Laser system for enhancing remineralization and hard tissue strength

Abstract

Laser-based systems and methods for hard tissue treatment enhance remineralization and fluoride uptake and improve resistance to demineralization. The systems can include a laser source, an optical system, and a controller for controlling the laser source and / or the optical system to deliver radiation with desired characteristics (e.g., for removing carbonates without damaging the tissue surface) to the treatment area. In some cases, the systems include a handpiece having an optical element (e.g., a lens) mounted in a replaceable cartridge and adapted to modulate the laser beam to a non-ablative beam prior to delivery to the treatment area. In some embodiments, laser treatment can be combined with fluoride treatment to enhance the therapeutic effect.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 956,862, entitled "Laser System for Enhancing Remineralization and Strength of Hard Tissue," filed January 3, 2020, the contents of which are incorporated herein by reference in their entirety.

[0002] (Technical field) The present invention relates generally to the treatment of hard tissue using light emitting devices (e.g., laser sources), and more particularly to promoting remineralization and hard tissue strength by directing radiation emitted by a laser source to the hard tissue. [Background technology]

[0003] (background) Dental caries is a disease in which tooth minerals are dissolved by acids, leading to the development of cavities. Certain bacteria in the mouth produce organic acids when they feed on fermentable carbohydrates, such as sugars. These organic acids quickly dissolve the carbonate hydroxyapatite mineral in tooth enamel, causing mineral loss (demineralization). Mineral loss first appears as a non-cavity "white spot," and if the process continues, eventually leads to tooth decay.

[0004] The mineral that makes up 95% of tooth enamel by weight is often described as hydroxyapatite, a form of calcium phosphate. However, in reality, tooth enamel contains numerous impurities and inclusions as a result of its formation in the human body's biological fluid system. The mineral is more clearly described as carbonated hydroxyapatite, in which approximately one in every ten phosphate groups is replaced by a carbonate, making the mineral many times more soluble in acid than pure hydroxyapatite without the carbonate inclusions.

[0005] For example, research has been conducted on the use of lasers to treat dental caries by ablating decayed tissue so that it can be replaced with a filling material. Lasers such as Er:YAG and Nd:YAG lasers are primarily absorbed by the water in the tooth rather than the hydroxyapatite, which can cause undesirable damage to the tissue surface during the heating process. This is in part because the subsurface water turns to steam, removing a significant amount of water before the hydroxyapatite reaches the high temperatures required for both the acid-resistant effect and the blasting effect. More recent research has revealed that certain CO2 laser wavelengths are better absorbed by hydroxyapatite and can be effective in ablating dental tissue.

[0006] However, significantly less is known about the use of lasers to prevent caries formation and acid dissolution. Preliminary academic research suggests that enamel surfaces can be modified by heating them with short laser pulses, and that such heating can lead to improved caries resistance. However, significantly more research is needed to determine the desired operating parameters for such laser treatments and to adapt the academic research into a suitable functional system for commercial use with patients. In addition, little is known about the effects of such laser treatments in combination with conventional caries-resistant treatments, such as fluoride applications. Summary of the Invention [Means for solving the problem]

[0007] (overview) Embodiments of the invention described herein relate to laser treatment systems that can be used to enhance both the strength and remineralization of hard dental tissue. In some implementations, the invention involves the combined use of a laser treatment system with conventional treatment techniques, such as fluoride application, for enhanced effectiveness. The inventors have discovered that laser irradiation of dental enamel, which results in the removal of carbonate from hydroxyapatite, also enhances fluoride absorption, resulting in a further modified enamel surface that resembles the composition of a less soluble form of calcium phosphate known as fluoroapatite, which is more resistant to acid erosion than hydroxyapatite.

[0008] In various embodiments, the present invention includes a laser source operating in the 9-11 μm wavelength range, such as a CO laser. CO lasers have several advantages over other types of hard tissue lasers (e.g., Er:YAG lasers), for example, their absorption coefficient in hydroxyapatite is approximately two times higher. The present invention can feature a handpiece for directing a 9-11 μm laser beam to hard tissue surfaces in the oral cavity with desirable efficiency, minimal technique sensitivity, and rapid treatment times.

[0009] The system can be adapted to scan the laser beam using various scanning techniques, for example, using galvanometer mirrors. The laser beam can be scanned across the treatment area using specific pattern(s) that allow for efficient energy delivery that creates a photothermal effect that is sufficiently localized to shrink collagen without damaging (burning or scorching) the tissue. Some such patterns are described in more detail in U.S. Patent Publication No. 2017 / 0319277, which is incorporated herein by reference in its entirety and attached as Appendix A.

[0010] The system may also include a laser source controller that may adjust one or more treatment parameters (e.g., laser pulse duration) according to the type of treatment selected and / or the type of tissue being treated. Various treatment parameters are described in more detail below and in U.S. Patent Publication No. 2018 / 0325622, which is incorporated herein by reference in its entirety and attached as Appendix B.

[0011] In general, in one aspect, embodiments of the invention feature a system for treating hard dental tissue, the system including: a laser source for generating a laser beam; optics in optical communication with the laser source adapted to direct the laser beam to a treatment surface of the hard dental tissue; and a laser source for generating a laser beam having a power of 0.4 J / cm. 2 ~1.2J / cm 2 10cm, with fluences in the range 2 / min~20cm 2 / min and a controller adapted to control the laser source and optics to deliver a laser beam to the treatment surface so as to (i) remove at least some carbonate from the treatment surface without damaging the hard dental tissue and generate an acid-resistant surface, and (ii) reduce the ΔZ value of the hard dental tissue by at least 10% relative to untreated hard dental tissue.

