Injectable piezoelectric ionic hydrogel precursor solution and injectable piezoelectric ionic hydrogel and applications

Abstract

The application relates to the technical field of surgical biomaterials, and particularly discloses an injectable piezoelectric ionic hydrogel precursor liquid, an injectable piezoelectric ionic hydrogel and applications. The injectable piezoelectric ionic hydrogel precursor liquid is prepared by mixing a neutral polymer containing a photosensitive functional group, an ionic polymer, a photoinitiator and a solvent in a light-proof manner, has excellent biological safety and in-vivo degradability, and can be in-situ cured within 20 seconds under light, thereby meeting the requirement of rapid molding in clinical treatment. The application also provides an injectable piezoelectric ionic hydrogel which is prepared by a photopolymerization reaction of the precursor liquid and inherits the advantages of biological safety and in-vivo degradability of the precursor liquid. The piezoelectric ionic hydrogel can realize mechano-electric conversion by applying mechanical pressure without external power stimulation, thereby solving the technical bottlenecks of poor biocompatibility, in-vivo non-degradability, slow in-situ curing speed and the need of external stimulation to generate an electric signal which are commonly existed in the prior art piezoelectric ionic hydrogels.

Description

Technical Field

[0001] This application relates to the field of surgical biomedical materials technology, and in particular to an injectable piezoelectric ion hydrogel precursor solution and an injectable piezoelectric ion hydrogel and their applications. Background Technology

[0002] Early research on piezoelectric ion hydrogels was inspired by the flow potential of articular cartilage and the mechatronic processes of skin, stemming from biomimetic exploration. Related studies have shown that when the fixed charge network in the hydrogel is compressed under external force, the difference in migration rates between anions and cations can generate significant transient currents and potentials within milliseconds. This provides a theoretical basis for developing mechatronic conversion materials that do not require an external power source.

[0003] By employing strategies such as strain gradient modulation, differential modification of interfacial functional groups, and microstructure reconstruction, researchers have successfully fabricated a device with voltage sensitivity reaching tens of kPa. -1 High-sensitivity ion-sensitive skin materials with linear detection ranges extended to the MPa level are emerging. However, these materials are primarily geared towards flexible wearable sensing applications. Their fixed charge density, ion environment, and water retention often rely on exogenous salt solutions for maintenance, lacking the biodegradability and biocompatibility required for implantation environments, making it difficult to meet the steady-state requirements for long-term implantation in vivo. With the development of regenerative medicine, the concept of mechatronics conversion has been introduced into the field of injectable scaffolds, aiming to provide continuous in-situ bioelectric stimulation for tissue damage repair. Existing research has attempted to combine short fibers, conductive polymers, or inorganic piezoelectric particles with biocompatible hydrogels for bone, cartilage, and nerve regeneration. Among these, some materials require external ultrasound or electromagnetic devices to activate the piezoelectric effect; others pose a potential risk of chronic inflammation due to the introduction of non-degradable inorganic components, limiting their clinical translational applications.

[0004] To date, there is a lack of a piezoelectric ion hydrogel system that requires no additional equipment, is composed entirely of biodegradable polymers, and possesses the ability to be injected and rapidly cured in situ. Summary of the Invention

[0005] In view of this, the purpose of this application is to provide an injectable piezoelectric ionic hydrogel precursor liquid and an injectable piezoelectric ionic hydrogel and its application, in order to solve the technical problems of traditional piezoelectric hydrogels, such as poor biocompatibility, non-degradability, slow in-situ curing speed, and the need for external stimulation to generate electrical signals.

[0006] To achieve the above-mentioned technical objectives, this application provides an injectable piezoelectric ionic hydrogel precursor solution, comprising a solvent, a photoinitiator, an ionic polymer, and a neutral polymer containing photosensitive functional groups; the mass-volume concentrations of the photoinitiator, the ionic polymer, and the neutral polymer containing photosensitive functional groups in the solvent are as follows: photoinitiator 0.05%~0.5% (w / v); ionic polymer 0.5%~5% (w / v); neutral polymer containing photosensitive functional groups 5%~20% (w / v).

[0007] The components of solvent, photoinitiator, ionic polymer, and neutral polymer containing photosensitive functional groups satisfy at least one of the following conditions (1) to (4):

[0008] (1) Neutral polymers containing photosensitive functional groups include at least one of polyether F127 diacrylate, acrylamide, poly(ethylene glycol) diacrylate, and N-acryloylglycine; (2) Ionic polymers include at least one of hyaluronic acid, chitosan, glucosamine hydrochloride, ε-polylysine, acrylic acid, and sulfopropyl methacrylate; (3) Photoinitiators include (3) At least one of phenyl-2,4,6-trimethylbenzoyl lithium phosphinate; (4) The solvent is at least one of deionized water and phosphate buffer.

