Smart Dental Implant System for Outpatient Dentistry

Abstract

A smart dental implant system and method for outpatient dental treatment are provided. In some embodiments, the disclosed subject matter includes a crown adapted to replicate a patient's anatomy and the position of a smart dental implant system. The crown may include piezoelectric nanoparticles disposed on a surface of the crown adapted to generate electricity from movements relative to the patient's mouth. In some embodiments, the disclosed subject matter includes an abutment coupled to the crown. The abutment may include an energy-harvesting circuit operatively coupled to the piezoelectric nanoparticles and adapted to harvest electricity, and a micro-LED array operatively coupled to the energy-harvesting circuit and adapted to photobiomodulate surrounding peri-implant soft tissue.

Description

[Technical Field]

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 038,494, filed June 12, 2020, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] While some technologies for osseointegrated dental implants can replace missing teeth while maintaining and stimulating natural bone, these technologies offer limited bioactivity (e.g., limited time for release of therapeutic or prophylactic agents) in the context of preventing peri-implant disease. Peri-implant disease is an inflammatory condition affecting the soft and hard tissues surrounding a dental implant. Under healthy conditions, peri-implant soft tissues protect osseointegrated implants from bacterial attack by enveloping the implant-supported restoration. However, due to the lack of true connective tissue attachment and a reduced vascular supply, the soft tissues adjacent to these restorations may be less effective than natural teeth in resisting bacterial attack and therefore more vulnerable to peri-implant disease.

[0003] Peri-implant disease can be divided into two categories: peri-implant mucositis and peri-implantitis. Peri-implant mucositis can be caused by the deposition of dental plaque (i.e., bacterial biofilm) at the soft tissue-implant interface. The resulting local inflammatory response of peri-implant mucositis can lead to peri-implantitis. Peri-implantitis can result in soft tissue inflammation and alveolar bone loss. This alveolar bone loss can in turn lead to dental implant failure. Dental implant failure can result in uncomfortable, painful, and expensive surgical replacement of the failed implant, potentially resulting in a breakdown in overall oral health.

[0004] While good plaque control by the patient and routine mechanical instrumentation by dental professionals can be the most effective means of preventing peri-implant disease, they can be inadequate due to poor patient compliance. Furthermore, existing techniques, such as the use of systemic antibiotics to treat peri-implant disease, are unpredictable and have low success rates (i.e., less than 60%). Summary of the Invention [Problem to be solved by the invention]

[0005] Therefore, there is a need in the art for advanced dental implant systems with improved bioactivity to prevent peri-implant disease. [Means for solving the problem]

[0006] Disclosed herein is a smart dental implant system and method for outpatient dental treatment.

[0007] In some embodiments, the disclosed subject matter includes a crown adapted to replicate a patient's anatomy and the position of a smart dental implant system. The crown may include piezoelectric nanoparticles disposed on a surface of the crown adapted to generate electricity from movements relative to the patient's mouth. In some embodiments, the disclosed subject matter includes an abutment coupled to the crown. The abutment may include an energy-harvesting circuit operatively coupled to the piezoelectric nanoparticles and adapted to harvest electricity, and a micro-LED array operatively coupled to the energy-harvesting circuit and adapted to photobiomodulate surrounding peri-implant soft tissue. In some embodiments, the disclosed subject matter further includes a metal post adapted to be inserted into the patient's jawbone and a retention screw adapted to couple the metal post to the abutment.

[0008] In some embodiments of the disclosed subject matter, the patient's oral activity can include at least one of chewing, biting, and brushing. In some embodiments, the energy-harvesting circuit can include an AC-DC rectifier adapted to convert electricity into a DC voltage and a power management unit adapted to store the DC voltage. In some embodiments, the abutment can include an LED driver circuit adapted to generate two different voltage levels and frequencies such that the micro LED array can be adapted to photobiomodulate surrounding peri-implant soft tissue at multiple wavelengths. In some embodiments, the micro LED array can further include at least four micro LEDs arranged 90 degrees apart, such that the micro LED array can be adapted to photobiomodulate surrounding peri-implant soft tissue. In some embodiments, the crown can have sufficient mechanical strength to withstand large occlusal forces. In some embodiments, the dental crown can have a two-phase composite material construction for enhanced mechanical strength.

[0009] In some embodiments, the disclosed subject matter includes inserting a metal post into a patient's jawbone; coupling a dental implant to the metal post, wherein the dental implant has piezoelectric nanoparticles disposed on a surface thereof such that the piezoelectric nanoparticles generate electricity from movements of the dental implant relative to the patient's mouth; harvesting the electricity from the piezoelectric nanoparticles as an energy source; and photobiomodulating the surrounding peri-implant soft tissue with the harvested electricity and a companion electronic device.

[0010] In some embodiments of the disclosed subject matter, piezoelectric nanoparticles can be fused to a dental material to create a crown. In some embodiments, the piezoelectric nanoparticles can be barium titanate nanoparticles. For example, the barium titanate nanoparticles can be fused to a dental material at a concentration between 0% and 40% by weight. In some embodiments, the barium titanate nanoparticles can be impregnated into the dental material with a ceramic dental material by a sintering process. In a non-limiting example, the barium titanate nanoparticles can be impregnated into the dental material as a bulk material by a sintering process.

[0011] In some embodiments, the piezoelectric nanoparticles may be further adapted to have anti-biofilm effects.

[0012] In some embodiments of the disclosed subject matter, the dental implant can be coupled to the metal post using a retaining screw. In some embodiments, the extracting can include converting electricity to a DC voltage and storing the DC voltage as extracted electricity. In some embodiments, the patient's mouth activity can include at least one of chewing, biting, and brushing. In some embodiments, the photobiomodulation can include multiple wavelengths.