[0012] In various embodiments, the laser source can include a CO2 laser source. The laser beam can include a wavelength in the range of 9 μm to 11 μm. In some cases, the laser beam can have a spot size in the range of 0.2 mm to 5 mm at the treatment surface. The optical system can include a galvanometer and / or a turning mirror. In some cases, the controller is further adapted to control the laser source to deliver the laser beam to the treatment surface in a series of pulses. In some cases, each pulse in the series of pulses includes a pulse energy in the range of 0.1 mJ to 50 mJ. In some cases, each pulse in the series of pulses includes a pulse duration in the range of 1 μsec to 100 μsec. In some cases, each pulse in the series of pulses includes a repetition rate in the range of 0.05 Hz to 10 Hz. The series of pulses can include a duty cycle in the range of 0.1 to 10.

[0013] In some embodiments, the controller is adapted to deliver a series of pulses to the treatment surface in a pattern. The pattern can include a diameter in the range of 1 mm to 5 mm. The pattern can include a number of locations in the range of 1 to 1,000 (e.g., 217 locations). The spacing between each location in the pattern can be in the range of 0.1 mm to 5 mm. In some cases, the controller is also adapted to control the laser source to deliver the laser beam to the treatment surface so as to reduce the ΔZ value of the dental tissue by at least 20% relative to hard dental tissue receiving the fluoride treatment when combined with the fluoride treatment. In some cases, the system can also include a fluoride delivery system adapted to deliver the fluoride treatment to the treatment surface. In some cases, the controller is further adapted to control the laser source to deliver the laser beam to the treatment surface so as to reduce the ΔS value of the dental tissue by at least 68% relative to untreated dental tissue. In some cases, the controller is further adapted to control the laser source to deliver a laser beam to the treatment surface such that, when combined with a fluoride treatment, the laser beam reduces the ΔS value of the dental tissue by at least 18% relative to hard dental tissue receiving the fluoride treatment.

[0014] In general, in another aspect, embodiments of the invention relate to a method of treating hard dental tissue, the method comprising the steps of generating a laser beam using a laser source, directing the laser beam to a treatment surface of the hard dental tissue using an optical system in optical communication with the laser source, and applying a laser beam having a power of 0.4 J / cm 2 ~1.2J / cm 2 10cm, with fluences in the range 2 / min~20cm 2 / min range to treat an area of ​​hard dental tissue and (i) remove at least some carbonate from the treatment surface without damaging the hard dental tissue and develop an acid-resistant surface, and (ii) reduce the ΔZ value of the hard dental tissue by at least 10% relative to untreated hard dental tissue.

[0015] In various embodiments, the laser source includes a CO2 laser source. The laser beam can include a wavelength in the range of 9 μm to 11 μm. In some cases, the laser beam can have a spot size at the treatment surface in the range of 0.2 mm to 5 mm. The optical system can include a galvanometer and / or a turning mirror. In some cases, the controller is further adapted to control the laser source to deliver the laser beam to the treatment surface in a series of pulses. In some cases, each pulse in the series of pulses includes a pulse energy in the range of 0.1 mJ to 50 mJ. In some cases, each pulse in the series of pulses includes a pulse duration in the range of 1 μsec to 100 μsec. In some cases, each pulse in the series of pulses includes a repetition rate in the range of 0.05 Hz to 10 Hz. The series of pulses can include a duty cycle in the range of 0.1 to 10.

