A semi-invasive, antimicrobial, electro-stimulating rehabilitation hydrogel flexible electrode

Abstract

The application belongs to the technical field of flexible conductive materials for medical rehabilitation devices, and discloses a semi-invasive antibacterial electric stimulation rehabilitation hydrogel flexible electrode, which is prepared from a PVA-CMC-Na-HA-calcium propionate four-element synergistic system hydrogel and is surface-modified by sodium L-lactate; a three-dimensional network is constructed through one-pot physical crosslinking, polyvinyl alcohol and sodium carboxymethyl cellulose form a hydrogen bond interpenetrating network, hydroxyapatite is used as a rigid filler for reinforcement, and calcium propionate simultaneously acts as an ionic crosslinking agent and an electrolyte; sodium L-lactate forms a hydrophobic-hydrophilic gradient layer on the surface of the hydrogel in situ through an esterification reaction. The application solves the problems of mechanical mismatch, high impedance, poor biocompatibility of traditional metal electrodes, and the difficulty of simultaneously considering the strength, toughness and lubricity of existing hydrogels, realizes the mechanical properties of strong outside and tough inside of the electrode, has excellent biocompatibility and low impedance electric stimulation performance, does not need external conductive paste, and improves the comfort and safety of pelvic floor muscle rehabilitation treatment.

Description

Technical Field

[0001] This invention belongs to the field of flexible conductive materials technology for medical rehabilitation devices, specifically relating to a semi-invasive antibacterial electrical stimulation rehabilitation hydrogel flexible electrode. Background Technology

[0002] Pelvic floor muscle dysfunction is a common condition among postpartum women and middle-aged and elderly individuals, with a global prevalence of approximately 30%-50%. It primarily manifests as stress urinary incontinence, pelvic organ prolapse, and sexual dysfunction, severely impacting patients' quality of life. Electrical stimulation therapy is currently the core non-surgical treatment for pelvic floor muscle rehabilitation. It delivers specific electrical currents to the pelvic floor muscles via electrodes, inducing passive muscle contraction, thereby strengthening muscles and improving neuromodulation.

[0003] Traditional electrical stimulation electrodes are mostly made of metals such as stainless steel and silver / silver chloride, which have three major limitations: First, the mechanical properties are mismatched. Metal electrodes are rigid and have a significantly different modulus from soft tissues such as the pelvic floor mucosa, which can easily cause mechanical damage and a strong foreign body sensation when in contact or implanted. Second, the interfacial impedance is high, and the charge transfer efficiency between the metal and the tissue is low, requiring a higher voltage to drive the electrode, which can easily cause stinging pain or even skin burns in patients. Third, the biocompatibility is insufficient. Long-term contact may release metal ions, inducing local inflammation or allergic reactions.

[0004] Hydrogels, due to their high water content (>70%), tissue-like softness, and ionic conductivity, are considered ideal flexible electrode substrate materials. Existing hydrogel electrodes are mainly based on polyvinyl alcohol (PVA) systems. For example, patent CN11447933A discloses a PVA / hydroxyapatite composite hydrogel that achieves physical cross-linking through freeze-thaw cycles, exhibiting both tensile strength and osteoinductive properties; patent CN112625332A discloses a CMC-PVA conductive hydrogel that enhances its network structure through hydrogen bonding. However, the above-mentioned existing technologies still have the following drawbacks: Mechanical limitations: The PVA crystal network formed solely by freeze-thaw cycles is prone to dissociation in a wet state, and the hydrogel is prone to permanent deformation when repeatedly stretched or compressed, which cannot meet the high-frequency deformation requirements in pelvic floor muscle rehabilitation. Insufficient ionic conductivity: Due to the lack of in-situ electrolyte doping, the ion mobility is low, and external conductive paste is required for clinical use, which increases the complexity of operation and the risk of cross-infection. Surface performance defects: The hydrogel surface has not been modified, resulting in poor adhesion and resistance to protein adsorption. Long-term contact with human tissue can easily lead to bacterial growth and biofilm formation, reducing electrode lifespan and safety. Summary of the Invention

[0005] To address the aforementioned technical problems, this invention provides a semi-invasive antibacterial electrostimulation rehabilitation hydrogel flexible electrode, which offers a pelvic floor muscle rehabilitation hydrogel flexible electrode with high mechanical strength, good biocompatibility, and excellent conductivity. At the same time, it simplifies the preparation process and resolves the contradiction of traditional hydrogels being unable to simultaneously achieve "strength-toughness-lubricity".

[0006] The present invention adopts the following technical solution: A semi-invasive antibacterial electrostimulation rehabilitation hydrogel flexible electrode is prepared by surface modification of a PVA-CMC-Na-HA-calcium propionate quaternary synergistic hydrogel with L-lactic acid. The quaternary synergistic hydrogel is physically cross-linked in a one-pot method to construct a three-dimensional network structure, wherein polyvinyl alcohol and sodium carboxymethyl cellulose form a hydrogen-bonded interpenetrating network, hydroxyapatite is used as a rigid filler for reinforcement, and calcium propionate serves as both an ionic cross-linking agent and an electrolyte. The L-lactic acid forms a hydrophobic-hydrophilic gradient layer in situ on the surface of the hydrogel through an esterification reaction.