[0013] The accompanying drawings, which are incorporated in and constitute a part of this disclosure, illustrate the disclosed subject matter. [Brief explanation of the drawings]

[0014] [Figure 1] FIG. 1 shows an existing implant with peri-implant mucositis and peri-implantitis. [Figure 2A] 1 is a diagram of a smart dental implant system according to some embodiments of the disclosed subject matter. [Figure 2B] 1 is a diagram of a smart dental implant system according to some embodiments of the disclosed subject matter. [Figure 2C]1 is a diagram of a smart dental implant system according to some embodiments of the disclosed subject matter. [Figure 3A] 1A-1C show SEM imaging of piezoelectric nanoparticles, in accordance with some embodiments of the disclosed subject matter. [Figure 3B] 1A-1C show SEM imaging of piezoelectric nanoparticles, in accordance with some embodiments of the disclosed subject matter. [Figure 3C] FIG. 1 illustrates Raman characterization of piezoelectric nanoparticles, according to some embodiments of the disclosed subject matter. [Figure 4A] 1A-1C are diagrams of an exemplary fabrication procedure in accordance with some embodiments of the disclosed subject matter. [Figure 4B] 1A-1C are diagrams of an exemplary fabrication procedure in accordance with some embodiments of the disclosed subject matter. [Figure 4C] 1A-1C are diagrams of an exemplary fabrication procedure in accordance with some embodiments of the disclosed subject matter. [Figure 4D] 1A-1C are diagrams of an exemplary fabrication procedure in accordance with some embodiments of the disclosed subject matter. [Figure 4E] 1A-1C are diagrams of an exemplary fabrication procedure in accordance with some embodiments of the disclosed subject matter. [Figure 4F] 1A-1C are diagrams of an exemplary fabrication procedure in accordance with some embodiments of the disclosed subject matter. [Figure 4G] 1A-1C are diagrams of an exemplary fabrication procedure in accordance with some embodiments of the disclosed subject matter. [Figure 4H] 1A-1C are diagrams of an exemplary fabrication procedure in accordance with some embodiments of the disclosed subject matter. [Figure 4I] 1A-1D are photographs of real pig teeth, 3D printed pig teeth, 3D printed cuboids, and 3D printed human teeth, according to some embodiments of the disclosed subject matter. [Figure 4J] 1 is a graph illustrating an exemplary sintering temperature profile, in accordance with some embodiments of the disclosed subject matter. [Figure 4K] 1 is a graph showing X-ray diffraction patterns of fabricated BaTiO3 ceramics before and after poling, in accordance with some embodiments of the disclosed subject matter. [Figure 4L] 1 is an exemplary illustration of a smart dental implant (SDI) crown including a two-phase composite material, according to some embodiments of the disclosed subject matter. [Figure 5A] 1 is a diagram of circuitry in an abutment, according to some embodiments of the disclosed subject matter; [Figure 5B] 1 is a diagram of circuitry in an abutment, according to some embodiments of the disclosed subject matter; [Figure 5C] 1 is a diagram of circuitry in an abutment, according to some embodiments of the disclosed subject matter; [Figure 5D] 1 is a diagram of circuitry in an abutment, according to some embodiments of the disclosed subject matter; [Figure 5E] 1 is a diagram of circuitry in an abutment, according to some embodiments of the disclosed subject matter; [Figure 6A] FIG. 1 is a diagram of an exemplary model that reproduces the chewing action. [Figure 6B] 10 is a graph showing a representative example of the voltage output of the mastication model from the SDI under masticatory activity. [Figure 6C] 1 is a graph showing an exemplary voltage output of a chewing model being converted to a pulse wave (PW) output. [Figure 6D] 10 is a graph illustrating an exemplary rectified output voltage of a chewing model. [Figure 6E] 10 is a graph showing the overall results of the average voltage output of the SDI under the action of chewing soft food. [Figure 7A] FIG. 1 illustrates an exemplary brushing model, according to some embodiments of the disclosed subject matter. [Figure 7B] Graph showing a representative example of the brushing model voltage output from an SDI under brushing motion. [Figure 7C] 1 is a graph showing an exemplary voltage output of a brushing model being converted to a pulse wave (PW) output. [Figure 7D]10 is a graph showing an exemplary rectified output voltage of a brushing model. [Figure 7E] 10 is a graph showing the overall results of the average voltage output of the SDI under brushing motion. [Figure 8A] FIG. 1 illustrates an exemplary system for light irradiance measurement and in vitro PBM therapy. [Figure 8B] 10 is a graph showing average optical irradiance at various PW frequencies from an SDI prototype. [Figure 9A] 10A-10C illustrate finite element analysis of occlusal loads on distal buccal cusps, in accordance with some embodiments of the disclosed subject matter. [Figure 9B] FIG. 1 is a diagram of an exemplary system for comprehensive mechanical assessment, according to some embodiments of the disclosed subject matter. [Figure 10A] FIG. 1 illustrates the anti-biofilm activity of piezoelectric nanoparticles, according to some embodiments of the disclosed subject matter. [Figure 10B] FIG. 1 illustrates the anti-biofilm activity of piezoelectric nanoparticles, according to some embodiments of the disclosed subject matter. [Figure 10C] FIG. 1 illustrates the anti-biofilm activity of piezoelectric nanoparticles, according to some embodiments of the disclosed subject matter. [Figure 11] FIG. 1 shows the viability of human gingival keratinocytes with and without photobiomodulation, according to some embodiments of the disclosed subject matter. [Figure 12] FIG. 1 shows a diagram illustrating a cellular response to pathogenic microbial cells, according to some embodiments of the disclosed subject matter. [Figure 13] FIG. 1 shows the number of primary human gingival keratinocytes (HGK) after microbial insult with or without near-infrared (NIR) irradiation, according to some embodiments of the disclosed subject matter. [Figure 14] FIG. 10 shows an example SDI implanted in the mouth of a minipig, according to some embodiments of the disclosed subject matter. DETAILED DESCRIPTION OF THE INVENTION

[0015] Throughout the drawings, the same reference numerals and characters, unless stated otherwise, are used to denote like features, elements, components, or portions of the illustrated embodiments. Furthermore, while the present invention will hereinafter be described in detail with reference to the figures, it is done so in connection with the illustrative embodiments.