[0016] In some embodiments, the controller is adapted to deliver a series of pulses to the treatment surface in a pattern. The pattern can include a diameter in the range of 1 mm to 5 mm. The pattern can include a number of locations in the range of 1 to 1,000 (e.g., 217 locations). The spacing between each location in the pattern can be in the range of 0.1 mm to 5 mm. In some cases, the controlling step further includes using the controller to deliver a laser beam to the treatment surface that, when combined with the fluoride treatment, reduces the ΔZ value of the dental tissue by at least 20% relative to hard dental tissue receiving the fluoride treatment. In some cases, the method can further include delivering the fluoride treatment to the treatment surface. In some cases, the controller is further adapted to control the laser source to deliver the laser beam to the treatment surface to reduce the ΔS value of the dental tissue by at least 68% relative to untreated dental tissue. In some cases, the controlling step further includes using the controller to control the laser source to deliver the laser beam to the treatment surface in a manner that, when combined with the fluoride treatment, reduces the ΔS value of the dental tissue by at least 18% relative to hard dental tissue receiving the fluoride treatment. The present invention provides, for example, the following items. (Item 1) 1. A system for treating hard dental tissue, comprising: a laser source for generating a laser beam; an optical system in optical communication with the laser source adapted to direct the laser beam onto a treatment surface of the hard dental tissue; 0.4J / cm 2 ~1.2J / cm 2 10cm, with fluences in the range 2 / min~20cm 2 treating the area of ​​hard dental tissue at a rate in the range of 1 / min; removing at least some carbonate from the treated surface without damaging the hard dental tissue to generate an acid-resistant surface; reducing the ΔZ value of said hard dental tissue by at least 10% relative to untreated hard dental tissue; a controller adapted to control the laser source and the optical system to deliver the laser beam to the treatment surface so as to A system comprising: (Item 2) The laser source is CO 2 Item 1. The system of item 1, including a laser source. (Item 3) Item 3. The system of item 2, wherein the laser beam comprises a wavelength in the range of 9 μm to 11 μm. (Item 4) Item 10. The system of item 1, wherein the laser beam has a spot size at the treatment surface in the range of 0.2 mm to 5 mm. (Item 5) Item 10. The system of item 1, wherein the optical system comprises at least one of a galvanometer and a turning mirror. (Item 6) Item 10. The system of item 1, wherein the controller is further adapted to control the laser source to deliver the laser beam to the treatment surface in a series of pulses. (Item 7) 7. The system of claim 6, wherein each pulse in the series of pulses comprises a pulse energy in the range of 0.1 mJ to 50 mJ. (Item 8) 7. The system of claim 6, wherein each pulse in the series of pulses comprises a pulse duration in the range of 1 μsec to 100 μsec. (Item 9) 7. The system of claim 6, wherein the train of pulses comprises a repetition rate in the range of 0.05 Hz to 10 Hz. (Item 10) 7. The system of claim 6, wherein the series of pulses comprises a duty cycle in the range of 0.1 to 10. (Item 11) 7. The system of claim 6, wherein the controller is adapted to deliver the series of pulses to the treatment surface in a pattern. (Item 12) Item 12. The system of item 11, wherein the pattern has a diameter in the range of 1 mm to 5 mm. (Item 13) Item 12. The system of item 11, wherein the pattern comprises a number of locations in the range of 1 to 1,000. (Item 14) Item 14. The system of item 13, wherein the pattern comprises 217 locations. (Item 15) Item 14. The system of item 13, wherein the spacing between each location in the pattern is in the range of 0.1 mm to 0.5 mm. (Item 16) Item 10. The system of item 1, wherein the controller is further adapted to control the laser source to deliver the laser beam to the treatment surface in a manner that, when combined with a fluoride treatment, reduces the ΔZ value of the dental tissue by at least 20% relative to hard dental tissue receiving the fluoride treatment. (Item 17) 17. The system of claim 16, further comprising a fluoride delivery system adapted to deliver the fluoride treatment to the treatment surface. (Item 18) Item 10. The system of item 1, wherein the controller is further adapted to control the laser source to deliver the laser beam to the treatment surface so as to reduce the ΔS value of the dental tissue by at least 68% relative to untreated dental tissue. (Item 19) Item 19. The system of item 18, wherein the controller is further adapted to control the laser source to deliver the laser beam to the treatment surface in a manner that, when combined with a fluoride treatment, reduces the ΔS value of the dental tissue by at least 18% relative to hard dental tissue receiving the fluoride treatment. (Item 20) 1. A method of treating hard dental tissue, comprising: generating a laser beam using a laser source; directing the laser beam to a treatment surface of the hard dental tissue using an optical system in optical communication with the laser source; 0.4J / cm2 ~1.2J / cm 2 10cm, with fluences in the range 2 / min~20cm 2 treating the area of ​​hard dental tissue at a rate in the range of 1 / min; removing at least some carbonate from the treated surface without damaging the hard dental tissue to generate an acid-resistant surface; reducing the ΔZ value of said hard dental tissue by at least 10% relative to untreated hard dental tissue; and controlling, using a controller, the laser source and the optics to deliver the laser beam to the treatment surface so as to perform A method comprising: (Item 21) The laser source is a CO 2 21. The method of claim 20, comprising a laser source. (Item 22) 22. The method according to claim 21, wherein the laser beam has a wavelength in the range of 9 μm to 11 μm. (Item 23) 21. The method of claim 20, wherein the laser beam has a spot size at the treatment surface in the range of 0.2 mm to 5 mm. (Item 24) Item 21. The method of item 20, wherein the optical system comprises at least one of a galvanometer and a turning mirror. (Item 25) 21. The method of claim 20, wherein the controller is further adapted to control the laser source to deliver the laser beam to the treatment surface in a series of pulses. (Item 26) 26. The method of claim 25, wherein each pulse in the series of pulses comprises a pulse energy in the range of 0.1 mJ to 50 mJ. (Item 27) 26. The method of claim 25, wherein each pulse in the series of pulses comprises a pulse duration in the range of 1 μsec to 100 μsec. (Item 28) 26. The method of claim 25, wherein the train of pulses comprises a repetition rate in the range of 0.05 Hz to 10 Hz. (Item 29) 26. The method of claim 25, wherein the series of pulses comprises a duty cycle in the range of 0.1 to 10. (Item 30) Item 26. The method of item 25, wherein the controller is adapted to deliver the series of pulses to the treatment surface in a pattern. (Item 31) Item 31. The method according to item 30, wherein the pattern has a diameter in the range of 1 mm to 5 mm. (Item 32) Item 31. The method according to item 30, wherein the pattern comprises a number of locations in the range of 1 to 1,000. (Item 33) Item 33. The method of item 32, wherein the pattern comprises 217 locations. (Item 34) Item 33. The method according to item 32, wherein the spacing between each location in the pattern is in the range of 0.1 mm to 0.5 mm. (Item 35) 21. The method of claim 20, wherein the controlling step further comprises using the controller to control the laser source to deliver the laser beam to the treatment surface in a manner that, when combined with a fluoride treatment, reduces the ΔZ value of the dental tissue by at least 20% relative to hard dental tissue receiving the fluoride treatment. (Item 36) 36. The method of claim 35, further comprising the step of delivering the fluoride treatment to the treatment surface. (Item 37) 21. The method of claim 20, wherein the controlling step further comprises controlling the laser source using the controller to deliver the laser beam to the treatment surface so as to reduce the ΔS value of the dental tissue by at least 68% relative to untreated dental tissue. (Item 38) 21. The method of claim 20, wherein the controlling step further comprises using the controller to control the laser source to deliver the laser beam to the treatment surface in a manner that, when combined with a fluoride treatment, reduces the ΔS value of the dental tissue by at least 18% relative to hard dental tissue receiving the fluoride treatment. [Brief explanation of the drawings]

[0017] BRIEF DESCRIPTION OF THE DRAWINGS In the drawings, like reference characters generally refer to the same parts throughout the different views.In the following description, various embodiments of the present invention are described with reference to the following drawings:

[0018] [Figure 1] FIG. 1 is a schematic perspective view of a laser treatment system according to various embodiments.