[0007] Furthermore, the mass fractions of each component are as follows: 8-12 parts polyvinyl alcohol, 2-4 parts sodium carboxymethyl cellulose, 1-3 parts hydroxyapatite, 0.5-2 parts calcium propionate, and 80-90 parts deionized water.

[0008] Furthermore, the hydrogel has a water content >85%, a modulus <10kPa, an elongation at break >500%, and an electrical conductivity of 0.1-1S / m.

[0009] This invention also discloses a method for preparing the above-mentioned hydrogel flexible electrode, comprising the following steps: (1) Add polyvinyl alcohol, sodium carboxymethyl cellulose and hydroxyapatite to deionized water according to the ratio, heat to 95-105℃ and stir to dissolve to obtain a uniform mixture; (2) Add calcium propionate to the mixture and continue stirring for 5-15 minutes until completely dissolved to obtain the precursor solution; (3) Pour the precursor liquid into the mold and freeze it at -18 to -22°C for 10 to 14 hours to obtain unmodified hydrogel; (4) Place the unmodified hydrogel in a 5-15wt% L-lactic acid sodium solution and soak it at 40-50℃ for 20-40 minutes to modify its surface. (5) After removal, rinse the surface with deionized water to obtain the hydrogel flexible electrode.

[0010] Furthermore, in step (1), the heating temperature is 100°C and the stirring time is 10 minutes.

[0011] Furthermore, in step (3), the freezing temperature is -20°C and the freezing time is 12 hours.

[0012] Furthermore, in step (4), the concentration of the L-lactic acid sodium solution is 10wt%, the modification temperature is 45℃, and the modification time is 30 minutes.

[0013] Compared with the prior art, the beneficial effects of the present invention are: Mechanical performance has been greatly improved, achieving a synergistic effect of "external strength and internal toughness". The hydrophobic-hydrophilic gradient layer constructed by surface modification with L-lactic acid improves the wear resistance of the hydrogel surface by more than 40%, with an overall elongation at break of >500%, exhibiting excellent fatigue resistance and withstanding tens of thousands of repeated frictions and deformations during pelvic floor muscle rehabilitation. Simultaneously, it maintains a high water content of >85%, preserving tissue-like softness and avoiding the brittleness problem caused by traditional integral cross-linking. The synergistic reinforcing effect of the quaternary components allows for achieving mechanical requirements with only a single freeze-forming process, eliminating the need for multiple freeze-thaw cycles and significantly simplifying the preparation process.

[0014] All components are biosafe, and the biomimetic interface provides a non-invasive feel. All raw materials (PVA, CMC-Na, HA, calcium propionate, and L-sodium lactate) are food-grade or medical-grade biocompatible materials, non-toxic and metabolizable, with no risk of metal ion release, cell survival rate >95%, and no inflammatory or allergic reactions with long-term contact. The hydrogel modulus is <10kPa, which is highly matched to the modulus of the pelvic floor mucosa, resulting in no foreign body sensation during application and improving patient comfort.

[0015] Excellent electrical stimulation performance, safe and convenient to use In-situ doping with calcium propionate forms a continuous ionic conductive network, resulting in a hydrogel conductivity of 0.1-1 S / m, achieving stable charge transfer without the need for external conductive paste. Compared to metal electrodes, the hydrogel exhibits over 70% lower interfacial impedance with human tissue and a 3-fold increase in charge transfer efficiency. It can induce effective pelvic floor muscle contraction even at low voltages (<5V), completely avoiding the risks of stinging and burning. Furthermore, the L-lactic acid modification significantly enhances the hydrogel's anti-protein adsorption and antibacterial properties, allowing for 3-5 reuses and reducing operating costs. Attached Figure Description

[0016] Figure 1 This is the microstructure of the electrode under a scanning electron microscope according to the present invention; Figure 2 This invention relates to the inhibitory effect of the hydrogel on Staphylococcus aureus and Escherichia coli; Figure 3 This is a diagram of the hydrogel cytotoxicity experiment of the present invention; Figure 4 The results of H&E staining of mouse dermal tissue using hydrogel according to this invention; Figure 5 This is the mechanical properties-stress-strain curve of the hydrogel of this invention. Detailed Implementation

[0017] Example 1 This embodiment provides a semi-invasive antibacterial electrical stimulation rehabilitation hydrogel flexible electrode, the preparation method of which is as follows: Weigh 10g PVA, 3g CMC-Na, and 2g HA and add them to 84g deionized water. Place the mixture in an oil bath and heat it to 100℃. Stir magnetically for 10 minutes until completely dissolved to obtain a homogeneous mixture. Add 1g of calcium propionate to the mixture and continue stirring for 10 minutes until completely dissolved to obtain a transparent precursor solution; The precursor solution was poured into a special mold for pelvic floor muscle electrodes, transferred to a -20°C freezer and frozen for 12 hours to form the gel. The unmodified PCCH hydrogel was then demolded. Prepare a 10wt% sodium L-lactic acid aqueous solution, preheat it to 45℃, and immerse the unmodified PCCH hydrogel in the solution for 30 minutes to perform surface modification. Remove the hydrogel and rinse the surface three times with deionized water to remove residual L-lactic acid solution, thus obtaining the S-PCCH hydrogel flexible electrode.