[0009] This application provides a method for preparing an injectable piezoelectric ionic hydrogel precursor solution, comprising the following steps: under light-protected conditions, a neutral polymer containing photosensitive functional groups, an ionic polymer, a photoinitiator, and a solvent are mixed uniformly in a preset ratio to obtain an injectable piezoelectric ionic hydrogel precursor solution.

[0010] This application provides a method for storing an injectable piezoelectric ion hydrogel precursor solution, wherein the injectable piezoelectric ion hydrogel precursor solution is stored in a light-proof and vacuum environment.

[0011] This application provides a method for using an injectable piezoelectric ionic hydrogel precursor solution, wherein the injectable piezoelectric ionic hydrogel precursor solution is injected into a target area, and ultraviolet light is used to irradiate the target area to cause the injectable piezoelectric ionic hydrogel precursor solution to crosslink and solidify in situ to form an injectable piezoelectric ionic hydrogel.

[0012] This application provides an injectable piezoelectric ion hydrogel, which is obtained by photocuring an injectable piezoelectric ion hydrogel precursor solution; the injectable piezoelectric ion hydrogel generates a piezoelectric ion effect under the action of mechanical external force and continuously generates periodic electrical signals.

[0013] This application provides an injectable piezoelectric ionic hydrogel, which is obtained by photocuring an injectable piezoelectric ionic hydrogel precursor solution. The injectable piezoelectric ionic hydrogel includes: a neutral framework formed by photocuring a neutral polymer containing photosensitive functional groups, the neutral framework having a three-dimensional network structure; and an ionizable ionic polymer mixed in the neutral framework; wherein the ionizable ionic polymer is interwoven and interspersed in the three-dimensional network pores of the neutral framework in the form of chain segments or microregions, and together with the neutral framework, forms a structurally stable and elastic hydrogel.

[0014] Furthermore, injectable piezoelectric ion hydrogels can generate a piezoelectric ion effect under the action of mechanical external force and continuously generate periodic electrical signals.

[0015] This application provides the application of an injectable piezoelectric ion hydrogel in skin repair, bone repair, articular cartilage repair, and nerve tissue repair.

[0016] In summary, this invention provides an injectable piezoelectric ionic hydrogel precursor solution, which is prepared by a light-shielded mixing process using a neutral polymer containing photosensitive functional groups, an ionic polymer, a photoinitiator, and a solvent. This precursor solution allows for precise control of the mechanical compatibility and electrical signal output characteristics of the subsequently formed hydrogel by systematically adjusting the concentration of the neutral polymer containing photosensitive functional groups, the type and concentration of the ionic polymer, and regulating the crosslinking density based on light conditions. Furthermore, the precursor solution provided in this application exhibits good biosafety and in vivo degradability, and can complete in-situ curing within 20 seconds under light conditions.

[0017] This invention also provides an injectable piezoelectric ionic hydrogel, which is prepared by photocuring the aforementioned injectable piezoelectric ionic hydrogel precursor solution. The hydrogel comprises a neutral framework and ionizable ionic polymers, wherein the ionic polymers are interwoven and interspersed in the three-dimensional network pores of the neutral framework in the form of chain segments or microregions, forming a structurally stable and elastic structure that generates a piezoelectric ionic effect under stress. This hydrogel requires no external power source. Under the stress or strain gradient caused by external force, it converts mechanical energy into detectable electrical output through mechanisms such as ion migration, the establishment of concentration and potential differences, and adsorption polarization at the electrode interface. Stable electrical signal output can be achieved under periodic mechanical loading or continuous deformation input, and it can be used for energy harvesting, sensing, and bioelectric stimulation.

[0018] This invention also provides an application of an injectable piezoelectric ion hydrogel. Before curing, the hydrogel can be injected to meet the medical and clinical needs of repairing cartilage defects or regenerating other weight-bearing tissues in different locations, showing broad application prospects in the field of regenerative medicine.

[0019] Compared with existing piezoelectric or conductive hydrogel technologies, the present invention has the following significant advantages:

[0020] (1) Biosafety: The injectable piezoelectric ionic hydrogel is constructed from biodegradable polymers and natural polysaccharides, avoiding the biotoxicity and long-term residue problems that may be caused by traditional conductive polymers or inorganic piezoelectric ceramics, and has good biosafety and in vivo degradability.

[0021] (2) Biocompatibility: Compared with traditional piezoelectric materials that rely mainly on electron transport, the piezoelectric ion mechanism based on ion migration of this invention has better stability in hydrated and electrolyte environments. It can achieve high sensitivity response under low-frequency micro-stress, without the need for pre-polarization treatment and rigid conductive phase. Furthermore, the hydrogel provided in this application can regulate the signal output intensity by adjusting the ion strength and fixed charge density, making it more suitable for the mechanical requirements of wet environments and low-modulus tissues in vivo.