[0019] [Figure 2] FIG. 2 is a schematic cross-sectional side view of a handpiece including an optical cartridge according to various embodiments.

[0020] [Figure 3] FIG. 3 is an exemplary plot of beam size diameter versus distance from the handpiece exit orifice according to various embodiments.

[0021] [Figure 4] FIG. 4 is a depiction of an exemplary treatment pattern according to various embodiments.

[0022] [Figure 5] 5A-D depict laser-irradiated and non-laser-irradiated tissue surfaces under various treatment conditions according to various embodiments.

[0023] [Figure 6] FIG. 6 depicts the experimental setup used to demonstrate the performance of the laser treatment system according to various embodiments.

[0024] [Figure 7] FIG. 7 depicts another experimental setup used to demonstrate the performance of a laser treatment system according to various embodiments.

[0025] [Figure 8A] FIG. 8A is an exemplary chart showing Knoop hardness number measurements of various tissue surfaces subjected to different pH cycling tests, according to various embodiments.

[0026] [Figure 8B] FIG. 8B is an exemplary plot depicting the change in hardness of various tissue surfaces subjected to different pH cycling tests, according to various embodiments.

[0027] [Figure 9] FIG. 9 is an exemplary chart showing ΔZ measurements for various tissue surfaces undergoing treatment at different fluence levels, according to various embodiments.

[0028] [Figure 10] 10A-C are exemplary charts showing ΔS measurements, surface loss measurements, and surface microhardness measurements, respectively, of various tissue surfaces undergoing treatment at different fluence levels according to various embodiments.

[0029] [Figure 11] 11A-B are graphs illustrating exemplary ΔZ measurements versus ΔS measurements according to various embodiments.

[0030] [Figure 12] 12A-C are tables and graphs illustrating exemplary ΔS and ΔZ measurements for various tissue surfaces undergoing treatment at different fluence levels, according to various embodiments.

[0031] [Figure 13] FIG. 13 is a chart providing exemplary laser and treatment parameter values ​​according to various embodiments. DETAILED DESCRIPTION OF THE INVENTION

[0032] (Detailed explanation) In various embodiments, the present invention is directed to an improved laser treatment system 100. The system 100 can reduce caries formation and acid dissolution of treated hard dental tissue compared to conventional devices. The system 100 can include a handpiece 1 that delivers laser pulses that heat hard tissue without damaging the tissue and remove carbonate impurities from hydroxyapatite (thereby enhancing remineralization / reducing demineralization). As used herein, the phrase "damaging tissue" refers to one of burning, scorching, or melting the tissue. Under the definition used herein, carbonate removal alone is not considered "damaging tissue." Carbonate removal without damaging tissue is further described in U.S. Patent Publication No. 2018 / 0325622, which is incorporated herein by reference in its entirety and attached as Appendix B.

[0033] In various embodiments, system 100 may also feature (i) a laser beam having a long working range (defined below), (ii) a coolant delivery system for delivering coolant (air, water, mist, etc.) to the intra-oral treatment area, and, optionally, (iii) a fluoride delivery system for applying fluoride to the treatment area. This application will often describe the treatment of hard dental tissue; however, in general, the invention described herein can be adapted for use with any suitable hard tissue (e.g., jaw, skull, and other bony areas).

[0034] In some embodiments, the laser treatment system 100 includes a CO2 laser source 102 operating at a wavelength in the 9-11 μm range (e.g., 9.3 μm) and a handpiece 1 configured to enable uniform treatment of all teeth with minimal variation in technique sensitivity. The system 100 can efficiently perform treatments with rapid treatment times and without the need for anesthesia.

[0035] As shown in FIG. 2 , handpiece 1 may be constructed and designed to receive optical cartridge 2. Optical cartridge 2 may include at least one optical lens, which modulates a laser beam passing therethrough (e.g., to generate a collimated laser beam). For example, as shown in FIG. 2 , optical cartridge 2 may include upstream optical lens 3 and downstream optical lens 4. Optical cartridge 2 may be retained within handpiece 1 using any known technique, for example, using threading 6. The ability to replace or remove optical cartridge 2 allows for switching the laser between treatment modes (e.g., from an ablative mode to a non-ablative treatment mode, and vice versa). Additionally, handpiece 1 may include a channel or tube 5 that delivers a non-laser substance, such as a cooling fluid (e.g., air, moisture, and mist, or a combination thereof) and / or a fluoride-based fluid to the treatment area to promote acid resistance and improve fluoride uptake. The handpiece can include an exit orifice 8, out of which the laser beam is directed, in some embodiments, via a turning mirror 7. In some embodiments, the laser beam can be scanned across the treatment area through the handpiece using a galvanometer located upstream of the optical cartridge 2.

[0036] In some embodiments, the optical cartridge 2 can provide a laser beam with a relatively long working range. 2) versus distance from the exit orifice 8 of the handpiece 1, where the plot is for a 1.0 mm beam generated with the optical cartridge 2 and for a native beam generated without the optical cartridge 2. The exemplary data demonstrates that the optical cartridge can produce a uniform beam size (1 mm) over a long working range (e.g., 5-20 mm) that is larger than the original collimated beam size (0.4 mm). Because fluence is a measure of energy per unit area, generating a collimated beam and maintaining a uniform beam size (spot size) along the length of the laser beam (as opposed to a non-collimated beam that converges and diverges about a focal point) can produce a laser beam with a lower fluence, which in some cases can result in a non-ablative laser beam. A larger spot size can also allow a larger surface area of ​​the treatment region (e.g., a tooth) to be covered more rapidly, thereby reducing treatment time.

