MXene (at) SA fiber electrode capable of reducing neural immune response as well as preparation method and application of MXene (at) SA fiber electrode
The MXene@SA fiber electrode, prepared by wet spinning, solves the problems of neuroinflammatory response and tissue mismatch during the implantation of MXene-based electrodes, realizes the directed differentiation of neural stem cells and the orderly arrangement of electrodes, and enhances the integration effect of neural electrodes.
Patent Information
- Application Number
- CN202511268355.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-09-05
- Publication Date
- 2025-11-18
AI Technical Summary
Existing MXene-based electrodes are prone to causing neuroinflammatory reactions and tissue-electrode mismatch during implantation, and it is difficult to regulate the differentiation of neural stem cells into neurons and achieve orderly arrangement.
MXene@SA fiber electrodes were prepared using a wet spinning process. MXene spinning slurry and sodium alginate solution were extruded into ZnCl2 coagulation liquid through a coaxial needle device to form an ordered pleated structure of MXene@SA composite fiber electrode. The flexibility of MXene and the biocompatibility of sodium alginate were used to reduce the neuroimmune response.
It effectively reduced neuroinflammatory responses, enhanced the differentiation and integration of nerve cells, improved the matching between electrodes and tissues, promoted the directional attachment and differentiation of neural stem cells, and improved the integration effect of neural electrodes.
Smart Images
Figure CN120959753A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of medical applications of MXene, and more particularly to an MXene@SA fiber electrode that can reduce neuroimmune responses, its preparation method, and its applications. Background Technology
[0002] Brain-computer interfaces (BCIs) facilitate bidirectional communication between the brain and external software and hardware, playing a crucial role in the treatment of neurological disorders such as epilepsy, depression, and Parkinson's disease. Traditional invasive electrodes, when implanted in the target area, often cause damage to healthy tissue due to the mechanical mismatch between the electrode material (~5 GPa) and neural tissue (10–150 kPa), inducing immune cascade reactions and leading to glial scarring around the electrode, thereby reducing the signal-to-noise ratio (SNR) of electrophysiological recordings. Therefore, effective strategies to reduce tissue damage caused by electrode implantation are urgently needed.
[0003] Among emerging materials, MXene stands out due to its "semi-flexible" mechanical strength, excellent hydrophilicity, and ordered wrinkled surface structure. However, in recent years, research on MXene-based electrodes has mainly focused on improving their mechanical and electrical properties; moreover, most traditional processing methods still produce thin-film MXene, which faces challenges such as brittleness and limited structural tunability, failing to meet the requirements for implantable electrodes.
[0004] There is currently no research on how MXene@SA fiber electrodes can effectively reduce neuroinflammatory responses during implantation, and even less attention has been paid to the tissue-electrode mismatch problem they cause, especially in terms of their ability to regulate neural stem cell differentiation into neurons and orderly arrangement along folds. Summary of the Invention
[0005] The purpose of this invention is to address the shortcomings of existing technologies by providing a novel MXene@SA fiber electrode with an ordered folded topology, which enhances cell behavior regulation and improves the integration of neural electrodes.
[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows:
[0007] The first aspect is to provide a method for preparing an MXene@SA fiber electrode that can reduce neuroimmune responses, including the following steps:
[0008] Step 1: The monolayer MXene dispersion is concentrated into an MXene spinning slurry with a concentration of 90-110 mg / mL by high-speed centrifugation;
[0009] Step 2: MXene spinning slurry and sodium alginate solution (SA) are injected into the outer and inner needles of the coaxial needle device of the wet spinning machine, respectively, and extruded. They are then passed through a 90° bent needle and a polytetrafluoroethylene tube into the rotating coagulation bath to form MXene@SA fibers.
[0010] The inner needle is used to extrude sodium alginate solution at a rate of 50-70 mL / h, and the outer needle is used to extrude MXene spinning slurry at a rate of 4-6 mL / h; the coagulation bath is a ZnCl2 solution.
[0011] Step 3: The MXene@SA fibers are washed with ethanol / water solution, collected, and dried to obtain MXene@SA fiber electrodes.