[0022] (3) Application conditions matching: Neutral polymers containing photosensitive functional groups have good flowability and can be compounded with ionic polymers to form injectable systems. Combined with photocrosslinking technology, they can achieve precise, rapid, and in-situ in vivo gelation, which significantly simplifies the operation process and reduces surgical trauma.

[0023] (4) Simplified system structure and reduced operating costs: Piezoelectric ion hydrogels do not require external power supply or additional energy input. They can achieve electromechanical signal conversion by relying on joint movement or physiological micro-stress, providing a continuous and stable electrical signal microenvironment, effectively activating chondrocyte differentiation and tissue regeneration. Compared with systems that rely on external ultrasound or electrode stimulation, this invention simplifies the system structure and usage requirements, and reduces the cost of medical equipment. Attached Figure Description

[0024] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0025] Figure 1 This is a schematic diagram illustrating the mechatronic conversion principle of piezoelectric ion hydrogels.

[0026] Figure 2 The graph shows the cyclic compression test results of the injectable piezoelectric ionic hydrogel provided in Example 1.

[0027] Figure 3 The voltage and current output curves of the injectable piezoelectric ionic hydrogel provided in Example 1 under 1N, 1Hz periodic compression conditions are shown.

[0028] Figure 4 The image shows a two-month comparison of the effects of the injectable piezoelectric ion hydrogel provided in Example 1 on the repair of cartilage defects in a rabbit knee joint model.

[0029] Figure 5 The graph shows the cyclic compression test results of the injectable piezoelectric ion hydrogel provided in Example 2.

[0030] Figure 6 The voltage and current output curves of the injectable piezoelectric ion hydrogel provided in Example 2 under 1N, 1Hz periodic compression conditions are shown.

[0031] Figure 7 Mechanical-electromechanical property test diagram of the injectable non-piezoelectric ionic hydrogel provided for Comparative Example 1: Voltage and current output curves formed by the hydrogel under 1N, 1Hz periodic compression conditions.

[0032] Figure 8 The mechanical-electromechanical properties test diagrams of the injectable single-component piezoelectric ionic hydrogel provided for Comparative Example 2 are shown in Figure 1. (a) The figure shows the actual image of the hydrogel after being compressed by 1N once and then breaking apart. (b) The figure shows the voltage and current output curves of the hydrogel under 1N and 1Hz periodic compression conditions.

[0033] Figure 9 The mechanical-electromechanical properties test diagrams of the injectable single-component piezoelectric ionic hydrogel provided for Comparative Example 3 are shown in the following figures: (a) Figure shows a physical image of the hydrogel with poor moldability; (b) Figure shows the voltage and current output curves of the hydrogel formed under 1N, 1Hz periodic compression conditions. Detailed Implementation

[0034] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this application. Based on the embodiments in this application specification, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection claimed in this application.

[0035] In the description of this application, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this application. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0036] Unless otherwise expressly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to fixed connections, detachable connections, or integral connections; they can refer to mechanical connections or electrical connections; they can refer to direct connections or indirect connections through an intermediate medium; and they can refer to the internal connection between two components. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.

[0037] The raw materials used in this invention are not particularly restricted in their source; they can be purchased on the market or prepared using conventional methods known to those skilled in the art.

[0038] This application provides an injectable piezoelectric ionic hydrogel precursor solution, comprising a solvent, a photoinitiator, an ionic polymer, and a neutral polymer containing photosensitive functional groups;

[0039] The mass-volume concentrations of photoinitiators, ionic polymers, and neutral polymers containing photosensitive functional groups in the solvent are as follows: photoinitiators: 0.05%~0.5% (w / v); ionic polymers: 0.5%~5% (w / v); neutral polymers containing photosensitive functional groups: 5%~20% (w / v).

[0040] The components of solvent, photoinitiator, ionic polymer, and neutral polymer containing photosensitive functional groups satisfy at least one of the following conditions (1) to (4):

[0041] (1) Neutral polymers containing photosensitive functional groups include at least one of polyether F127 diacrylate, acrylamide, poly(ethylene glycol) diacrylate, and N-acryloylglycine; (2) Ionic polymers include at least one of hyaluronic acid, chitosan, glucosamine hydrochloride, ε-polylysine, acrylic acid, and sulfopropyl methacrylate; (3) Photoinitiators include (3) At least one of phenyl-2,4,6-trimethylbenzoyl lithium phosphinate; (4) The solvent is at least one of deionized water and phosphate buffer.

[0042] It should be noted that neutral polymers containing photosensitive functional groups can form a three-dimensional network structure through cross-linking reactions under the action of an initiator via their inherent photosensitive diene groups, providing mechanical strength to the hydrogel. Ionic polymers can serve as functional enhancement components, introducing fixed-charge groups (including positive, negative, or zwitterions) into the three-dimensional network structure formed by neutral polymers containing photosensitive functional groups, forming migratory ion channels. This enables the hydrogel formed by the precursor solution to achieve a pressure-responsive ion redistribution effect, generating ionic electrical signal output, ultimately achieving passive electrical signal output. Furthermore, the photoinitiator selected in this invention is a type commonly used in the medical field, and its concentration is controlled within a safe and effective range.

