Light therapy may accelerate the healing of burns, according to a University at Buffalo-led study.
The research, published in Scientific Reports, found that photobiomodulation therapy – a form of low-dose light therapy capable of relieving pain and promoting healing and tissue regeneration – sped up recovery from burns and reduced inflammation in mice by activating endogenous TGF‐beta 1, a protein that controls cell growth and division.
The findings may impact therapeutic treatments for burn injuries, which affect more than 6 million people worldwide each year, says lead investigator Praveen Arany, DDS, Ph.D., assistant professor of oral biology in the UB School of Dental Medicine.
“Photobiomodulation therapy has been effectively used in supportive cancer care, age-related macular degeneration and Alzheimer’s disease,” says Arany. “A common feature among these ailments is the central role of inflammation.
This work provides evidence for the ability of photobiomodulation-activated TGF-beta 1 in mitigating the inflammation, while promoting tissue regeneration utilizing an elegant, transgenic burn wound model.”
The study measured the effect of photobiomodulation on the closure of third-degree burns over a period of nine days.
The treatment triggered TGF‐beta 1, which stimulated various cell types involved in healing, including fibroblasts (the main connective tissue cells of the body that play an important role in tissue repair) and macrophages (immune cells that lower inflammation, clean cell debris and fight infection).
The researchers also developed a precise burn healing protocol for photobiomodulation treatments to ensure additional thermal injuries are not inadvertently generated by laser use.
The effectiveness of photobiomodulation in treating pain and stimulating healing has been documented in hundreds of clinical trials and thousands of academic papers.
The therapy was recently recommended as a standard treatment for pain relief from cancer-associated oral mucositis (inflammation and lesions in the mouth) by the Multinational Association for Supportive Care in Cancer.
THE NEED TO CARE for a population with chronic wounds is a growing challenge that requires innovative approaches. Two approaches that specifically address the identified patho- physiological processes involved in wound healing are hyper- baric oxygen (HBO) therapy and light therapy. HBO therapy is currently the standard of care for ischemic, hypoxic, infected, and otherwise slowly healing, problem wounds.
We believe that the use of NASA light-emitting diodes (LED) for light therapy alone, and in conjunction with HBO, will greatly en- hance the natural wound healing process. This will save valu- able time and resources for both patients and health care facili- ties. Furthermore, improved wound healing will reduce the risk of infection for the patient, decrease the amount of costly dress- ings required, and more quickly return the patient to a prein- jury/illness level of activity.
Laser light and HBO have been widely acclaimed to speed wound healing of ischemic, hypoxic, and infected wounds.1 Lasers provide low-energy stimulation of tissues that results in increased cellular activity during wound healing.2,3
These activities include collagen production and angiogene- sis.4 HBO therapy, which is currently standard therapy in the treatment of diabetic ulcers, graft failures, radiation necrosis, and other ischemic wounds, has also been shown to beneficially affect these processes.
However, there are a variety of instances in which a patient who may benefit from HBO is unable or un- willing to be treated in a high-pressure environment. These sit- uations include lack of access to a facility equipped with HBO, claustrophobia, and certain current or chronic medical condi- tions that would make HBO therapy contraindicated. In these instances, light therapy provides an alternative for the patient.
Wound healing has three phases: first, a substrate is laid down, second, cells proliferate, and third, there is remodeling of tissue. The data published so far suggests that laser biostimula- tion produces its primary effect during the cell proliferation phase of the wound healing process. It has been demonstrated that mitochondria are receptive to monochromatic near-infrared light and that laser light likely increases respiratory metabolism of certain cells.2,3,5 Processes such as fibroblast proliferation,
attachment and synthesis of collagen and procollagen, growth factor production (including keratinocyte growth factor [KGF], transforming growth factor [TGF], and platelet-derived growth factor [PDGF]), macrophage stimulation, lymphocyte stimula- tion,6 and greater rate of extracellular matrix production have been reported with laser light treatment.7–14
Animal studies on the enhanced wound healing effect of laser light of low-power density have been performed in toads, mice, rats, guinea pigs, and swine.15,16 Human studies with laser light have demon- strated greater amounts of epithelialization for wound closure and stimulation of skin graft healing.1,9 An excellent review of recent human experience with near-infrared light therapy for wound healing was published by Conlan et al. in 1996.1
Lasers, however, have some inherent characteristics that make their use in a clinical setting problematic, including limi- tations in wavelength capabilities and beam width. The combined wavelengths of the light for optimal wound healing can- not be efficiently produced, the size of wounds that may be treated is limited (due to laser production of a beam of light—a fact inconsistent with treating large areas), heat production from the laser light itself can actually damage tissue, and the pinpoint beam of laser light can damage the eye. NASA developed LEDs to offer an effective alternative to lasers.
These diodes can be configured to produce multiple wavelengths, can be arranged in large, flat arrays (allowing treatment of large wounds), and produce no heat. It is also of importance to note that LED light therapy has been deemed a nonsignificant risk by the FDA; thus, FDA approval for the use of LEDs in humans for light therapy has been obtained.
NASA LEDs stimulate the basic energy processes in the mi- tochondria (energy compartments) of each cell, particularly when near-infrared light is used to activate the wavelength sen- sitive constituents inside (chromophores, cytochrome systems). Optimal light wavelengths (proven in prior studies of laser and LED light)2,3,8,11–14,17,18 to speed wound healing include 680, 730, and 880 nm. These wavelengths can be produced accu- rately by NASA LEDs, which have a bandwidth of 25 nm.
The depth of near-infrared light penetration into human tissue has been measured spectroscopically.2,3,19 Spectra taken from the wrist flexor muscles in the forearm and muscles in the calf of the leg demonstrate that most of the photons at wavelengths of 630–800 nm travel approximately 23 cm through the skin sur- face (light input) and muscle, exiting at the photon detector.