[0012] Furthermore, in step two, the inner needle of the coaxial needle device is a 22G needle, and the outer needle is a 17G needle; the inner diameter of the polytetrafluoroethylene tube is 0.8–1 mm.
[0013] Furthermore, in step two, the inner needle is used to extrude sodium alginate solution at an extrusion rate of 60 mL / h, and the outer needle is used to extrude MXene spinning slurry at an extrusion rate of 5 mL / h.
[0014] Furthermore, in step two, the concentration of the ZnCl2 solution is 1–10 wt%; and the concentration of the sodium alginate solution is 30–50 mg / mL.
[0015] Furthermore, in step three, the volume ratio of ethanol to water in the ethanol / water solution is 1:(2-5).
[0016] Furthermore, in step three, the MXene@SA fiber collection rate is 100-400 μL / min.
[0017] The second aspect is to provide an MXene@SA fiber electrode prepared by the above preparation method that can reduce neuroimmune response.
[0018] The third aspect is to provide the application of the aforementioned MXene@SA fiber electrodes, which can reduce neuroimmune responses, in the fabrication of neural interface devices for treating nervous system diseases.
[0019] Furthermore, the neurological disorders include epilepsy, depression, Parkinson's disease, and spinal cord injury.
[0020] The present invention adopts the above technical solution and has the following technical effects compared with the prior art:
[0021] This invention employs a wet spinning process, in which MXene spinning slurry and sodium alginate solution are extruded into a ZnCl2 coagulation solution using a coaxial needle device. During the spinning process, the MXene liquid crystals align under shear force to form an interlocking structure, while the Zn in the coagulation solution... 2+ Sodium alginate enters the fiber through a double diffusion process, inducing ionic cross-linking and gelation to form the final MXene@SA composite fiber electrode structure.
[0022] The MXene@SA fiber of the present invention uses sodium alginate (SA) as a support structure. Sodium alginate itself has good biocompatibility and low immunogenicity. Combined with MXene, the MXene@SA fiber electrode can effectively reduce the neuroimmune response triggered during implantation and avoid the problem of tissue-electrode mismatch.
[0023] Using the preparation method of this invention, the ordered axial wrinkled structure formed by the shrinkage of MXene@SA fibers during the drying process (utilizing the flexibility of MXene) provides a favorable microenvironment for the directional attachment and differentiation of nerve cells, significantly influencing and promoting the behavior of neural stem cells (such as differentiation into neurons), thereby enhancing neural integration at the implantation site. Furthermore, the hydrophilicity of the MXene@SA fiber electrode surface (thanks to the hydrophilic functional groups on the MXene surface and the hydrophilicity of SA) facilitates protein adsorption, regulates bond strength and conformation, forms a more suitable interface for cell adhesion and growth, further reduces neuroimmune responses, and significantly enhances and maintains long-term cell-electrode interactions (chronic neural interface function).
[0024] The MXene@SA fiber electrode of the present invention, when used as a brain implant electrode, can effectively reduce the neuroinflammatory response generated during implantation and avoid the problem of tissue-electrode mismatch, thereby enhancing cell behavior regulation and improving the integration of neural electrodes. Attached Figure Description
[0025] Figure 1 A schematic diagram of the fabrication of the MXene@SA fiber electrode; a schematic diagram of the neuroinflammatory response generated after the MXene@SA fiber electrode and metal electrode are inserted into the surface of brain tissue.
[0026] Figure 2 The stress-strain test curve of the MXene@SA fiber electrode that can reduce neuroimmune response prepared in Example 1 of the present invention is shown.
[0027] Figure 3 This is a hydrophilicity test diagram of the MXene@SA fiber electrode prepared in Example 1 of the present invention, which can reduce neuroimmune response.
[0028] Figure 4The conductivity test curve of the MXene@SA fiber electrode that can reduce neuroimmune response prepared in Example 1 of the present invention is shown.
[0029] Figure 5 This is an identification diagram of neural stem cells in Embodiment 4 of the present invention (in the figure, Nestin is green, Ki67 is red, and DAPI is blue).