[0043] In some specific embodiments, the photoinitiator is 0.05% (w / v), 0.10% (w / v), 0.15% (w / v), 0.20% (w / v), 0.25% (w / v), 0.30% (w / v), 0.35% (w / v), 0.45% (w / v), or 0.50% (w / v); the ionic polymer is 0.05% (w / v), 0.10% (w / v), 0.15% (w / v), 0.20% (w / v), 0.25% (w / v), 0.30% (w / v), 0.35% (w / v), 0.45% (w / v), or 0.50% (w / v); and the neutral polymer containing photosensitive functional groups is 5% (w / v), 10% (w / v), 15% (w / v), or 20% (w / v).

[0044] It should be noted that by adjusting the component ratio, the amplitude and duration of the electrical signal of the subsequently formed hydrogel, as well as the elastic modulus and adhesion and lubrication properties of the hydrogel, can be specifically controlled. In addition, the above ratio can also ensure that the precursor liquid remains injectable, highly fluid, and rapidly gels in situ, and the hydrogel formed by the above precursor liquid has in vivo degradable properties.

[0045] In some embodiments, the neutral polymer containing photosensitive functional groups includes, but is not limited to, one of the following materials: polyether F127 diacrylate (F127DA), acrylamide (AAm), poly(ethylene glycol) diacrylate (PEGDA), and N-acryloylglycine (NAGA); and / or, the ionic polymer includes, but is not limited to, at least one of hyaluronic acid (HA), chitosan (CS), glucosamine hydrochloride (GH), ε-polylysine (PLA), acrylic acid (AA), and sulfopropyl methacrylate (SBMA); and / or, the photoinitiator includes, One of the materials including (Irgacure 2959), lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP); and / or, the solvent is at least one of deionized water and phosphate buffer.

[0046] In some specific embodiments, the pH of the phosphate buffer solution is 4.5 to 7.5.

[0047] It should be noted that the neutral and ionic polymers containing photosensitive functional groups in the precursor solutions used in this invention are all biodegradable polymers or natural polysaccharides. This effectively avoids the potential biotoxicity and long-term in vivo residue risks associated with using traditional conductive polymers or inorganic piezoelectric ceramics, exhibiting good biosafety and biodegradability. Furthermore, the functions of each component in the hydrogel are as follows: F127DA, AAm, PEGDA, or NAGA perform photocrosslinking and provide overall mechanical support; HA provides carboxylic acid groups to fix negative charges, while also imparting lubricity and adhesion to the hydrogel; CS provides amine groups to provide positive charges, further enhancing the bioadhesive properties of the hydrogel; GH provides amine groups to provide positive charges; PLA provides amine groups to provide positive charges, increasing cation density and imparting antibacterial properties to the hydrogel; AA increases the number of carboxylic acid groups that fix negative charges; and SBMA provides a zwitterionic structure to enhance ion migration rates.

[0048] This application provides a method for preparing an injectable piezoelectric ionic hydrogel precursor solution, comprising the following steps: under light-protected conditions, a neutral polymer containing photosensitive functional groups, an ionic polymer, a photoinitiator, and a solvent are mixed uniformly in a preset ratio to obtain an injectable piezoelectric ionic hydrogel precursor solution.

[0049] In some embodiments, the injectable piezoelectric ionic hydrogel precursor solution comprises the following components: a neutral polymer containing photosensitive functional groups selected from F127DA, AAm, PEGDA, or NAGA, with a mass-volume concentration of 8-12% (w / v); an ionic polymer selected from HA, CS, GH, PLA, AA, or SBMA, with different types of ionic polymers having different mass-volume concentrations in the precursor solution, and the following concentration ranges: HA 2-4% (w / v), CS 0.5-1.5% (w / v), GH 0.5-1.5% (w / v), PLA 2-4% (w / v), AA 0.5-1.5% (w / v), and SBMA 2-4% (w / v); 1 mL of deionized water as the solvent; and Irgacure 2959 photoinitiator at 0.1-0.2% (w / v).

[0050] In some specific embodiments, when the neutral polymer containing photosensitive functional groups is selected from F127DA, AAm, PEGDA, or NAGA, its mass-volume concentration is 8% (w / v), 9% (w / v), 10% (w / v), 11% (w / v), or 12% (w / v); when the ionic polymer is selected from HA, CS, GH, PLA, AA, or SBMA, the mass-volume concentration of different types of ionic polymers in the precursor solution is different, and the addition concentrations are as follows: HA is 2% (w / v) or 3% (w / v). 0.5% (w / v), 1.0% (w / v), or 1.5% (w / v) of CS; 0.5% (w / v), 1.0% (w / v), or 1.5% (w / v) of GH; 2% (w / v), 3% (w / v), or 4% (w / v) of PLA; 0.5% (w / v), 1.0% (w / v), or 1.5% (w / v) of AA; 2% (w / v), 3% (w / v), or 4% (w / v) of SBMA; using 1 mL of deionized water as solvent; and 0.1% (w / v) or 0.2% (w / v) of photoinitiator Irgacure 2959.