Data collection and cataloging to elucidate the absorption coef- ficients of the various human tissues are currently underway by the principle investigator.
. . . . . .
LED WOUND HEALING IN HUMAN SUBJECTS
Clinical LED wound healing studies have been reported pre- viously;11–13 additional data on human trials are summarized below.
Military Special Operations are characterized by lightly equipped, highly mobile troops entering situations requiring optimal physical conditioning at all times. Wounds are an obvi- ous physical risk during combat operations. Any simple and lightweight equipment that promotes wound healing and mus- culoskeletal rehabilitation and conditioning has potential merit.
An LED array with three wavelengths combined in a single unit (670, 720, and 880 nm) was delivered to Naval Special Warfare Group–2 (SEALS) in Norfolk, Virginia. Treatment was with 4 J/cm2. A data collection system has been implemented for musculoskeletaltraining injuries treated with LEDs. Data collection instruments now include injury diagnosis, day from injury, range of motion measured with goniometer, pain intensity scales reported on scale 1–10, girth-circumferential measure-
ments in centimeters, percent changes over time in all of the aforementioned parameters, and number of LED-treatments re- quired for the subject to be fit-for-full-duty (FFD). These in- juries were sustained 1 month to 1 year prior to LED treatment and had been chronic and unimproving in nature. See summary of data in Figure 11.
In collaboration with U.S. Navy Submarine Squadron ELEVEN, data have also been received from the USS Salt Lake City (submarine SSN 716 of the U.S. Naval Pacific Fleet). Sub- marine atmospheres are low in oxygen and high in carbon dioxide, which compounds the absence of crew exposure to sunlight, making wound healing slower than on the surface.
Reports indicate a 50% faster healing of lacerations in crew members treated with a LED array with three wavelengths combined in a single unit (670, 720, 880 nm) compared to untreated control healing (7 days compared to approximately 14 days, respectively). Complete analysis of data is still underway. Receipt of control data from submarines without LED arrays on board continues, and another submarine recently deployed from
U.S. Naval Station–San Diego on a 6-month mission is equipped with a LED snap-light array on board.
In addition, we have recently begun using NASA LEDs to promote healing of acute oral lesions in pediatric leukemia pa- tients. As a final life-saving effort, leukemia patients are given healthy bone marrow from an HLA-matched donor. Prior to the transplant, the patient is given a lethal dose of chemotherapy in order to destroy his or her own cancerous bone marrow. Be- cause many chemotherapeutic drugs, as well as radiation ther- apy, kill all rapidly dividing cells indiscriminately, the mucosal linings of the gastrointestinaltract are often damaged during the treatment.
As a result of these gastrointestinal effects, greater than one-third of patients treated with cytotoxic drugs develop ulcers in their mouths (oral mucositis) and/or suffer from nau- sea and diarrhea. Oral mucositis, which causes severe pain, bleeding, an increased risk for infection, and compromised abil- ity to chew and swallow, is a significant risk for this population. Current treatment for mucositis addresses pain management and infection prevention.
The use of oral agents to promote cleansing, debridement, and comfort are recommended, and prophylactic oral antiviral and antifungal agents have been used to minimize infections. Because lasers have been shown to speed healing of oral mucositis,25,26 we have recently expanded the wound-healing abilities of LED light therapy to include these oral lesions.
A 4 J/cm2, 50 mW/cm2 dose of 670-nm light from LEDs was applied daily to the outside of each patient’s left cheek begin- ning on the day of bone marrow transplantation. The status of their oral mucosa, mouth, and throat pain was assessed three times a week by two calibrated dental clinicians.
Each side of the mouth was scored using the Schubert Oral Mucositis Index (OMI), the mucosa were photographed, and mouth and throat pain were assessed using a 1–10 Visual Analog scale.27 We have now completed treatment to half of our intended patient population and have noticed some very encouraging trends, but statistical significance will require more patients, as intended in our current study design.
We have assessed left cheek, right cheek, and throat pain in each patient, and have noted that there is no statistical difference in perceived pain on either side of the mouth, consistent with the expected tissue penetration (23 cm) of LED light. Throat pain, however, was consistently higher than mouth pain, and because our light does not extend into this region, we have used this pain as our control. Although mouth and throat pain were initially similar, mouth pain peaked at 86% of throat pain on day 5 after transplant and subsequently fell to only 53% of reported throat pain by day 7 (Table 1, Fig- ures 12 and 13). The greatest difference between throat and mouth pain was reported on day 7, when, surprisingly, oral mu- cosal ulceration is believed to be worst in untreated patients.
Additionally, we are determining extent of ulceration, healing rate in mm2/day, and healing time in days for these patients, and we will compare these values with epidemiological control data. A chart review is also in progress to assess morphine pump use and requirements for intravenous feedings in LED- treated patients compared to controls.
Contact with the FDA’s Richard Felten of the General Surgery Devices Branch has pro- duced an avenue for guidance to final data collection and FDA approval of this technology as the standard of therapy for treat- ment of mucositis. FDA review of our current data and protocol design is ongoing, and has already led to an FDA recommendation for expanding our study to include at least three more aca- demic medical centers, in addition to our own, to be supplied with NASA LED arrays by Quantum Devices, Inc. A multisite trial is being planned through the International Bone Marrow Transplant Registry.
reference link :DOI:10.1089/104454701753342758
More information: Imran Khan et al, Accelerated burn wound healing with photobiomodulation therapy involves activation of endogenous latent TGF-β1, Scientific Reports (2021). DOI: 10.1038/s41598-021-92650-w