[0030] Figure 6 The images show the fluorescence of neural stem cells after 3 days of proliferation and the statistical chart of cell survival rate in Example 4 of this invention (live cells are green and dead cells are red).
[0031] Figure 7 The images show the cytoskeleton fluorescence and cell deflection angle statistics of neural stem cells after 3 days of proliferation in Example 4 of this invention (in the figures, F-actin is green and DAPI is blue).
[0032] Figure 8 The images show fluorescence images of neurons (Tuj-1) and astrocytes (GFAP) 7 days after differentiation of neural stem cells in Example 4 of this invention, as well as a statistical graph of the neuronal differentiation ratio (in the figure, GFAP is green, Tuj-1 is red, and DAPI is blue).
[0033] Figure 9 These are fluorescence images and fluorescence intensity statistics of astrocytes (GFAP) after 1 day, 2 weeks, and 8 weeks following implantation of the MXene@SA fiber electrode in the brain region in Example 5 of this invention. Detailed Implementation
[0034] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but this is not intended to limit the invention. It should be noted that, unless otherwise specified, the embodiments and features described in the embodiments of the present invention can be combined with each other.
[0035] Example 1
[0036] The reagents used in this embodiment are as follows:
[0037] Ti3AlC2 MAX powder, 98% purity, 400 mesh, purchased from Jilin Eleven Technology Co., Ltd.
[0038] Hydrochloric acid, mass fraction 36-38%, purchased from Sinopharm Chemical Reagent Co., Ltd.
[0039] Anhydrous ethanol, 99.7% purity, purchased from Sinopharm Chemical Reagent Co., Ltd.
[0040] Lithium fluoride, 98% purity, purchased from Alfa Aesar;
[0041] Zinc chloride, 99.9% purity, purchased from Aladdin Biochemical Technology Co., Ltd.
[0042] Deionized water was prepared using the Millipore water purification system (18.2 MΩ·cm).
[0043] This embodiment provides a method for preparing an MXene@SA fiber electrode that can reduce neuroimmune responses, specifically including the following steps:
[0044] Step 1: Take the monolayer MXene dispersion and concentrate it into an MXene spinning slurry with a concentration of 100 mg / mL by high-speed centrifugation (9000 rpm, 30 min);
[0045] Step 2: The above-mentioned MXene spinning slurry and sodium alginate solution (40mg / mL) are injected into the outer needle (17G) and inner needle (22G) of the coaxial needle device of the wet spinning machine, respectively. The slurry is extruded and passed through a 90° bent needle and a polytetrafluoroethylene tube (inner diameter of 0.8-1mm) into a rotating coagulation bath. The fibers are soaked for 2 hours to form MXene@SA fibers.
[0046] The inner needle is used to extrude sodium alginate solution at a rate of 60 mL / h, the outer needle is used to extrude MXene spinning slurry at a rate of 5 mL / h, and the coagulation bath is a 10 wt% ZnCl2 solution.
[0047] Step 3: Rinse twice with an ethanol / water solution with a volume ratio of 1:2, then collect the MXene@SA fibers on a square frame at a collection rate of 200 μL / min and allow them to air dry to obtain the MXene@SA fiber electrode.
[0048] The preparation method of the above-mentioned monolayer MXene dispersion is as follows:
[0049] Lithium fluoride, hydrochloric acid solution, and Ti3AlC2 MAX powder were mixed and etched to obtain a mixed solution. The mixed solution was centrifuged and washed until neutral to obtain a neutral solution. The neutral solution was then sonicated and centrifuged to obtain a monolayer MXene dispersion with a concentration of 5-15 mg / mL.
[0050] Preferably, the ratio of LiF to HCl is (3.2g):(6-12mol / L), which allows Li ions to penetrate into the etched layers.