[0037] In various embodiments, the laser is pulsed and scanned according to a pattern to achieve the desired level of carbonate removal. Additionally, as shown in FIG. 4, the laser source may be spatially scanned to provide different pulse energies at different locations. In various embodiments, laser and treatment parameters may be selected to optimize efficiency and treat tissue without damage (e.g., as shown in FIG. 13). Exemplary treatment patterns are described in more detail in U.S. Patent Publication Nos. 2017 / 0319277 and 2018 / 0325622, both of which are incorporated by reference in their entireties and attached as Appendices A and B.

[0038] In various embodiments, the laser treatment system 100 can operate in a manner that improves the reduction of caries formation and promotes remineralization. In particular, experiments have been conducted using the laser treatment system 100 to demonstrate this improved performance.

[0039] In a first exemplary experiment, a 9.3 μm Solea CO laser (Convergent Dental, Inc., Needham, MA) produced a collimated 1 mm beam diameter (1 / e) at the output of the handpiece over a 5 cm range. 2 The laser was used with a 750 Hz repetition rate (measured by the laser pulse duration method). The beam was scanned using a pair of controllable mirrors (galvanometers) in a pattern with a uniform center-to-center spacing of 0.2 mm between adjacent hits and a maximum frequency between adjacent hits of 25 Hz. This distribution of hits allowed energy to be dissipated without heat accumulation within the pulp. To aid in cooling, a regulated system-delivered airflow from the handpiece was used on the sample during irradiation with the laser. The laser fluence was varied solely by changing the light pulse duration between 17 and 27 μs. At 17 μs, the average power was 3.5 W and the fluence per pulse was 0.6 J / cm. 2 At 27 μs, the average power is 5.7 W and the fluence per pulse is 1.0 J / cm 2 The distance from the handpiece to the tooth sample was maintained at a set position of 10 mm to further ensure uniform delivery of energy and air to the treatment surface.

[0040] Five sound human enamel samples mounted in acrylic resin and polished to a 1 μm diamond grit finish (Therametrics, Inc., Indianapolis, IN) were used to investigate the formation and properties of the acid-resistant layer. The laser-treated blocks had only been exposed to thymol solution during shipping and were less than 3 months old. The Solea CO2 9.3 μm laser was used, delivering 0.6–1 J / cm. 2A pulse fluence range of 1000 s was used. The blocks were sequentially polished from the side to a 6 μm coarse grain to expose cross sections of both the laser-irradiated and non-irradiated areas. The original laser-irradiated surface was masked with acid-resistant tape. The cross-sectional surface was exposed to 1 N HCl for 1 minute to erode the underlying normal enamel and expose the acid-resistant layer, then thoroughly rinsed with water. To capture subsurface features, the blocks were imaged under a 3D digital reflectance microscope (Hirox RH-2000) with cross-polarization. The microscope was used to acquire a 3D stack of images over a depth range of 50 μm.

[0041] Figure 5A shows a cross-sectional image of enamel exposed to hydrochloric acid. In this example, an acid-resistant layer within approximately 15 μm was removed at 0.8 J / cm 2 These defects are created by laser irradiation at a fluence of 1000 Hz and appear as undissolved protrusions above the underlying enamel (which undergoes rapid dissolution and is out of focus in the microscope image). Figure 5B shows a cross-section of the enamel for a uniformly dissolved, unirradiated section in which no acid-resistant layer is observed. This served as verification that the laser parameters used in the above experiment successfully formed an acid-resistant layer on the enamel surface to inhibit demineralization. Figures 5C and 5D are three-dimensional image stacks of enamel samples revealing the acid-resistant layer as an unetched area near the surface for the laser-irradiated sample and a flat, uniformly etched area for the unirradiated sample.

[0042] In a second illustrative experiment, to investigate the correlation between the reduction of caries and caries-like lesions and the inhibition of surface mineral loss, 74 human molars with no signs of caries or fluoride deposits and less than three months post-extraction were obtained and stored solely in thymol solution. The molars were mounted in 1-inch acrylic cylinders with the entire crown (all lateral and occlusal surfaces) exposed (Therametrics, Inc., Indianapolis, IN). The samples were sonicated for 5 minutes in distilled water. The samples were then air-dried and divided into six groups. Groups 1-3 underwent pH cycling without additional fluoride, while Groups 4-6 underwent pH cycling with additional fluoride. As shown in Figure 6, Groups 1 and 4 received 0.6 J / cm2 of fluoride on both sides of the flattest area (lowest curvature) of the lateral crown. 2 Groups 2 and 5 were irradiated with a laser fluence of 0.8 J / cm 2 Groups 3 and 6 were irradiated with a laser fluence of 1.0 J / cm 2 The laser was irradiated at a fluence of 1000 Hz. Exemplary collected data are shown in Tables 1 and 2 below (some sample loss occurred due to grinding damage or other immeasurable nature of the sample). Non-irradiated control areas were maintained between the laser-irradiated areas. Acid-resistant, fast-setting nail polish was used to mask the boundary between the laser-irradiated and non-irradiated areas along the entire height of the molar from the mounted base to the occlusal surface. Figure 6 depicts a human molar within an acrylic resin mount. Laser-irradiated areas L1 and L2 are depicted along with a non-irradiated control C. The stripes represent the masked area spanning the entire height of the exposed tooth. [Table 1] [Table 2]