[0016] Technology for a smart dental implant system for outpatient dental treatment is presented. The smart dental implant system can include a crown and an abutment. The crown can replicate the patient's anatomy and the position of the smart dental implant system, and the abutment can be coupled to the crown. Piezoelectric nanoparticles can be placed on the surface of the crown and adapted to convert the patient's oral movements into electricity. The abutment can include an energy-harvesting circuit capable of harvesting electricity from the piezoelectric nanoparticles and a micro-LED array that uses the harvested electricity to photobiomodulate the surrounding peri-implant soft tissue. The smart dental implant system can also include a metal post that can be inserted into the patient's jawbone and a retention screw that can couple the abutment to the metal post.

[0017] FIG. 1 illustrates an existing implant with peri-implant mucositis and peri-implantitis. Peri-implant disease can be divided into two categories: peri-implant mucositis 102 and peri-implantitis 104. Peri-implant mucositis 102 can be caused by the deposition of dental plaque (i.e., bacterial biofilm) at the soft tissue-implant interface. The resulting local inflammatory response of peri-implant mucositis 102 can lead to peri-implantitis 104. Peri-implantitis 104 can result in soft tissue inflammation and alveolar bone loss. This alveolar bone loss can in turn lead to dental implant failure.

[0018] 2A-2C are diagrams of a smart dental implant system according to some embodiments of the disclosed subject matter. The smart dental implant (SDI) system can be used for outpatient dental treatment and can include a crown 202 and an abutment 204. The crown 202 can convert human oral movements (e.g., chewing, biting, brushing, etc.) into electrical power by fusing piezoelectric nanoparticles 208 to the dental material. For example, the dental material can include a two-component dental material or a ceramic-based dental material. The piezoelectric nanoparticles 208 can be fused to a two-component dental material, such as a resin, by mixing the piezoelectric nanoparticles with the dental material. Alternatively, the piezoelectric nanoparticles 208 can be fused to a ceramic-based dental material, such as a ceramic (e.g., zirconia) or porcelain, and then sintered, resulting in a single dental crown. To enable the manufacture of patient-specific dental crowns that replicate the patient's unique anatomy, crowns can be produced using 3D printing technology. Piezoelectric nanoparticles can be impregnated into 3D printable dental crowns (C&B Micro Filled Hybrid from NextDent BV) and 3D printed in open mode (Form3 from Formlab Inc.).

[0019] As shown in Figure 2B, the polarization process 216 can be performed by applying a high voltage (>2 kV / mm) while heating above the Curie temperature. By aligning the randomly oriented electric polarization, the polarization process 216 can improve or optimize the electrical performance of the piezoelectric nanoparticles 208 to achieve orders of magnitude improved piezoelectric performance. The piezoelectric nanoparticles 208 can also have an anti-biofilm effect by preventing adhesion or selectively killing only attached bacteria, thereby reducing or minimizing antibacterial resistance and disrupting the homeostasis of the microbiota.

[0020] The electrical energy generated by the piezoelectric nanoparticles 208 can be appropriately managed to optimize LED illumination. The abutment 204 can include an energy-harvesting circuit 210 and a micro-LED array 212. The energy-harvesting circuit 210 can be operatively coupled to the piezoelectric nanoparticles 208 such that the energy-harvesting circuit 210 can harvest electricity generated by the piezoelectric nanoparticles 208. The micro-LED array 212 can be operatively coupled to the energy-harvesting circuit such that the micro-LED array 212 receives electricity harvested from the energy-harvesting circuit 210. The micro-LED array can then enable in situ photobiomodulation (“PBM”) therapy of surrounding peri-implant soft tissue.

[0021] The crown 202 and abutment 204 can be assembled together using dental adhesive (Panavia by Kuraray Medical Co., Ltd.). A retention screw 214 can securely attach the crown-abutment assembly onto the metal implant post 206. The metal post 206 can be inserted into the patient's jawbone, and then the retention screw 214 can connect the metal post to the abutment.

[0022] 3A-3C show SEM imaging and Raman characterization of piezoelectric nanoparticles according to some embodiments of the disclosed subject matter. Piezoelectric nanoparticles can be impregnated onto the surface of a crown. For example, as depicted in FIG. 3A, the piezoelectric nanoparticles can be barium titanate (BaTiO) nanoparticles ("BTO-NP") (400 nm, US Research Nanomaterials, Inc.). BTO-NPs are preferred due to their piezoelectric properties and low cytotoxicity. Using open-mode 3D printing (Form3, Formlab Inc.), BTO-NPs can be impregnated into a 3D-printable crown (C&B Micro Filled Hybrid, NextDent BV). BTO-NPs can also be sintered into dental materials to create a single bulk material, as depicted in FIG. 3B. As shown in FIG. 3C, a 306 cm -1 The peak at 0.05 may indicate a tetragonal signature (i.e., piezoelectricity). Furthermore, the optical properties of BTO-NPs (i.e., their white color) may be suitable for dental materials because they can balance the opacity and translucency of the crown to match existing teeth. Other inorganic and organic piezoelectric nanoparticles with low cytotoxicity may also be suitable. For example, suitable inorganic piezoelectric nanoparticles include barium titanate, sodium potassium niobate, and bismuth titanate ceramics, as well as zinc oxide nanostructures. Suitable organic piezoelectric nanoparticles include polyvinylidene fluoride.

[0023] Prior to fabrication, the two-part dental material (e.g., resin) can be mixed overnight on a rotating mixer platform. After the introduction of BTO-NP, this is allowed to mix for an additional 24 hours. The two-part dental material can then be degassed for approximately 30 minutes. The molar design can be obtained from a 3D scanned design. The molar design can be modified to include a honeycomb design for enhanced mechanical strength. After 3D printing, the hollow areas of the honeycomb structure can be filled with BTO-NP-impregnated dental material, which can then be UV-cured. The fabricated molar can then be post-processed, which involves cleaning with IPA under heated sonication followed by ethanol. After 2 hours of sonication, the Smart Crown can be cleaned again using ethanol.