[0051] Example 2
[0052] This embodiment provides a method for preparing an MXene@SA fiber electrode that can reduce neuroimmune responses, specifically including the following steps:
[0053] Step 1: Take the monolayer MXene dispersion (prepared in Example 1) and concentrate it into an MXene spinning slurry with a concentration of 110 mg / mL by high-speed centrifugation (9000 rpm, 30 min);
[0054] Step 2: The above-mentioned MXene spinning slurry and sodium alginate solution (50 mg / mL) are injected into the outer needle (17G) and inner needle (22G) of the coaxial needle device of the wet spinning machine, respectively. The slurry is then extruded and passed through a 90° bent needle and a polytetrafluoroethylene tube (with an inner diameter of 0.8-1 mm) into a rotating coagulation bath. The fibers are soaked for 2.5 hours to form MXene@SA fibers.
[0055] The inner needle is used to extrude sodium alginate solution at a rate of 70 mL / h, the outer needle is used to extrude MXene spinning slurry at a rate of 6 mL / h, and the coagulation bath is an 8 wt% ZnCl2 solution.
[0056] Step 3: Rinse twice with an ethanol / water solution with a volume ratio of 1:5, then collect the MXene@SA fibers on a square frame at a collection rate of 400 μL / min and allow them to air dry to obtain the MXene@SA fiber electrode.
[0057] Example 3
[0058] The MXene@SA fiber electrode prepared in Example 1 was characterized as follows:
[0059] (1) The tensile properties of the MXene@SA fiber electrode were evaluated using a universal testing machine equipped with a 100N load cell. The specific method is as follows: The MXene@SA fiber electrode was mounted on a rectangular frame with a length of 1cm, and the test was conducted at a strain rate of 1mm / min. The results are as follows: Figure 2 As shown, the modulus of the MXene@SA fiber electrode is 4.21 ± 0.22 GPa.
[0060] (2) The contact angle of the MXene@SA fiber electrode was tested using the seated drop method on a contact angle tester. The results are as follows: Figure 3 As shown, the contact angle of the MXene@SA fiber electrode is 60.1°.
[0061] (3) The conductivity of the MXene@SA fiber electrode was tested using a three-electrode system on an electrochemical workstation. The results are as follows: Figure 4 As shown, the conductivity of the MXene@SA fiber electrode is 130.1 ± 1.2 S / cm.
[0062] Example 4 Cell Experiment
[0063] (1) Isolation and culture of neural stem cells (NSCs)
[0064] Neurospheres (NSCs) were isolated from the cerebral cortex of C57BL / 6J mice at 13.5 days of gestation and immersed in DMEM medium containing 20 U / mL LDNase I and 20 U / mL papain. The tissues were mechanically separated using a pipette, filtered through a 40 μm cell filter, resuspended, and the supernatant was discarded. The cells were then cultured in DMEM medium containing 2% B27, 1% N2, 20 ng / mL epidermal growth factor (EGF), 20 ng / mL basic fibroblast growth factor (bFGF), and 1% penicillin-streptomycin at 37°C in a 5% CO2 incubator. After three passages, the neurospheres were purified, and single NSCs from the third passage were seeded onto MXene@SA fiber electrodes (prepared in Example 1, hereinafter the same) for proliferation and differentiation experiments.
[0065] The results are as follows Figure 5 As shown, Nestin and Ki67 staining of cells that have proliferated for 3 days is positive. It can be seen that the neurospheres purified by 3 generations were seeded on MXene@SA fiber electrodes. After 3 days of culture, the individual NSCs maintained the characteristics of stem cells.
[0066] (2) Staining of live and dead cells
[0067] The separated NSCs were divided into 5×10 4 Cells were seeded at a density of 1 / mL on MXene@SA fiber electrodes pre-coated with matrix gel. After 3 days of proliferation culture, cell viability was assessed using the Calcein-AM / PI kit (Beyotime, China). 250 μL of Calcein-AM / PI working solution was added to each well, and the cells were incubated at 37°C in the dark for 30 min. The staining effect was observed under a fluorescence microscope.
[0068] The results are as follows Figure 6 As shown, the cells proliferated for 3 days were stained for live and dead cell characteristics. Statistical analysis showed that the cell viability of the MXene@SA fiber electrode (90.1±1.4%) was the same as that of the normal control (91.7±0.5%, P=0.676) and higher than that of the metal electrode group (29.7±3.7%, P<0.001). It can be seen that the MXene@SA fiber electrode has no significant effect on cell viability.
