Device for realizing time-space regulation and control of dental pulp repair and regeneration by utilizing active occlusion movement

Abstract

The invention belongs to the field of oral medicine, and particularly relates to a device for realizing space-time regulation and control of dental pulp repair and regeneration by utilizing active occlusion movement. The device is composed of a miniature magnetoelectric generating device, an inert metal electrode connected with the miniature magnetoelectric generating device through an electric conductor, a hydrophobic insulating coating wrapping the inert metal electrode and a personalized tooth filling module, and dental pulp stem cells are promoted to migrate to an injured part through the magnetoelectric effect generated by active occlusion movement. According to the present invention, with the dental pulp stem cell culture medium, the dryness of the dental pulp stem cells is maintained, the early differentiation is inhibited, the dental pulp dispersive calcification is avoided, and the dentin forming ability of the dentin forming cells differentiated from the dental pulp stem cells is improved; when the oral cavity is in a resting state, the capability of differentiating the dental pulp stem cells of the injured part to the dentin-forming cells under physiological stimulation is recovered; and through alternate generation of active occlusion and resting states, dental pulp repair is promoted, the repair period is shortened, live pulp is preserved, and a new thought and choice are provided for dental pulp repair and regeneration.

Description

Technical Field

[0001] The present invention belongs to the field of oral medicine, and in particular relates to a device for realizing spatiotemporally controlled dental pulp repair and regeneration by utilizing active occlusal motion. Background Art

[0002] There are populations of mesenchymal stem cells in adult tissues that contribute to tissue cell renewal and respond to tissue damage. In dental pulp tissue, in addition to playing an active role in self-renewal and multipotent differentiation, dental pulp stem cells can also respond to external stimuli to regulate dental pulp repair and regeneration. When the dental pulp is exposed to external stimuli such as caries or trauma, odontoblasts are destroyed, dental pulp stem cells are recruited to the site of injury, and differentiate into odontoblast-like cells to form reparative dentin, ultimately repairing all or part of the damaged area. Although the various behaviors of dental pulp stem cells contribute to dental pulp repair, the migration of dental pulp stem cells is considered a prerequisite for dental pulp repair and regeneration, and the formation of reparative dentin by odontoblasts is the determining factor.

[0003] Regardless of the materials used, current vital pulp preservation treatments are essentially a pulpal response to chemical stimulation from materials with a high pH. This differs from the physiological process of pulp-dentin complex formation, resulting in a disordered dentin-like structure and even tunnel defects, compromising treatment efficacy. Therefore, stem cell-guided approaches to promote the body's spontaneous defense response to restore a physiological pulp-dentin complex, preserve vital pulp, and promote hard tissue repair are important future research directions.

[0004] External electrical stimulation can influence cell behavior, including transmembrane potential shifts, stem cell differentiation, cell proliferation, cell migration, inflammatory cytokine secretion, and collagen production. These cellular behaviors are beneficial for promoting tissue healing, such as bone and skin healing. In dentistry, electrical stimulation has been shown to be useful for assessing dental pulp, locating root apexes, improving the properties of dental biomaterials, accelerating orthodontic tooth movement, promoting implant osseointegration, addressing maxillofacial malignancies, and managing neuromuscular dysfunction.

[0005] Although a large number of studies have explored the effects of electrical stimulation on cell behavior, in the field of dental pulp repair and regeneration, no researchers have focused on the effect of electrical stimulation on the migration ability of dental pulp stem cells. Summary of the Invention

[0006] In view of the shortcomings of the existing technology, the present invention provides a device for realizing spatiotemporally controlled dental pulp repair and regeneration by utilizing active occlusal motion.

[0007] A personalized electrical stimulation device comprises a micro-magnetoelectric generator (6), an inert metal electrode (8), an insulating coating (9) and a tooth filling module (10); the micro-magnetoelectric generator (6) and the inert metal electrode (8) are connected by an electrical conductor (7); the insulating coating (9) wraps the inert metal electrode (8); and the micro-magnetoelectric generator (6), the electrical conductor (7) and the inert metal electrode (8) are embedded in the tooth filling module (10).

[0008] Preferably, the micro magnetoelectric generating device (6) comprises a ferromagnetic droplet (1), a super-hydrophobic base (2), a coil (3), a plate-shaped magnet (4) and a resin insulating base (5); the coil (3), the plate-shaped magnet (4) and the resin insulating base (5) are connected in sequence.

[0009] Preferably, the ferromagnetic droplet (1) flows in the super-hydrophobic base (2) and generates an induced current with the plate-shaped magnet (4).

