System and Method For Healing and/or Disinfecting Wounds and Burns

A system for healing and/or disinfecting wounds and burns includes an emitter including one or more blue light sources configured to emit blue light at a therapeutic energy level at a wound or burn area of a human or animal subject and one or more ultraviolet-A (UVA) light sources configured to emit UVA light at u therapeutic energy level at the wound or burn area. A controller coupled to the emitter is configured to control the therapeutic energy level of the blue light and the UVA light and one or more parameters associated with the blue light and the UVA light to produce a photobiomodulation effect in order to induce a cytokine response in cells of the wound or burn area to elicit recruitment and proliferation of cells to promote healing of the wound or burn area.

FIELD OF THE INVENTION

This invention relates to a system and method for healing and/or disinfecting wounds and burns.

BACKGROUND OF THE INVENTION

The emergence and re-emergence of antimicrobial resistance leads to an enormous clinical burden which may result in death of millions of people and a tremendous socioeconomic burden globally each year. Multidrug and Pandrug resistance microorganisms include a class of elite pathogens with enhanced virulence and pathogenicity traits. For example, Methicillin resistanceStaphylococci aureus(MRSA) in the U.S. alone is responsible for nearly 20,000 deaths per year and carries an estimated 3 to 4 billion dollars in added healthcare costs. Individuals seeking medical treatment in a hospital often acquire a hospital acquired infection (HAIs), as some hospitals have  become notorious repositories harboring extremely pathogenic and drug-resistant microbes. Additionally, surgical wounds and sores are common sites for opportunistic pathogens to establish life threatening infections. Burns are equally at risk, but are particularly problematic because they can affect large areas of the epidermis depending on the degree of the burned skin. One of the major reasons that open wounds and bums are prone to infections may be attributed to the function of intact skin to provide a barrier to the entry of microorganisms. Certain individuals, such as diabetics, the elderly, or immune-compromised patients, and the like, are especially at risk due to an impaired ability to heal.

Moreover, it has been established that skin pigmentation, which is caused by the presence and accumulation of endogenous chromophores within the pathogen, may be associated with virulence. One classification of pigments found in pathogens is porphyrin. Light energy within the visible, e.g., blue light and red light, and the ultraviolet spectrum has been proven effective in eliciting of microbial pathogen eradication at some level. The effect of light to eradicate pathogens correlates and is dependent upon the presence of oxygen. The photoexcitation of endogenous chromophores, including porphyrins, leads to the production of reactive oxygen species (ROS), such as hydroxyl radicals, superoxides, peroxides, and singlet oxygen, which elicit killing of microbial cells. Under normal conditions, pigmentation confers a competitive advantage for the pathogen because the pigments are antioxidants which help to protect the pathogen from destruction by the host immune system.

UVA light does not occur alone in the environment. UVA light is always present with ultraviolet-B (UVB), all of which enter the atmosphere and are generated by the sun  About 90% of all photodamage to human cells is associated with UVB light which cross-links DNA in leading to mutagenesis in the cell. UVA light, unlike UVB light, is generally well tolerated by cells because it is weakly absorbed by DNA. This is because UVB directly damaging DNA, whereas UVA excites endogenous chromophores, leading to the expression of ROS.

Collagen is the main structural component of skin. IFN-C is an interferon. Interferons are members of a class of chemicals known as cytokines. Cytokines play a key role in cellular communication and serve to prime the immune system which aids in the clearance of foreign antigens such as those expressed by bacteria or mutagenized cells in the case of some cancers. Cytokines can initiate cellular repair.

UV light (with both UVA and UVB) has been proposed as a potential modulator of keratinocyte-melanocyte cross talk in promoting wound healing. Keratinocytes, the main cell type in the epidermis produce collagen, form a self-renewing epithelial barrier to protect the skin against environmental hazards, while melanocytes, located in the basal layer of the epidermis, are dendritic-like pigment-producing cells, which protect keratinocytes against the DNA-damaging effects of UVB irradiation through production of melanin.

Thus, there is a need for an effective system and method for healing and/or disinfecting wounds and bums that utilizes visible light (blue and red) and only UVA light which when applied properly to a wound or burn area elicits a cellular response in humans and animals to produce phototoxic byproducts that kills pathogens to disinfect the wound or burn area and initiates a repair response which leads to cellular proliferation and regrowth of the affected tissue to promote healing of the wound or burn area.

