Hydrogel devices and methods for oral pH detection and sonodynamic therapy

Abstract

The application discloses a hydrogel device and method for oral pH detection and sonodynamic therapy. The device comprises a hydrogel packaging layer and a pH sensing coupled sonodynamic therapy module; the hydrogel packaging layer is formed by two layers of network crosslinking, the first layer of network acts as a rigid but fragile skeleton, and the second layer of network is soft and stretchable, so that the hydrogel device has excellent mechanical properties and deformation ability; the pH sensing coupled sonodynamic therapy module is a wrapped structure, the outside is used for pH sensing, and reflects the caries damage condition of the oral cavity; the inside of the pH sensing coupled sonodynamic therapy module is a sonodynamic therapy module, which is used for generating active oxygen under ultrasonic stimulation, realizes the double effect of disinfection and tooth whitening on oral cariogenic bacteria, and the method provides an instant detection and nursing platform for oral health condition, and has the advantages of adhesion type, customizability, in-situ sensing and non-invasive treatment.

Description

Technical Field

[0001] This invention relates to a technique for early diagnosis and treatment of oral caries and teeth whitening, and more particularly to a hydrogel device and method for visual detection of oral pH, non-invasive elimination of cariogenic bacteria, and teeth whitening. Background Technology

[0002] A healthy mouth is a unique and precious asset, closely related to overall health and quality of life. Dental caries and food-induced staining are major global public health issues related to oral health. When cariogenic bacteria become the dominant oral flora, calcium and phosphorus are lost, leading to enamel demineralization and tooth surface roughness, which can result in dental caries and food-induced staining. Currently, the diagnosis and treatment of dental caries lacks customized point-of-care testing technologies and efficient sterilization strategies, while the care of food-induced staining lacks non-invasive teeth whitening solutions. Traditional dental caries detection mainly relies on clinical examinations, requiring expensive and bulky instruments, resulting in high costs, inconvenience, and the inability to monitor immediately. The acidification of the oral microenvironment can reflect the metabolic level of cariogenic bacteria. Existing work can monitor local oral pH levels using electrochemical methods, but due to the size limitations of batteries and Bluetooth modules, complete flexibility is not possible. Some strategies use silicone materials to monitor oral health markers, but because the pore size of silicone materials is too small, they can only detect gas molecules, not liquid molecules. Currently, there is no fully flexible, adhesive device that can continuously monitor pH fluctuations in the oral fluid environment in situ.

[0003] Currently, the main treatment for dental caries involves mechanical debridement of the affected area supplemented with topical medications, while teeth whitening typically involves professional cleaning and physical polishing. However, debridement alone is insufficient to completely remove infection from irregularly shaped tooth surfaces, and postoperative pain can cause psychological distress for patients. Furthermore, frequent or excessive use of medications as adjunctive therapy can lead to bacterial resistance and side effects such as nausea, dry mouth, and stomach pain. Existing teeth whitening veneers only have the function of removing surface stains and cannot simultaneously address oral health issues such as dental caries. Therefore, developing a fully flexible, multifunctional, adhesive hydrogel device and method for in-situ pH detection and sonodynamic therapy in the oral cavity is of great significance for early diagnosis and treatment of dental caries and teeth whitening. Summary of the Invention

[0004] The purpose of this invention is to address the shortcomings of existing technologies and products by providing a hydrogel device and method for oral pH detection and sonodynamic therapy, in order to solve the problems of early in situ non-invasive diagnosis and treatment of dental caries and food-induced staining of teeth.

[0005] The objective of this invention is achieved through the following technical solution: a hydrogel device for oral pH detection and sonodynamic therapy, comprising: a hydrogel encapsulation layer and a pH-sensing coupled sonodynamic therapy module; the hydrogel encapsulation layer is composed of a first rigid hydrogel network and a second flexible hydrogel network cross-linked together; the first rigid hydrogel network is highly cross-linked and pre-stretched, formed by physical bonding with agar through heating and cooling, and acts as a rigid skeleton in the hydrogel encapsulation layer; the second flexible hydrogel network is sparsely cross-linked and relatively concentrated, soft and stretchable, and chemically bonded with acrylamide through ultraviolet light polymerization, used to improve the mechanical properties and deformation capacity of the hydrogel encapsulation layer; the pH... The sensor-coupled sonodynamic therapy module is embedded in a hydrogel encapsulation layer and includes a pH sensing module and a sonodynamic therapy module. It is composed of a polymer structure of barium titanate nanoparticles encapsulated by polyaniline nanoparticles. The pH sensing module consists of a polyaniline layer on the outside of the sonodynamic therapy module and is used to detect the acidification of the oral microenvironment caused by cariogenic bacteria. The sonodynamic therapy module consists of barium titanate nanoparticles inside the pH sensing-coupled sonodynamic therapy module and is used to generate a piezoelectric catalytic effect under ultrasonic stimulation. The fully flexible multifunctional adhesive hydrogel veneer, fully flexible multifunctional adhesive hydrogel dental veneer, and fully flexible multifunctional adhesive hydrogel dental crown are composed of a hydrogel encapsulation layer and a pH sensing-coupled sonodynamic therapy module and are formed by casting.