[0051] In some preferred embodiments, the injectable piezoelectric ionic hydrogel precursor solution comprises the following components: a neutral polymer containing photosensitive functional groups selected from F127DA, AAm, PEGDA, or NAGA, with a mass-volume concentration of 10% (w / v); an ionic polymer selected from HA, CS, GH, PLA, AA, or SBMA, with different types of ionic polymers having different mass-volume concentrations in the precursor solution, specifically added at the following concentrations: HA 3% (w / v), CS 1% (w / v), GH 1% (w / v), PLA 3% (w / v), AA 1% (w / v), and SBMA 3% (w / v); 1 mL of deionized water as the solvent; and Irgacure 2959 photoinitiator at 0.2% (w / v). The injectable piezoelectric ionic hydrogel precursor solution provided in this embodiment can be dispensed using a disposable injection needle and can be photocured within 20 seconds under 365nm UV light irradiation to form an injectable piezoelectric ionic hydrogel.

[0052] It should be noted that the injectable piezoelectric ionic hydrogel prepared using the above component ratio has the following beneficial effects: (1) In terms of physical properties, the hydrogel has a water content of more than 80% and excellent mechanical properties: the compressive modulus is in the range of 10~150kPa, the tensile strain exceeds 150%, and the compressive strain exceeds 80%. Its mechanical parameters are highly matched with the physiological characteristics of tissues and organs, and can adapt to the complex mechanical environment in the body. (2) In terms of electromechanical conversion performance, the hydrogel has stability and durability: under simulated physiological conditions (1Hz frequency, 30kPa periodic compression), the hydrogel can stably and continuously generate an open circuit voltage of 100~500mV and a short circuit current of 10~50μA, and after 1000 cycles of testing, the signal attenuation rate is less than 5%. (2) At the level of biological mechanism, it can promote the functional regeneration of cartilage tissue: The bioregulatory effect of the hydrogel comes from its internal endogenous micro electric field, which can effectively activate the relevant signaling pathways of chondrocytes and bone marrow-derived mesenchymal stem cells, and play a regulatory role in cell adhesion, proliferation and differentiation.

[0053] This application provides a method for storing an injectable piezoelectric ion hydrogel precursor solution, wherein the injectable piezoelectric ion hydrogel precursor solution is stored in a light-proof and vacuum environment.

[0054] This application provides a method for using an injectable piezoelectric ion hydrogel precursor solution. The injectable piezoelectric ion hydrogel precursor solution is injected into a target area, and ultraviolet light is used to irradiate the target area to cause the injectable piezoelectric ion hydrogel precursor solution to crosslink and solidify in situ to form an injectable piezoelectric ion hydrogel.

[0055] In some specific embodiments, the injectable piezoelectric ion hydrogel precursor solution can be irradiated with UV light at a wavelength of 365 nm for a duration of less than 20 seconds.

[0056] It should be noted that the injectable piezoelectric ion hydrogel precursor solution can achieve in-situ rapid molding within 20 seconds under the above light conditions, which can fully meet the actual clinical needs of rapid shaping within the wound, so as to ensure the convenience and molding accuracy in the clinical operation process.

[0057] This application provides an injectable piezoelectric ionic hydrogel, which is obtained by photocuring an injectable piezoelectric ionic hydrogel precursor solution. The injectable piezoelectric ionic hydrogel comprises: a neutral framework formed by photocuring a neutral polymer containing photosensitive functional groups, the neutral framework having a three-dimensional network structure; and an ionizable ionic polymer mixed in the neutral framework; wherein the ionizable ionic polymer is interwoven and interspersed in the three-dimensional network pores of the neutral framework in the form of chain segments or microregions, forming a structurally stable and elastic hydrogel together with the neutral framework.

[0058] In some embodiments, the injectable piezoelectric ionic hydrogel contains a neutral polymer with photosensitive functional groups, including but not limited to one of the following materials: polyether F127 diacrylate (F127DA), acrylamide (AAm), poly(ethylene glycol) diacrylate (PEGDA), and N-acryloylglycine (NAGA); and / or, an ionic polymer, including but not limited to at least one of hyaluronic acid (HA), chitosan (CS), glucosamine hydrochloride (GH), ε-polylysine (PLA), acrylic acid (AA), and sulfopropyl methacrylate (SBMA).