SUMMARY OF THE INVENTION

In one aspect, a system for healing and/or disinfecting wounds and burns, the system includes an emitter including one or more blue light sources configured to emit blue light at a therapeutic energy level at a wound or burn area of a human or animal subject and one or more ultraviolet-A (UVA) light sources configured to emit UVA light at a therapeutic energy level at the wound or burn area. A controller coupled to the emitter is configured to control the therapeutic energy level of the blue light and the UVA light and one or more parameters associated with the blue fight and the UVA light to produce a photobiomodulation effect in order to induce a cytokine response in cells of the wound or burn area to elicit recruitment and proliferation of cells to promote healing of the wound or burn area.

In one embodiment, the controller may be configured to control the therapeutic energy level of the blue light and the UVA light and one or more parameters associated with the blue light and the UVA light to activate photoexcitation of intracellular accumulated chromophores and production of cytotoxic reactive oxygen species in opportunistic pathogens such that a synergistic effect of the combination of the blue light at the therapeutic energy level and the UVA light at the therapeutic energy level and the one more parameters associated with the blue light and the UVA light kills opportunistic pathogens in the wound or burn area to disinfect an infected wound area or art infected burn area. The therapeutic energy level of the blue light and the UVA light may be in the range of about 0.4 J/cm2to about 4 J/cm2. The one or more parameters of the blue light and the UVA light controlled by the controller may include one or more of:  a wavelength of the blue light, a wavelength of the UVA light, a frequency of the blue light, a frequency of the UVA light, one or more waveforms of the blue light, one or more waveforms of the UVA light, one or more duty cycles of the blue light, and/or one or more duty cycles of the UVA light. The wavelength of the blue light may be in the range of about 405 nm to about 470 nm. The wavelength of the UVA light may be in the range of about 315 nm to about 400 nm. The frequency of the blue light may be in the range of about 0.5 Hz to about 1.000 Hz. The frequency of the UVA light may be in the range of about 0.5 Hz to about 1,000 Hz. The one or more waveforms may include one or more of a sinewave, a square wave, a triangle wave, and/or a sawtooth wave. The controller may be configured to control the one or more blue light sources and the one or more UVA light sources to emit the blue light and the UVA light as pulsed light. The controller may be configured to control the one or more blue light sources and the one or more UVA light sources to emit the blue light and the UVA light as continuous light. The controller may be configured to control the one or more blue light sources and the one or more UVA light sources the blue light and the UVA light in a combination of pulsed light and continuous light. The one or more duty cycles of the blue light may include one or more of: a 25% duty cycle, a 50% duty cycle, or a 75% duty cycle. The one or more duty cycles of the UVA light may include one or more of: a 25% duty cycle, a 50% duty cycle, or a 75% duty cycle. The one or more blue light sources and the one or more UVA light sources may be configured as a multi-emitter array. The controller may be configured to control the multi-emitter array to provide the blue light at the therapeutic energy level and the UVA light at the therapeutic energy level and at the one or more parameters associated with the blue light and the UVA light. The controller may  be configured to shut off the one or more blue light sources and the one or more UVA sources when a predetermined therapeutic dosage of blue light and UVA light is applied to the wound or burn area. The emitter may include one or more red light sources configured to emit red light at a therapeutic energy level at the wound or burn area. The controller may be coupled to the one or more red light source and is configured to control the therapeutic energy level of the red light and one or more parameters associated with the red light to increase oxygenation, vascularization and recruitment of immune cells in the wound or burn area and to enhance the photoexcitation of accumulated intracellular chromophores and production of cytotoxic reactive oxygen species in opportunistic pathogens. The one or more blue light sources, the one or more UVA light sources, and the one or more red light sources may be configured as a multi-emitter array. The controller may be configured to control the multi-emitter array to provide the blue light at the therapeutic energy level, the UVA light at the therapeutic energy level, and the red light at the therapeutic energy level, and one or more parameters associated with the blue light, the UVA light, and the red light. The controller may be responsive to a wound or burn area detection device and is configured to determine a size of the wound or burn area. The controller may be configured to provide the therapeutic energy level of the blue light, the therapeutic energy level of the UVA light, and the one or more parameters associated with the blue light and the UVA light by controlling the power applied to the emitter. The system may include a display device coupled to the controller.

In another aspect, a system for healing and/or disinfecting wounds and burns is featured. The system includes an emitter including one or more blue light sources configured to emit blue light at a therapeutic energy level at a wound or burn area of a  human or animal subject one or more (ultraviolet) UVA light sources configured to emit UVA light at a therapeutic energy level at the wound or burn area. A controller coupled to the one or more blue light sources and the one or more UVA light sources is configured to control the therapeutic energy level of the blue light and the UVA light and one or more parameters associated with the blue light and the UVA light to activate photoexcitation of intracellular accumulated chromophores in the production of cytotoxic reactive oxygen species in opportunistic pathogens such that a synergistic effect of the combination of the blue light at the therapeutic energy level and the UVA light at the therapeutic energy level and the UVA light at the therapeutic energy level and the one or more parameters associated with the blue light and the UVA light kills the opportunistic pathogens in the wound or burn area to disinfect tin infected wound or an infected burn area.

In another aspect, a system for healing and/or disinfecting wounds and burns is featured. The system includes an emitter including one or more blue light sources configured to emit blue light at a therapeutic energy level at a wound or burn area of a human or animal subject and one or more (ultraviolet) UVA light sources configured to emit UVA light at a therapeutic energy level at the wound or burn area. A controller coupled to tire one or more blue light sources and the one or more UVA light sources is configured to control the therapeutic energy level of the blue light and the UVA light and one or more parameters associated with the blue light and the UVA light to produce a photobiomodulation effect in order to induce a cytokine response in cells of the wound or burn area to elicit recruitment and proliferation of cells to promote healing of the wound or burn area and to activate photoexcitation of intracellular accumulated chromophores  and production of cytotoxic reactive oxygen species a opportunistic pathogens such that a synergistic effect of the combination of blue light at the therapeutic energy level and UVA light at the therapeutic energy level and the UVA light at the therapeutic energy level and the one or more parameters associated with the blue light and the UVA light kills the opportunistic pathogens in the wound or burn area to disinfect an infected wound area or an infected born area.

In yet another aspect, a method for healing and/or disinfecting wounds and burns is featured. The method includes applying blue light at a therapeutic energy level at a wound or born area of a human or animal subject, applying ultraviolet-A (UVA) light at a therapeutic energy level at the wound or hum area, and controlling lite therapeutic energy level of the blue light and the UVA light and one or more parameters associated with the blue light and the UVA light to produce a photobiomodulation effect in order to induce a cyctokine response in the cells of the wound or burn area to illicit recruitment and proliferation of cells to promote heating of the wound or burn area.

In one embodiment, controlling the therapeutic energy level of the blue light and the UVA light and the one or more parameters associated with the blue light and the UVA light may activate photoexcitation of intracellular accumulated chromophores and the production of cytotoxic reactive oxygen species in the opportunistic pathogens such that a synergistic effect of the combination of the blue light at the therapeutic energy level and the UVA light at the therapeutic energy level and the UVA light at the therapeutic energy level and the one or more parameters associated with the blue light and the UVA light kills opportunistic pathogens in the wound or burn area to disinfect an infected wound area or an infected burn area. The one or more parameters of the blue  light and the UVA light may include controlling one or more of: a wavelength of the blue light, a wavelength of the UVA light, a frequency of the blue light, a frequency of the UVA light, one or more waveforms of the blue light, one or more waveforms of the UVA light, one or more duty cycles of the blue light, and one or more duty cycles of the UVA light. The blue light and the UVA light may be applied at a therapeutic energy level in the range of about 0.4 J/cm2to about 4 J/cm2. The blue light may be applied at a wavelength in the range of about 405 nm to about 470 nm. The UVA light may be applied at a wavelength in the range of about 315 nm to about 400 nm. The one or more waveforms may include a sinewave, square wave, a triangle wave, and/or a sawtooth wave. The blue light may be applied at a frequency in the range of about 0.5 Hz to about 1,000 Hz. The UVA light may be applied at a frequency in the range of about 0.5 Hz to about 1,000 Hz. The one or more duty cycles of the blue light may include one or more of: 25%, 50%, or 75% duty cycle. The one or more duty cycles of the UVA light may include one or more of: 25%, 50%, or 75% duty cycle. The method may include applying red light at a therapeutic energy level and one or more parameters associated with the red light at the wound or born area. The method may include applying red light at a therapeutic energy level and one or more parameters associated with the red light at the wound or burn area to increase vascularization and recruitment of immune cells of the wound area and oxygenation in the cells of the wound or burn area to enhance the photobiomodulation and/or the photoexcitation of intracellular chromophores and production of cytotoxic reactive oxygen species in opportunistic pathogens. The therapeutic energy level of the blue light, the therapeutic energy level of the UVA light, and the one or more parameters associated with the one blue light and the UVA light may be control led by adjusting a power level  applied to one or more blue light sources and one or more UVA light sources.

DETAILED DESCRIPTION OF THE INVENTION

There is shown inFIG. 1, one embodiment of system10and the method thereof for healing and/or disinfecting wounds and burns. System10includes emitter11which includes one or more blue light sources, exemplarily indicated at12, configured to emit blue light14at a therapeutic energy level at a wound or burn area of a human or animal subject, e.g., wound or burn area16. In this example, wound or burn area16is located on  a leg of a human subject as shown. In other examples, wound or burn area16may be any area of a human or animal subject has a wound area, e.g., a diabetic foot ulcer or any wound area caused by disease or medical condition, e.g., diabetic mellitus, hypertension, hyperlipidemia, arthrosclerosis, AIDS, malignancy, morbid obesity, hepatitis C virus, or any other disease or medical condition that creates a wound on a human subject or animal, or an event resulting in a contusion, hematomas, crush injury, abrasions, lacerations, incisions, punctures, or any other penetrating type wound or burn resulting from a fire, hot liquid, steam, hot metal, glass or other objects, electrical currents, radiation from X-rays, radiation therapy, sunlight or ultraviolet light from a sunlamp or tanning bed, or damaging chemicals or agents, such as strong acids, lye, paint thinner, gasoline, and the like, or a burn area.

In one design, the therapeutic energy level of blue light14is preferably in the range of about 0.4 J/cm2to about 4 J/cm2, although the therapeutic energy level may be higher or lower than this range, but is preferably low enough to not damage the cells of wound or burn area16and high enough to effectively heal and/or disinfect an infected wound or burn area16. Preferably, the wavelength of blue light14is in the range of about 405 nm to about 470 nm.

Emitter11also includes one or more UVA light sources18configured to emit UVA light20at a therapeutic energy level at wound or burn area16. In one design, the therapeutic energy level of UVA light20is preferably in the range of about 0.4 J/cm2to about 4 J/cm2, although the therapeutic energy level may be higher or lower than this range, but is preferably low enough to not damage the cells of wound or burn area16effectively heal and/or disinfect an infected wound or burn area16. Preferably, the  wavelength of UVA light20is in the range of about in the range of about 315 nm to about 400 nm.

In one example, one or more blue light sources12and the one or more UVA light may be light emitting diodes (LEDs), beam collimation devices, beam shaping devices, or a beam sweeping/painting device, or similar type light source. In one design, one or more blue light sources12and one or more UVA light sources18may be configured as a multi-emitter array, e.g., multi-emitter array22.FIG. 2, where like parts have been given like numbers.FIG. 3shows an example of system10configured on stand30having swivel arm32coupled to multi-emitter array22.

System10,FIG. 1, also includes controller24coupled to emitter11,FIG. 1, or multi-emitter22,FIG. 2, configured to variably control the therapeutic energy level of blue light14, the therapeutic energy level of UVA light20, and one or more parameters associated with the blue light14and the UVA light20such that blue light14and UVA light20produce photobiomodulation effect to induce a cytokine response in the cells of wound or burn area16to illicit recruitment and proliferation cells to promote healing of wound or burn area16, as discussed in further detail below. Controller24is also preferably configured to control the therapeutic energy level of the blue light14and the UVA light16and the one or more parameters associated with the blue light and the UVA light such that blue light14and UVA light20activate phothexcitation of intracellular accumulation of chromophores and production of cytotoxic reactive oxygen species (ROS) and opportunistic pathogens such that a synergistic effect of the combination of the blue light and the UVA light at their respective therapeutic energy levels and the one or more parameters associated with the  blue light and the UVA light kills opportunistic pathogens in wound or burn area16.

Controller24may be a processor, one or more processors, an application-specific integrated circuit (ASIC), firmware, hardware, and/or software (including firmware, resident software, micro-code, and the like) or a combination of both hardware and software that may all generally be referred to herein as a “controller”, “module”, “engine” or “system” which may be part of controller24or system10. Computer program code for the programs for carrying out the instructions or operation of one or more embodiments system10and method for healing and/or disinfecting wounds and bums may be written in any combination of one or more programming languages, including an object oriented programming language, e.g., C++, Smalltalk, Java, and the like, or conventional procedural programming languages, such as the “C” programming language or similar programming languages or in assembly code and may be integrated or separate from processor24. Controller24may be a programmable integrated circuit board.

Data for controller24may be stored in storage device32,FIGS. 1 and 4. Storage device32may include any combination of computer-readable media or memory. The computer-readable media or memory may be a computer-readable signal medium or a computer-readable storage medium. A computer-readable storage medium or memory may be, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the foregoing. Other examples may include an electrical connection having one or more wires, a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or Flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage  device, a magnetic storage device, or any suitable combination of the foregoing. As disclosed herein, the computer-readable storage medium or memory may be any tangible medium that can contain, or store one or more programs for use by or in connection with one or more processors on a company device such as a computer, a tablet, a cell phone, a smart device, or similar type device.

System10,FIGS. 1-3, also preferably includes power supply36coupled to controller24. In the example shown inFIGS. 2 and 3, controller24and power supply36(shown in phantom) are enclosed in housing38and coupled to one or more blue light sources12and one or mote UVA light sources configured as multi-emitter array22by line40. System10may also include display44which may display the total amount of energy delivered to wound or burn area16in a single treatment or over the course of all treatments, and the like. System10also preferably includes user interface46coupled to controller24which is configured to allow a user of system10to input the desired therapeutic energy level of the blue light14and the VA light20and the one or more parameters associated with blue light14and UVA light20. In one example, user interface46may include control knobs48,FIG. 7.

Controller24preferably controls and provides the therapeutic energy level of the blue light (0.4 J/cm2to about 4 J/cm2) and the therapeutic energy level of the UVA light (0.4 J/cm2to about 4 J/cm2) and one or more of the parameters associated with one or more blue light sources12and one or more UVA light sources18by controlling the power applied by power supply36to emitter11having one or more blue light sources12and the one or more UVA light sources.

The one or more parameters of blue light14and UVA light20controlled by  controller24preferably include one or more of the wavelength of blue light14, the wavelength of UVA light20, the frequency of the blue light, e.g., about 0.5 Hz to about 1,000 Hz, the frequency of the UVA light, e.g., about 0.5 Hz to about 1,000 Hz, and one or more duty cycles of the blue light14and UVA light20(when blue light14and UVA light20are pulsed as discussed below), e.g., a 25% duty cycle, a 50% duty cycle, or a 75% duty cycle. The one or more parameters controlled by controller24also include one or more waveforms of blue light14and UVA light20. e.g., sine wave50,FIG. 4, square wave52, triangle wave54, or sawtooth wave56, or similar type waveform. In one example, wave generator60,FIG. 1, coupled to emitter11and controller24may be utilized to create the various waveforms of the therapeutic energy level of blue light14and UVA light20and the one or more parameters associated with blue light14and UVA light20, discussed above, as known by those skilled in the art.

In one example, controller24is configured to enable one or more blue light sources12and one or more UVA light sources18to emit blue light14and UVA light as continuous light, pulsed light, or a combination of pulsed light and continuous light. When blue light14and UVA light20is pulsed, controller24may control the one or more duty cycles of the pulsed light discussed above.

FIG. 5, where like parts have been given like numbers, shows an example of system10with multi-emitter array22placed proximate and above wound or burn area16, in this example a foot of a human subject. In this example, multi-emitter array22is emitting blue light14at the therapeutic energy level and at one or more parameters associated with and blue light14as discussed above and UVA light20at the therapeutic energy level and at one or more parameters associated with and UVA light20as  discussed above at wound or burn area16to produce a photomodulation effect in order to induce a cytokine response in the cells of a wound or burn area to illicit recruitment and proliferation of cells to promote healing of the wound or burn area16and/or to activate photoexcitation of intracellular accumulated chromophores and production of cytotoxic ROS and opportunistic pathogens such that a synergistic effect of the combination of blue light and UVA light at the respective energy levels kills opportunistic pathogens in wound or hum area16to disinfect an infected wound or burn area16.

In this example, system10also preferably includes wound or burn area size detection device40, e.g., a CCD camera or similar type device which, in combination with imaging software utilized by controller24, defects and determines the size of wound or burn area16such that controller12can calculate or determine the required therapeutic energy level and one or more parameters associated with blue light14and the therapeutic energy level of UVA light20and the one or more parameters associated with UVA light to be delivered for healing and/or disinfecting wound or burn area16.

In one design, controller24is configured to shut off one or more blue light sources12and one or more UVA light sources18when a predetermined therapeutic dosage of blue light14and UVA light20is applied to wound or burn area16, e.g., 4 J/cm2, 10 J/cm220 J/cm2.

In one design, emitter11,FIG. 6, where like parts have been given like numbers, may also include one or more red light sources70configured to emit red light72at a therapeutic energy level, e.g., 0.4 J/cm2to about 4 J/cm2, to wound or burn area16. Similar, as discussed above, controller24is coupled to emitter11having the one or more red light sources70and is configured to control the therapeutic energy level of red light72and one or more parameters associated with the red light, e.g., similar to the one or more parameters of the blue light and UVA light discussed above, to increase oxygenation, vascularization, and recruitment of immune cells in wound or burn area16and to enhance photoexcitation of accumulated intracellular chromophores and production of ROS and opportunistic pathogens, in one design, one or more red light sources72are preferably included in multi-emitter array22,FIG. 2, as shown

One example of the method for healing and disinfecting wounds of this invention includes applying blue light at a therapeutic energy level at a wound or burn area of a human or animal subject, step100,FIG. 7, UVA light is applied at a therapeutic energy at a wound or burn area, step102. The therapeutic energy of the blue light and the UVA light and one or more parameters associated with the blue light and the UVA light is controlled to product a photobiomodulation effect to induce a cytokine response in the cells of the wound or burn area to illicit recruitment and proliferation of cells to promote healing of the wound or burn area, step104. In one example, the therapeutic energy level of the blue light and the UVA light and the one or more parameters associated with the blue light and the UVA light is controlled to activate photoexcitation of intracellular accumulated chromophores and the production of cytotoxic reactive oxygen species in the opportunistic pathogens such that a synergistic effect of the combination of the blue light at the therapeutic energy level and the UVA light at the therapeutic energy level kills opportunistic pathogens in the wound or burn area to disinfect an infected wound or burn area,106.

Blue light14applied wound or burn area16at the therapeutic energy level and one or more parameters associated with blue light discussed above stimulates activation  of keratinocytes. Activation of keratinocytes is required for production of collagen, a structural component of the epidermis and cytokine signaling to illicit an immune response which aids in the clearance of microbes.

Blue light14has not shown any inflammatory cell response and does not produce any significant change in p53 gene expression. This means blue light14may not be phototoxic to mammalian cells. An increase of p53 may lead to cell cycle arrest which may be useful in treating a skin cancer and increases further lead to cell apoptosis, (cellular death). Therefore, no increase to p53 expression from cells exposed to blue light14means blue light14does not contribute to cell death. Blue light14is non-cytotoxic and assists in cell signaling repair leading to regeneration and healing of damaged cells and tissue.

The antimicrobial effect of bloc light14applied to wound or burn area16by system10and the method thereof, as discussed above, referred herein as blue light inactivation, may be provided by excitation of endogenous bacterial chromophores, such as porphyrins. The absorption of energy by the porphyrins leads to an excited energy-state of the chromophore resulting in the production of a reactive oxygen species (ROS), most notably singlet oxygen. Additionally, photosensitizers activated by the wavelengths of blue light14may be combined to enhance therapy.

In general, wound healing typically involves homeostasis, inflammation, granulation, fibrogenesis, re-epithelialization, neovascularization, and maturation contraction. Clinical trials using UVA light to promote wound healing have shown that UVA treatment is associated with an increase in production of MMP-1 and IFN-C production. These are associated with collagen production, stimulation of phagocytosis,  promotion of lymphocytes, and a key component of innate and adaptive host immune functions thereby priming the immune system to attack foreign material such as host pathogens.

MMP-1 (Matrix metalloproteinase-1) is a collagen use encoded by humans. Collagenase cleaves proto-collagen to form the stable extracellular matrix of collagen supporting epithelia. Collagen is the main structural component of skin. IFN-C is an interferon. Interferons ate members of a class of chemicals known as cytokines. Cytokines play a key role in cellular communication and serve to prime the immune system which aids in the clearance of foreign antigens such as those expressed by bacteria or mutagenized cells in the case of some cancers. Cytokines can initiate cellular repair.

UV light (specifically, UVA) has been proposed as a potential modulator of keratinocyte-melanocyte cross talk in promoting wound healing. Keratinocytes, the main cell type in the epidermis, form a self-renewing epithelial barrier to protect the skin against environmental hazards, while melanocytes, located in the basal layer of the epidermis, are dendritic-like pigment-producing cells, which protect keratinocytes against the DNA-damaging effects of UVB irradiation through production of melanin.

UVA light20, unlike UVB and UVC, applied to wound or burn area16by system10and the method thereof at the therapeutic energy level and one or more parameters associated with UVA light20discussed above is generally well-tolerated by cells because it is weakly absorbed by DNA. This is because UVB is directly damaging DNA, whereas UVA excites endogenous chromophores, leading to the expression of ROS.

While all forms of UV radiation are potentially damaging the predominant form of naturally occurring damage is attributed to UVB. In contrast, UVA is associated with formation of (6-4) pyrimidine and pyrimidine photoproducts which are effectively repaired in human cells. DNA aside, another well-characterized photo damage signaling molecule is trans-urocanic acid (trans-UCA) which is isomerized to cis-UCA and exhibits potent immunosuppressive qualities through activation of Treg cells upon exposure to UVC light and UVB light, but not UVA light20. This difference may be correlated to the relative protection of the cell nucleus to UVA damage, unlike UVB and UVC.

Therefore low doses of UVA light20applied to wound or burn area16at the therapeutic energy level and one or more parameters associated with UVA light by system10and the method thereof, discussed above may not be significantly cytotoxic and instead initiates a repair response will lead to cellular proliferation and regrowth of the affected tissue.

When wound or burn area16is exposed to UVA light20by system10and the method thereof, Eukaryotic Initiation Factor 2a subunit (eIF2a-Ser51) phosphorylation occurs and is implicated in cell proliferation and apoptosis, and eIF2a-Ser51 executes a key translational control mechanism following UV irradiation that is dose and time-dependent. Low doses of UVA light20at the therapeutic energy level and one or more parameters associated with UVA light20promote tissue regeneration, instead of cellular death.

Keratinocytes cells make up about 95% of the cells of the epidermis (skin). Keratinocytes also serve as a scaffold to hold Langerhans cells and lymphocytes in place. In addition to providing a structural barrier, keratinocytes serve a chemical immune role  as immunomodulators, responsible for secreting inhibitory cytokines in the absence of injury and stimulating inflammation and activating Langerhans cells in response to injury. Langerhans cells serve as antigen-presenting cells when there is a skin infection and are the first cells to process microbial antigens entering the body from a skin breach.

The antimicrobial properties of UVA Light20are similar to blue light14but with different absorption spectra on the chromophores.

FIG. 8shows an example of the process of photoinactivation by photoexcitation of endogenous chromophores by blue light14and UVA light20at their therapeutic energy levels and the one or more parameters associate with blue light14and UVA light20into reactive oxygen species (ROS).

The combination of the blue light14at the therapeutic energy level and UV light20at therapeutic energy level and the one or more parameters associated with the blue light14and UVA light20stimulates multiple signaling pathways of the host epithelia and cells of the immune system. Because system10and the method thereof combines blue light14and UV light20at the therapeutic energy level and the one or more parameters associated with the blue light14and UVA light20, a healing and disinfection effect is achieved on the wound or burn area16such that the total result is not simple an additive function of one plus the other, but a synergistic effect. This is because when blue light14and UVA light20are administered in combination, a maximizing effect is achieved thereby multifold increasing cellular production of key chemicals and molecules leading to a robust effect.

Because the therapeutic dosage of the blue light14and the UVA light20is controlled and the damaging wavelengths of UVA and UVB light are omitted, the cells of wound or burn area16respond as though damage has occurred (since in nature UVA light20does not occur in the absence of UV-B). Essentially the process hijacks the cells defense response to photodamage in order initiate a robust cellular regeneration, proliferation, and immune response. Because this response is controlled and not found in nature it is most aptly defined herein as photobiomodulation—the use of light to elicit a predictable cellular response.

Thus, system10system and the method thereof for healing and/or disinfecting wounds and burns utilizes multiple wavelengths of blue light14and UVA light20delivered in various parameters, combinations and waveforms to control activation of multiple different cellular pathways that ultimately results in a maximized and cascade like healing function. This is because multiple cell types are activated, all of which individual serve to recruit repair and defense responses.

Because system10and the method thereof utilizes multiple pathways, lower doses of blue light14and UVA light20are required compared to one wavelength of light alone. This means controlled variable emitter11and multi-emitter array22.FIGS. 1-3 and 5, with one more blue light sources12and one or more one or more UVA light sources18controlled by controller24can achieve efficacy in shorter time or with lower doses of blue light14and UVA light20. Graph130,FIG. 9, shows an example of the lower doses of blue light14and UVA light20provided by the synergistic effect of system10and the method thereof compared to conventional treatment, indicated by graph152. This feature may reduce the costs of the components of system10.

As discussed above, controller24is preferably configured to variably control emitter11and multi-emitter array22such that the therapeutic energy level of the dosage or amount of blue light14and UVA light20are collectively reduced. This is a key feature of system10because there is a threshold where the therapeutic energy level of blue light14and UVA light20may be too high and damage to the cells of the epithelia, as known by those skilled in the art. There is also a level of blue light14an UVA light20at the therapeutic energy level that may be too low and may have an insufficient effect on reducing the pathogen load, e.g., 0.01 J per cm2. Therefore, system10provides a synergistic response in both wound healing and pathogen killing.

Moreover, by selecting blue light14and UVA light20and omitting harmful UVB and UVC, which are typically produced in a conventional broad band UV system, up to about 90% of the damaging component of UV light is removed. This allows for a greater dose of UVA light20and blue light14to be administered on wound or burn area16without causing unwanted cellular damage. Additionally, blue light14and UVA light20are is well tolerated by the patient or animals.