[0010] Preferably, the inert metal electrode (8) is selected from at least one of a platinum electrode and a titanium electrode;

[0011] and / or, the insulating coating (9) is selected from a hydrophobic insulating coating;

[0012] And / or, the hydrophobic insulating coating is selected from at least one of polytetrafluoroethylene and ceramic coating.

[0013] The present invention also provides use of the personalized electrical stimulation device in manufacturing medical devices for promoting dental pulp repair and regeneration.

[0014] Preferably, the electrical stimulation device is used to promote the migration of dental pulp stem cells.

[0015] Preferably, the electrical stimulation device is used to maintain the stemness of dental pulp stem cells.

[0016] Preferably, the electrical stimulation device is used to accelerate the formation of reparative dentin.

[0017] Preferably, the electrical stimulation device generates electrical stimulation when the oral cavity moves, and does not generate electrical stimulation when the oral cavity is in a resting state.

[0018] Preferably, the electric field strength generated by the electric stimulation device is 100mV / mm-200mV / mm, the electric stimulation time is 8 to 12 hours / day, and the length extending into the dental pulp is 0.8 to 1.2mm.

[0019] The present invention consists of a micro-magnetoelectric generator, an inert metal electrode connected to the micro-magnetoelectric generator via a wire, a hydrophobic insulating coating wrapped around the inert metal electrode, and a personalized tooth filling module. During oral movement, the electrical stimulation device of the present invention can generate constant electrical stimulation, promote the migration of undifferentiated dental pulp stem cells, retain their stemness, promote the differentiation of already differentiated dental pulp cells, and accelerate the formation of reparative dentin; during the resting process (without electrical stimulation), the undifferentiated dental pulp stem cells that have migrated to the damaged area begin to differentiate into odontoblasts under external stimulation. The device realizes the full-cycle application of temporally and spatially controllable dental pulp repair and regeneration, and improves the quality and rate of dental pulp repair. At the same time, the device is compact, does not require an external power supply, is small and convenient, and provides a new and effective way for dental pulp repair and regeneration.

[0020] Obviously, based on the above contents of the present invention, according to common technical knowledge and customary means in this field, without departing from the above basic technical ideas of the present invention, other various forms of modifications, replacements or changes can be made.

[0021] The following further describes the above content of the present invention in detail through specific embodiments in the form of examples. However, this should not be construed as limiting the scope of the above subject matter of the present invention to the following examples. All technologies implemented based on the above content of the present invention fall within the scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 Schematic diagram of the magnetoelectric dental filling module. (a) The internal structure of the micro-magnetoelectric generator; (b) An abstract cross-sectional view of the new clinical magnetoelectric dental filling module; (c) A left side view of the new magnetoelectric dental filling module; (d) A three-dimensional cross-sectional view of the new clinical magnetoelectric dental filling module.

[0023] Figure 2 This is a detection diagram of the changes in the movement and migration rate of dental pulp stem cells in a DC electric field.

[0024] Figure 3 Effects of direct current electric field on the proliferation of dental pulp stem cells.

[0025] Figure 4 This figure shows the test results of the effect of direct current electric field stimulation for 1 day and 2 days after the stimulation is withdrawn on the odontoblast differentiation potential of human dental pulp stem cells.

[0026] Figure 5 This is the result of the detection of the changes in positive factors of stemness differentiation of human dental pulp stem cells under the influence of direct current electric field.

[0027] Figure 6 This figure shows the test results of the odontoblasts' odontoblastic ability after 3 days of odontoblast induction culture and then 3 days of direct current electric field stimulation.

[0028] The names of the components are: 1- ferromagnetic droplet, 2- superhydrophobic base, 3- coil, 4- plate-shaped magnet, 5- resin insulating base plate, 6- micro magnetoelectric generator, 7- conductor, 8- inert metal electrode, 9- insulating coating, 10- dental filling module. DETAILED DESCRIPTION

[0029] In the following examples and experimental examples, reagents and raw materials not specifically described are all commercially available.

[0030] Example 1 Personalized electrical stimulation device and its application in pulp capping treatment of deep caries

[0031] The patient's deeply carious teeth are caries-removed and cavity-shaped to create an oral model. A 3D scan of the patient's teeth is performed using an oral scanner to create a digital 3D model. 3D printing technology is then used to create a personalized filling module 10 adapted to the cavity's shape. Space is reserved on the module for a micro-magnetoelectric generator 6. The micro-magnetoelectric generator consists of a ferromagnetic droplet 1, a super-hydrophobic base 2, a coil 3, a plate-shaped magnet 4, and a resin insulating base 5, all of which are connected in sequence. The ferromagnetic droplet 1 flows within the super-hydrophobic base 2, generating an induced current with the plate-shaped magnet 4.