[0006] Furthermore, the pH-sensing coupled sonodynamic therapy module is composed of 114 parts by mass of ammonium persulfate, 40 parts by mass of barium titanate, 5 parts by mass of aniline, 18 parts by mass of concentrated hydrochloric acid, and 430 parts by mass of deionized water through in-situ polymerization.

[0007] Furthermore, the hydrogel encapsulation layer is composed of 10 parts by weight of agar powder, 100 parts by weight of acrylamide, 3 parts by weight of 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone, 4 parts by weight of methylenebisacrylamide, 30 parts by weight of pH-sensing coupled sonodynamic therapy module, and 270 parts by weight of deionized water through a two-step crosslinking method.

[0008] Furthermore, the first rigid hydrogel network is composed of agar physical cross-linking, specifically: after heating the pH sensing coupled sonodynamic therapy module, agar, and acrylamide solution until completely dissolved, it is cooled to form the first rigid hydrogel network.

[0009] Furthermore, the second layer of flexible hydrogel network is composed of acrylamide photocuring crosslinking by ultraviolet light polymerization, that is, irradiated under an ultraviolet lamp with a power of 10W and a wavelength of 365nm for 55 minutes.

[0010] Furthermore, the fully flexible multifunctional adhesive hydrogel patch, fully flexible multifunctional adhesive hydrogel dental strip, and fully flexible multifunctional adhesive hydrogel dental crown are made by casting, that is, teeth and alveolar bone are 3D printed by transparent photosensitive resin and then cross-linked by a two-step cross-linking method.

[0011] Furthermore, the pH sensing module consists of a polyaniline layer on the outside of the sonodynamic therapy module. It is used to detect the acidification of the oral microenvironment caused by cariogenic bacteria and can output corresponding color responses according to different pH values ​​to accurately detect the lesion sites of teeth. The data is received and recorded by a smartphone.

[0012] Furthermore, the sonodynamic therapy module is composed of barium titanate nanoparticles inside the pH-sensing coupled sonodynamic therapy module, which are used to generate a piezoelectric catalytic effect under ultrasonic stimulation, thereby generating active oxygen to disinfect cariogenic bacteria in the oral cavity.

[0013] Furthermore, the external ultrasound stimulation device in the sonodynamic therapy module has a frequency of 2MHz and a power of 2.0W / cm². 2 The duty cycle is 8s.

[0014] A method for preparing a hydrogel device for oral pH detection and sonodynamic therapy includes the following steps:

[0015] S1: Add 12.5 mL of 400 μM ammonium persulfate solution to a 30 mL aqueous solution containing 0.39737 g barium titanate nanoparticles, 4.5 mL of 11 mol / L hydrochloric acid, and 455.6 μL of aniline.

[0016] S2: Place the composite solution from step S1 on a mixer and stir continuously for 4 hours at a temperature of 25°C and a speed of 1000 rpm to obtain a uniform dispersion of polyaniline-coated barium titanate nanoparticles.

[0017] S3: The dispersion of polyaniline-coated barium titanate nanoparticles from step S2 is centrifuged at 12,000 rpm, and the precipitate of polyaniline-coated barium titanate nanoparticles is collected; the precipitated polyaniline-coated barium titanate nanoparticles are redispersed in ultrapure water using an ultrasonic device, and the final concentration is 20 mg / mL.

[0018] The beneficial effects of this invention are as follows: This invention provides a hydrogel device and method for oral pH detection and sonodynamic therapy, enabling early in-situ non-invasive diagnosis and treatment of dental caries and teeth whitening. By combining visualized, high-sensitivity pH monitoring with high spatiotemporal precision sonodynamic therapy, the hydrogel device proposed in this invention can effectively achieve early, in-situ detection of dental caries progression, on-demand, precise elimination of cariogenic bacteria, and non-invasive teeth whitening. When the oral microenvironment becomes acidified due to cariogenic bacteria, the hydrogel device reflects the pH fluctuations of the local oral environment through color changes, and records and analyzes the signals via a smartphone. The smartphone displays the fluctuations in the oral acidic environment and issues a warning that dental caries may be developing. Ultrasonic equipment catalyzes the hydrogel device, reacting it with its internal sonodynamic therapy module to generate reactive oxygen species, achieving high spatiotemporal precision elimination of cariogenic bacteria, thereby timely preventing or even reversing the caries lesion stage. Furthermore, the reactive oxygen species generated by the ultrasonic-catalyzed sonodynamic therapy module can also degrade plaque on the tooth surface, achieving a non-invasive teeth whitening effect. The hydrogel device is customizable and easy to operate; it can be customized into any shape according to the user's needs and is not limited by the place of use.