[0069] (3) Phalloidin staining
[0070] The separated NSCs were divided into 5×10 4Cells were seeded at a density of 1 / mL on MXene@SA fiber electrodes pre-coated with matrix gel. After 3 days of proliferation culture, the culture medium was aspirated, cells were washed twice with 1×PBS, fixed with 4% paraformaldehyde at room temperature for 10 min, permeabilized with 0.5% Ttiton X-100 for 5 min, blocked with 3% BSA for 30 min, and then incubated in a dark chamber for 1 h with phalloidin (a marker of phalloidin) directly coupled with 488 antibody. After washing with 1×PBS, cell nuclei were stained with DAPI, and the staining effect was observed under a fluorescence microscope.
[0071] The results are as follows Figure 7 As shown, cytoskeleton staining was performed on cells that had proliferated for 3 days. The staining results showed that NSCs were elongated along the long axis of the MXene@SA fiber electrode folds, with minimal growth in other directions, while cells on the metal electrode group and the normal control group spread in all directions. Statistical analysis showed that the deflection angle of NSCs cultured on the MXene@SA fiber electrode (13.45±3.43°) was smaller than that of the metal electrode group (44.79±15.31°, P=0.268) and the normal control group (51.65±8.31°, P=0.002), indicating that the MXene@SA fiber electrode exhibited a better ability to regulate the arrangement of NSCs.
[0072] (4) Neural stem cell differentiation experiment
[0073] The separated NSCs were divided into 1×10 5 Cells were seeded at a density of 1 / mL on MXene@SA fiber electrodes pre-coated with matrix gel. After 7 days of differentiation culture, the culture medium was aspirated, cells were washed twice with 1×PBS, fixed with 4% paraformaldehyde at room temperature for 10 min, permeabilized with 0.5% Ttiton X-100 for 5 min, stained with 3% BSA solution containing primary antibodies against Tuj-1 (an early neuronal marker) and GFAP (astrocytes), and incubated overnight at 4°C. The next day, cells were washed three times with 1×PBS and co-incubated with secondary antibodies 488 and 555 in a dark chamber for 1 h. After washing three times with 1×PBS, cell nuclei were stained with DAPI, and the staining effect was observed under a fluorescence microscope.
[0074] The results are as follows Figure 8 As shown, Tuj-1 and GFAP staining was performed on cells differentiated for 7 days. Statistical analysis showed that the proportion of Tuj-1 positive cells in the MXene@SA group (55.67±5.71%) was significantly higher than that in the normal control group (29.55±4.07%, P=0.014) and the metal electrode group (32.38±4.66%, P=0.033). This indicates that the MXene@SA fiber electrode promotes the differentiation of neural stem cells into neurons.
[0075] Example 5 Animal Experiment
[0076] (1) Implantation of MXene@SA fiber electrodes using stereotactic brain imaging techniques
[0077] Male C57BL / 6J mice aged 6-8 weeks (average weight 20-25g) were anesthetized preoperatively with 1% sodium pentobarbital (40mg / kg intraperitoneally) and fixed on a stereotactic table (RWD, China). A constant temperature blanket set to 37℃ was placed under the anesthetized mice to prevent hypothermia. Erythromycin ointment was applied to both eyes to protect them from damage. The hair on the top of the mouse's skull was removed and disinfected with povidone-iodine solution. After leveling, a 1cm longitudinal incision was made along the sagittal sinus with a scalpel, exposing a 6mm × 8mm portion of the skull. 1% hydrogen peroxide was applied to the skull surface to remove surface connective tissue until the suture line was clearly visible. A 1mm diameter hole was drilled using a cranial drill according to the following coordinates: posterior (AP) = -1.5mm; medial (ML) = -1.6mm; dorsoventral (DV) = +1.7mm. Then, a UV-sterilized MXene@SA fiber electrode was implanted, the incision was sutured with 4-0 sutures, and disinfected with povidone-iodine solution. Postoperatively, a large amount of antibiotic ointment was applied around the wound, and the mouse was placed on a 37°C heated blanket to monitor its vital signs until it was fully awake.