[0032] Assemble a micro magnetoelectric generator 6, an inert metal electrode 8 connected to the micro magnetoelectric generator via an electrical conductor 7, and a hydrophobic insulating polytetrafluoroethylene coating 9 wrapped around the inert metal electrode, wherein the inert metal electrode is placed in the reserved nail hole to ensure that the electric field intensity generated by the electric stimulation is 150mV / mm and the electric stimulation time is 12 hours; embed the assembled components into the personalized dental filling module 10 to form a personalized electric stimulation device ( Figure 1 The patient wears the device for 1-2 months for soothing treatment before undergoing permanent repair.

[0033] Comparative Example 1 Composite resin material

[0034] The traditional tooth filling method is used to remove caries and prepare the cavity shape of the patient's deep caries teeth, and then fill them with composite resin materials.

[0035] Example 2: Personalized electrical stimulation device for vital marrow preservation treatment

[0036] The device is essentially the same as that in Example 1. For young permanent teeth exposed due to trauma or deep caries, pulpotomy and necrotic pulp removal are performed, and the cavity is prepared. A 3D scan of the patient's tooth is performed using an oral scanner to create a digital 3D model. 3D printing technology is then used to create a personalized temporary sealing module 10 adapted to the cavity's shape. Regular follow-up visits are conducted at intervals of 1, 3, 6 months, and 1 year. A permanent filling is performed when there are no significant symptoms and the root continues to develop.

[0037] Control case 2MTA undergoes vital pulp preservation treatment

[0038] Chemical material MTA is used to perform vital pulp preservation treatment on young permanent teeth with pulp exposure caused by trauma or deep caries.

[0039] The technical solution of the present invention is further illustrated by experiments below.

[0040] The electrical stimulation used in this experimental example was generated by the electrical stimulation device in patent CN115584340A.

[0041] Experimental Example 1: Effect of DC electric field on the migration rate of dental pulp stem cells

[0042] 1. Experimental Methods

[0043] 1. Culture of dental pulp stem cells

[0044] Dental pulp stem cells were isolated and cultured from dental pulp tissue, and cultured in MEM-a (minimum essential medium-a) supplemented with 10% fetal bovine serum and 1% penicillin (U)-streptomycin (μg) double antibody.

[0045] 2. Cell scratch test

[0046] A scratch was made in the middle area of ​​the culture dish filled with dental pulp cells. The healing of the scratched area was observed 12 hours after electrical stimulation to determine the migration rate.

[0047] 2. Experimental Results

[0048] from Figure 2 As can be seen from the figure, the migration rate of dental pulp stem cells using electrical stimulation is significantly higher than that of the control group, indicating that electrical stimulation can promote the migration of dental pulp stem cells.

[0049] Experimental Example 2: Effect of DC electric field on the proliferation of dental pulp stem cells

[0050] 1. Experimental Methods

[0051] CCK8 method: CCK-8 reagent is added to the electrically stimulated dental pulp stem cells, and after incubation in a cell culture incubator, the absorbance value at 450nm is detected using a microplate reader.

[0052] 2. Experimental Results

[0053] from Figure 3 It can be seen that there is no significant difference in the proliferation ability of dental pulp stem cells after electrical stimulation compared with the control group, indicating that electrical stimulation does not affect the proliferation ability of dental pulp stem cells.

[0054] Experimental Example 3: Effect of DC electric field on the odontoblast differentiation potential of dental pulp stem cells

[0055] 1. Experimental Methods

[0056] ALP staining was performed on dental pulp stem cells after electrical stimulation for 12 hours within one day and 2 days after electrical stimulation was withdrawn to analyze the odontoblast differentiation level.

[0057] 2. Experimental Results

[0058] from Figure 4 As can be seen in the figure, the odontoblast differentiation potential of dental pulp stem cells after electrical stimulation was significantly reduced 12 hours after electrical stimulation and returned to normal levels after the electrical stimulation was withdrawn. This suggests that electrical stimulation can preserve the stemness of dental pulp stem cells but does not affect their subsequent differentiation ability in a resting state.

[0059] Experimental Example 4: Effects of DC Electric Field on Changes in Stemness Positive Factors in Dental Pulp Stem Cells I. Experimental Methods

[0060] Flow cytometry was used to detect the stemness positive markers STRO-1 and CD164 and the stemness negative marker CD34 of dental pulp stem cells.