[0019] Compared to traditional oral surgery and drug treatments, the ultrasonic catalytic release of reactive oxygen species using hydrogel devices offers significant advantages such as being non-invasive, non-drug-resistant, and possessing high spatiotemporal precision. This invention integrates visual detection and sonodynamic therapy into a hydrogel device, achieving early closed-loop diagnosis and treatment of dental caries and non-invasive teeth whitening. Furthermore, the hydrogel device proposed in this invention possesses excellent mechanical properties and complete flexibility, capable of withstanding maximum occlusal forces. The hydrogel device can be designed in different shapes to meet the needs of different users, achieving fully personalized design, conformal tooth surface, and high user experience and biocompatibility. Based on these advantages, the hydrogel device and method of this invention can be widely used for early diagnosis and treatment of dental caries and non-invasive teeth whitening. Attached Figure Description

[0020] The accompanying drawings, which are included to provide a further understanding of this application and form part of this application, illustrate exemplary embodiments of this application and are used to explain this application, but do not constitute an undue limitation of this application. In the drawings:

[0021] Figure 1 This is a schematic diagram of the hydrogel device network structure provided in the embodiments of the present invention;

[0022] Figure 2 This is a schematic diagram of a hydrogel device patch model provided in an embodiment of the present invention;

[0023] Figure 3 This is a schematic diagram of a hydrogel dental sticker model provided in an embodiment of the present invention;

[0024] Figure 4 This is a schematic diagram of a hydrogel device dental brace model provided in an embodiment of the present invention;

[0025] Figure 5 This is a schematic diagram of the synthesis of a hydrogel device pH sensing coupled acoustic dynamic therapy module provided in the embodiments of the present invention;

[0026] Figure 6 This is a schematic diagram of the synthesis of a dual-network hydrogel encapsulation layer for a hydrogel device provided in an embodiment of the present invention;

[0027] Figure 7 This is a compressive strain test curve of the hydrogel device provided in the embodiments of the present invention;

[0028] Figure 8 This is a pH absorbance detection curve of the hydrogel device provided in the embodiments of the present invention;

[0029] Figure 9 This is a graph showing the color change results of the hydrogel device provided in the embodiments of the present invention under different concentrations for pH value detection;

[0030] Figure 10 This is a graph showing the color change of pH value of the hydrogel device provided in the embodiments of the present invention over time.

[0031] Figure 11 This is a linear fitting curve of pH value detection for the hydrogel device provided in the embodiments of the present invention;

[0032] Figure 12 This is a pH value detection selectivity test chart of the hydrogel device provided in the embodiments of the present invention;

[0033] Figure 13 This is a test diagram of singlet oxygen release from reactive oxygen species in the sonodynamic therapy module of the hydrogel device provided in the embodiments of the present invention;

[0034] Figure 14 This is a comparison diagram of different experimental groups showing the release of singlet oxygen from reactive oxygen species in the sonodynamic therapy module of the hydrogel device provided in the embodiments of the present invention;

[0035] Figure 15 This is a test diagram of hydroxyl radical release from reactive oxygen species in the sonodynamic therapy module of the hydrogel device provided in the embodiments of the present invention;

[0036] Figure 16 This is a comparative diagram of different experimental groups showing the release of hydroxyl radicals from reactive oxygen species in the sonodynamic therapy module of the hydrogel device provided in the embodiments of the present invention;

[0037] Figure 17 This is a comparison chart of different experimental groups of the hydrogel device acoustic dynamic therapy module provided in the embodiments of the present invention, showing the results of releasing active oxygen to disinfect Streptococcus mutans.

[0038] Figure 18 This is a test diagram of the reactive oxygen species release degradation of pigments in the hydrogel device sonodynamic therapy module provided in the embodiments of the present invention;

[0039] Figure 19 This is a comparison chart of different experimental groups showing the reactive oxygen species release degradation of pigments in the hydrogel device sonodynamic therapy module provided in the embodiments of the present invention;

[0040] Figure 20 This is a comparison chart of different experimental groups of teeth whitening using the hydrogel device sonodynamic therapy module with active oxygen release provided in the embodiments of the present invention;

[0041] Figure 21 This is a flowchart illustrating the process of a hydrogel device provided in an embodiment of the present invention;

[0042] Figure 22 This is a schematic diagram of a hydrogel device provided in an embodiment of the present invention capturing color change signals via a smartphone;

[0043] Figure 23 This is a schematic diagram illustrating the dual effects of active oxygen release in the hydrogel device acoustic therapy module provided in this embodiment of the invention, which kills cariogenic bacteria and whitens teeth.