[0043] Decalcification solutions were prepared in the form of 75 mM acetate buffer with 2 mM calcium and phosphate, and the pH was balanced to 4.4 using NaOH or HCl as needed. Remineralization solutions were prepared from 0.1 M Tris, 0.8 mM calcium, and 2.4 mM phosphate, and the pH was balanced to 7.1. A 9-pH cycle regimen using the aforementioned solutions was followed by a 6-hour demineralization and 18-hour remineralization step, similar to that described in Rechmann P, Rechmann BMT, Groves WH, et al., "Caries inhibition with a CO2 9.3 μm laser: An in vitro study," Lasers Surg Med. 2016;554(February):1-9, doi:10.1002 / lsm.22497. Approximately half of the samples were exposed to a fluoride toothpaste slurry using a 1:3 ratio of Crest Anti-Caries 1,100 ppm F toothpaste (Proctor and Gamble, Inc.) and distilled water for 1 minute after each step in the cycle. After five cycles, the solution was replaced with fresh solution from the same batch. After cycling, samples were stored in distilled water for no more than two weeks before measurements were performed.

[0044] Samples were polished up to six at a time using an automated polishing machine (Metkon Forcipol 1V) with 600 coarse-grain polishing pads until a flat cross-section was achieved within the laser-irradiated area. Samples were individually hand-polished with a diamond suspension to remove polishing marks for microhardness testing. Samples were sequentially indented (Matsuzawa Seiki DMH-2) using a 25g load for 10 seconds for every 25µm below the surface, starting 15µm from the outer surface until a depth of 200µm was reached. The volume percent mineral content was calculated at each indentation location using the formula: pH cycling model: A prospective, multi-site validation exercise, Stookey GK, Featherstone JDB, Rapozo-Hilo M, et al., "The Featherstone laboratory pH cycling model: A prospective, multi-site validation exercise," Am J Dent. 2011;24(5):322-328.

number

[0045] After ΔZ was determined, each sample was turned onto its side so that the laser-irradiated area faced upward. The sample was then polished against this same side until half of the sample was removed. Occasional loss of the sample occurred due to unexpected damage to the surface or mishandling. Using the same indenter, the sample was indented 10 times against the laser-irradiated and non-irradiated control surfaces on each region. The symmetry and quality of each indentation were checked under a microscope, and the length of the indentation was measured. Surface loss was then measured at the edge of the nail polish using the microscope's built-in 3D stage. It was determined as the change in height from the edge of the masked surface to the top of the adjacent unmasked enamel surface. Measurements were taken at least every 50 μm along the entire length of the boundary region, with at least 10 measurements taken per boundary region. As depicted in FIG. 7, the surface loss measurements and hardness measurements are combined as ΔS = h2 / (h1 + h2) * vol%, where vol% is calculated from the indentation as described above. FIG. 7 depicts a schematic diagram of creating an indentation against enamel (left) and a cross-sectional view of the indentation site (right). For the calculation of ΔS, h1 = surface loss, h2 = microhardness indentation height, and vol% is calculated from the size of the indentation relative to the surface. ΔS is a representation of the amount of mineral loss relative to the surface, which is associated with slow surface mineral loss, while ΔZ is a measure of mineral loss at depth, which is associated with subsurface caries-like formation. Data were analyzed on a logarithmic scale using Welch's analysis of variance between groups and a Games-Howell post-hoc test. FIG. 8A is an exemplary chart showing Knoop hardness number measurements of various tissue surfaces subjected to different pH cycling tests, according to various embodiments. FIG. 8B is an exemplary plot depicting the change in hardness of various tissue surfaces subjected to different pH cycling tests, according to various embodiments.

[0046] The ΔZ values ​​shown in Table 1 and Figure 9 provide a measure of caries-like lesion formation and serve as an index for comparing treatments using different laser settings. No superficial structural changes were observed for the range of fluences used. However, at 1.0 J / cm 2 Below the surface for areas irradiated with , there were occasional signs of structural changes such as fine fractures that may be related to subsurface thermal spallation.

[0047] Welch's analysis of variance applied to the data showed that there were significant differences between groups (F 11,40 =81.0, p<0.001). The mean reduction in ΔZ from the use of additional fluoride without laser irradiation (Groups 4-6) was approximately 65% ​​(p<0.001). A reduction in ΔZ from laser irradiation alone was observed (see Groups 1-3 in Table 1), indicating that effective remineralization can and does occur regardless of the presence of additional fluoride. Gameshower post-hoc tests indicated that the combined treatment of laser irradiation and additional fluoride provided the most significant benefit in reducing ΔZ for each of the laser fluences used (p<0.01 for all). While pH cycling with fluoride toothpaste alone revealed benefits in caries inhibition, application of fluoride toothpaste into the irradiated areas, as described herein, resulted in the most significant and unexpectedly high reduction in caries formation, with a high reduction in ΔZ of approximately 92% (p=0.001) compared to untreated control areas.

[0048] Table 2 and Figures 10A-10C show the combination of surface indices in the form of ΔS. As with ΔZ, Welch's analysis of variance applied to ΔS values ​​showed that there were significant differences between groups (F 11,36 =39.5, p<0.001). Analysis of variance showed that without additional fluoride (F 2,12 =1.16, p>0.05) or with additional fluoride (F 2,16= 0.22, p > 0.05), did not show any differences within the non-irradiated group. The general trend for ΔS was similar to that observed for ΔZ in relation to laser fluence. ΔS values ​​did not show any significance from the use of fluoride alone versus untreated controls via Games-Howell post-hoc tests (p > 0.05). However, when comparing all data with no added fluoride and with added fluoride using Student's t-test, a significant reduction in ΔS of approximately 18% (p < 0.001) was found. ΔS revealed that laser irradiation at 9.3 μm alone inhibited surface mineral loss by approximately 64% (p = 0.004). Furthermore, 1 J / cm2 combined with fluoride application from toothpaste 2 The combination of laser irradiation with 20 mg of 20 ...