[0018] Performance testing The performance of the S-PCCH hydrogel flexible electrode prepared in this embodiment was tested, and the results are as follows: Mechanical properties: Elongation at break is 580%, tensile strength is 0.8 MPa, surface abrasion resistance is improved by 45% compared with unmodified hydrogel, and mechanical property retention rate is >90% after 1000 cycles of tensile testing; Electrical conductivity: 0.5 S / m at room temperature; interfacial impedance with the pig pelvic floor mucosa: 210 Ω·cm. 2 It is only 28% of that of stainless steel electrodes; Biocompatibility: L929 cells were used for cytotoxicity testing. After 24 hours of culture, the cell viability was 96.2%, and there was no obvious hemolysis. Electrical stimulation effect: At 4.5V voltage and 20Hz frequency, it can effectively induce contraction of rabbit pelvic floor muscles, and the contraction force is comparable to the stimulation effect of stainless steel electrodes at 10V voltage.

[0019] Example 2 The only difference between this embodiment and Example 1 is that the mass fractions of each component are: 8 parts PVA, 2 parts CMC-Na, 1 part HA, 0.5 parts calcium propionate, and 88.5 parts deionized water; the concentration of L-sodium lactate solution is 5wt%, the modification temperature is 40℃, and the modification time is 20 minutes.

[0020] The prepared hydrogel flexible electrode had a breakage elongation of 520%, an electrical conductivity of 0.12 S / m, and a cell viability of 95.8%.

[0021] Example 3 The only difference between this embodiment and Example 1 is that the mass fractions of each component are: 12 parts PVA, 4 parts CMC-Na, 3 parts HA, 2 parts calcium propionate, and 79 parts deionized water; the concentration of L-lactic acid sodium solution is 15wt%, the modification temperature is 50℃, and the modification time is 40 minutes.

[0022] The prepared hydrogel flexible electrode had a breakage elongation of 550%, an electrical conductivity of 0.95 S / m, and a cell viability of 95.5%.

[0023] Although embodiments of the present invention have been shown and described, those skilled in the art will understand that various changes, modifications, substitutions and variations can be made to the above embodiments without departing from the principles and spirit of the present invention, the scope of which is defined by the claims and their equivalents.

Claims

1. A semi-invasive, antimicrobial, electro-stimulating, rehabilitative hydrogel flexible electrode, characterized in that, The hydrogel was prepared by surface modification with L-lactic acid sodium by a quaternary synergistic system of PVA-CMC-Na-HA-calcium propionate. The quaternary synergistic system hydrogel was constructed into a three-dimensional network structure by physical cross-linking in a one-pot method. Polyvinyl alcohol and sodium carboxymethyl cellulose formed a hydrogen-bonded interpenetrating network, hydroxyapatite was used as a rigid filler for reinforcement, and calcium propionate served as both an ionic cross-linking agent and an electrolyte. The L-lactic acid sodium formed a hydrophobic-hydrophilic gradient layer in situ on the surface of the hydrogel through an esterification reaction.

2. The hydrogel flexible electrode according to claim 1, characterized in that, The mass fractions of each component are as follows: 8-12 parts polyvinyl alcohol, 2-4 parts sodium carboxymethyl cellulose, 1-3 parts hydroxyapatite, 0.5-2 parts calcium propionate, and 80-90 parts deionized water.

3. The hydrogel flexible electrode according to claim 1, characterized in that, The hydrogel has a water content >85%, a modulus <10kPa, an elongation at break >500%, and an electrical conductivity of 0.1-1S / m.

4. The method for preparing the hydrogel flexible electrode according to claim 1, characterized in that, Includes the following steps: (1) Add polyvinyl alcohol, sodium carboxymethyl cellulose and hydroxyapatite to deionized water according to the ratio, heat to 95-105℃ and stir to dissolve to obtain a uniform mixture; (2) Add calcium propionate to the mixture and continue stirring for 5-15 minutes until completely dissolved to obtain the precursor solution; (3) Pour the precursor liquid into the mold and freeze it at -18 to -22°C for 10 to 14 hours to obtain unmodified hydrogel; (4) Place the unmodified hydrogel in a 5-15wt% L-lactic acid sodium solution and soak it at 40-50℃ for 20-40 minutes to modify its surface. (5) After removal, rinse the surface with deionized water to obtain the hydrogel flexible electrode.

5. The preparation method according to claim 4, characterized in that, In step (1), the heating temperature is 100℃ and the stirring time is 10 minutes.

6. The preparation method according to claim 4, characterized in that, In step (3), the freezing temperature is -20℃ and the freezing time is 12 hours.

7. The preparation method according to claim 4, characterized in that, In step (4), the concentration of L-lactic acid sodium solution is 10wt%, the modification temperature is 45℃, and the modification time is 30 minutes.

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