[0059] In some embodiments, neutral polymers containing photosensitive functional groups can be photocured by adding a photoinitiator, which can be... One of the materials including (Irgacure 2959), lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP); and / or, the solvent is at least one of deionized water and phosphate buffer.

[0060] It should be noted that the cured polyether F127 diacrylate (F127DA) and other neutral polymers serve as the neutral framework of the hydrogel. This neutral framework is a three-dimensional network structure, and its core function is to provide mechanical support for the hydrogel. Meanwhile, the ionic polymers, as charged phases, can endow the hydrogel with fixed charge sites to construct ion transport channels. Together, they achieve the piezoelectric ion effect of the system.

[0061] In some embodiments, injectable piezoelectric ion hydrogels generate periodic electrical signals based on the piezoelectric ion effect under the action of mechanical external force.

[0062] It should be noted that, Figure 1 This diagram illustrates the migration paths of cations / anions and the formation mechanism of transient potential differences in the fixed charge network of a hydrogel under pressure. Figure 1 As can be seen, the fixed charge network in injectable piezoelectric ion hydrogels can induce differential migration of positive and negative ions under pressure, thereby constructing an instantaneous electric field gradient; this process can stably output electrical signals without relying on external power input or high-intensity physical stimulation.

[0063] This application provides an application of injectable piezoelectric ion hydrogel in skin repair, bone repair, articular cartilage repair, and nerve tissue repair.

[0064] It should be noted that the injectable piezoelectric ion hydrogel can trigger mechano-electric signal conversion through joint movement or physiological pressure, stably outputting microcurrents and microvoltages without an external power source. This enables passive electrical stimulation regulation of cell adhesion, proliferation, and differentiation, ultimately promoting tissue repair. Furthermore, this hydrogel exhibits excellent biocompatibility and inducing activity against target cells such as mesenchymal stem cells and chondrocytes, meeting the core needs of tissue damage repair and possessing broad application prospects in regenerative medicine. Compared to traditional piezoelectric materials that rely on lattice dipole changes to achieve the piezoelectric effect, this invention completes the mechano-electric signal conversion through ion transport mechanisms. Its characteristics are more adaptable to physiological electrolyte environments and low-frequency load scenarios, better meeting the needs of in vivo applications.

[0065] The applicant further provides the following specific embodiments to describe the present invention. It should be noted that these embodiments are merely descriptive and do not limit the present invention in any way.

[0066] Example 1

[0067] This embodiment provides an injectable piezoelectric ion hydrogel precursor solution, comprising the following preparation steps:

[0068] Dissolve 1.0 g of F127DA in 10 mL of deionized water, add 0.3 g of hyaluronic acid, and stir with a magnetic stirrer at 4°C for 2 hours until all substances are completely dissolved to form a homogeneous solution. Add 10 mg of photoinitiator Irgacure2959 to the above solution and stir in the dark for 30 minutes to obtain an injectable (liquid) piezoelectric ionic hydrogel precursor solution. Vacuum the injectable piezoelectric ionic hydrogel precursor solution to remove air from the piezoelectric ionic hydrogel, and then load it into a 1 mL syringe for later use.

[0069] This embodiment provides a method for using an injectable piezoelectric ion hydrogel precursor solution: the prepared piezoelectric ion hydrogel precursor solution is injected into an experimental mold using a syringe, and the experimental mold is placed under a 365nm UV lamp for irradiation. Within 20 seconds, the liquid piezoelectric ion hydrogel precursor solution is photocured and crosslinked in situ to form an injectable piezoelectric ion hydrogel, and the resulting injectable piezoelectric ion hydrogel is transparent.

[0070] See Figure 2 The injectable piezoelectric ionic hydrogel obtained in this embodiment was subjected to compression cycling tests at room temperature under 80% strain. During the 1500-second test, the gel's modulus remained stable, demonstrating the material's excellent fatigue resistance.

[0071] The injectable piezoelectric ionogel obtained in this embodiment exhibits good mechatronics stability: [from...] Figure 3It can be seen that under the action of 1N external force, the hydrogel can continuously generate a stable open circuit voltage and current, and the measured output peak voltage is 500mV and the output peak current is 28μA.

[0072] The injectable piezoelectric ion hydrogel obtained in the examples exhibits good tissue repair capabilities: [The text abruptly ends here, likely due to an incomplete sentence or missing information.] Figure 4 It is evident that in the rat cartilage injury model experiment, only the experimental group rats that received injection of injectable piezoelectric ionic hydrogel precursor solution to the cartilage injury site and allowed it to solidify in situ, combined with exercise intervention, showed significant repair in the cartilage injury area. This result indicates that injectable piezoelectric ionic hydrogel can efficiently convert the mechanical stress generated during joint movement into electrical signals, significantly promoting cartilage tissue regeneration and repair through this mechatronics conversion effect.