[0078] (2) Immunofluorescence staining of astrocytes (GFAP) in paraffin-embedded brain sections
[0079] Mouse brain tissue was harvested via whole-body perfusion at 1 day, 2 weeks, and 8 weeks post-MXene@SA fiber electrode implantation. Brain tissue was fixed overnight with 4% paraformaldehyde, followed by gradient dehydration with ethanol and paraffin embedding. After standard histological procedures including sectioning, antigen recovery, infiltration, and blocking, the tissue was stained with 3% BSA containing anti-GFAP primary antibody. After overnight incubation at 4°C, the tissue was washed three times with 1×PBS the next day and incubated with 488 secondary antibody in a dark chamber for 1 hour. After washing three times with 1×PBS, cell nuclei were stained with DAPI, and the staining effect was observed under a fluorescence microscope.
[0080] The results are as follows Figure 9As shown, both the MXene@SA fiber electrode group and the metal electrode group exhibited astrocyte activation at 1 day, 2 weeks, and 8 weeks post-implantation. Statistical analysis revealed that at 1 day post-implantation, the metal electrode group (4.36±0.39) induced a more significant increase in GFAP expression than the MXene@SA fiber electrode group (1.64±0.11, P<0.001), indicating a reduction in acute immune reactivity induced by MXene@SA. At 8 weeks post-implantation, the difference between the two groups became more pronounced (metal electrode group: 4.72±0.50, MXene@SA fiber electrode group: 1.31±0.26, P<0.001), demonstrating that the MXene@SA fiber electrode significantly reduced chronic neuroinflammation, leading to a more stable neural interface.
[0081] The above description is merely a preferred embodiment of the present invention and does not limit the implementation and protection scope of the present invention. Those skilled in the art should realize that any equivalent substitutions and obvious changes made based on the content and illustrations of the present invention should be included within the protection scope of the present invention.
Claims
1. A method for preparing an MXene@SA fiber electrode that can reduce neuroimmune responses, characterized in that, Includes the following steps: Step 1: The monolayer MXene dispersion is concentrated into an MXene spinning slurry with a concentration of 90-110 mg / mL by high-speed centrifugation; Step 2: MXene spinning slurry and sodium alginate solution are injected into the outer and inner needles of the coaxial needle device of the wet spinning machine, respectively, and extruded. They are then passed through a 90° bent needle and a polytetrafluoroethylene tube into the rotating coagulation bath to form MXene@SA fibers. The inner needle is used to extrude sodium alginate solution at a rate of 50-70 mL / h, and the outer needle is used to extrude MXene spinning slurry at a rate of 4-6 mL / h; the coagulation bath is a ZnCl2 solution. Step 3: The MXene@SA fibers are washed with ethanol / water solution, collected, and dried to obtain MXene@SA fiber electrodes.
2. The preparation method according to claim 1, characterized in that, In step two, the inner needle of the coaxial needle device is a 22G needle, and the outer needle is a 17G needle; the inner diameter of the polytetrafluoroethylene tube is 0.8-1mm.
3. The preparation method according to claim 1, characterized in that, In step two, the inner needle is used to extrude sodium alginate solution at an extrusion rate of 60 mL / h, and the outer needle is used to extrude MXene spinning slurry at an extrusion rate of 5 mL / h.
4. The preparation method according to claim 1, characterized in that, In step two, the concentration of the ZnCl2 solution is 1-10 wt%; the concentration of the sodium alginate solution is 30-50 mg / mL.
5. The preparation method according to claim 1, characterized in that, In step three, the volume ratio of ethanol to water in the ethanol / water solution is 1:(2-5).
6. The preparation method according to claim 1, characterized in that, In step three, the MXene@SA fiber collection rate is 100-400 μL / min.
7. An MXene@SA fiber electrode prepared by the method according to any one of claims 1-6, which can reduce neuroimmune response.
8. The use of the MXene@SA fiber electrode as described in claim 7, which reduces neuroimmune response, in the fabrication of a neural interface device for treating nervous system diseases.
9. The application according to claim 8, characterized in that, The neurological disorders include epilepsy, depression, Parkinson's disease, and spinal cord injury.