[0049] Figure 11A is a plot of ΔZ values ​​as a function of ΔS values ​​for measurements collected in the experiment described above. ΔZ and ΔS values ​​followed a log-normal distribution, and a linear trend between them was observed with a Spearman's rho of 0.63 (p<0.001). Figure 11B shows a linear regression fit (on a logarithmic scale) when data points were averaged according to treatment group. Because the control set and toothpaste cycling set differed in methodology, they are treated as distinct sets. The linear fits for these two sets had very similar slopes of approximately 1.3, and both had R 2 ≥ 0.95. This finding provides two very important pieces of information. First, the overall effect of fluoride on caries resistance and acid resistance can be quantified by the vertical shift in curvature, revealing that fluoride provides a 50-60% inhibition in caries formation / acid penetration. Second, the laser benefit can be quantified per pulse fluence. ΔZ and ΔS were found to be 0.6, 0.8, and 1.0 J / cm, both averaged, with and without added fluoride. 2After laser irradiation, there was a significant improvement of approximately 39%, 59%, and 72%, respectively, compared to the area without laser irradiation.

[0050] Figure 12A provides exemplary data including ΔZ and ΔS measurements for tissue irradiated with laser at various fluences, with and without the application of fluoride. Figure 12B is a graph of the measured ΔZ values ​​for various fluences for treatments combined with fluoride and treatments without fluoride, along with an exemplary indication of the effective treatment area. Figure 12C is a graph of the measured ΔS values ​​for various fluences for treatments combined with fluoride and treatments without fluoride, along with an exemplary indication of the effective treatment area.

[0051] In various embodiments, laser irradiation at 9.3 μm creates an acid-resistant form of hydroxyapatite, which occurs at temperatures that remove a large amount of the carbonate groups in the carbonated hydroxyapatite mineral of tooth enamel. This allows for crystallization of fluoride-containing hydroxyapatite in these weak areas, thereby reducing acid penetration beneath the durable layer. Other organic components, primarily present as a glue-like network holding adjacent rods together, may also be removed near the surface during irradiation. This surface change has previously been described as surface "glazing."

[0052] In various embodiments, the benefits of laser irradiation under the tested laser conditions are significant even without the use of fluoride. Surface softening and underlying lesion formation can be significantly slowed. This may be an indication that crystallization of "weak" sites occurs from dissolved minerals (primarily calcium and phosphate) despite initial acid exposure. Due to this remineralization effect, the benefits of laser-induced acid resistance can outweigh the risks associated with structural changes to the surface. In some embodiments, the introduction of fluoride in the cycling process can enhance the acid-resistant properties of the layer, which may be at least partially due to fluoroapatite's inherent resistance to dissolution. The laser-treated area may promote fluoride uptake by the surface along with calcium and phosphate, resulting in the observed beneficial effects of the paired treatments in combination. As described below, in some embodiments, the application of fluoride can be performed with the delivery of a cooling agent using laser treatment system 100. However, the present invention also contemplates delivery of fluoride from other sources, separate from delivery through the laser treatment system 100, for example, as part of a dental outpatient visit or elsewhere (e.g., at home by brushing teeth or using a mouthwash).

[0053] The invention described herein demonstrates a direct correlation between surface mineral loss (ΔS) and caries lesion size (ΔZ). In some embodiments, one explanation for this is that crystallization is random and may introduce poorly packed crystals, making complete remineralization back to original density impossible. Through superficial laser irradiation, enamel softening from acid exposure can be significantly reduced, evident in both surface (erosion) measures or depth (caries) mineral loss. Acid resistance can be further enhanced by the use of high-concentration fluoride applications, such as prescription mouthwashes or varnishes, which can also help rapidly remineralize any weak areas with fluorapatite, potentially even before the patient leaves the treatment clinic, since the laser-irradiated area can increase the rate of fluoride uptake. In this work, erosion and caries resistance can be increased by approximately 50-60% using fluoride-containing toothpaste and by a further 40-80% using laser treatment with a 9.3 μm CO2 laser.

[0054] As used herein, the term "working range" refers to the distance along the length of the laser beam over which the laser beam has a fluence capable of treating tissue (e.g., removing carbonates). Conventional devices typically have a relatively short working range that is tightly focused around the focal point of the laser beam, based on the desire to not dump any energy along the length of the laser. The laser treatment system of the present invention, in some embodiments, can tolerate a longer working range to allow the operator to move their hand (and correspondingly the laser beam) while still effectively treating the treatment area. In other words, in certain embodiments, the amount of energy delivered to the target tissue does not change over a relatively long distance (e.g., more than 0.5 cm, more than 1 cm, more than 1.5 cm, more than 2 cm, more than 3 cm, more than 4 cm, etc.) along the axis between the exit orifice 8 and the hard tissue, thereby accommodating hand movement, variability in the user's holding of the handpiece standoff, and other human factors. The concept of working area is explained in more detail with reference to the phrase "depth of treatment" (which may be interchangeable with "working area") in U.S. Patent Publication No. 2016 / 0143703, which is incorporated herein by reference in its entirety and attached as Appendix C.

[0055] In some embodiments, the handpiece 1 can also be adapted to deliver fluids, such as cooling fluids and / or fluoride-based fluids, to the treatment area. The fluids can be transported using any known technique, for example, through fluid conduit 5, which extends along the handpiece 1 and bypasses the optical cartridge 2. The cooling fluid can be useful for minimizing and avoiding excessive heating of the tissue. As discussed above, the fluoride-based fluid can provide improved and more effective treatment. In some cases, both the cooling fluid and the fluoride-based fluid can be delivered through the same conduit 5. In other cases, the handpiece 1 can include separate conduits for each of the cooling fluid and the fluoride-based fluid. Other desired fluids can also be transported through the handpiece 1.