[0024] Alternatively, piezoelectric nanoparticles can be incorporated into ceramic dental materials such as zirconia. The combination of piezoelectric nanoparticles and ceramic dental materials can be sintered. A BTNP colloidal suspension can be prepared as shown in Figures 4A-4H. As shown in Figure 4A, a base binder solution can be prepared by first mixing zirconia or polyvinyl fluoride (PVDF) in N,N-dimethylformamide (DMF, Sigma-Aldrich, Inc.) at a weight ratio of 1:8.8 at 80 °C for 15 min. As shown in Figure 4B, BTO-NPs are slowly added to the binder solution with constant manual stirring until a high volume concentration is reached. The experimental results show that the binder solution can incorporate up to 332 wt% BTO-NPs. As shown in Figure 4C, the BTO-NP suspension is then loaded into a syringe, which is then loaded into a paste extrusion 3D printer. In some examples, the printing speed can be adjusted to approximately 1 mm / s with a z-resolution of approximately 400 μm. The printed SDI can then be dried at 120 °C for 2 hours to evaporate the DMF and produce a green material. Post-processing by debinding and sintering can then be performed using a furnace tube (Figure 4D). 3D printing enables the creation of a variety of dental specimens without sacrificing their antibiofilm and mechanical properties. Figure 4I shows examples of 3D printing, such as a human molar, an animal tooth, or a simple cuboid, suggesting that SDIs can be tailored to correspond to any anatomical structure.

[0025] Figure 4J shows an exemplary temperature profile: debinding at about 650 °C for about 1 hour (ramp rate = 5 °C / min), followed by sintering at about 1400 °C for about 3 hours (ramp rate = 5 °C / min). After post-processing, the SDI can be poled to align the randomly oriented ferroelectric domains. To do this, the SDI can be given temporary electrodes on the top and bottom by applying silver epoxy. The SDI can then be placed on a custom-made poling stage, which can have a copper bottom plate and a spring-loaded needle electrode from the top. The poling stage can have a built-in heating element in the silicone oil bath. Figure 4E shows the poling process. Using the poling stage and high-voltage source, a uniform electric field of 1 kV / mm can be applied across the SDI, while the temperature of the silicone oil bath can be set below the Curie temperature of BTO-NP (80 °C). In some examples, the total poling time can be 4 hours. FIG. 4K shows the X-ray diffraction patterns of the fabricated BaTiO ceramic before and after poling. The tetragonal phase of the BaTiO ceramic can be confirmed by the peak splitting at 2Θ near 45°. In a non-limiting example, the ratio of the (002) to (200) peaks can be increased from about 0.43 in the unpoled sample 401 to about 1.23 in the poled sample 402. This may indicate that crystalline domains can be reoriented by poling. In some examples, the (001) diffraction peak at about 22° in the poled sample can be more pronounced compared to the unpoled sample, indicating that many crystalline domains are aligned along the same direction.

[0026] In certain embodiments, SDI crowns can be constructed with a two-phase composite, i.e., a dispersion of piezoelectric nanoparticles (0-3 composite, i.e., 0-D BTNPs embedded in a 3-D matrix), and attributes of conventional dental materials (1-3 composite, i.e., 1-D dental resin pillars embedded in a 3-D BTNP-based composite), as shown in Figure 4L for sintered samples. The two-phase composite can enable multiple functions. For example, the 0-1 composite can provide piezoelectric nanoparticles that more directly affect oral biomechanics for efficient energy harvesting, while the 1-3 composite with conventional dental materials provides sufficient mechanical strength under the mechanical stresses resulting from oral movements.

[0027] Hybrid composites can be fabricated by modifying SDI crowns. For example, for a 1-3 composite configuration (as seen in Figure 4F), the SDI crown can be laser machined to create honeycomb-inspired trenches, which enhance mechanical strength. Figure 4L shows the laser-machined base of a 1-3 composite. The trench size can be 0.5–1 mm in diameter. As seen in Figure 4G, the trench is filled with an ultraviolet (UV) light-cured dental crown resin (C&B Micro Filled Hybrid from NextDent BV). In some embodiments, various dental materials (e.g., dental resin, metal, and / or ceramic (e.g., zirconia)) can be used for filling. Before filling the trench, the dental resin must be stirred overnight on a rotating mixer platform. The sidewalls of the dental crown can also be strengthened by coating them with dental resin. After filling, the SDI can be degassed for 1 hour and then UV light cured. The fabricated piezoelectric dental crown can be sanded and polished to a final finish. The filling process may leave residue on the surface, so the dental crown can be further polished as needed to adjust to the desired shape. In some embodiments, the dental crown can be a two-phase composite for increased mechanical strength. For example, a dispersion of piezoelectric nanoparticles (0-3 composite, i.e., 0-dimensional barium titanate nanoparticles embedded in a 3-dimensional matrix) and the attributes of traditional dental materials (1-3 composite, i.e., 1-dimensional dental resin pillars embedded in a 3-dimensional barium titanate nanoparticle-based composite) can be used.

[0028] To test the conformality of BTO-NPs in dental materials, 3D-printed crowns were stored in phosphorus buffer solution (PBS, Sigma-Aldrich, Inc.) at 55°C for 24 hours to monitor whether BTO-NPs would leach out of the dental material. Four different concentrations (5, 10, 20, and 30 wt%) in the dental material were examined for their leaching behavior. At 30 wt%, BTO-NPs were uniformly dispersed, reducing aggregation in the dental material.

[0029] 5A-5E are diagrams of circuitry in an abutment according to some embodiments of the disclosed subject matter. The energy harvesting circuit can be optimized for low-frequency applications, such as human oral motion. As depicted in FIGS. 5A and 5C, the energy harvesting circuit 210 can include an AC-DC rectifier 502 and a power management unit 504. The AC-DC rectifier 502 can be coupled to piezoelectric nanoparticles 208 in the crown 202 and can convert human oral motion into electrical power, as shown in FIG. 5B. The power management unit 504 can store up to 3.3V with a quick charge (1 minute), which is sufficient for 90 minutes (effective duration based on three 30-minute meals per day). Such power generation can operate the microLED array 212. For example, low-current microLEDs require only 1.8V for maximum brightness.