[0073] Example 2

[0074] This embodiment provides an injectable piezoelectric ionic hydrogel precursor solution, which differs from Embodiment 1 in that an equal amount of ε-polylysine is used instead of hyaluronic acid. The specific steps are as follows:

[0075] Dissolve 1.0 g of F127DA in 10 mL of deionized water, add 0.3 g of ε-polylysine, and stir with a magnetic stirrer at 4°C for 2 hours until all substances are completely dissolved to form a homogeneous solution. Add 10 mg of photoinitiator Irgacure2959 to the above solution and stir in the dark for 30 minutes to obtain an injectable (liquid) piezoelectric ionic hydrogel precursor. Vacuum the injectable piezoelectric ionic hydrogel precursor to remove internal air, and then fill it into a 1 mL syringe for later use.

[0076] The method of using the injectable piezoelectric ion hydrogel precursor solution provided in this embodiment is the same as in Example 1. See also... Figure 5 The injectable piezoelectric ionic hydrogel obtained in this embodiment was subjected to compression cycling tests at room temperature under 80% strain. During the 1500-second test, the gel's modulus remained stable, demonstrating the material's excellent fatigue resistance.

[0077] The injectable piezoelectric ion hydrogel obtained in this embodiment can produce a stable piezoelectric ion effect: see [link] Figure 6 Under an external force of 1N, the hydrogel can continuously generate a stable open-circuit voltage and current. The measured peak voltage of the output is 400mV and the peak current of the output is 28μA.

[0078] Comparative Example 1

[0079] This comparative example provides an injectable non-piezoelectric ionic hydrogel precursor solution. The difference from Example 1 is that hyaluronic acid was not added; only neutral polymers were retained (indicating that the precursor solution provided in this comparative example can form a three-dimensional network-like neutral framework under light conditions, but does not possess ionizable ionic polymers). The specific steps are as follows:

[0080] Dissolve 1.0 g of F127DA in 10 mL of deionized water and stir at 4°C for 2 hours with a magnetic stirrer until all substances are completely dissolved to form a homogeneous solution. Add 10 mg of photoinitiator Irgacure2959 to the above solution and stir in the dark for 30 minutes to obtain an injectable (liquid) piezoelectric ionic hydrogel precursor solution.

[0081] The method of using the injectable non-piezoelectric ionic hydrogel precursor solution provided in this comparative example is the same as that in Example 1. The injectable non-piezoelectric ionic hydrogel obtained in this comparative example does not possess a piezoelectric ionic effect: see [link to example]. Figure 7 Under 1N and 1Hz periodic compression loading, no stable open-circuit voltage and current were detected. This indicates that hydrogels containing only neutral polymers with photosensitive functional groups as a neutral backbone, without the addition of ionic polymers, cannot achieve mechatronic conversion.

[0082] Comparative Example 2

[0083] This comparative example provides an injectable single-component piezoelectric ionic hydrogel precursor solution. The difference from Example 1 is that it retains only the anionic polymer and no neutral polymer (indicating that the precursor solution provided in this comparative example is difficult to form a three-dimensional network-like neutral framework under light conditions). The specific steps are as follows:

[0084] Dissolve 0.5g of methacrylamide hyaluronic acid in 10mL of deionized water and stir with a magnetic stirrer in an ice bath for 1 hour until all substances are completely dissolved to form a homogeneous solution. Add 10mg of photoinitiator Irgacure2959 to the above solution and stir in the dark for 30 minutes to obtain an injectable (liquid) single-component piezoelectric ionic hydrogel precursor solution.

[0085] The method of using the injectable one-component piezoelectric ionic hydrogel precursor solution provided in this comparative example is the same as that in Example 1. The injectable one-component piezoelectric ionic hydrogel obtained in this comparative example cannot generate a stable open-circuit voltage and current, and the hydrogel's mechanical properties are poor, making it prone to breakage under cyclic mechanical pressure. See [link to relevant documentation]. Figure 8 Figure (a) shows that the hydrogel prepared without the addition of a neutral polymer containing photosensitive functional groups breaks under 1N and 1Hz periodic compression conditions, indicating that the mechanical properties of the hydrogel are unable to withstand weak mechanical pressure; see also Figure 8Figure (b) shows that under 1N and 1Hz periodic compression conditions, almost no stable voltage and current can be detected. This indicates that although hydrogels composed solely of ionic polymers have the function of fixing negative charges, they lack the support of a three-dimensional network structure provided by a neutral framework and the synergistic regulation of ion transport pathways, making it difficult to form effective differential ion migration and instantaneous electric field gradients.

