Testing the effects of photobiomodulation on angiogenesis in a newly established CAM burn wound model.

Burn wounds are a common challenge for medical professionals. Current burn wound models hold several limitations, including a lack of comparability due to the heterogeneity of wounds and differences in individual wound healing. Hence, there is a need for reproducible in vivo models. In this study, we established a new burn wound model using the chorioallantoic membrane assay (CAM) as a surrogate model for animal experiments. The new experimental setup was tested by investigating the effects of the auspicious biophysical therapy, photobiomodulation (PBM), on the wound healing of an induced CAM burn wound with a metal stamp. PBM has been shown to positively influence wound healing through vascular proliferative effects and the increased secretion of chemotactic substances. The easily accessible burn wounds can be treated with various therapies. The model enables the analysis of ingrowing blood vessels (angiogenesis) and diameter and area of the wounds. The established model was used to test the effects of PBM on burn wound healing. PBM promoted angiogenesis in burn wounds on day 4 (p = 0.005). Furthermore, there was a not significant trend toward a higher number of vessels for day 6 (p = 0.065) in the irradiated group. Changes in diameter (p = 0.129) and the burn area (p = 0.131) were not significant. Our results suggest that CAM can be a suitable model for studying burn wounds. The novel experimental design enables reproducible and comparable studies on burn wound treatment.

Effects of photobiomodulation with blue Light Emitting Diode (LED) on the healing of skin burns.

The management of skin burns is still challenging. Among the therapeutic methods used, there are topical treatments with pharmacological and herbal agents, low-intensity therapeutic ultrasound, use of biomaterials, reconstructive techniques and photobiomodulation therapy. The aim of this study was to evaluate the effects of photobiomodulation with blue Light Emitting Diode (LED) on burn healing. Fifty Wistar rats were divided into control (CTRL) (n = 25) and blue LED (LED) (n = 25), with subgroups (n = 5) for each time of euthanasia (7, 14, 21, 28 and 32 days). Treated animals were daily irradiated (470 nm, 1W, 0.44 W/cm2, 50 J/cm2). Clinical evaluations were performed and the Wound Retraction Index (WRI) was determined. Histological sections were submitted to hematoxylin-eosin, toluidine blue and the immunohistochemical technique, with anti-α-SMA and anti-TGF-ß1 antibodies. All data were directly collected by previously calibrated evaluators in a blind manner. The values were included in a statistical program. For all statistical tests used, 5% significance level (p < 0.05) was considered. No statistically significant differences in WRI between groups were observed (p > 0.05). Re-epithelialization was higher using LED at 7 and 14 days (p < 0.05) and greater amount of inflammatory cells was observed at 7 days (p = 0.01). With LED at 21 and 32 days, greater number of mast cells were observed (p < 0.05), as well as smaller number of myofibroblasts at 14, 21, 28 and 32 days (p < 0.05) and lower percentage of TGF-ß1 positive cells in the conjunctiva at 7, 14 and 21 days (p < 0.05). Negative correlations were observed in LED between the percentage of TGF-ß1 in the epithelium and the mean number of inflammatory cells and number of myofibroblasts (p < 0.05). The results suggest that, depending on the period, blue LED can modulate the healing processes of third-degree skin burns, such as re-epithelialization, inflammatory response, mast cell concentration, myofibroblast differentiation and TGF-ß1 immunoexpression. Despite these effects, this therapy does not seem to have significant influence on the retraction of these wounds. Future studies, using different protocols, should be carried out to expand the knowledge about the photobiomodulatory mechanisms of this type of light in the healing process.

The efficacy of low-level laser therapy for the healing of second-degree burn wounds on lower limbs of glucocorticoid-dependent patients.

This study was designed to investigate the effect of 630 ~ 650-nm red light on treating second-degree burns on lower limbs of glucocorticoid-dependent patients. Sixty-two glucocorticoid-dependent patients with the second-degree burns on lower limbs were divided into the control group (n = 25) and the observation group (n = 37) according to the treatment sequence and the patients' willingness. The patients in both groups were conventionally treated with 1% sulfadiazine silver cream dressing, with the only difference that the observation group received an additional 630-650-nm red light irradiation for 20 min before dressing. Each group was observed for 21 days, and observation ended if the wound healing was terminated. The wound healing rates, wound secretions, marginal response, and pain/itching levels were monitored and assessed. Compared with the control group, the observation group showed higher wound healing rate, fewer wound secretions, and more relief in marginal response. Clinical observation showed that 630-650-nm red light could effectively reduce wound purulent drainage/discharge, relieve the marginal response as well as pain, and promote wound healing.

Dual-NIR wavelength (pulsed 810 nm and superpulsed 904 nm lasers) photobiomodulation therapy synergistically augments full-thickness burn wound healing: A non-invasive approach.

A thermal burn is the most frequent, distressing form of trauma. Globally, there is a critical necessity to explore novel therapeutic strategies for burn wound care. Combination therapy has marked therapeutic efficacy in positively regulating various phases of wound repair. Photobiomodulation (PBM) is a biophysical, non-thermal therapeutic healing modality to treat chronic non-healing wounds. It hypothesized that PBM using combined NIR wavelengths may absorb through different cellular photoacceptors with varying degrees of tissue penetration, which can potentially regulate the pace of healing. Therefore, the current study investigates the efficacy of dual-NIR wavelength treatment employing pulsed 810 nm and superpulsed 904 nm lasers PBM on transdermal burn repair in rats and unveils the associated molecular mechanistic insights. Rats were randomized into five groups: uninjured skin, burn control (sham-exposed), standalone treatment with pulsed 810 nm laser, superpulsed 904 nm laser, and dual combination groups. The present findings revealed that PBM with dual-NIR wavelength synergistically augmented burn wound healing compared to control and standalone treatments. The efficacy of combined treatment was exhibited by significantly enhanced wound area contraction (α-smooth muscle actin), proliferation (PCNA, cytokeratin-14, TGF-ß2), angiogenesis (HIF-1α, CD31), ECM accumulation/ organization (collagen type 3, fibronectin), dermal hydration (AQP3), calcium homeostasis (TRPV3, calmodulin), and bioenergetics activation (CCO, AMPK-α, ATP). Collectively, PBM with dual-NIR wavelength (pulsed/ superpulsed-mode) treatment accelerates full-thickness burn wound healing, which could be used as a non-invasive translational approach in clinical significance in conjunction with existing burn wound care management.

Effect of combination of photobiomodulation 904 nm superpulsed laser therapy and Hippophae rhamnoides L. on third-degree burn wound healing.

BACKGROUND: Burn is a traumatic injury and aesthetic scarless repair poses a great challenge in area of cosmetic dermatology. Focus on multimode therapeutic strategies to promote healing of burns by regulating various stages of healing is warranted. Photobiomodulation therapy (PBMT), a non-invasive modality grabs the attention to repair impaired wounds. