Patent Description:
This document pertains generally, but not by way of limitation, to instruments for treating microorganisms within and around the oral cavity and within and around anatomical passages or cavities.

Endodontic treatment includes, in part, bacterial disinfection of a root-canal system and the prevention of re-infection. In some examples, endodontic treatment involves chemical and mechanical debridement of the canal space for disinfection. Chemical irrigation infiltrates the root-canal system, and disinfects or dissolves tissue and removes necrotic debris from the canal wall.

For instance, irrigation of the canal system after mechanical formation of a passage removes tissue remnants, microorganisms and dentin chips by a continual flushing of the canal space. A combination of irrigants in sequence is optionally used for treatment. One example of an irrigant includes sodium hypochlorite (NaOCl) for its efficacy for disinfection and ability to dissolve organic material. In other examples, sodium hypochlorite is used in combination with Ethylenediaminetetraacetic acid (EDTA). The addition of chlorhexidine (CHX) as an irrigant is also used in some example because of its antimicrobial activity, for instance against Enterococcus faecalis (E.

<CIT> discloses an optical apparatus in accordance with the preamble of claim <NUM> having utility in medical procedures, more particularly dental procedures and especially disinfection procedures. The optical apparatus comprises a handpiece housing, a light emitting diode light source and a light delivery system comprising a light guide having a proximal end mountable to the light delivery system to receive light from the light source and a distal end from which light is emitted. The light-emitting diode light source is a single light-emitting diode and the handpiece comprises cooling means adapted to cool the light-emitting diode light-source.

<CIT> discloses a method of cutting physiologic tissue in the mouth of a patient, comprising: providing a tunable laser which is tunable to produce laser radiation at any one of at least two different wavelengths, including a first wavelength which is effective for cutting physiologic tissue of a first type and a second wavelength for cutting physiologic tissue of a second type; tuning the laser to produce radiation at one first and second wavelengths; emitting the radiation being produced by the laser and directing the emitted radiation at physiologic tissue of the type corresponding to the radiation wavelength which the laser is tuned to produce; and at least when the laser is tuned to produce radiation at a selected wavelength, directing a cooling liquid at the physiologic tissue at which the emitted radiation is being directed simultaneously with performance of the directing step.

<CIT> discloses a light based dental treatment device that includes a handle configured for placement within the oral cavity of a user. An instrument shaft extends from the handle. An instrument profile of the instrument shaft is configured for delivery into a passage or cavity of a tooth. The instrument shaft includes at least one light delivery port at a distal end portion of the instrument shaft, and a light passage extending at least from the handle to the light delivery port. A light source is in communication with the light delivery port through the light passage. The light source is configured to generate light in one or more wavelengths including ultraviolet wavelengths.

<CIT>, which corresponds to <CIT>, discloses a measuring instrument comprising a pair of probe elements moveable relative to one another to vary the spacing between sensing areas of each probe, means for producing a signal representing the spacing of said sensing areas, means for monitoring the rate of change of said signal, and means for recording and/or displaying a value representative of said signal upon the rate of change of said signal reaching a predetermined value. Preferably there is a probe including a probe element and a sheath, the probe element being slideable within the sheath and protruding therefrom by a variable amount, means for producing a depth signal representing the amount of protrusion of the probe element from the sheath, means for monitoring the rate of change of said depth signal, and means for recording and/or displaying a value representative of said depth signal upon the rate of change of said depth signal reaching a predetermined value.

<CIT> discloses a hand piece for the delivery of light and a system employing the hand piece. The hand piece typically includes a body and an optical element such as an optical fiber coextensive with the body. The system can include a remote light source and an optical element (e.g., a source optical fiber) for providing light to the hand piece.

<CIT> discloses an intra-oral lighting device for illuminating a tooth located in the mouth of a patient, the device including a source of light, and a probe through which light from the source of light is transmitted, the probe including a tip from which light received from the source of light by the probe is emitted, the tip being insertable by a user into an aperture bored into the enamel of the patient's tooth whereby the tooth is illuminated from within by light emitted from the tip. Also, a method of illuminating a tooth disposed in the mouth of a patient, including the steps of drilling into the tooth a hole that extends into the tooth enamel, inserting into the drilled hole the tip of a light-transmitting probe connected to a source of light, and emitting light from the probe tip disposed in the drilled hole, whereby the tooth is illuminated from within by light transmitted into and through the tooth enamel from the probe tip.

The present inventors have recognized, among other things, that a problem to be solved includes enhancing the disinfection of the canal system (or other anatomical passage or cavity). The instrumentation of the canal space is a step in the process of cleaning and disinfection. Mechanical instruments have limitations due to the complexity of the canal systems (e.g., lateral canals, fins and crevices along canal walls or the like). This has been demonstrated by microcomputed tomography (CT) scanning which showed large areas of the root canal walls that were left untouched by instruments. The instruments have limited ability to navigate the canal space and reach tissue remnants, microorganisms and dentin chips retained in these tortuous spaces. Accordingly, the clinician is reliant on the chemical irrigation of the canal system to disinfect the untouched canal features and achieve a successful outcome. However, chemical irrigants are also subject to the tomography of the canal (e.g., lateral canal passages, crevices, fins or the like) and in some examples fail to disinfect features of the canal. For instance, the flushed chemical irrigants fail to adequately reach tortuously hidden features along or extending from the canal. Additionally, remnant tissues, microorganisms or the like are, in some examples, suspended in or concealed by biofilms, collections of proteins, carbohydrates or the like that further complicate access by irrigants.

The present subject matter helps provide a solution to this problem by providing a light-based dental treatment system in accordance with claim <NUM>, which is configured to broadcast one or more wavelengths of therapeutic light within a cavity or passage of the tooth or other treatment location including, but not limited to, implants (treatment for prevention of acute peri-implantitis), periodontics (periodontal disease), possible operative (treatment of caries). The delivered therapeutic light achieves one or more therapeutic benefits (e.g., disinfection, tissue regeneration, revascularization of tissue, reduction of inflammation or pain or the like). The light-based dental treatment system includes a handle generator and one or more selectively coupled delivery shaft assemblies aligned and retained to the handle generator. The delivery shaft assemblies include profiles, such as distal shaft profiles (e.g., shapes, sizes, angles or the like) to facilitates access to a passage in the tooth or other treatment location through manipulation and application of the system within the oral cavity.

The light-based dental treatment device further includes at least one light delivery port along the instrument shaft, for instance a distal light port. Optionally, the device includes a plurality of light delivery ports configured to broadcast light in one or more directions including laterally, distally or the like and accordingly reach complex features found in and around the treatment location. The delivery shaft of the assembly may further include a reflective inner wall, fiberoptic element or the like that extends through the shaft to the at least one delivery port. A light element (e.g., an LED, laser diode, laser, quantum cascade laser or the like) remote from the at least one delivery port is in communication with the light passage and is configured to broadcast therapeutic light at one or more wavelengths. The delivery shaft conveys light to the at least one delivery port for delivery to the treatment location. In some examples, the distal shaft profile includes a varied profile relative to a proximal (base) shaft profile of the delivery shaft. The varied distal shaft profile delivers the therapeutic light to treatment locations in difficult to access regions of the oral cavity, locations having different shapes or sizes or the like.

The therapeutic light is broadcast into the cavity or passage and reaches the specified targets (tissues, microorganisms or the like) even in difficult to reach locations (lateral canals, fins and crevices along canal walls, and within biofilms, collections of proteins, carbohydrates or the like). Additionally, manipulation of the device including translation into and out of the tooth, rotation or the like increases the coverage of the one or more light delivery ports by moving the ports across arcs, along linear routes or the like. Further, by using one or more wavelengths of light a variety of microorganisms are killed to enhance the disinfection of the cavity or passage in the tooth.

It is not intended to provide an exclusive or exhaustive explanation of the disclosure.

Embodiments regard selective sterilization of dental tissue using light energy. The light energy acts as a germicide. Infected or inflamed tissues (e.g., endodontic tissues or other internal tissues) can be treated using a chemo-mechanical debridement of canal spaces and closure of a canal opening. Some methods are available to further sterilize infected areas or initiate regeneration of local tissues. Embodiments regard light emitting diode (LED) treatment (e.g., at a specific wavelength <NUM> and <NUM>, among others) for the sterilization of internal tissues and the production of biomarkers related to tissue regeneration.

Antimicrobial effects of LED treatments on cultures of E. faecalis (E. faecalis) and the effects of LED treatment, in combination, on the production of osteoinductive, angiogenic, proliferative, and proinflammatory biomarkers from LED-treated HEPM cells and primary human gingival fibroblasts were determined. The LED treatment reduced the viability of E. The LED treatment did not appreciably affect the viability of HEPM cells and human primary fibroblasts. The LED treatment at a first wavelength, alone or in combination with LED treatment at a second wavelength, of HEPM cells and human primary fibroblasts induced the production of biomarkers related to endodontic tissue regeneration.

Embodiments provide a new system for disinfection of infected canals, especially the apical third of a canal (the deepest part of the infected tissue) that is likely not receiving a full effect of a chemical debridement (<NUM>% bleach solution). This solution (<NUM>% bleach) is quite caustic if expressed past the canal of a tooth. Embodiments show that there is a synergistic approach between an irrigation solution to tissue disinfection and a light source treatment (the LED treatment). Embodiments indicate that future disinfection of the infected tissue can be accomplished with a lower concentration bleach solution with decreased risk to patients. Embodiments have been assessed with infected root canals. The devices described herein have shown positive results for bactericidal benefits (anti-microbial) and have also initiated the production of markers indicating proliferation (tissue regeneration).

Embodiments regard devices for precisely applying light energy for invasive disinfection (or potential regeneration) of a target volume of tissue. In some embodiments, these devices are applied to a patient, such as a human being or other living organism, through an open incision, opening or the like. A delivery shaft assembly emits electromagnetic energy generated by a light element (or other light energy generation element) of one or more specified wavelengths into/onto a targeted volume of tissue to reduce infectious tissue volume and prohibit the tissue from proliferating or to destroy existing infectious tissue. In some embodiments, application of <NUM> nanometer (nm) wavelength energy is used. Energy of this wavelength is sometimes called "germicidal ultraviolet light".

This specified wavelength has been proven to kill some bacteria. The effectiveness of the disclosed devices can be a function of the amount of electromagnetic energy applied and the duration of application (e.g., the "time power product"). In the example application of <NUM> wavelength energy (known for deleterious effects on bacteria) a precision applicator is used. The precision applicator includes a delivery shaft selectively coupled (e.g., based on profile of the patient opening, positioning of the opening or the like) with a handle generator including the light generating element. The disclosed devices can be used to apply the light energy to infected tissue, through an incision or other opening in the subject.

<FIG> illustrates, by way of example, a perspective view diagram of an embodiment of a light-based dental treatment system <NUM> in accordance with claim <NUM> (conductive heat sink not shown here). <FIG> illustrates, by way of example, another perspective view diagram of an embodiment of the treatment system <NUM>. The system <NUM> as illustrated includes a generator housing <NUM>, an light energy delivery shaft assembly <NUM>, an alignment collet <NUM>, a power toggle <NUM>, indicator elements <NUM>, <NUM>, and a light energy delivery trigger <NUM>.

The generator housing <NUM> provides an enclosure for circuitry. The circuitry is configured to control operations of the tissue treatment system <NUM>. The generator housing <NUM> is used by tissue treatment personnel as a handle. The generator housing <NUM> is thus made of an electrically insulating material (a dielectric) in some embodiments. The generator housing <NUM> is made of one or more of a variety of materials, such as metal, ceramic, polymer, or the like, in some embodiments. The generator housing <NUM> is an elongate structure configured to fit comfortably in a palm of a hand.

The delivery shaft assembly <NUM> guides light energy to a distal electromagnetic energy delivery port <NUM> thereof. The delivery port <NUM>, in embodiments, includes one or more component delivery ports. Electromagnetic energy received at the delivery port <NUM> can be directed in a distributed manner to the component delivery ports (e.g., broadcast, sprayed, scattered, directed along one or more specified vectors, or the like). The delivery shaft assembly <NUM> includes a proximal light energy port (shown in <FIG> among other FIGS. ) to receive light energy from a light energy element of circuitry in the generator housing <NUM>. The light energy travels out the distal electromagnetic energy delivery port <NUM> of the delivery shaft assembly <NUM> to a therapy target. The delivery shaft assembly <NUM> thus provides a path for light energy to travel from the circuitry in the generator housing <NUM> to a therapy target. The delivery shaft assembly <NUM> includes a variety of profiles (e.g., shapes or sizes) in differing embodiments. The different profiles include respective different bends (at different angles) along a length of the delivery shaft assembly <NUM>, lengths, widths (e.g., diameters), or perimeters of the shaft assemblies <NUM>, or the like. The different bends provide access to different internal tissues, cavities, or other targets. Examples of delivery shaft assemblies <NUM> are provided in <FIG>.

The alignment collet <NUM> retains the delivery shaft assembly <NUM> to the generator housing <NUM>. Further, the alignment collet <NUM> aligns the proximal electromagnetic energy port of the delivery shaft assembly <NUM> with the light energy port of the circuitry of the generator housing <NUM>. A collet is a type of chuck, clamp, fitting, grip, collar, or the like that surrounds at least a portion of the delivery shaft assembly <NUM> and applies a clamping force to ensure alignment of a generator component <NUM> and a light port with tightening of the collet <NUM>. The collet <NUM>, in some embodiments, is squeezed against a matching taper of the delivery shaft assembly <NUM> and the inner surface of the collet <NUM> contracts to a smaller diameter, clamping the delivery shaft assembly <NUM> to hold it securely.

The alignment collet <NUM> includes an interior collet profile complementary to a shaft fitting <NUM> of the delivery shaft assembly <NUM> (see <FIG> for example). The alignment collet <NUM> applies opposing biases to the shaft fitting <NUM> to fix the delivery shaft <NUM> to the generator housing <NUM>. The alignment collet <NUM> aligns the proximal light port <NUM> with the light element axis <NUM> of the energy generator component <NUM> (sometimes called a "light element"). The alignment with the light element axis <NUM> causes the light to be transmitted through the proximal light port <NUM>, a delivery shaft <NUM>, and out the distal light port <NUM> to a proximate structure (a therapy target).

The power toggle <NUM> is electrically coupled to a battery or other power source of the system <NUM>. The power toggle <NUM> is a switch, button, pin or the like that opens or closes an electrical path between the circuitry of the generator housing <NUM> and the power source. In some embodiments, the power toggle <NUM> includes a push button, toggle, single pull single throw, single pull double throw, or other switch. A user operates the power toggle <NUM> to open or close the electrical coupling between the circuitry and the power source, thus providing electrical power to, or cutting off power to the circuitry.

The indicator elements <NUM>, <NUM> provides one or more of a visible, audible, tactile indication of electrical power to the circuitry or delivery of the electromagnetic energy by the system <NUM>. The indicator elements <NUM>, <NUM> include, but are not limited to, a light source (e.g., an LED or other optical device), a speaker, a motor, a mechanism, or the like. In some embodiments one of the indicator elements <NUM>, <NUM> indicate whether electrical power is provided to circuitry of the system <NUM> and another of the indicator elements <NUM>, <NUM> indicates whether the system <NUM> is delivering light energy.

The delivery trigger <NUM>, in some embodiments, includes one or more of a switch, button, pin, or the like similar to the power toggle <NUM>. The delivery trigger <NUM> operates to close or open an electrical path between the delivery shaft assembly <NUM> and an light energy generation component of the circuitry or alternatively power (as another toggle) the electromagnetic energy generation component (e.g., after powering on of the system <NUM> with the power toggle <NUM>).

In operation, a delivery shaft assembly <NUM> is attached to the system <NUM> by inserting the delivery shaft assembly <NUM> into the alignment collet <NUM> and tightening the alignment collet <NUM> around the delivery shaft assembly <NUM>. The alignment collet <NUM> retains and aligns the delivery shaft assembly <NUM> with the light energy port of the generator housing. The user then activates the circuitry using the power toggle <NUM> (e.g., powers on the system <NUM>). The indicator element <NUM>, <NUM> indicates that the circuitry is activated in response to the user activating the power toggle <NUM>. The light energy component of the circuitry is activated with the delivery trigger <NUM>. Another, or the same, indicator element <NUM>, <NUM> indicates that the light energy component is activated in response to the user activating the delivery trigger <NUM>. The energy generator component of the circuitry produces electromagnetic energy and delivers the light energy the delivery shaft assembly <NUM> via the light energy port of the generator housing <NUM>. The light energy is guided by the delivery shaft assembly <NUM> to the therapy target (e.g., through the delivery port <NUM>).

<FIG> illustrates, by way of example, another perspective view diagram of an embodiment of a light-based dental treatment system in accordance with claim <NUM> (conductive heat sink not shown). In <FIG>, the delivery shaft assembly <NUM> is disconnected from the generator housing <NUM>. In <FIG>, a light generator component <NUM> is shown in dotted lines indicating that it is in the generator housing <NUM>. The shaft assembly <NUM> illustrated in <FIG> is one example of one size and shape (collectively a profile) of the components of the shaft assembly <NUM>. Additional examples of shaft assemblies are provided in <FIG>.

The light generator component <NUM> receives electrical energy and produces light energy. The light energy (or optical energy) is focused, such as by a waveguide, optical fiber, or the like, along a light element axis <NUM>. The optical energy is provided to a proximal light port <NUM> of the delivery shaft assembly <NUM>. An alignment of the proximal light port <NUM> and the energy generator component <NUM> is controlled by the alignment collet <NUM>. The light energy generator component <NUM> includes one or more visible light generating elements, non-visible light generating elements (e.g., that generate electromagnetic energy with wavelengths outside of visible light) combinations of the same or the like-For example, the energy generator component <NUM> includes, but is not limited to, an electronic oscillator circuitry, electrooptical lamps of various types, solid state electrooptical devices (lasers, LEDs, or the like).

The delivery shaft assembly <NUM>, as illustrated, includes the proximal light port <NUM>, the shaft fitting <NUM>, the delivery shaft <NUM>, and the distal light port <NUM>. The proximal light port <NUM> receives energy from the light energy generator component <NUM>. The shaft fitting <NUM> is configured for reception and coupling with the generator housing <NUM> via the alignment collet <NUM>. The shaft fitting <NUM> minimizes (e.g., eliminates or minimizes) deformation of the shaft <NUM> of the shaft assembly <NUM>. In some embodiments, the shaft fitting <NUM> includes a pliable material (including elastomeric, pliable, partially pliable or semi-pliable) that is readily grasped by the alignment collet <NUM>. The shaft fitting <NUM> includes a profile complementary to an interior profile of the alignment collet <NUM>. The complementary profiles of the shaft fitting <NUM> and the alignment collet <NUM> enhances alignment of the proximal light port <NUM> with the energy generator component <NUM>. Additionally, the complementary profiles of the shaft fitting <NUM> and the alignment collet <NUM> enhance retention of the shaft assembly <NUM> with the generator housing <NUM>.

The delivery shaft <NUM>, in some embodiments, includes a tubular element for transmitting the electromagnetic energy from the light energy generator element <NUM> to the distal light port <NUM> of the shaft assembly <NUM>. The delivery shaft <NUM>, in some embodiments, includes one or more of a reflective hollow interior, solid fiber optic element, or the like.

The delivery shaft <NUM> includes a proximal shaft portion <NUM> that includes a proximal shaft profile and a distal shaft portion <NUM> that includes a distal shaft profile. The distal shaft portion <NUM> is distal to the proximal shaft portion <NUM>. The proximal shaft portion <NUM> is proximate (and distal to) the shaft fitting <NUM>. The proximal shaft portion <NUM> and the distal shaft portion <NUM> include respective profiles (e.g., sizes, shapes or the like) identical, similar or different from each other. In some embodiments, a cross-sectional area of the proximal shaft portion <NUM> perpendicular to the length of the shaft assembly <NUM> is smaller or larger than a cross-sectional area of the distal shaft portion <NUM> perpendicular to the length of the shaft assembly <NUM>. In some embodiments, the shape (e.g., shape, angle, perimeter or the like) or size (e.g., length, width, diameter, or the like), collectively the profile, of either of the portions <NUM>, <NUM> are varied to alter energy transmission efficiency or a capability to provide electromagnetic energy to a specified therapy target.

The electromagnetic energy output of the energy generator component <NUM> is applied through a conduit (e.g., delivery shaft assembly <NUM>), such as a modular delivery shaft coupled with the generator housing <NUM>. The light energy from the energy generator component <NUM> flows through the conduit to a target location (e.g., dental root, cavity, tissue or the like). The conduit focuses the emitted energy to the target location while minimizing dispersal around the energy generator component <NUM>. One example of a conduit includes a light pipe, such as a fiberoptic element, coupled to an optical electrooptical generator. Light flows through the structure of the light pipe, and the light pipe channels and focuses the light and ensures emission from the distal light port of the lightpipe which has a desired profile (delivery profile) according to the light pipe design (e.g., the porting, shape of the delivery shaft tip or the like).

In various examples, the conduit, such as the delivery shaft <NUM>, is inserted through an incision or opening to a target location, whether manually or under automated control. Optionally, insertion includes positioning of the distal light port <NUM> of the delivery shaft <NUM> to apply light energy from the conduit to the target location (e.g., tissue or cavity). The light energy, at a specified intensity, is applied to the target location for a specified duration shown to produce the desired effect on the target bacteria. The conduit, such as the distal light port <NUM>, is stationary or moved during the application, depending on the desired coverage or effect. One example of delivery of the delivery shaft <NUM> is shown in <FIG> and includes the delivery shaft <NUM> navigated into a cavity formed in a tooth and ready for delivery of light energy to a specified target location, in this example the interior of the root.

<FIG> illustrates, by way of example, a perspective view diagram of one or more heat sinks <NUM>, a lens assembly <NUM>, and an interior collet profile <NUM>, in addition to items previously shown in <FIG> and described herein.

The energy generator component <NUM> includes one or more LEDs (that operate to produce electromagnetic emissions of a same or different wavelength), laser light elements (that operate to produce electromagnetic emissions of a same or different wavelength), or the like. The wavelength or intensity of the electromagnetic energy provided by the energy generator component <NUM>, in some embodiments, are variable and controlled by an intensity control or a frequency control (see <FIG>). In some embodiments, the energy generator component <NUM> generates light with a wavelength between (and including) <NUM> to <NUM>. These wavelengths, when applied to (e.g., incident on) tissue, are antimicrobial and promote regeneration of the tissue. In some embodiments, the energy generator component <NUM> generates light with a wavelength between (and including) <NUM> to <NUM>. These wavelengths, when incident on tissue, are antimicrobial and promote regeneration of the tissue. In some embodiments, the energy generator component <NUM> generates light with a wavelength of about <NUM>.

The heat sink <NUM> conductively transfers heat away from the energy generator component <NUM>, for instance through the proximate generator housing <NUM>. The heat sink <NUM> includes metal, ceramic, or other material with a thermal conductivity configured to readily transfer heat away from the energy generator component <NUM>. The heat sink <NUM>, in some embodiments, includes one or more plates, fins, coils, tubes, posts, or the like, configured to transmit heat away from the energy generator component <NUM>. As shown in <FIG> the heat sink <NUM> is coupled between the generator housing <NUM> and the energy generator component <NUM> and, in this example, conductively transfers heat from the energy generator component <NUM> to the generator housing <NUM>.

The lens assembly <NUM> focuses electromagnetic energy toward the proximal light port <NUM> of the delivery shaft assembly <NUM>. The lens assembly <NUM> includes one or more optical elements, such as a lens (convex or concave), a collimator, mirror, beam splitter, or the like. The optical elements are arranged to direct and focus the electromagnetic energy from the energy generator component <NUM> toward the proximal light port <NUM>.

The interior collet profile <NUM> is interior to the alignment collet <NUM>. The interior collet profile is complementary to a profile of the shaft fitting <NUM>. In some embodiments, the interior collet profile <NUM> includes a tapered shaped that reduces width so that the delivery shaft assembly <NUM> has an interference fit thereto. The complementary profiles facilitate initial fitting of the delivery shaft assembly <NUM> and alignment with the energy generator component <NUM>. The complementary profiles additionally aid retention of the delivery shaft assembly <NUM> to the generator housing <NUM>.

The shaft fitting <NUM> is situated over the shaft assembly <NUM> and is manufactured as a separate part. In any case, the shaft fitting includes a fitting profile complementary to the interior collet profile, such as to facilitate alignment between the collet <NUM> and the delivery shaft assembly <NUM> and retention of the delivery shaft assembly <NUM> to the collet <NUM>. For example, the fitting profile and complementary profile include, but are not limited to, ovular, triangular, keyed, like sized circular profiles or the like.

<FIG> illustrates, by way of example, a perspective view of a portion of the generator housing <NUM>. The perspective of <FIG> provides an example of some components optionally proximal to the view provided in <FIG>. As shown, the generator housing <NUM> includes an intensity control <NUM> and a frequency control <NUM>.

The intensity control <NUM> includes a user input such as a knob, touch screen, dial, or the like, for adjusting the intensity of the electromagnetic energy generated by the energy generator component <NUM>. The intensity is optionally graduated in terms of Joules, Joules per area, or the like. The intensity is adjusted (and optionally limited) to control the intensity of therapy delivered to the therapy target, enhance treatment efficacy and minimize (e.g., minimize or eliminate) potential harm at the therapy target. Optionally, if the intensity is increased (using the intensity control <NUM>) the treatment time is in one example decreased and vice versa.

The frequency control <NUM> includes a user input such as a knob, touch screen, dial, or the like. In embodiments that include a touch screen, both of the frequency and the intensity are optionally controlled through the same touch screen. The frequency control <NUM> provides an adjustable control to vary the frequency of the electromagnetic energy generated by the energy generator component <NUM>. In some examples, different frequencies of the delivered electromagnetic energy provide differing therapeutic benefits (or combinations of benefits) to the target area. For example, a first frequency includes enhanced antimicrobial effects (e.g., improved bactericidal properties) than a second frequency potentially having other therapeutic benefits (e.g., tissue regeneration, antimicrobial effect for a different bacteria or the like). In another example, a third frequency is better for regenerative effects than a fourth frequency.

<FIG> illustrates, by way of example, a perspective view diagram of embodiments of delivery shaft assemblies <NUM>. Note that reference numbers with an alphabetic suffix are example embodiments of a component. Thus, each of delivery shaft assemblies 104A, 104B, 104C, 104D, 104E, 104F are example embodiments of the delivery shaft assembly <NUM>, and each of distal shaft portions 230A, 230B, 230C, 230D, 230E, 230F are example embodiments of the distal shaft portion <NUM>, and so on.

A previously discussed, the distal shaft portion <NUM>, in various embodiments, is varied relative to the proximal shaft portion <NUM> of the delivery shaft assembly <NUM>. Each of the distal shaft portions 230A-230F include different configurations relative to one another. For example, the different configurations include, but are not limited to, one or more of different tapers, lengths, widths, diameters, angles, bend angle at locations along the length of the assemblies, such as the distal shaft portions, or the like (collectively, profiles). In one example, the distal shaft portion 230A includes a greater length than the distal shaft portions 230C-230F. In another example, the distal shaft portion 230A further includes a narrow portion <NUM> relative to other portions of the distal shaft portion 230A. The narrow portion 660A (sometimes called a shaft joint) facilitates deflection of the distal light port 116A. The deflection of the distal light port 116A facilitates specified delivery of electromagnetic energy to a therapy target (e.g., navigated to the therapy target, guided to the therapy target, arranged for the delivery port <NUM> to be proximate the therapy target, or the like).

The distal shaft portion 230B includes a narrow portion 660B similar to the distal shaft portion 230A. The distal shaft portion 230B further includes a taper 662A (exaggerated for this illustration) proximate to the distal tip of the distal shaft portion 230A. The taper 662A facilitates access to a therapy target or enhances distribution of electromagnetic energy in a specified pattern (e.g., a specified spread, shape, arc, pattern, fan, angle or the like). The distal shaft portion 230B, similar to the distal shaft portion 230A, includes a greater length than the distal shaft portions 230C-230F.

The distal shaft portion 230C includes a length shorter than the distal shaft portions 230A-230B, but larger than the distal shaft portions 230D-230F. The distal shaft portion 230C includes a taper 662B in a most distal light portion thereof. The taper 662B is optionally less severe than the corresponding taper 662A of the distal shaft portion 230B, thus allowing the distal light port 116C access to different therapy targets than the distal light port 116B. For example, the taper 662A can facilitate delivery of electromagnetic energy to a like shaped cavity and tissues, while the taper 662B facilitates delivery of the electromagnetic energy to a narrower corresponding cavity.

The distal shaft portion 230D includes a bend angle that causes the delivery shaft assembly 104D to transmit electromagnetic energy generally perpendicular to a length of a proximal shaft portion 228D. The distal shaft portion 230D is shorter than the distal shaft portions 230A-230C and the distal shaft portions 230E-230F. The distal shaft portion 230D is generally uniform in width (e.g., diameter) along its length.

The distal shaft portion 230E is short and blunt. The distal shaft portion 230E is shorter than the other distal shaft portions 230A-230D and 230F shown in <FIG>. The distal shaft portion 230E is generally uniform in width along its length, similar to the distal shaft portion 230D.

The distal shaft portion 230F includes a bend angle 664B that is smaller than the bend angle 664A of the distal shaft portion 230D. The distal shaft portion 230F further includes a taper 662C in a most distal light portion thereof. The taper 662C (or the tapers 662A-662B), in some embodiments, terminates in widths greater than, less than, or equal to a width of another portion of the distal shaft portion 230A-230F.

Each of proximal shaft portion 228A, 228B, 228C, 228D, 228E, 228F include generally uniform widths and varying lengths. However, the proximal shaft portions 228A-228F in other embodiments have a variety of lengths, widths, bends, tapers, angles, or the like.

The differing angles, tapers, bends, lengths, widths or the like of the distal shaft portions 230A-230F and the proximal shaft portions 228A-228F facilitate access to different treatment locations, features of treatment locations, or treatment locations having different features.

As previously discussed, the shaft fitting <NUM> include a fitting profile (e.g., size or shape (e.g., circular, elliptical, ovular, triangular, rectangular, or the like) complementary to the interior collet profile <NUM>. The interior collet profile <NUM> facilitates alignment and retention between the collet <NUM> and the proximal light port 224A, 224B, 224C, 224D, 224E, 224F. In some embodiments, the complementary fitting profile includes a keyed shape matched to a corresponding keyed shape of the interior collet profile <NUM>.

<FIG> illustrates, by way of example, a diagram of an embodiment of an antimicrobial and tissue regeneration system <NUM> situated to provide electromagnetic light energy to a therapy target <NUM>. The system <NUM> and its components are discussed regarding <FIG> and elsewhere herein. The heat sink <NUM> conducts heat away from the energy generator component <NUM> and to the generator housing <NUM>. Positioning the energy generator component <NUM> outside of a body housing the therapy target <NUM> reduces an amount of heat conducted inside the body and allows the heat sink <NUM> to transfer the heat to atmosphere.

In the embodiment of <FIG>, the therapy target <NUM> is an oral cavity (e.g., a recess for a root canal, a decay-based cavity, or the like). The distal shaft portion <NUM> illustrated in <FIG> includes an angle and taper for accessing a vertically oriented cavity. In some embodiments, the delivery shaft assembly <NUM> is flexible, semi-rigid, rigid, or the like.

<FIG> illustrates, by way of example, a diagram of an embodiment of a device <NUM>. The device <NUM> as illustrated includes components similar to the components of the system <NUM> discussed previously. The device <NUM> further includes circuitry in the generator housing <NUM> and an optional charging stand <NUM>. The device <NUM> produces light energy <NUM> for therapeutic effects on a therapy target. The circuitry of the device <NUM> illustrated includes a power source <NUM> and power converter circuitry <NUM>. The power source <NUM>, in some embodiments, includes an electrical power storage device, such as a battery, capacitor, or the like. In some embodiments, the power source <NUM> is a cord that can provide electrical power from an outlet to circuitry of the device <NUM>. The power converter circuitry <NUM> can include an analog to digital converter, digital to analog converter, a voltage conditioner, a voltage or current regulator, or the like. The charging stand <NUM>, in embodiments, is battery powered, plugged into an outlet, or the like. The charging stand <NUM> electrically charges the power source <NUM> so that the device <NUM> can be cordless during operation.

<FIG> illustrates, by way of example, a diagram of an embodiment of a device <NUM> in accordance with claim <NUM>. The device <NUM> as illustrated includes components similar to the components of the system <NUM> discussed previously. The device <NUM> further includes circuitry mounted on a printed circuitry board (PCB) <NUM> in the generator housing <NUM>. The circuitry on the PCB <NUM>, in embodiments, includes the power converter circuitry <NUM>, light element control circuitry (e.g., wavelength modulator, pulse modulator, therapy delivery time control circuitry (e.g., an oscillator, counter, or the like), or the like), the light energy generator component <NUM>, or other circuitry, such as a transistor, resistor, capacitor, multiplexer, processing device (e.g., an application specific integrated circuitry (ASIC), field programmable gate array (FPGA), central processing unit (CPU), graphics processing unit (GPU), or the like), diode, inductor, or the like, for operation of the device <NUM>. In some embodiments, the PCB <NUM> includes a rigid or flexible substrate with traces or other electrically conductive elements (e.g., pads, vias, or the like) that provide electrical paths for electricity between components.

<FIG> illustrates, by way of example, a perspective view diagram of an embodiment of another light-based therapy system <NUM>. The system <NUM> as illustrated includes components similar to the components of the system <NUM> discussed previously. The system <NUM> further includes control contacts <NUM>. The control contacts <NUM> complete or open an electrical path between the power source <NUM> and the energy generator component <NUM>. The control contacts <NUM>, in embodiments, act as heat sinks to conduct thermal energy away from the energy generator component <NUM>.

The devices described herein are contained in a handheld device that are battery, cord powered, or remotely powered implements. The handheld device is sometimes called a handle generator. The clinician or other personnel couples the delivery shaft assembly <NUM> to the handle generator housing <NUM> and align a proximal light port <NUM> of the delivery shaft assembly <NUM> with the light energy generator component <NUM> (e.g., LED element, bulb, laser generator, oscillating circuit or the like). The clinician, or other personnel, operates a control to activate the light energy generator component <NUM> and apply light energy from the distal light port <NUM> of the delivery shaft assembly <NUM> to the therapy target <NUM>. In another example, an onboard battery is exchanged for an umbilical cord to an external power source.

<FIG> illustrates, by way of example, a plot of an embodiment of wavelengths of electromagnetic energy for antimicrobial and tissue regeneration. In the plot, an optimal wavelength range for antimicrobial effects is provided at <NUM>, a generalized wavelength range for antimicrobial effects is provided at <NUM>, an optimal wavelength range for tissue regeneration is provided at <NUM>, and a generalized wavelength range for tissue regeneration is provided at <NUM>. The optimal wavelength range for antimicrobial effects is about <NUM> to about <NUM>. The generalized wavelength range for antimicrobial effects is about <NUM> to about <NUM>. The optimal wavelength range for tissue regeneration is about <NUM> to about <NUM>. The generalized wavelength range for tissue regeneration is about <NUM> to about <NUM>. The optimal ranges for antimicrobial effects and tissue regeneration overlap in the <NUM> to about <NUM> wavelength range.

The electromagnetic energy output of the generator (e.g., a handle generator) is applied through a conduit, such as a modular delivery shaft coupled with the generator. The electromagnetic energy flows through the conduit to a target location (e.g., dental root, tissue or the like). The conduit focuses the emitted energy to the target location while minimizing dispersal around the generator. One example of a conduit includes a light pipe, such as a fiberoptic element, coupled to an optical electrooptical generator. Light flows through the structure of the light pipe, and the light pipe channels and focuses the light and ensures emission from the distal light port of the lightpipe in a desired profile (delivery profile) according to the light pipe design (e.g., the porting, shape of the delivery shaft tip or the like).

As previously discussed, successful treatment of infected or inflamed endodontic tissues can include chemo-mechanical debridement of the canal spaces and proper sealing of coronal and apical canal openings. Methods are available to further sterilize infected areas or initiate regeneration of local tissues. The ability of <NUM> and <NUM> light emitting diode (LED) treatment to kill E. faecalis and induce the production of cellular biomarkers related to endodontic tissue regeneration were assessed. The antimicrobial effects of <NUM> and <NUM> LED treatment on E. faecalis and the effects of <NUM> and <NUM> LED treatment on the production of osteoinductive, angiogenic, proliferative, and proinflammatory biomarkers from human embryonic palatal mesenchyme (HEPM) cells and gingival fibroblasts were assessed. It was observed that <NUM>) at least <NUM> LED treatment killed E. faecalis, <NUM>) <NUM> LED and NaCIO efficiently killed E. faecalis, <NUM>) neither <NUM> nor <NUM> LED treatment affected the viability of HEPM cells and gingival fibroblasts, and <NUM>) <NUM> LED treatment, alone or in combination with <NUM> LED treatment, of HEPM cells and gingival fibroblasts induced the production of biomarkers related to endodontic tissue regeneration. The results suggest a new treatment modality using periods of <NUM> LED treatment as an adjunct to chemo-mechanical debridement for the sterilization of infected and inflamed sites and the production of biomarkers related to endodontic tissue regeneration. A few methods are available to sterilize infected canals or induce the production of biomarkers related to endodontic tissue regeneration. Treatment of canals with <NUM> light emitting diodes (LED) has the potential to sterilize infected and inflamed sites and induce the production of biomarkers related to endodontic tissue regeneration.

Successful treatment of infected or inflamed endodontic tissues can depend on disinfection of the root-canal system through chemo-mechanical debridement of the canal space and closure of the canal opening to prevent re-infection. Successful treatment is dependent upon i) bacterial disinfection of the root-canal system to prevent re-infection, and ii) chemical irrigation to disinfect, dissolve, and remove necrotic debris from the canal wall and spaces. The instrumentation of the canal space can be a step in these processes, but has limitations due to the complexity of the lateral canals, fins, and crevices along the walls of the canal systems. This has been demonstrated by microcomputed tomography (CT) scanning which showed extensive root canal configuration and large areas of the root canals walls that were left untouched by the instruments.

Light based technologies involving ultraviolet C (UVC, <NUM>-<NUM>) and blue light (<NUM>-<NUM>) therapies offer attractive approaches as an adjunct to chemo-mechanical debridement for controlling microbial infections with beneficial impacts on local tissues. Both UVC and blue light are antimicrobial with relatively minor effects to host tissues compared to their high antimicrobial activity to microbial pathogens. Also attractive is the reported ability of laser irradiation to increase proliferation of mesenchymal cells, increase proliferation and mineralization of dental pulp constructs, increase cell proliferation and bone sialoprotein expression in dental pulp stem cells (DPSCs), and induce the production of TGF-β1, which is involved in differentiation of DPSCs.

faecalis induces persistent infections and is often associated with root canal infections and endodontic disease. In this study, the ability of <NUM> and <NUM> LED to kill E. faecalis was assessed. The effect of <NUM> and <NUM> LED on the viability of HEPM cells and gingival fibroblasts and the ability of <NUM> and <NUM> LED combination treatment of HEPM cells and gingival fibroblasts to induce the production of osteoinductive, angiogenic, proliferative, and proinflammatory biomarkers was also assessed.

faecalis was cultivated in BBL trypticase soy broth with <NUM>% yeast extract and on trypticase soy broth, yeast extract containing Difco <NUM>% agar at <NUM>. Three hour bacterial cultures were adjusted in TSBYE broth to an optical density of <NUM> at <NUM>. Plate counts determined that these cultures contained <NUM>-<NUM> × <NUM><NUM> colony forming units (CFU) E. faecalis/ml.

For surface killing assays, a sterile swab was dipped into the adjusted culture and streaked onto a TSBYE agar plate to create a 'bacterial lawn' of confluent growth.

To determine the kinetics of antimicrobial activity, the adjusted culture was then diluted <NUM>-<NUM>-fold to contain ~<NUM><NUM> CFU/ml. <NUM> discs were punched from cellulose nitrate filter membranes (<NUM>-<NUM> plain cellulose nitrate filter membrane, <NUM>) and placed on TSBYE agar plates. <NUM>µl of microbial culture was added to each disc and incubated for <NUM> minutes.

To determine the synergistic effects of <NUM> LED and NaClO treatments, E. faecalis was diluted tenfold from <NUM>-<NUM> -fold to contain ~<NUM><NUM> colony forming units/ml.

Human embryonic palatal mesenchyme (HEPM) cells are pre-osteoblast cells and were obtained. These cells are responsive and have been used to i) study epigenetic regulation of osteogenesis and bone regeneration; evaluate craniofacial palatal closure; and study osteoblast growth, adhesion, spreading patterns, and differentiation. HEPM cells were cultivated in Dulbecco's Modified Eagle Medium (DMEM). The DMEM complete medium contained <NUM>/L D-glucose, L-glutamine, <NUM>/L sodium pyruvate, <NUM>% fetal bovine serum (No. <NUM>-<NUM>, ATCC), and <NUM>% penicillin-streptomycin (No. <NUM>-<NUM>, Penicillin-Streptomycin, <NUM>,<NUM> U/ml). The identity of the HEPM cell line was authenticated by genetic profiling of their polymorphic short tandem repeat (STR) loci. Eight STR loci (TH01, TPOX, vWA, CSF1PO, D16S539, D7S820, D13S317 and D5S818) were examined for cell line authentication, and amelogenin was examined for gender identification and human cell line authentication. The STR profile results for the HEPM cell line used in this study were identical to the STR profile for the ATCC HEPM cell line.

Primary human gingival fibroblasts were also used and obtained. Gingival fibroblasts were cultivated in Fibroblast Basal Medium (ATCC PCS-<NUM>-<NUM>) with the added fibroblast growth kit (PCS-<NUM>-<NUM>) containing <NUM>/L rh FGFb (<NUM> ng/ml); <NUM>/L L-glutamine (<NUM>); <NUM>/L ascorbic acid (<NUM>µg/ml); <NUM>/L hydrocortisone hemisuccinate (<NUM>µg/ml); <NUM>/L recombinant human insulin (<NUM>µg/ml) and <NUM>% fetal bovine serum (No. <NUM>-<NUM>). These were primary cells and thus could not be authenticated.

Both HEPM cells and gingival fibroblasts were cultivated in T75 flasks at <NUM> in a humidified incubator with <NUM>% CO<NUM>. At ~<NUM>-<NUM>% confluent growth, cells were detached with <NUM>% trypsin-<NUM> EDTA solution, washed in their respective media, counted, and adjusted to contain <NUM> × <NUM><NUM> viable cells/ml. <NUM>µl aliquots were removed and put into <NUM>-well microtiter plates. The plates were incubated for <NUM> hours in a humidified incubator at <NUM> with <NUM>% CO<NUM>.

<NUM> and <NUM> LEDs were obtained. Wavelengths and energy dose were determined. The energy dose (J/cm<NUM>) was calculated as the irradiance (mW/cm<NUM>) × time (s). For <NUM> seconds, cells were exposed to <NUM> J/cm<NUM> (<NUM> LED) and <NUM> J/cm<NUM> (<NUM> LED).

LEDs were put into <NUM>-dimentional printed holders, which served as a heat sink to prevent both LED and sample from heating during LED treatment. The LEDs were supported by clamps hooked to a ring stand above a scissors jack. An aluminum canula was placed into the LED source to direct LED light onto agar plates containing the cultures of E. faecalis and into the tissue culture wells of the <NUM>-well plate containing HEPM cells and gingival fibroblasts.

To assess the effects of <NUM> and <NUM> LED treatments on E. faecalis viability, TSBYE agar plates were swabbed with E. faecalis and treated with <NUM> LED or <NUM> LED for <NUM>, <NUM>, <NUM>, and <NUM> seconds. After treatment, the plates were incubated for <NUM> hours at <NUM> and examined for areas void of microbial growth. The surface of membrane discs containing E. faecalis were treated with <NUM> LED or <NUM> LED for <NUM>, <NUM>, <NUM>, and <NUM> seconds. The discs were then removed from the agar surface, placed in <NUM> TSBYE broth, and mixed. <NUM>µl of each broth culture was put onto TSBYE agar plates in triplicate. Plates were incubated at <NUM> for <NUM> hours. Colonies per spot were counted, multiplied by <NUM> to get CFU/ml, and the percent killing was determined by comparing the concentrations of each treatment time point to the non-treatment time point control.

To assess the synergistic effects of <NUM> LED and sodium hypochlorite (NaClO) treatments on E. faecalis viability, <NUM>µl of a <NUM>-<NUM> bacterial dilution was put into holes (<NUM> dia. ) punched in blood agar plates containing trypticase soy agar with <NUM>% defibrinated sheep blood and incubated for <NUM> minutes to allow absorption of the culture media into the agar leaving E. faecalis on the walls of the wells. Each well was then administered a different treatment. One well was filled with <NUM>µl of distilled water and served as the untreated control. A second well was treated for <NUM> seconds with <NUM> LED. A third well was treated with <NUM>µl of <NUM>% NaClO solution for <NUM> seconds. A fourth well was treated for <NUM> seconds with <NUM> LED and then <NUM> seconds with <NUM>µl <NUM>% NaClO. A fifth well was treated for <NUM> seconds with <NUM>µl <NUM>% NaClO and then for <NUM> seconds with <NUM> LED. After each treatment, wells were rinsed with <NUM>µl of TSBYE broth to remove bacteria and suspended into <NUM> of TSBYE broth. Each tube was mixed and <NUM>µl was removed and spotted on to blood agar in triplicate. Plates were incubated overnight at <NUM> with <NUM>% CO<NUM> and colonies were counted the next day.

To assess the effects of <NUM> and <NUM> LED treatments on HEPM cell and gingival fibroblast metabolism (e.g., the conversion of resazurin to resorufin), <NUM>µl of tissue culture media was removed from the adherent cells leaving <NUM>µl of media in each well to prevent the cell monolayer from drying during treatment. HEPM cells and gingival fibroblasts were each treated with <NUM> LED for <NUM>, <NUM>, <NUM>, and <NUM> seconds. HEPM cells and gingival fibroblasts in other wells were treated with <NUM> LED for <NUM>, <NUM>, <NUM>, and <NUM> seconds. In additional experiments, HEPM cells and gingival fibroblasts were exposed to <NUM> LED for <NUM> seconds, <NUM> LED for <NUM> seconds, or a combination of <NUM> LED for <NUM> seconds followed by <NUM> LED for <NUM> seconds. After treatment, <NUM>µl of complete media with <NUM>% Alamar Blue was added per well and the cells were incubated in a humidified incubator at <NUM> with <NUM>% CO<NUM>. Median fluorescence intensity (MFI) for the conversion of resazurin to resorufin was measured at <NUM>, <NUM>, <NUM>, <NUM>, and <NUM> hours post-LED treatment. MFI of the metabolic reduction of resazurin to resorufin was determined using an excitation wavelength of <NUM> and an emission wavelength of <NUM>.

To assess the effects of <NUM> and <NUM> LED treatment on HEPM cell and fibroblast viability, <NUM>µl of tissue culture media was removed from the adherent cells in culture. HEPM cells and fibroblasts were each treated with <NUM> LED for <NUM>, <NUM>, <NUM>, and <NUM> seconds. HEPM cells and fibroblasts in other wells were treated with <NUM> LED for <NUM>, <NUM>, <NUM>, and <NUM> seconds. In additional experiments, HEPM cells and fibroblasts were exposed to <NUM> LED for <NUM> seconds, <NUM> LED for <NUM> seconds, and a combination of <NUM> LED for <NUM> seconds followed by <NUM> LED for <NUM> seconds. Immediately after treatment, <NUM>µl of the LIVE/DEAD working solution, containing <NUM> calcein AM and <NUM> ethidium homodimer-<NUM> (EthD-<NUM>), was added per well and the cells were photographed. Calcein AM is a non-fluorescent compound that is converted to a green-fluorescent calcein by intracellular esterase activity in viable cells and EthD-<NUM> is a weakly fluorescent compound until bound to DNA in non-viable cells. The plates were incubated for <NUM> minutes and read in the spectrophotometer. Calcein was excited at <NUM> and detected at <NUM>. EthD-<NUM> was excited at <NUM> and detected at <NUM>.

To assess the effects of <NUM> and <NUM> LED treatment on the production of osteoinductive (BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, and BMP-<NUM>), angiogenic (VEGFA, PDGF-A, FGF-acidic, and PIGF), proliferative (EGF and TGFα), and proinflammatory factors (IL6, IL8, and TNFα) from HEPM cells and fibroblasts, <NUM>µl of media was removed from the adherent cells in culture. HEPM cells and fibroblasts were each treated with <NUM> LED for <NUM> seconds, <NUM> LED for <NUM> seconds, and a combination of <NUM> LED for <NUM> seconds followed by <NUM> LED for <NUM> seconds. After treatment, <NUM>µl complete media was added to the plates containing HEPM cells and fibroblasts and incubated in a humidified incubator at <NUM> with <NUM>% CO<NUM>. Cell culture media was removed at <NUM>, <NUM>, and <NUM> hours post-LED treatment and frozen at -<NUM> until analysis.

The concentrations of osteoinductive (BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, and BMP-<NUM>), angiogenic (VEGFA, PDGF-A, FGF-acidic, and PIGF), proliferative (EGF and TGFα), and proinflammatory factors (IL6, IL8, and TNFα) in HEPM and fibroblast culture media were determined in triplicate wells using multiplex immunoassays (Luminex Human Magnetic Assay, R&D Systems, Minneapolis, MN) read on the Luminex100 (Luminex, Madison, WI). These immunoassay kits use antibody-coated magnetic beads to bind the desired analyte and use a standard curve of known concentrations to determine the unknown concentrations. Curves were constructed from the standards and their respective MFI readings and values were interpolated directly on the instrument and readout files.

To perform a statistical analysis, the MFI values and biomarker concentrations were first transformed by adding <NUM> MFI unit or <NUM> pg/ml to each respective value. A log10-transformation was then applied. The log transformation attenuates the positive skew in the distributions of the MFI and chemokine concentrations and makes the normality assumption more defensible. One-way fixed-effect ANOVA models were fit to the log-transformed concentrations. Pairwise group comparisons were conducted using the method of Tukey's Honestly Significant Difference (HSD). A <NUM> level was used to determine statistically significant differences. In plots, bar values with the same letter(s) were not significantly different. All analyses were conducted using JMP (Version <NUM>, SAS, Cary, NC).

Two assays were used to demonstrate the killing effects of <NUM> and <NUM> LED treatment on E. The first assay assessed the killing effect of LED on a lawn of E. faecalis on TSBYE agar. <NUM> LED killed E. faecalis at <NUM>, <NUM>, and <NUM> seconds exposure, and no growth was seen in the areas of LED treatment after the treated plates were incubated overnight at <NUM>. There was no killing of the untreated <NUM> seconds control. In contrast, <NUM> LED did not kill E. faecalis at <NUM>, <NUM>, <NUM>, and <NUM> seconds exposure, and growth was seen in all areas of LED treatment after the plates were incubated overnight at <NUM>.

To quantitate the effects of <NUM> and <NUM> LED treatment on microbial viability, E. faecalis was spotted onto <NUM> discs, treated, suspended in <NUM> TSBYE broth, plated onto TSBYE agar, and incubated overnight at <NUM>. <NUM> LED treatment significantly (p<<NUM>) reduced E. faecalis viability at <NUM>, <NUM>, and <NUM> seconds exposure. There was no significant killing by <NUM> LED treatment at <NUM>, <NUM>, <NUM>, and <NUM> seconds exposure.

<FIG> illustrates, by way of example, a plot of E. faecalis vs treatment group. faecalis remained viable in control treatments (<NUM>±<NUM> SEM CFU, n=<NUM>). In comparison, E. faecalis treated with <NUM> LED had significantly less CFU (<NUM>+<NUM> SEM CFU, n=<NUM>, p < <NUM>) and E. faecalis treated with <NUM>% NaClO had significantly less CFU (<NUM>±<NUM> SEM CFU, n=<NUM>, p < <NUM>). faecalis treated with <NUM> LED followed by <NUM>% NaClO also had significantly less CFU (<NUM>±<NUM> SEM CFU, n=<NUM>, p < <NUM>) and E. faecalis treated with <NUM>% NaClO followed by <NUM> LED had significantly less CFU (<NUM>+<NUM> SEM CFU, n=<NUM>, p < <NUM>).

<FIG> illustrates MFI vs time for HEPM cells after <NUM> treatment. <FIG> illustrates MFI vs time for fibroblasts after <NUM> treatment. <FIG> illustrates MFI vs time for HEPM cells after <NUM> treatment. <FIG> illustrates MFI vs time for fibroblasts after <NUM> treatment. To assess the effects of <NUM> and <NUM> LED treatment on cell metabolism, adhered HEPM cell and gingival fibroblast monolayers were treated with <NUM> or <NUM> LED for <NUM>, <NUM>, <NUM>, and <NUM> seconds and cultured with tissue culture media containing resazurin. At <NUM> hours of incubation, there were no significant differences (p><NUM>) among the log10 transformed MFI values of resorufin for either HEPM cells (<FIG>, <FIG>) or gingival fibroblasts (<FIG>, <FIG>) after <NUM> (<FIG>, <FIG>) or <NUM> LED treatments (<FIG>, <FIG>).

<FIG> illustrates % of viable HEPM cells vs time after <NUM> treatment. <FIG> illustrates % of viable fibroblasts vs time after <NUM> treatment. <FIG> illustrates % of viable HEPM cells vs time after <NUM> treatment. <FIG> illustrates % of viable fibroblasts vs time after <NUM> treatment. To assess the effects of <NUM> and <NUM> LED treatment on HEPM cell and fibroblast viability, adhered HEPM cell and fibroblast monolayers were treated with <NUM> or <NUM> LED for <NUM>, <NUM>, <NUM>, and <NUM> seconds and incubated with LIVE/DEAD working solution. At <NUM> minutes of incubation, there were no significant differences (p><NUM>) among the log10 transformed MFI values of HEPM cells (<FIG>, <FIG>) or gingival fibroblasts (<FIG>, <FIG>) after <NUM> (<FIG>) or <NUM> (<FIG>) LED treatment.

<FIG> illustrates MFI vs time for HEPM cells after combination treatment with <NUM> and <NUM> wavelength electromagnetic energy. <FIG> illustrates MFI vs time for HEPM cells after combination treatment with <NUM> and <NUM> wavelength electromagnetic energy. <FIG> illustrates % of viable HEPM cells vs time after combination treatment with <NUM> and <NUM> wavelength electromagnetic energy. <FIG> illustrates MFI vs time for fibroblast cells after combination treatment with <NUM> and <NUM> wavelength electromagnetic energy. <FIG> illustrates MFI vs time for fibroblast cells after combination treatment with <NUM> and <NUM> wavelength electromagnetic energy. <FIG> illustrates % of viable fibroblast cells vs time after combination treatment with <NUM> and <NUM> wavelength electromagnetic energy.

To assess the effects of combination LED treatment on HEPM cell and fibroblast metabolism, adhered HEPM cell and fibroblast monolayers were treated with <NUM> LED for <NUM> seconds, <NUM> LED for <NUM> seconds, and a combination of <NUM> LED for <NUM> seconds followed by <NUM> LED for <NUM> seconds, and cultured with tissue culture media containing resazurin. At <NUM> hours of incubation, there were no significant differences (p><NUM>) among the log10 transformed MFI values of resorufin for either HEPM cells (<FIG>) or fibroblasts (<FIG>, <FIG>) after combination LED treatment.

To assess the effects of combination LED treatment on HEPM cell and fibroblast viability, adhered HEPM cell and fibroblast monolayers were treated with <NUM> LED for <NUM> seconds, <NUM> LED for <NUM> seconds, and a combination of <NUM> LED for <NUM> seconds followed by <NUM> LED for <NUM> seconds and incubated with LIVE/DEAD working solution. At <NUM> minutes of incubation, there were no significant differences (p><NUM>) among the log10 transformed MFI values of HEPM cells (<FIG>) or fibroblasts (<FIG>) after combination LED treatment.

To assess the effects of LED treatment on the production of cell biomarkers, adhered HEPM cell and gingival fibroblast monolayers were treated with <NUM> LED for <NUM> seconds, <NUM> LED for <NUM> seconds, and a combination of <NUM> LED for <NUM> seconds followed by <NUM> LED for <NUM> seconds and cell culture media was added back to each well. At <NUM>, <NUM>, and <NUM> hours post-LED treatment, media was removed and saved to assess osteoinductive, angiogenic, proliferative, and proinflammatory regenerative biomarkers. LIVE/DEAD working solution was added back to each well.

At each time point, there were no differences in the morphologies of HEPM cells or gingival fibroblasts treated with <NUM>, <NUM>, or <NUM>/<NUM> LED. There was a small drop in cell viability and the LIVE/DEAD assay revealed that the cells were still <NUM>-<NUM>% viable (data not shown).

HEPM cell and gingival fibroblasts (n=<NUM> replications per group) produced osteoinductive, angiogenic, proliferative, and proinflammatory biomarkers <NUM>-<NUM> hours (Table <NUM>). Concentrations of biomarkers produced by both cell types continued to increase over time. At <NUM> hours, HEPM cells and gingival fibroblasts produced low concentrations of proliferative factors (<NUM>-<NUM> pg/ml EGF and TGFα), low concentrations of osteoinductive factors (<NUM>-<NUM> pg/ml BMP-<NUM>, BMP-<NUM>, and BMP-<NUM>), and moderate concentrations of osteoinductive factors (<NUM>-<NUM> pg/ml BMP-<NUM>). HEPM cells and gingival fibroblasts also produced low (<NUM>-<NUM> pg/ml TNFα), moderate (<NUM>-<NUM> pg/ml IL6), and high (<NUM>-<NUM> pg/ml IL8) concentrations of proinflammatory factors and low (<NUM>-<NUM> pg/ml PDGF-AB), moderate (<NUM>-<NUM> pg/ml FGF-acidic and PIGF), and high (<NUM>-<NUM> pg/ml VEGFA) concentrations of angiogenic factors.

In the first series of experiments (n=<NUM> replications per group), <NUM> and <NUM>/<NUM> combination LED induced production of biomarkers at <NUM> hours post-LED exposure (Table <NUM>). There were significant differences (p<<NUM>) in IL6, IL8, and VEGFA in HEPM cells at <NUM> hours and there were significant differences (p<<NUM>) in IL6, PIGF, and BMP9 in gingival fibroblasts at <NUM> hours.

In the second series of experiments (n=<NUM> replications per group), <NUM> and <NUM>/<NUM> combination LED induced production of biomarkers at <NUM>-<NUM> hours post-LED exposure (Table <NUM>). There were significant differences (p<<NUM>) in TNFα, IL6, VEGFA, BMP10, and PIGF at <NUM> hours and IL6 and BMP10 at <NUM> hours in HEPM cells post-LED exposure. There were significant differences (p<<NUM>) in TGFα at <NUM> hours and IL6 and FGF-acidic in gingival fibroblasts at <NUM> hours post-LED exposure.

Methods to assist in the resolution of endodontic tissue infection and inflammation after chemo-mechanical debridement of canal spaces reduce infections, regenerate tissues, lessen pain, and improve overall patient recovery. These methods include the use of LED treatment to assist in the sterilization of canal spaces and induce the production of biomarkers to initiate endodontic tissue regeneration. In this study, it was shown that <NUM> and <NUM> LED light could facilitate these processes. It was demonstrated that <NUM>) at least <NUM> LED treatment killed E. faecalis, <NUM>) <NUM> LED and NaClO efficiently killed E. faecalis, <NUM>) neither <NUM> nor <NUM> LED treatment affected the viability of HEPM cells and gingival fibroblasts, and <NUM>) at least <NUM> LED treatment or <NUM>/<NUM> combination LED treatment of HEPM cells and gingival fibroblasts induced the production of biomarkers related to endodontic tissue regeneration.

Evidence suggests that UVC (<NUM>) and blue (<NUM>-<NUM>) wavelengths of light kill many microbial species and viruses. When used at higher energy doses or for prolonged time periods, these wavelengths are also be cytotoxic to eukaryotic cells. However, at lower energy levels for shorter time periods like those used in this study, these wavelengths induce cells to release biomarkers related to tissue recovery and regeneration.

<NUM> light has antimicrobial activity and is used in a variety of applications related to treating localized tissue infections. <NUM> light has time-dependent and energy dose-dependent effects on prokaryotic and eukaryotic cells. <NUM> J/cm<NUM> is antimicrobial to prokaryotic microorganisms but not cytotoxic to eukaryotic cells. <NUM> J/cm<NUM> is cytotoxic to eukaryotic cells. The antimicrobial and cytotoxic mechanisms involve reactive oxygen species related to oxidative stress, H<NUM>O<NUM> generation, and other ROS, all contributing to cellular damage. Together, this information suggests that there is increased susceptibility of prokaryotic microorganisms compared to eukaryotic cells that could lead to a treatment modality to preferentially inactivate microorganisms in infected tissues.

The potential for LED to induce the production of biomarkers related to tissue recovery and regeneration is equally novel and important. Work with low level laser irradiation has been shown to promote proliferation of mesenchymal cells, cardiac stem cells, bone marrow stem cells, and dental pulp stem cells. Low level laser irradiation also promotes bone marrow stem cell growth factor secretion, myogenic differentiation, accelerates pulp healing, and bone sialoprotein expression. Lasers also activate TGF-β1 in dental pulp stem cells.

The production of osteoinductive, angiogenic, proliferative, and proinflammatory biomarkers are important to tissue recovery and regeneration. <NUM> biomarkers in various categories were studied. Osteoinductive factors included the bone morphogenic proteins (BMPs) belonging to the TGF-β superfamily of structurally related signaling proteins. There are <NUM> molecules (BMP-<NUM> to BMP-<NUM>) and <NUM> of these proteins were selected. BMP-<NUM> is capable of inducing bone and cartilage formation. BMP-<NUM> is involved in the development and maintenance of bone and cartilage. BMP-<NUM> (aka Growth/Differentiation Factor-<NUM>) is involved in the remodeling and maintenance of tissues and it inhibits endothelial cell proliferation and migration. BMP-<NUM> is structurally related to BMP-<NUM>, and both inhibit endothelial cell proliferation and migration. For both HEPM cells and gingival fibroblasts, osteoinductive responses were minimal for BMP-<NUM>, BMP-<NUM>, and BMP-<NUM> (<NUM>-<NUM> pg/ml) and moderate for BMP-<NUM> (<NUM>-<NUM> pg/ml). Exposure of HEPM cells to <NUM> LED alone or <NUM>/<NUM> LED produced variations in concentrations of BMP10 at <NUM>- and <NUM>-hours post-LED exposure (Table <NUM>, and Table <NUM>).

Angiogenesis is important to the regeneration of injured or infected dental tissue, and angiogenic and other growth factors are important to the reformation and survival of regenerated pulp. <NUM> angiogenic factors were selected. VEGFA is a potent growth and angiogenic cytokine. It stimulates proliferation and survival of endothelial cells and promotes angiogenesis and vascular permeability. PDGF-A is a potent mitogen for connective tissue cells, bone, and cartilage cells. FGF-acidic is a member of the Fibroblast Growth Factor superfamily. FGF-acidic regulates the development, restoration, and redistribution of tissue and serves as to facilitate angiogenesis, wound healing, and chronic inflammation. PIGF is an angiogenic factor that stimulates and endothelial cell proliferation and migration. HEPM cells and gingival fibroblasts produced low concentrations of PDGF-AB (<NUM>-<NUM> pg/ml), moderate concentrations of FGF-acidic and PIGF (<NUM>-<NUM> pg/ml), and high concentrations of VEGFA (<NUM>-<NUM> pg/ml) (Table <NUM>). Exposure of cells to <NUM> LED or <NUM>/<NUM> combination LED produced variations in concentrations of VEGFA, PIGF, and FGF-acidic (Table <NUM> and Table <NUM>). There were no significant increases in PDGF-AB, FGF-acidic, and PIGF responses for HEPM cells and VEGF, PDGF-AB, and FGF-acidic responses for fibroblasts.

Proliferation of cells is an important step to the regeneration of injured or infected dental tissues. <NUM> cell proliferation related factors were selected. EGF is a potent growth factor that stimulates the proliferation of various epidermal and epithelial cells and is involved in wound healing. TGFα is an EGF-related growth factor that stimulates the proliferation of a wide range of epidermal and epithelial cells. HEPM cells and fibroblasts produced low concentrations of EGF and TGFα (<NUM>-<NUM> pg/ml). Exposure of fibroblasts to <NUM> or <NUM>/<NUM> combination LED produced higher concentrations of TGFα at <NUM> hours post-LED exposure (Table <NUM> and Table <NUM>).

Proinflammatory chemokines that chemoattracts and activates neutrophils will likely be produced and three proinflammatory factors were selected. IL6 regulates inflammatory responses and regulates bone metabolism. IL8 is a proinflammatory chemokine that chemoattracts and activates neutrophils. TNFα is a proinflammatory cytokine that plays a role in the induction of inflammation. HEPM cells and gingival fibroblasts produced low concentration of TNFα (<NUM>-<NUM> pg/ml), moderate concentrations of IL6 (<NUM>-<NUM> pg/ml), and high concentrations of IL8 (<NUM>-<NUM> pg/ml). There were LED-induced angiogenic responses in IL6 for HEPM cells and in fibroblasts, but there were no differences in IL8 and TNFα for HEPM cells and for gingival fibroblasts (Table <NUM> and Table <NUM>). Exposure of HEPM cells to <NUM> LED or <NUM>/<NUM> LED produced variations in concentrations of TNFα, IL6, at <NUM> hours and IL6 at <NUM> hours post-LED exposure. Exposure of fibroblasts to <NUM> or <NUM>/<NUM> produced higher concentrations of IL6 at <NUM> hours post-LED exposure.

Advances in LED technology allow concepts and methodologies to be applied in the form of a small hand-held device. This device is self-contained and consists of a hand piece with a small flexible probe to deliver <NUM> LED deep into canal depths and spaces. Short <NUM> second treatments of low energy doses are antimicrobial yet, minimally harmful to endodontic tissues and cells. In summary, the results in this study suggest a new treatment modality using <NUM> LED for the sterilization and regeneration of infected and inflamed endodontic tissues.

<FIG> shows one example of a tooth <NUM> after mechanical removal of material (e.g., enamel, dentin, pulp or the like) to form one or more passages or cavities (treatment locations) within the tooth <NUM>. For instance, in the example shown in <FIG>, the tooth <NUM> includes a root canal <NUM> bored out along each of the roots <NUM> and through the upper tooth structure. As further shown in <FIG>, the light-based dental system <NUM> is shown in an operative configuration, for instance, with the delivery shaft assembly <NUM> extending into the tooth <NUM> and along one of the roots <NUM>. One or more distal light ports <NUM> (in this example a plurality) corresponding to the distal light port are provided at a variety of locations along the delivery shaft assembly <NUM> proximate the distal shaft profile. The delivery ports <NUM> facilitate the broadcast of light at one or more wavelengths from the delivery shaft assembly <NUM> and into the tooth <NUM> or other treatment location to provide one or more therapeutic effects to features <NUM> within the roots <NUM> as well as the remainder of the tooth <NUM>.

In one example, the delivery shaft assembly <NUM> is manipulated by translation, rotation or the like to accordingly bathe a portion (including the entirety) of the root canal <NUM> with therapeutic light delivered from the delivery ports <NUM>. As shown in the example in <FIG>, the delivery ports <NUM> are at various locations along the delivery shaft assembly <NUM> to facilitate the broadcast of light from the instrument shaft assembly <NUM> in one or more directions and one or more patterns (e.g., light profiles or patterns, broadcast profiles or patterns, or the like). In other examples, the delivery ports <NUM> include a single or multiple light delivery ports, for instance at a distal tip.

As also shown in <FIG>, in one example, the tooth <NUM> includes one or more features <NUM>. The features <NUM> include, but are not limited to, one or more lateral canals, passages (for instance, extending from a main root canal <NUM>), crevices, fins, biofilms, collections of proteins, carbohydrates or the like. As previously described herein, biofilms, proteins, carbohydrates and the like may hide, conceal or protect one or more microorganisms therein. These features <NUM> frustrate the removal or killing of microorganisms with one or more or chemical irrigants, mechanical debridement or the like. Light in one or more wavelengths, including wavelengths of <NUM> to <NUM> nanometers, <NUM> to <NUM> nanometers or the like, delivered into these features <NUM> including canals, passages, crevices, fins, biofilms, proteins, carbohydrates or the like reaches difficult to access microorganisms and kills them. Optionally, light delivered from the system <NUM> cooperates with chemical irrigants to enhance the effectiveness of the irrigants, for instance within the features <NUM>.

In the configuration shown in <FIG>, for instance, with the tooth <NUM> bored out and in the process of disinfection with the light-based dental system <NUM>, a root canal <NUM> (one example of a cavity, passage, treatment location or the like) is formed, in one example, with a dental drill and one or more tools including dental files. The root canal <NUM> is thereafter mechanically cleaned, for instance, by mechanical debridement with a dental file to remove dental pulp including the nerve, blood vessels or other soft tissue provided within the tooth <NUM>. As further shown, the tooth <NUM> is optionally irrigated, for instance, with one or more bactericidal irrigants including, but not limited to, one or more of sodium hypochlorite, EDTA, chlorhexidine (CHX) or the like. These irrigants are, in some examples, found to kill microorganisms. In the example shown in <FIG>, a surface of the irrigant <NUM> is shown in the tooth <NUM> with a broken line and is pooled therebelow. In other examples, the irrigant <NUM> is flushed into the tooth <NUM> and aspirated out.

At least a portion of the irrigant <NUM> remains within the tooth <NUM>, for instance, along one or more of the features <NUM> provided within the root canal <NUM>, within the main portion of the tooth <NUM> or the like. In one example, the light-based dental system <NUM> is used in combination with the irrigant <NUM>. The provision of light having one or more wavelengths to the irrigant <NUM>, for instance, adjacent to the features <NUM> generates one or more free radicals including chloride ions or the like configured to readily engage with and break down the one or more features <NUM> within the tooth <NUM>. Because the irrigant is already present the generation of free radicals with the application of light from the light-based dental system <NUM> immediately applies the resulting free radicals to the features <NUM> and readily breaks down one or more biofilms, proteins, carbohydrates or the like and kills microorganisms otherwise concealed within biofilms, carbohydrates, proteins or the like.

In still other examples, after mechanical debridement (removal of one or more features of the tooth <NUM> including nerves, blood vessels, tissue or the like) the light-based dental system <NUM> is used by itself, for instance, in a configuration shown as in <FIG> to broadcast therapeutic light (without an irrigant) into the root canals <NUM>. The disbursed therapeutic broadcasting of light, for instance, from the one or more delivery ports <NUM> (optionally with one or more of rotational or translational manipulation) distributes one or more wavelengths of light into the root canal <NUM> and the remainder of the tooth <NUM> to accordingly interact with one or more of the features <NUM> (e.g., side canals, irregular features such as fins, biofilms, proteins, carbohydrates or the like). The light by itself interacts with the microorganisms in the passage or cavity (and optionally within features <NUM>) to accomplish one or more of killing microorganisms, initiating tissue regeneration or providing a cleaned tooth <NUM> ready for one or more dental procedures including filling, crowns or the like.

The above detailed description includes references to drawings, which form a part of the detailed description.

Claim 1:
A light-based dental treatment system (<NUM>) comprising:
a handle generator configured to generate therapeutic light, the handle generator including:
a generator housing (<NUM>); and
at least one light element (<NUM>) configured to generate the therapeutic light;
at least one delivery shaft assembly (<NUM>) selectively coupled with the handle generator, the at least one delivery shaft assembly (<NUM>) including:
a delivery shaft (<NUM>) having a proximal shaft profile (<NUM>) and a distal shaft profile (<NUM>);
a proximal light port (<NUM>) aligned with the at least one light element (<NUM>); and
a distal light port (<NUM>) configured to deliver light from the delivery shaft (<NUM>) to a treatment location;
a conductive heat sink (<NUM>) coupled between the at least one light element (<NUM>) and the generator housing (<NUM>),
characterized in that the handle generator includes an alignment collet (<NUM>) that surrounds at least a portion of the delivery shaft assembly (<NUM>) and applies a clamping force with tightening of the alignment collet (<NUM>), the alignment collet (<NUM>) having a light passage extending along an interior collet profile (<NUM>),
wherein the interior collet profile (<NUM>) of the alignment collet (<NUM>) is configured to grasp the delivery shaft (<NUM>) and align the proximal light port (<NUM>) with the at least one light element (<NUM>),
wherein the at least one delivery shaft (<NUM>) includes a shaft fitting (<NUM>) having a fitting profile coupled with the delivery shaft (<NUM>), and the fitting profile is complementary to the interior collet profile (<NUM>) of the alignment collet (<NUM>).