[0030] As depicted in Figure 5C, the energy harvesting circuitry can be fabricated by microfabrication for further miniaturization. The circuit can be divided into multiple blocks and fabricated on a flexible substrate (e.g., copper-clad polyimide, Pylex, from DuPont Inc.). Ribbon cables can be attached to each block, allowing them to be folded and stacked. Discrete electronic components with sub-mm dimensions include microLEDs (SML-P11x from ROHM Co., Ltd., 1 × 0.6 × 0.2 mm). 3), transistor (Panasonic Corporation FK4B01110L1, 0.6 × 0.6 × 0.1 mm 3 ), supercapacitor (Seiko Instruments Inc. CHP3225A, 3 × 2 × 1 mm 3 , Schottky diode (Central Semiconductor Corp. CMRSH-4DO, 0.9 × 0.7 × 0.4 mm) 3 ), and resistors (CRCW0201, 0.6 × 0.3 × 0.2 mm, manufactured by Vishay Intertechnology, Inc. 3 Once all the discrete components are assembled, the abutment can be coated with Parylene C (5 μm) for protection.

[0031] As depicted in Figure 5D, the energy harvesting circuitry 210 and micro LEDs 212 can be integrated onto the abutment 204. The abutment 204 can have a small space at the top to accommodate the miniaturized circuitry and to interface with the crown 202, and a groove at the bottom to place the micro LEDs 212 and connect them via electrical connections 506, where peri-implant disease is typically found. At least four micro LEDs can be used, one every 90 degrees, to cover all of the surrounding peri-implant soft tissue.

[0032] As shown in Figure 5E, in some embodiments, the energy harvesting circuit can convert human mouth movements into a DC voltage using an internal low-loss rectifier in the energy harvesting IC chip (Linear Technology LTC3588). The IC chip can manage the DC voltage using an under-voltage lockout (UVLO), which allows charge to accumulate in a supercapacitor (Seiko Instruments Inc. CPH3225A) until the stored charge can be efficiently transferred to the output by a bulk converter. Unlike a battery, the voltage of a supercapacitor drops linearly as it delivers energy. Therefore, the quiescent current (I) of the energy harvesting IC must be reduced to sufficiently drop the voltage and still draw the required current. Q It can be important to keep the current (=450 nA) very low.

[0033] In some embodiments, the abutment may include an LED driver circuit that can generate two different voltage levels and frequencies for multi-wavelength PBM (MW-PBM). The LED driver circuit can generate two different voltage levels and frequencies for low-power LEDs (I F It may contain two individually tuned timers (via resistor-capacitor circuits) with switching circuitry (via transistors) for simultaneously operating multiple timers (currents of approximately 2 mA). The voltage level can be adjusted from 0.2 to 2.8 V, and the frequency can be set to 0, 5, or 500 Hz (CW, PW5, or PW) with a 50% duty cycle. 500 ) can be adjusted.

[0034] 6A and 7A are diagrams from tests that replicate chewing motions and measure corresponding voltage outputs, according to some embodiments of the disclosed subject matter. For effective PBM therapy, it may be necessary to generate enough power to illuminate an LED using the motions associated with a human mouth. BTO-NPs may be promising due to their biocompatibility, piezoelectric properties, and nonlinear optical characteristics. Therefore, it may be possible to test whether such piezoelectric dental materials can convert chewing motions (modeled on a human mouth) into power for LED illumination.

[0035] In certain embodiments, the energy-harvesting performance of an SDI can be evaluated using a dynamic model of human oral movements such as chewing and tooth brushing. As shown in FIG. 6A, the voltage can be measured when the SDI is stimulated by chewing using a force-application machine, which can simulate antagonist strikes according to controlled parameters. In a non-limiting example, to examine the efficiency of mechanical-to-electrical transduction, an SDI can first be tested without circuitry. FIG. 6B shows a representative example of voltage output from an SDI under chewing (e.g., the applied force can be approximately 90 N at a frequency of 5 Hz). The output can exhibit three different regimes: positive voltage during compression, negative voltage during decompression, and then an idling trend between the two different force directions. When the indenter begins to compress the SDI, the electrical energy can begin to increase proportionally to the applied force. Upon maximum compression (i.e., maximum load), a subsequent decrease in the polarity of voltage generation can occur as the applied force direction reverses, which explains the negative voltage. In some embodiments, when the indenter returns to its home position and is potentially lifted off the SDI, the voltage output can also return to an idle point until the next cycle begins. In some embodiments, experimental piezoelectric measurements can be approximately 202 (±10.87) pC / N. In some embodiments, the voltage output can be managed via a diode and capacitor pair, which converts the sinusoidal voltage output into a pulsed wave (PW) output, as shown in FIG. 6C. Driving the PW output with an LED in frequency mode can be beneficial for PBM therapy. The frequency can be determined by the movement of the mouth, but can be adjusted to a continuous wave (CW) by implementing a rectifier circuit with a large capacitor (e.g., 47 μF or more to compensate for low frequencies), as shown in FIG. 6D. FIG. 6E shows the overall results of the average voltage output of the SDI under soft food chewing motions ranging from about 30 N to about 100 N (f=5 Hz).The measured average voltage output can range from 0.4 V (±2.6 mV) to 1.3 V (±2.8 mV) as a function of the applied chewing force (V = 0.014F + 0.058, R2 = 0.97, where V is voltage and F is applied force).