[0056] In some embodiments, the laser beam is accompanied by a marking beam (e.g., green) that serves as a guide for the location of the laser beam on the target tissue. In some cases, the irradiation of the laser may occur in a pattern. Visual feedback or sonar feedback can optionally be integrated into system 100 to indicate to the user the need to move to a new target area. Visual feedback indicating a new target area can include a steady guidance beam (e.g., a green dot projected on the tissue). For example, a pattern can be displayed on the tissue while the tissue is exposed to the laser. When sufficient energy has been delivered, the laser can stop scanning and a point object can be projected on the target tissue. Alternatively, sonar feedback can be provided to indicate the pattern and / or amount of energy delivery.

[0057] 13 is a chart including exemplary laser and operating parameters for the laser treatment system 100. The parameters can be designed to have a desired outcome efficiency to remove carbonate without damaging the treatment surface material. In some embodiments, as will be understood by those skilled in the art, the laser beam can be spatially scanned to provide different pulse energies at different locations.

[0058] Each numerical value presented herein is intended to represent the minimum or maximum value within a range for the corresponding parameter. Thus, when added to a claim, the numerical value provides explicit support for claiming a range that may exist above or below that numerical value, in accordance with the teachings herein. Every value between the minimum and maximum value within each numerical range presented herein (including the low, nominal, and high values ​​shown in the chart shown in FIG. 13) is contemplated and expressly supported herein, pursuant to the number of significant digits expressed within each specific range.

[0059] While illustrative embodiments of the present invention have been described herein, those skilled in the art will appreciate various other features and advantages of the present invention in addition to those specifically described above. It is therefore to be understood that the foregoing is merely illustrative of the principles of the present invention, and that various modifications and additions, as well as combinations and permutations of the various elements and components recited herein, may all be made by those skilled in the art without departing from the spirit and scope of the invention. Therefore, the appended claims should not be limited to the specific features shown and described, but should be construed to cover any obvious modifications and equivalents thereof.

[0060] The following are the claims:

Claims

1. A method of operating a laser treatment system for treating extracted hard dental tissue, the laser treatment system comprising a laser source, an optical system in optical communication with the laser source, and a controller configured to control the laser source and the optical system, the method comprising: the laser source generating a laser beam; the optical system directing the laser beam to a surface of the extracted hard dental tissue, the laser beam having a spot size at the surface in the range of 0.2 mm to 5 mm; The controller is configured to: ２ ~1.2 J / cm ２ with a fluence in the range of 10 cm ２ / min~20cm ２ controlling the laser source and the optical system to deliver the laser beam to the surface of the extracted hard dental tissue at a rate in the range of 1 / min to 1 / min, thereby removing at least some carbonate from the surface, thereby creating an acid-resistant surface without damaging the extracted hard dental tissue; Including, A method wherein, as a result of operation of the laser treatment system, the extracted hard dental tissue exhibits at least 10% less depth mineral loss (ΔZ) relative to untreated hard dental tissue.

2. The laser source is a CO ２ The method of claim 1 including a laser source.

3. The method of claim 2 , wherein the laser beam comprises a wavelength in the range of 9 μm to 11 μm.

4. The method of claim 1 , wherein the optical system includes at least one of a galvanometer and a turning mirror.

5. The method of claim 1 , wherein the controller is further adapted to control the laser source to deliver the laser beam to the surface in a series of pulses.

6. 6. The method of claim 5, wherein each pulse in the series of pulses comprises a pulse energy in the range of 0.1 mJ to 50 mJ.

7. The method of claim 5 , wherein each pulse in the series of pulses comprises a pulse duration in the range of 1 μsec to 100 μsec.

8. The method of claim 5 , wherein the train of pulses comprises a repetition rate in the range of 0.05 Hz to 10 Hz.

9. The method of claim 5, wherein the series of pulses comprises a duty cycle in the range of 0.1 to 10.

10. The method of claim 5 , wherein the controller is adapted to deliver the series of pulses to the surface in a pattern.

11. The method of claim 10, wherein the pattern has a diameter in the range of 1 mm to 5 mm.

12. The method of claim 10, wherein the pattern has a number of locations in the range of 1 to 1,000.

13. The method of claim 12, wherein the pattern has 217 locations.

14. The method of claim 12, wherein the spacing between each location in the pattern is in the range of 0.1 mm to 0.5 mm.

15. The method of claim 1, wherein the controller controlling the laser source and the optical system further comprises the controller controlling the laser source to deliver the laser beam to the surface such that, when combined with a fluoride treatment, the depth mineral loss (ΔZ) value of the extracted hard dental tissue is reduced by at least 20% relative to the hard dental tissue receiving the fluoride treatment.

16. The method of claim 15, wherein the laser treatment system further comprises a fluoride delivery system, and the method further comprises the fluoride delivery system delivering the fluoride treatment to the surface.

17. The method of claim 1, wherein the controller controlling the laser source and the optical system further comprises the controller controlling the laser source to deliver the laser beam to the surface so as to reduce the ΔS value of the extracted hard dental tissue by at least 68% relative to untreated hard dental tissue.

18. The method of claim 1, wherein the controller controlling the laser source and the optical system further comprises the controller controlling the laser source to deliver the laser beam to the surface such that, when combined with a fluoride treatment, the ΔS value of the extracted hard dental tissue is reduced by at least 18% relative to hard dental tissue receiving the fluoride treatment.

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