[0044] In the diagram: 1. Hydrogel encapsulation layer; 2. pH-sensing coupled sonodynamic therapy module; 3. First layer rigid hydrogel network; 4. Second layer flexible hydrogel network; 5. Fully flexible multifunctional adhesive hydrogel patch; 6. Fully flexible multifunctional adhesive hydrogel dental strip; 7. Fully flexible multifunctional adhesive hydrogel dental crown; 8. Polyaniline nanoparticles; 9. Barium titanate nanoparticles; 10. pH sensing module; 11. Sonodynamic therapy module; 12. Agar; 13. Acrylamide; 14. Dental lesion site; 15. Smartphone; 16. Cariogenic bacteria; 17. Tooth surface stains; 18. Ultrasonic stimulation; 19. Cariogenic bacteria elimination; 20. Non-invasive teeth whitening; 21. Healthy teeth. Detailed Implementation

[0045] The embodiments, features, and aspects of this disclosure will be described in detail below with reference to the accompanying drawings, but this is not intended to limit the invention. All other embodiments obtained by those skilled in the art based on any extension of the embodiments of this invention, without inventive effort, are within the scope of protection of this invention. The same reference numerals in the drawings denote the same or similar functional elements. Although various aspects of the embodiments are shown in the drawings, they are not necessarily drawn to scale unless specifically indicated otherwise.

[0046] In addition, to better illustrate this disclosure, numerous specific details are set forth in the following detailed description. Those skilled in the art should understand that this disclosure can be implemented without certain specific details. Some methods and means well known to those skilled in the art, as well as the use of components, are not described in detail in order to highlight the main points of this disclosure.

[0047] like Figure 1 As shown, this embodiment of the invention provides a hydrogel device for oral pH detection and sonodynamic therapy, comprising: a hydrogel encapsulation layer 1, a pH-sensing coupled sonodynamic therapy module 2, a first rigid hydrogel network 3, and a second flexible hydrogel network 4. The hydrogel encapsulation layer 1 is formed by the cross-linking of the first rigid hydrogel network 3 and the second flexible hydrogel network. The first rigid hydrogel network 3 is highly cross-linked and pre-stretched, physically connected by agar 12 through heating and cooling, and acts as a rigid framework in the hydrogel encapsulation layer 1. The second flexible hydrogel network 4 is sparsely cross-linked and relatively concentrated, soft and stretchable, chemically connected by acrylamide 13 through ultraviolet light polymerization, used to improve the mechanical properties and deformation capacity of the hydrogel encapsulation layer 1. The pH-sensing coupled sonodynamic therapy module 2 is embedded in the hydrogel encapsulation layer 1, including a pH sensing module 10 and a sonodynamic therapy module 11, and is composed of a polymer structure of barium titanate nanoparticles 9 encapsulated by polyaniline nanoparticles 8. The pH sensing module 10 consists of a polyaniline layer on the outside of the sonodynamic therapy module 11. It is used to detect the acidification of the oral microenvironment caused by cariogenic bacteria 16, and can output corresponding color responses according to different pH values ​​to accurately detect the tooth lesion site 14. The data is received and recorded by the smartphone 15. The sonodynamic therapy module 11 consists of barium titanate nanoparticles inside the pH sensing coupled sonodynamic therapy module 2. It is used to generate a piezoelectric catalytic effect under ultrasonic stimulation 18, thereby generating active oxygen to disinfect cariogenic bacteria in the oral cavity 19. In addition, active oxygen can also be used to degrade tooth surface dirt 17, achieving the effect of non-invasive teeth whitening 20 and obtaining healthy teeth 21. The fully flexible multifunctional adhesive hydrogel patch 5, the fully flexible multifunctional adhesive hydrogel dental strip 6, and the fully flexible multifunctional adhesive hydrogel dental cover 7 are composed of a hydrogel encapsulation layer 1 and a pH sensing coupled sonodynamic therapy module 2, and are formed by casting.

[0048] like Figures 2-4As shown, the hydrogel devices are customized into fully flexible multifunctional adhesive hydrogel patches 5, fully flexible multifunctional adhesive hydrogel dental strips 6, and fully flexible multifunctional adhesive hydrogel dental crowns 7 using a casting method. Specifically, teeth and alveolar bone are 3D printed using transparent photosensitive resin, and then cross-linked through a two-step cross-linking method. All three fully flexible multifunctional adhesive hydrogel patches 5, 6, and 7 internally encapsulate a pH-sensing coupled sonodynamic therapy module 2, providing functions for monitoring the local acidic environment of the oral cavity and sonodynamic therapy. The fully flexible multifunctional adhesive hydrogel patch 5 has a patch radius of 0.2 mm and a thickness of 1 mm. The fully flexible multifunctional adhesive hydrogel dental strip 6 is 8 cm long, 8 mm thick, and 1 mm high. The fully flexible multifunctional adhesive hydrogel dental crown 7 is cast according to different users' tooth models. The hydrogel devices can adhere well to the tooth surface, achieving tooth surface conformal design.