The antimicrobial effect of blue light14is oxygen dependent. Thus, increased oxygenation using red light70,FIG. 6, leads to an enhanced effect of blue light14and UVA light20. Because pigmentation is associated with virulence, more virulent microbes, e.g., greater pigmentation, ate at greater susceptibility to inactivation with the addition of red light72which means that any surviving microorganisms are anticipated to be more susceptible to antibiotic treatment. Thus, system10and the method thereof provides an additional way to control the bacterial load in wound and burn area16leading to the body's ability to heal naturally.

The pigments of the pathogen (virulence factors) under normal conditions serve to scavenge free radicals, which is a microbial defense response to the immune system of the host. However, the pigments are illicitly turned into agents of the pathogens own destruction thereby toxifying them directly and making them more susceptible to the hosts own inactivation mechanisms (peroxide attack through lysosome digestion).

The healing and regenerative properties of red light72may include an increased circulation and formation of new capillaries (blood How provides additional oxidation and nutrients to the damaged region of tissue) allowing for an increase in phagocytes (white blood cells) and components of both the innate and adaptive immune systems. White blood cells, for example, digest bacteria thereby decreasing the presence of toxins while also removing dead or damaged host cells which bacteria would otherwise consume as nutrients to further their own proliferation. This leads to a reduction of inflammation. Red light72stimulates the lymphatic system and reduces lymphedema. Red light72also stimulates proliferation of fibroblasts which synthesize collagen, elastin, and proteoglycans, all of which are critical to the healing process. The production of collagen leads to wound closure. Red light72also stimulates tissue granulation which allows for new connective tissue and vascularization at the surface of the wound.

The antimicrobial mechanism of red light72is the same blue light14and UVA light20discussed above, e.g., photoexcitation of endogenous chromophores, such as protoporphyrin IX. Porphyrins are a group of heterocyclic macrocycle organic compounds, composed of four modified pyrrole subunits interconnected at their a carbon atoms via methine bridges, in addition to photoexcitation, red light72stimulates the immune system, the natural defense system of tire host against pathogens.

Additionally, photosensitizers (PS) activated by at the wavelengths of red light72discussed above may be combined to enhance therapy, e.g., Toluidine Blue O. PS are a chemical agents that act similarly to chromophores but are not endogenously produced by the cell, typically these are dyes. When exposed to some wavelength of light these chemicals become photoexcited resulting in produce of ROS which are toxic to the pathogen.

The result is system10and method for healing and/or disinfecting wounds and bums of one or more embodiments of this invention controls the application of blue light14, UVA light20and/or red light72to wound or burn area16to initiate a cellular response that tricks the cell into responding to a photodamaging event that is largely ameliorated and such a combinatorial treatment represents a photobiomodulation approach. The body initiates a cytokine mediated repair response in the presence of UVA light20, without the damaging effects of UVB or UVC light. Thus, system10and the method thereof provides a treatment that heals and/or disinfects wounds that initiates cells, including chronic non-healing cells, to execute various molecular pathways that lead to recruitment of healthy cells, such as keratinocytes, that will subsequently populate, regrow, and repair wound or burn area16. The cells of the wound or burn area16also initiate a series of repair mechanisms. Because significant photodamage is unlikely to occur, the damaged cells can repair. In cases where repair is not possible, the cellular response will lead to apoptosis, a controlled form of cell death. At the same time, recruitment of adaptive immunity components (macrophages, T-cells) occur at the wound or burn area16leading to the removal of dead cellular material, debris, and initiate  destruction of pathogens by phagocytosis. These series of events, ultimately will also facilitate reducing inflammation of the wound area.

System10and method for healing and/or disinfecting wounds and hums provides a multi-modal technology for disinfecting pathogens present on wound bed or burn area16using phototoxic by-products and coupling their destruction by cells of the host immune system. At the same time, system10and the method thereof elicits a cellular driven mechanism to repair of damaged host cells and recruitment of keratinocytes to produce collagen and regrow the wound area. Treatment of infected non healing wounds using system10and the method thereof provides an enhanced or synergistic response that effectively and efficiently provides disinfection and wound healing. Thus, system10provides fast healing when compared to untreated wounds and wounds or burns treated only with conventional antimicrobial modalities. System10and the method thereof provides for simultaneously killing drug resistant pathogens present on the wound or burn area16and healing wound or burn area16. System10is less complex than conventional systems and methods and can easily be used in many different physical environments, including places that antibiotics/antimicrobials are not readily accessible. The result is, system10is highly effective, versatile, and cost efficient.