[0086] Comparative Example 3

[0087] This embodiment provides an injectable single-component piezoelectric ionic hydrogel precursor solution. The difference from Example 2 is that it retains only the cationic polymer and no neutral polymer (indicating that the precursor solution provided in this comparative example is difficult to form a three-dimensional network-like neutral framework under light conditions). The specific preparation steps are as follows:

[0088] 1.5 g of methacrylamide polylysine was dissolved in 10 mL of deionized water and stirred at 4°C for 1 hour using a magnetic stirrer until all substances were completely dissolved to form a homogeneous solution. 10 mg of photoinitiator Irgacure 2959 was added to the solution, and the mixture was stirred in the dark for 30 minutes to obtain an injectable (liquid) single-component piezoelectric ionic hydrogel precursor solution. Its usage method is the same as in Example 1.

[0089] The method of using the injectable one-component piezoelectric ionic hydrogel precursor solution provided in this comparative example is the same as that in Example 1. The injectable one-component piezoelectric ionic hydrogel obtained in this comparative example is difficult to completely solidify and lacks a stable piezoelectric ionic effect: from... Figure 9 As can be seen in Figure (a), hydrogels are difficult to inject and cure, and cannot form hydrogels with complete structures; from Figure 9 As shown in Figure (b), under 1N, 1Hz periodic compression conditions, the voltage and current output values ​​of the gel are close to the noise baseline, and significant signal drift occurs during cyclic testing. This indicates that the hydrogel struggles to achieve a stable piezoelectric ion effect under repeated mechanical pressure. This suggests that the gel system, without the addition of a neutral polymer containing photosensitive functional groups as a supporting framework, relies solely on ionic polymers to construct a cation network. This makes it difficult to overcome the strong binding effect of counterions and to form continuous ion transport channels. Ultimately, this results in the hydrogel failing to generate an effective differential ion migration effect and instantaneous electric field gradient, thus hindering stable electromechanical conversion.

[0090] The above are merely preferred embodiments of this application and are not intended to limit the present invention. Although this application has been described in detail with reference to examples, those skilled in the art can still modify the technical solutions described in the foregoing examples or make equivalent substitutions for some of the technical features. However, any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. An injectable piezoelectric ionic hydrogel precursor solution, characterized in that, This includes solvents, photoinitiators, ionic polymers, and neutral polymers containing photosensitive functional groups; The mass-volume concentrations of the photoinitiator, ionic polymer, and neutral polymer containing photosensitive functional groups in the solvent are as follows: the photoinitiator is 0.05%~0.5% (w / v); the ionic polymer is 0.5%~5% (w / v); and the neutral polymer containing photosensitive functional groups is 5%~20% (w / v). The neutral polymer containing photosensitive functional groups includes at least one of polyether F127 diacrylate and poly(ethylene glycol) diacrylate. The ionic polymer includes at least one of hyaluronic acid, chitosan, and ε-polylysine. The photoinitiator includes at least one of 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropionyl phenyl ketone and phenyl-2,4,6-trimethylbenzoyl lithium phosphinate. The solvent is at least one of deionized water and phosphate buffer.

2. A method for preparing the injectable piezoelectric ionic hydrogel precursor solution according to claim 1, characterized in that, Includes the following steps: Under light-protected conditions, a neutral polymer containing photosensitive functional groups, an ionic polymer, a photoinitiator, and a solvent are mixed uniformly in a preset ratio to obtain an injectable piezoelectric ionic hydrogel precursor solution.

3. The injectable piezoelectric ionic hydrogel precursor solution according to claim 1, characterized in that, The method for storing the injectable piezoelectric ion hydrogel precursor solution is as follows: the injectable piezoelectric ion hydrogel precursor solution is stored in a light-proof and vacuum environment.

4. An injectable piezoelectric ionic hydrogel, characterized in that, The injectable piezoelectric ionic hydrogel is obtained by photocuring the injectable piezoelectric ionic hydrogel precursor liquid according to claim 1; the injectable piezoelectric ionic hydrogel generates a piezoelectric ion effect under the action of mechanical external force and continuously generates periodic electrical signals.

5. An injectable piezoelectric ionic hydrogel, characterized in that, The injectable piezoelectric ionic hydrogel is obtained by photocuring the injectable piezoelectric ionic hydrogel precursor solution according to claim 1. The injectable piezoelectric ionic hydrogel comprises: A neutral framework formed by photocuring a neutral polymer containing photosensitive functional groups, the neutral framework having a three-dimensional network structure; and an ionizable ionic polymer mixed in the neutral framework; The ionizable ionic polymers are interspersed and interwoven in the three-dimensional network pores of the neutral framework in the form of chain segments or microregions, forming a structurally stable and elastic hydrogel together with the neutral framework.

6. The injectable piezoelectric ionic hydrogel according to claim 5, characterized in that, The injectable piezoelectric ion hydrogel generates a piezoelectric ion effect under the action of mechanical external force and continuously generates periodic electrical signals.

7. The use of the injectable piezoelectric ionic hydrogel of claim 4 or any one of claims 5 to 6 in the preparation of materials for skin repair, bone repair, articular cartilage repair and nerve tissue repair.

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