[0049] like Figure 5 As shown, the pH-sensing coupled acoustic dynamic therapy module 2 is fabricated using an in-situ polymerization method. It comprises polyaniline nanoparticles 8 and barium titanate nanoparticles 9. 2.4 parts by weight of ammonium persulfate, 2.1 parts by weight of barium titanate nanoparticles 9, 80 parts by weight of ultrapure water, 3 parts by weight of concentrated hydrochloric acid, and 1 part by weight of aniline are mixed thoroughly and stirred at 23 degrees Celsius for 5.5 hours. The solution is centrifuged at 11550 rpm at 5 degrees Celsius for 25 minutes. The supernatant is collected and redispersed to obtain the pH-sensing coupled acoustic dynamic therapy module 2. The external ultrasonic stimulation device in the pH-sensing coupled acoustic dynamic therapy module 2 has a frequency of 2 MHz and a power of 2.0 W / cm². 2 The duty cycle is 8s.

[0050] like Figure 6 As shown, the hydrogel encapsulation layer 1 is formed by cross-linking a first rigid hydrogel network 3 and a second flexible hydrogel network 4. Specifically, the hydrogel encapsulation layer 1 is composed of 10 parts by weight of agar powder, 100 parts by weight of acrylamide, 3 parts by weight of 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone, 4 parts by weight of methylenebisacrylamide, 30 parts by weight of pH-sensing coupled sonodynamic therapy module 2, and 270 parts by weight of deionized water through a two-step cross-linking method.

[0051] The first rigid hydrogel network 3 is formed by physically linking agar 12 through heating and cooling, serving as a rigid framework in the hydrogel encapsulation layer 1. The pH-sensor-coupled sonodynamic therapy module 2, agar 12, and acrylamide 13 solution are heated to 98 degrees Celsius until completely dissolved, then cooled at 23 degrees Celsius for 50 minutes to form the first rigid hydrogel network 3. The second flexible hydrogel network 4 is chemically linked by acrylamide 13 through ultraviolet light polymerization, used to improve the mechanical properties and deformation capacity of the hydrogel encapsulation layer 1. After the first rigid hydrogel network 3 is successfully prepared, it is placed under a 10W, 365nm ultraviolet lamp for photopolymerization for 55 minutes to form the second flexible hydrogel network 4.

[0052] This invention provides a method for preparing a hydrogel device for oral pH detection and sonodynamic therapy, comprising the following steps:

[0053] S1: Add 12.5 mL of 400 μM ammonium persulfate solution to a 30 mL aqueous solution containing 0.39737 g barium titanate nanoparticles, 4.5 mL of 11 mol / L hydrochloric acid, and 455.6 μL of aniline.

[0054] S2: Place the composite solution from step S1 on a mixer and stir continuously for 4 hours at a temperature of 25°C and a speed of 1000 rpm to obtain a uniform dispersion of polyaniline-coated barium titanate nanoparticles.

[0055] S3: The dispersion of polyaniline-coated barium titanate nanoparticles from step S2 is centrifuged at 12,000 rpm, and the precipitate of polyaniline-coated barium titanate nanoparticles is collected; the precipitated polyaniline-coated barium titanate nanoparticles are redispersed in ultrapure water using an ultrasonic device, and the final concentration is 20 mg / mL.

[0056] The hydrogel device provided by this invention possesses excellent mechanical properties (such as...). Figure 7 As shown, the hydrogel device underwent a maximum compressive force cyclic test using a universal testing machine. First, the hydrogel device was compressed to 100% at a rate of 0.1 mm per second, at which point it withstood a maximum compressive stress of 3.24 MPa. Then, it was restored to its initial shape at the original rate, and its shape remained unchanged, demonstrating that the hydrogel device can withstand extremely high compressive forces without deformation. The excellent mechanical properties of the hydrogel device ensure its integrity during daily activities such as chewing and speaking.

[0057] like Figure 8As shown, the pH sensing module 10 can detect pH changes from 4 to 8 in real time and is calibrated using a UV spectrophotometer before use. First, a buffer solution with pH values ​​of 4-8 is prepared for UV spectral characterization and calibrated using a pH meter. Two mL of buffer solutions with different pH values ​​are added to 1 mL of polyaniline nanoparticle 8 solution, and the absorbance changes of the polyaniline nanoparticle 8 solution reacting with solutions of different pH values ​​are recorded using a UV spectrophotometer. When the pH value is 8, the polyaniline nanoparticle 8 solution has two peaks at wavelengths of 325 nm and 620 nm. As the pH value decreases, the peak values ​​of the polyaniline nanoparticle 8 solution shift to 420 nm and 800 nm, indicating that the polyaniline nanoparticle 8 transforms from the emerald base form to the emerald salt form.

[0058] The hydrogel device of this invention uses a pH sensing module 10 of optimal concentration embedded in the hydrogel, which can maximize the sensing of pH value, such as... Figure 9 As shown in the figure, B / G is defined as the ratio of the intensity value of the hydrogel device in the blue (B) channel to the intensity value in the green (G) channel of the RGB spectrum, used to quantify the color change of the hydrogel device. Polyaniline nanoparticles 8 at concentrations ranging from 1 mg / ml to 5 mg / ml were embedded in the hydrogel encapsulation layer. All these hydrogel devices exhibited color change reactions with buffer solutions of different pH values. The 2 mg / ml concentration of polyaniline nanoparticles 8 embedded in the hydrogel device showed the most significant color change in buffer solutions at different pH values; therefore, this concentration was selected for subsequent testing.

[0059] like Figure 10 As shown, the color signal output by the hydrogel device of this invention for pH sensing is time-dependent. The hydrogel device was immersed in a buffer solution with pH values ​​ranging from 4 to 8 for 150 minutes, and color changes were recorded every 30 minutes. The degree of color change of the hydrogel device depended on the pH value of the buffer solution and the immersion time. Under pH 4 conditions, the patch color remained green throughout the test. As the pH value increased, the color gradually turned blue, indicating that the polyaniline nanoparticles 8 in the hydrogel device transformed from emerald base to emerald salt. After immersion in buffer solutions with different pH values ​​for 30 minutes, significant color differences existed between the patches, and the B / G value no longer changed significantly over time. To evaluate the pH sensitivity of the hydrogel device, the B / G value at 30 minutes was plotted as a function of pH value, and fitted with a linear equation, R0. 2 The value was 0.9992. To ensure the repeatability of the sensor, three repeated measurements were performed using different electrodes, and the results showed good consistency among the different electrodes (e.g., ...). Figure 11 (As shown). Selective characterization experiments were performed by preparing 30 mM K. + 2mMCa 2+20mM Na + 800 μM glucose and 0.5 mM Mg 2+ The solution was used for verification. With the addition of different interfering substances, the effect was observed in H₂O. + With the concentration remaining constant, the color signal remained essentially unchanged, except for a sudden change when the buffer solution was changed from pH=4 to pH=7 (e.g. Figure 12 (As shown). This demonstrates that the pH sensing module 10 is sensitive to the pH in the oral microenvironment. + It has strong specificity detection capabilities and can adapt to the complex oral environment in terms of selectivity.

[0060] The acoustic dynamic therapy module 11 of the hydrogel device of this invention can generate reactive oxygen species, such as singlet oxygen and hydroxyl radicals, under ultrasonic stimulation. Figure 13 As shown, the generation of singlet oxygen was characterized by the specific degradation of diphenylisobenzofuran solution using singlet oxygen. The maximum absorption wavelength of diphenylisobenzofuran solution is approximately 410 nm. Under ultrasonic catalysis, the hydrogel device degraded the maximum absorption peak of diphenylisobenzofuran solution by 6.67 times within 35 min, indicating that the generation of singlet oxygen is time-dependent. To quantitatively reveal the role of piezoelectricity in the generation of singlet oxygen under ultrasonic stimulation, the relative concentration difference A0-A of the solution was plotted as a function of the ultrasonic time for various treatments, where A0 and A are the initial and residual concentrations of the solution, respectively. Under ultrasonic catalysis, the hydrogel device showed the most significant promoting effect on the decomposition of diphenylisobenzofuran solution, while ultrasonic treatment alone, hydrogel device treatment, and no treatment had almost no effect on the diphenylisobenzofuran solution (e.g., Figure 14 As shown). Figure 15 As shown, the generation of hydroxyl radicals was characterized by the specific degradation of methylene blue solution using hydroxyl radicals. The maximum absorption wavelength of methylene blue solution is approximately 664 nm. Under ultrasonic catalysis, the hydrogel device degraded the maximum absorption peak of methylene blue solution by 3.71 times within 35 minutes, indicating that the generation of hydroxyl radicals is time-dependent. To quantitatively reveal the role of piezoelectricity in the generation of hydroxyl radicals under ultrasonic stimulation, the degradation of methylene blue solution by the hydrogel device under different experimental conditions was investigated. The promoting effect of ultrasonic catalysis on the decomposition of diphenylisobenzofuran solution was most significant, while ultrasonic treatment alone, hydrogel device treatment, and no treatment had almost no effect on diphenylisobenzofuran solution (e.g., Figure 16 (As shown). This demonstrates that under ultrasonic catalysis, the piezoelectric effect generated by barium titanate nanoparticles 9 in the hydrogel device promotes the generation of singlet oxygen and hydroxyl radicals, which is more conducive to the dual therapeutic effects of eliminating cariogenic bacteria and whitening teeth.

[0061] like Figure 17As shown, the sonodynamic therapy module 11 of the hydrogel device of this invention can effectively disinfect cariogenic bacteria. *Streptococcus mutans*, one of the most representative cariogenic bacteria in the oral cavity, was selected as a model for the experiment. The concentration of *Streptococcus mutans* was adjusted to 1.0 × 10⁻⁶ using a culture medium containing 1 wt% sucrose. 8 CFU / mL. The sterilization effect of the hydrogel device under sonic catalysis was evaluated by counting colony-forming units. Compared with no treatment, the number of *Streptococcus mutans* under hydrogel treatment and sonication treatment was almost unchanged, while the hydrogel device under sonic catalysis almost completely eliminated *Streptococcus mutans*. The antibacterial rate of the hydrogel device under sonic catalysis was 99.4%, significantly higher than other control groups, demonstrating a good effect in eliminating *Streptococcus mutans*. This proves that the hydrogel device under sonic catalysis can achieve a non-invasive and highly effective oral antibacterial treatment.