[0036] Figure 7A shows a brushing motion that can be applied to an SDI using a custom shear force application machine. Voltage outputs similar to those from a chewing machine can be observed (see Figures 7B-7D). Without the circuitry, the voltage output induced by the brushing motion can have three regimes: a positive voltage when the brush fibers begin their sweeping motion, a negative voltage when the brush fibers finish their sweeping motion and are slowly lifted off the SDI, and an idle period. In some embodiments, the duration of the rising and falling voltages can be about half that of a chewing motion (e.g., 20 ms versus 40 ms). This can be attributed to the relationship between the direction of force application and the polarization direction of the SDI. During fabrication, the SDI is oriented 33 The chewing motion can be in the same direction as the polarization, which may be the preferred direction for energy harvesting in certain circumstances. In a non-limiting example, the brushing motion can be in the same direction as the polarization, d 31 The piezoelectric constant, which relates the open-circuit voltage to the input mechanical stress, may be perpendicular to the major polarization direction (i.e., the transverse direction), and its piezoelectric constant, which relates the open-circuit voltage to the input mechanical stress, may be approximately half that of the major polarization direction (measured at 113 (±4.08) pC / N). Despite the half-piezoelectric constant, the dental crown under brushing motion can generate a voltage output comparable to that under chewing motion, i.e., 0.7 V (±5.4 mV) versus 1.0 V (±2.8 mV). The average output of the SDI (n=3) may be linearly proportional to the applied force, as shown in Figure 7E (V = 0.009F-0.005, R2 = 0.99). This may be due to the symmetrical nature (i.e., low aspect ratio) of the SDI geometry, which affected the majority of the dental crown to deform with longitudinal forces even under transverse brushing motion (Poisson's ratio is a constant d 33 and constant d 31 (compensating for differences in

[0037] In certain embodiments, the disclosed subject matter provides various human oral movements (e.g., chewing and brushing). FIG. 6A shows a chewing model using a programmable electromechanical universal testing machine (TestResources, Inc. 311R). By adjusting the path and speed of the shaft, it is possible to parametrically simulate impacts on an opponent. A series of complete chewing cycles can be performed on the distal buccal cusps of the SDI. The counterweight can load the antagonist and generate contact pressure during abrasive movements, which can be varied. In certain embodiments, parameters for chewing movements of soft food can be employed (e.g., speed = 20-40 mm / s, force = 0-200 N, frequency = 1-5 Hz).

[0038] Figure 7A shows a brushing model using a custom-designed rotating device. Rotation can be driven by a motor (Caframo Limited BDC3030), which holds a steel central rod with square blades at the base. Two toothbrush heads can be attached to each end of the blades. The central rod can then be placed on a circular platform, which can also hold multiple plastic rods on its edges, so that as the central rod rotates, the brush heads can sweep SDIs attached to plastic rods. In a non-limiting example, a designated space can be provided on the plastic rod to accommodate the SDIs. The brush filaments overlap the SDI by approximately 5 mm. In some examples, brushing parameters can be used (e.g., speed = 2 mm / s, normal force = 12 N (assuming 600 filaments sweep the SDI per stroke, and the normal force due to a single filament can be approximately 20 mN), shear force = 15-70 N, and frequency = 1-5 Hz).

[0039] Figure 8A shows an exemplary configuration for optical irradiance measurement and in vitro PBM therapy, in which the SDI under chewing or brushing can be connected to mechanical and electronic components, i.e., a rectifier and a micro-LED. Energy harvesting results from chewing and brushing actions showed that they could sufficiently power a low-power LED. The average voltage measurement could be 1.3 V under chewing (e.g., 70 N) or brushing (e.g., 100 N) actions. The corresponding optical irradiance measurement for the red LED was approximately 0.3 mW / cm. 2 A near-infrared LED for the same light irradiance can be 0.8 V, which can be derived from a chewing motion of about 60 N or a brushing motion of about 90 N. In a specific embodiment, all light measurements can be performed by silicon photodiodes inside the black box.

[0040] In some embodiments, the effectiveness of photobiomodulation therapy using SDI can be evaluated. For example, a single LED per well can be used to quantify the baseline effect of light intensity on primary human gingival keratinocytes (HGK) in near-contact mode. In some embodiments, multiple LEDs can be powered by the SDI under chewing or brushing motions by connecting them in a parallel configuration. In a non-limiting example, SDI-mediated PBM therapy can be evaluated using pulsed wave (PW) and continuous wave (CW) light, since PW light therapy may be more effective than CW light therapy in certain biological environments. Figure 8B shows the average light irradiance at various PW frequencies from an SDI prototype. The average light irradiance can be greater at higher frequencies because the capacitor can be charged more frequently, resulting in increased energy harvesting efficiency.

[0041] Figure 9A shows a finite element analysis (FEA) of occlusal loads on a distal buccal cusp according to some embodiments of the disclosed subject matter. Because crowns are frequently exposed to large chewing / biting forces, especially in the molar region, smart dental implant systems can have sufficient mechanical strength to withstand these forces. For example, the average maximum bite force can be approximately 700-900 N. For dental implants, FEA simulations are widely used to evaluate mechanical performance, including FDA guidelines. Therefore, FEA simulations (COMSOL Multiphysics) can be performed to evaluate stress conditions for various molar designs. Figure 6 shows the von Mises stress simulation results of occlusal loads on a BTONP-impregnated molar. The simulation results revealed that the engineered dental material can withstand von Mises stresses of up to 42 MPa, which may be a clinically acceptable level.

[0042] A comprehensive mechanical evaluation can be performed using an electromechanical universal testing machine (TestResources, Inc. 310) with ISO 4049 (Dentistry - Polymer-based restorative materials) specified test equipment and a biomedical bath (to mimic body temperature). A three-point flexural bend fixture can be used, as seen in Figure 9B. Using engineered dental materials, a 25 x 2 x 2 mm 3 A total of 10 beam-like structures are prepared. The forces and deformations can be measured virtually. Then FS and FM can be calculated using:

number

[0043] The simulation results can be further verified by measuring the flexural strength ("FS") and factual modulus ("FM") of smart dental implant crowns containing BTO-NPs in the dental material. Table I summarizes the comparison of the mechanical strength of our SDI with other materials. The dental composite material used in the SDI exhibits a FS of 50 MPa and a FM of 6630 MPa, which are comparable to the mechanical strength of dental resins reported elsewhere (FS: 65–130 MPa, FM: 2000–7500 MPa). This indicates that the engineered dental crown can reasonably withstand impact forces (flexural strength) while undergoing less deflection (flexural modulus). [Table 1]

[0044] Figures 10A-10C show the anti-biofilm activity of piezoelectric nanoparticles, according to some embodiments of the disclosed subject matter. Minimizing bacterial exposure to human gingival keratinocytes ("HGK") is crucial to repel microbial adhesion and subsequent colonization on crown surfaces, thereby reducing the prevalence of peri-implant disease pathogenesis. Figure 10 depicts the anti-biofilm activity of BTO-NPs embedded in dental material surfaces against Streptococcus mutans, a representative oral bacterium, using an in vitro biofilm model. S. mutans biofilms can be cultured for 19 hours on saliva-covered BTO-NP-embedded discs.

[0045] As shown in Figure 10A, a significant number of S. mutans colonies could be evenly distributed on the disc without BTO-NPs. As shown in Figure 10B, the surface of the BTO-NP-embedded dental material almost completely prevented biofilm formation (i.e., a biomass reduction of over 90%). Overall, the data in Figure 10C demonstrate the excellent anti-biofilm effect of BTO-NPs, which can reduce inflammation against bacterial insults and thereby significantly enhance the immunity of HGK.

[0046] FIG. 11 shows the survival rate of HGK with and without PBM therapy. The efficiency of PBM therapy can be examined based on the survival rate of HGK from bacterial infestation using red ("R") and near-infrared ("NIR") irradiation under chewing motion. Continuous wave and pulsed wave (PW5 for 5 Hz or PW5 for 500 Hz) were used. 500 ) can be tested. First, lipopolysaccharide (LPS), which may be a major toxic component of the outer membrane of Gram-negative bacteria that stimulates host cells and induces cellular inflammation, induced inflammation in HGK cells. The effectiveness of PBM therapy on LPS-inflamed HGK cells can be tested using the following two parameters: 1) a 90-minute R and NIR exposure time, which simulates daily human oral activity, and 2) 10 μg / mL LPS, which resulted in the initiation of inflammation without severe cell death. Note that blue and green light emissions can be excluded because they substantially reduced cell viability.

[0047] HGK cells can be cultured in KGM-2 growth medium (Lonza Group Ltd., Walkersville, MD) supplemented with human keratinocyte growth supplement containing standard insulin (8.6 × 10 M) in a humidified atmosphere of 5% CO at 37°C. Initially, HGK cells were plated at 5 × 10 in 24-well plates. 4Cells are seeded per well and allowed to grow for 48 hours at 37°C. After 48 hours of culture, the cells can be washed with 1x PBS and, after relevant treatment (LED irradiation and / or LPS treatment), cultured for an additional 48 hours in medium without human keratinocyte growth supplement. Cell viability can be determined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (Cell Proliferation Kit I, F. Hoffmann-La Roche Ltd., Germany). 50 μL of MTT labeling reagent (final concentration 0.5 mg / mL) can be added to each well. The cells can then be cultured for 4 hours at 37°C in a CO2 incubator. 500 μL of solubilization buffer (10% SDS in 0.01 M HCl) can be added, and the plate can be left overnight in the incubator to solubilize the formazan crystals. The optical density (OD) values ​​of the samples can then be measured at a wavelength of 570 nm using a microplate reader (BioTek, Winooski, VT). OD values ​​of treated groups can always be normalized to an untreated control group.

[0048] To examine cellular responses to bacterial inflammation, cells can be exposed to LPS (Sigma-Aldrich, Inc., St. Louis, MO). First, the optimal concentration of LPS for inflammation induction can be determined by adding various concentrations of LPS (0-100 μg / mL). HGK cells can be grown for 48 hours, after which the cells can be washed and the medium replaced with fresh medium (without growth supplements). LPS can then be added, followed by incubating the cells for another 48 hours. Using the previously determined optimal concentration of LPS (0-20 μg / mL), cells can be pretreated with LED before exposure to LPS, followed by incubating the cells for another 48 hours. Cell viability can then be assessed using an MTT assay.

[0049] The data in Figure 11 show that all conditions not only fully restore the viability of HGK cells against LPS stimulation (compared to the control with LPS), but also significantly improve cell viability (compared to the control without LPS). Interestingly, different levels of therapeutic efficacy can be observed under different conditions (i.e., the effect of R-CW or NIR-PW on the control when LPS was used). 500 Up to 85% increase in cell viability with HGK), indicating that specific wavelengths or frequencies can stimulate the chromophores in HGK in different ways.

[0050] Figure 12 shows the cellular response to pathogenic microbial cells. To examine the cellular response to pathogenic microbial cells, the fungus Candida albicans and the bacterium Streptococcus oralis can be introduced into HGKs. The data in Figure 12 demonstrate that red or near-infrared irradiation can fully restore HGK confluency against pathogenic microbial invasion. In the absence of microbial exposure, cells can exhibit high confluency and intercellular tight junctions. Tight junctions are intercellular adhesion complexes in epithelia. Tight junctions can help maintain cell polarity by enclosing adjacent epithelial cells in a thin band just below their apical surfaces and inhibiting intermixing of apical and basolateral transmembrane components. When HGKs are exposed to bacteria or fungi, they exhibit proliferation and loss of tight junctions. In a non-limiting example, co-infection with bacteria and fungi can cause severe tissue destruction. However, these are almost completely restored when HGKs are exposed to red or infrared irradiation. In some examples, NIR irradiation can improve HGK growth against microbial challenge, which may be a synergistic bacterial-fungal complex invasion. Thus, this data demonstrates that the disclosed PBM therapy can restore human keratinocytes from microbial infection.

[0051] The data in Figure 13 show the number of HGKs after microbial insult with or without NIR irradiation. When HGKs are infected with the bacteria Staphylococcus aureus (Sa) or Streptococcus oralis (So), or the fungus Candida albicans (Ca), or a combination thereof for 24 hours, the number of HGKs can be reduced (e.g., species 2 and 3 infections). Although the difference is significant, when stimulated with NIR light, the number of HGKs can be fully restored to the level of uninfected cells (dotted line). This data supports the superior efficacy of the disclosed PBM therapy in improving cellular immunity against prolonged and formidable microbial challenges.

