in vivo, and the magnetic field generating device is used for applying a guiding magnetic field in vitro; the system delivers the implant through a blood vessel intervention mode, and controls the implant to be positioned in a target region of the brain through the guiding magnetic field.

10. Use of the polymeric film material of any one of claims 1-5 in a vascular implantable brain-machine interface targeted delivery system. ​

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