[0062] like Figure 18 As shown, the sonodynamic therapy module 11 of the hydrogel device of this invention has a teeth whitening effect. The teeth whitening ability of the hydrogel device was characterized by the specific degradation of the pigment component, indigo carmine, by reactive oxygen species. The maximum absorption peak of indigo carmine appeared at a wavelength of 611 nm. When the time of ultrasonic catalysis on the hydrogel device increased to 35 min, its absorption peak degraded to 6.10 times the initial value. To illustrate that the piezoelectric catalytic effect generated by the hydrogel device under ultrasonic irradiation is the main factor affecting the degradation of indigo carmine, other control groups were also set up. For example... Figure 19 As shown, after 35 minutes of ultrasonic catalysis, over 87% of the indigo carmine solution was degraded by the hydrogel device, a degradation rate significantly higher than that under untreated, hydrogel device-only, and ultrasonic catalysis-only conditions. The therapeutic effect of the hydrogel device on teeth whitening was further validated using a real tooth simulation experiment. Food-induced staining was simulated by immersing human teeth in a mixture of black tea, red wine, and blueberry juice for one week. Figure 20 As shown, the most significant change in tooth crown color was observed after 6 hours of ultrasonic catalysis using the hydrogel device, and the longer the ultrasonic stimulation time, the more obvious the teeth whitening effect. Within the same treatment time, the color changes in stained tooth crowns were barely noticeable under no treatment, hydrogel device treatment only, and ultrasonic catalysis only. This demonstrates that hydrogel devices, under ultrasonic catalysis, can achieve non-invasive and highly effective teeth whitening.

[0063] The workflow diagram of the hydrogel device is as follows: Figure 21 As shown. When the pH of the oral microenvironment fluctuates, the pH sensing module 10 in the hydrogel device outputs different color signals to reflect the degree of oral acidification. The color signals are received and linearly analyzed by a smartphone. When the pH is too low, posing a risk of tooth decay, an alert is issued to the user (e.g., ...). Figure 22(As shown). Users can use an ultrasonic device to stimulate the sonodynamic therapy module 11 in the hydrogel device, which generates reactive oxygen species through a carrier migration reaction with the piezoelectric barium titanate nanoparticles 9 therein. Reactive oxygen species can non-invasively and efficiently disinfect cariogenic bacteria in the oral cavity and remove plaque from the tooth surface, achieving a dual treatment of efficient and non-invasive sterilization and teeth whitening (e.g., Figure 23 (As shown).

[0064] This invention relates to a hydrogel device for oral pH monitoring and sonodynamic therapy, enabling non-invasive and highly efficient early diagnosis and treatment of dental caries and teeth whitening. Combined with a smartphone, the hydrogel device is customizable, easy to operate, and can be tailored to any shape according to the user's needs, without being limited by the location of use. By attaching the hydrogel to the tooth surface, RGB analysis software developed for smartphones captures and alerts users to the color signals emitted by the hydrogel device. Then, an ultrasonic device catalyzes the release of reactive oxygen species in the sonodynamic therapy module for non-invasive and highly efficient treatment. This invention achieves in-situ high-sensitivity pH monitoring, high spatiotemporal precision sterilization, and non-invasive teeth whitening, and can be effectively used for early diagnosis and treatment of dental caries and teeth whitening.

[0065] It should be noted that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention can have various modifications and variations. Any modifications, equivalent substitutions, improvements, etc., made without creative effort should be included within the protection scope of the present invention.

Claims

1. A hydrogel device for oral pH detection and sonodynamic therapy, characterized in that, It includes: The hydrogel encapsulation layer (1) and the pH-sensing coupled sonodynamic therapy module (2) are described. The hydrogel encapsulation layer (1) is composed of a first rigid hydrogel network (3) and a second flexible hydrogel network (4) that are cross-linked together. The first rigid hydrogel network (3) is highly cross-linked and pre-stretched, and is formed by physical connection of agar (12) through heating and cooling, serving as a rigid skeleton in the hydrogel encapsulation layer (1). The second flexible hydrogel network (4) is sparsely cross-linked and relatively concentrated, soft and stretchable, and is formed by chemical connection of acrylamide (13) through ultraviolet light polymerization, used to improve the mechanical properties of the hydrogel encapsulation layer (1). The pH sensing coupled acoustic dynamic therapy module (2) is embedded in the hydrogel encapsulation layer (1) and includes a pH sensing module (10) and an acoustic dynamic therapy module (11), which is composed of a polymer structure of barium titanate nanoparticles (9) wrapped by polyaniline nanoparticles (8); the pH sensing module (10) is composed of a polyaniline layer outside the acoustic dynamic therapy module (11) and is used to detect the acidification of the oral microenvironment caused by cariogenic bacteria (16); the acoustic dynamic therapy module (11) is composed of barium titanate nanoparticles inside the pH sensing coupled acoustic dynamic therapy module (2) and is used to generate a piezoelectric catalytic effect under ultrasonic stimulation (18); The fully flexible multifunctional adhesive hydrogel patch (5), the fully flexible multifunctional adhesive hydrogel dental veneer (6) and the fully flexible multifunctional adhesive hydrogel dental crown (7) are composed of a hydrogel encapsulation layer (1) and a pH-sensing coupled sonodynamic therapy module (2), and are formed by casting.