[0061] 2. Experimental Results

[0062] Stemness-positive markers are usually associated with the self-renewal and pluripotency of stem cells; stemness-negative markers are usually associated with the differentiation state of stem cells, and an increase in their expression level means that the cells are losing their stem cell characteristics and differentiating into specific types of cells. Figure 5 As shown in the figure, the DC electric field reduces the proportion of stemness-positive markers and increases the proportion of negative markers. This indicates that dental pulp cells continue to differentiate after electrical stimulation, effectively preventing pulp cell differentiation during migration and shortening the repair cycle.

[0063] Experimental Example 5: Effect of DC electric field on the ability of odontoblasts to form dentin

[0064] 1. Experimental Methods

[0065] Dentinogenic differentiation: Dental pulp stem cells were induced for 3 days using odontoblast-inducing medium (OM) containing dexamethasone, sodium β-glycerophosphate, and ascorbic acid. Following OM, electrical stimulation was applied at 1.5V for 12 hours for 3 days, and the cells were stained for ALP and analyzed for odontoblast differentiation.

[0066] 2. Experimental Results

[0067] from Figure 6 As can be seen from the results, compared with the control group, electrical stimulation can enhance the odontoblastic ability of dental pulp stem cells after they differentiate into odontoblasts. This indicates that electrical stimulation of odontoblasts can accelerate the formation of dentin.

[0068] The above experiments demonstrate that the personalized electrical stimulation device provided by the present invention can, during vital pulp preservation treatment, promote the migration of dental pulp stem cells to the damaged area through the magnetoelectric effect generated by active occlusal movement, thereby maintaining the stemness of dental pulp stem cells, inhibiting their early differentiation, and preventing the occurrence of diffuse pulp calcification. It also enhances the odontoblastic capacity of odontoblasts derived from dental pulp stem cells. Furthermore, when the oral cavity is in a resting state, the device restores the ability of dental pulp stem cells at the damaged area to differentiate into odontoblasts under physiological stimulation. Therefore, by actively adjusting oral movement patterns through scientific methods, the repair cycle can be shortened, vital pulp can be preserved, and the repair and regeneration of damaged dental hard tissue can be promoted, providing a new and effective approach for dental pulp repair and regeneration.

Claims

1. A personalized electrical stimulation device, characterized in that: The device comprises a micro magnetoelectric generator (6), an inert metal electrode (8), an insulating coating (9) and a tooth filling module (10); the micro magnetoelectric generator (6) and the inert metal electrode (8) are connected by an electric conductor (7); the insulating coating (9) wraps the inert metal electrode (8); the micro magnetoelectric generator (6), the electric conductor (7) and the inert metal electrode (8) are embedded in the tooth filling module (10).

2. The personalized electrical stimulation device according to claim 1, characterized in that: The micro magnetoelectric generating device (6) comprises a ferromagnetic droplet (1), a super-hydrophobic base (2), a coil (3), a plate-shaped magnet (4) and a resin insulating base plate (5); the coil (3), the plate-shaped magnet (4) and the resin insulating base plate (5) are connected in sequence.

3. The personalized electrical stimulation device according to claim 2, characterized in that: The ferromagnetic droplet (1) flows in the super-hydrophobic base (2) and generates an induced current with the plate-shaped magnet (4).

4. The personalized electrical stimulation device according to claim 1, characterized in that: The inert metal electrode (8) is selected from at least one of a platinum electrode and a titanium electrode; and / or, the insulating coating (9) is selected from a hydrophobic insulating coating; And / or, the hydrophobic insulating coating is selected from at least one of polytetrafluoroethylene and ceramic coating.

5. Use of the personalized electrical stimulation device according to any one of claims 1 to 4 in manufacturing medical devices for promoting dental pulp repair and regeneration.

6. The use according to claim 5, characterized in that: The electrical stimulation device is used to promote the migration of dental pulp stem cells.

7. The use according to claim 5, characterized in that: The electrical stimulation device is used to maintain the stemness of dental pulp stem cells.

8. The use according to claim 5, characterized in that: The electrical stimulation device is used to accelerate the formation of restorative dentin.

9. The use according to claim 5, characterized in that The electrical stimulation device generates electrical stimulation when the oral cavity moves, and does not generate electrical stimulation when the oral cavity is in a resting state.

10. The use according to claim 5, characterized in that The electric field strength generated by the electric stimulation device is 100mV / mm-200mV / mm, the electric stimulation time is 8-12 hours / day, and the length extending into the dental pulp is 0.8-1.2mm.

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