[0052] To verify the feasibility of our device, the SDI can be installed in the mouth of a minipig. The minipig model can be used due to its striking anatomical similarities with humans and the availability of established models of periodontal disease with varying degrees of severity. As shown in Figure 14, the disclosed minipig model for peri-implant disease can be used to demonstrate successful surgical protocols and verify the functionality of a prototype SDI system. For example, periodontal disease-free minipig aged 3-4 months and weighing an average of 30 kg can be used. Surgical extraction of the mandibular premolars and / or first molars can be performed using approved general anesthesia protocols under aseptic conditions. After surgical extraction of the mandibular premolars and / or first molars, the alveolar bone is prepared for titanium implants, and titanium implants can be placed in each mandibular hemilateral. The soft tissues are then closed, and the structure is allowed to heal. After approximately 6 weeks, the minipig is anesthetized and Smart Crowns and Smart Abutments are placed on the implants. The disclosed protocol can be used in dental offices.

[0053] The results of individual experiments can be expressed as the mean ± SD. Statistical analysis of experimental data can be performed using the Student's t-test. Experiments can be repeated at least twice for each assay. Data can be considered statistically significant when the P value is less than 0.01.

[0054] The foregoing merely illustrates the principles of the disclosed subject matter. Various changes and modifications to the described examples will become apparent to those skilled in the art upon review of the teachings herein. It will thus be appreciated that those skilled in the art will be able to devise numerous techniques not explicitly described herein, but which embody the principles of the disclosed subject matter and are therefore within its spirit and scope.

Claims

1. 1. A smart dental implant system for outpatient dental treatment of a patient, comprising: a crown adapted to replicate a patient's anatomy and a position of the smart dental implant system, the crown further comprising piezoelectric nanoparticles disposed on a surface of the crown, the piezoelectric nanoparticles adapted to generate electricity from oral movements of the patient, the oral movements including chewing, biting, and brushing; an abutment coupled to the crown; an energy harvesting circuit operatively coupled to the piezoelectric nanoparticles and adapted to harvest the electricity; and and a micro LED array operatively coupled to the energy harvesting circuitry, the micro LED array adapted to photobiomodulate surrounding peri-implant soft tissue.

2. 10. The smart dental implant system of claim 1, further comprising a metal post adapted to be inserted into the patient's jawbone, and a retention screw adapted to couple the metal post to the abutment.

3. The smart dental implant system of claim 1 , wherein the piezoelectric nanoparticles are disposed within a dental material on the surface of the crown.

4. The smart dental implant system of claim 3, wherein the piezoelectric nanoparticles are barium titanate nanoparticles.

5. 5. The smart dental implant system of claim 4, wherein the barium titanate nanoparticles are disposed in the dental material at a concentration between 1% and 40% by weight.

6. 10. The smart dental implant system of claim 1, wherein the crown comprises a ceramic dental material impregnated with barium titanate nanoparticles.

7. 10. The smart dental implant system of claim 1, wherein the piezoelectric nanoparticles are further adapted to have an anti-biofilm effect.

8. 10. The smart dental implant system of claim 1, wherein the energy harvesting circuit further comprises: an AC-DC rectifier adapted to convert the electricity into a DC voltage; and a power management unit adapted to store the DC voltage.

9. 10. The smart dental implant system of claim 1, wherein the abutment further comprises an LED driver circuit adapted to generate two different voltage levels and frequencies such that the micro LED array is adapted to photobiomodulate surrounding peri-implant soft tissue at multiple wavelengths.

10. 10. The smart dental implant system of claim 1, wherein the micro LED array further comprises at least four micro LEDs arranged 90 degrees apart, whereby the micro LED array is adapted to photobiomodulate surrounding peri-implant soft tissue.

11. 10. The smart dental implant system of claim 1, wherein the crown is further adapted to have a two-phase composite construction, a flexural strength (FS) of 50 MPa, a flexural modulus (FM) of between 2000 MPa and 7500 MPa, and to withstand an occlusal force of between about 700 N and 900 N.

12. 1. A smart dental implant for use in a method for promoting healthy tissue and preventing bone loss at an interface between the dental implant and a patient's soft tissue, comprising: a metal post insertable into the patient's jawbone; a dental implant coupled to the metal post, the dental implant having piezoelectric nanoparticles on a surface thereof, the piezoelectric nanoparticles configured to generate electricity from oral movements of the patient, the oral movements including chewing, biting, and brushing; an energy harvesting circuit operatively coupled to the piezoelectric nanoparticles and adapted to harvest electricity; a micro LED array operatively coupled to the energy harvesting circuit, the micro LED array adapted to photobiomodulate surrounding peri-implant soft tissue using the harvested electricity.

13. The smart dental implant of claim 12, wherein the dental implant is coupled to the metal post using a retaining screw.

14. 13. The smart dental implant of claim 12, wherein the harvesting comprises converting the electricity to a DC voltage and storing the DC voltage as the harvested electricity.

15. 13. A method of manufacturing a smart dental implant according to claim 1 or claim 12, comprising fusing the piezoelectric nanoparticles into a dental material to create the dental implant.

16. The method of claim 15, wherein the piezoelectric nanoparticles are barium titanate nanoparticles.

17. 17. The method of claim 16, wherein the barium titanate nanoparticles are disposed within the dental material on the surface of the dental implant at a concentration of between 1% and 40% by weight.

18. 17. The method of claim 16, wherein the barium titanate nanoparticles are impregnated into the dental material as a bulk material by a sintering process.

19. 13. The smart dental implant of claim 12, wherein said piezoelectric nanoparticles repel biofilm adhesion and prevent subsequent biofilm colonization on said dental implant.

20. The smart dental implant of claim 12 , wherein the photobiomodulation comprises multiple wavelengths.

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