2. The hydrogel device for oral pH detection and sonodynamic therapy according to claim 1, characterized in that, The pH sensing coupled acoustic therapy module (2) is composed of 114 parts by mass of ammonium persulfate, 40 parts by mass of barium titanate, 5 parts by mass of aniline, 18 parts by mass of concentrated hydrochloric acid and 430 parts by mass of deionized water through in-situ polymerization.

3. The hydrogel device for oral pH detection and sonodynamic therapy according to claim 1, characterized in that, The hydrogel encapsulation layer (1) is composed of 10 parts by weight of agar powder, 100 parts by weight of acrylamide, 3 parts by weight of 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone, 4 parts by weight of methylenebisacrylamide, 30 parts by weight of pH sensing coupled sonodynamic therapy module (2) and 270 parts by weight of deionized water through a two-step crosslinking method.

4. The hydrogel device for oral pH detection and sonodynamic therapy according to claim 1, characterized in that, The first rigid hydrogel network (3) is composed of agar physical cross-linking, specifically: after heating the pH sensing coupled acoustic dynamic therapy module (2), agar, and acrylamide solution to complete dissolution, it is cooled to form the first rigid hydrogel network (3).

5. The hydrogel device for oral pH detection and sonodynamic therapy according to claim 1, characterized in that, The second layer of flexible hydrogel network (4) is composed of acrylamide photocuring crosslinking by ultraviolet light polymerization, that is, irradiated for 55 minutes under an ultraviolet lamp with a power of 10W and a wavelength of 365nm.

6. The hydrogel device for oral pH detection and sonodynamic therapy according to claim 1, characterized in that, The fully flexible multifunctional adhesive hydrogel patch (5), the fully flexible multifunctional adhesive hydrogel dental strip (6), and the fully flexible multifunctional adhesive hydrogel dental crown (7) are made by casting, that is, teeth and alveolar bone are 3D printed by transparent photosensitive resin and then cross-linked by a two-step cross-linking method.

7. The hydrogel device for oral pH detection and sonodynamic therapy according to claim 1, characterized in that, The pH sensing module (10) consists of a polyaniline layer outside the acoustic therapy module (11). It is used to detect the acidification of the oral microenvironment caused by cariogenic bacteria (16) and can output corresponding color responses according to different pH values ​​to accurately detect the lesion site (14) of the tooth. The data is received and recorded by a smartphone (15).

8. The hydrogel device for oral pH detection and sonodynamic therapy according to claim 1, characterized in that, The sonodynamic therapy module (11) is composed of barium titanate nanoparticles inside the pH-sensing coupled sonodynamic therapy module (2), which are used to generate a piezoelectric catalytic effect under ultrasonic stimulation (18), thereby generating active oxygen to disinfect cariogenic bacteria in the oral cavity (19).

9. The hydrogel device for oral pH detection and sonodynamic therapy according to claim 1, characterized in that, The external ultrasound stimulation device in the sonodynamic therapy module (11) has a frequency of 2MHz and a power of 2.0W / cm². 2 The duty cycle is 8s.

10. The method for preparing a hydrogel device for oral pH detection and sonodynamic therapy according to any one of claims 1-9, characterized in that, Includes the following steps: S1: Add 12.5 mL of 400 μM ammonium persulfate solution to a 30 mL aqueous solution containing 0.39737 g barium titanate nanoparticles, 4.5 mL of 11 mol / L hydrochloric acid, and 455.6 μL of aniline. S2: Place the composite solution from step S1 on a mixer and stir continuously for 4 hours at a temperature of 25°C and a speed of 1000 rpm to obtain a uniform dispersion of polyaniline-coated barium titanate nanoparticles. S3: The dispersion of polyaniline-coated barium titanate nanoparticles from step S2 is centrifuged at 12,000 rpm, and the precipitate of polyaniline-coated barium titanate nanoparticles is collected; the precipitated polyaniline-coated barium titanate nanoparticles are redispersed in ultrapure water using an ultrasonic device, and the final concentration is 20 mg / mL.

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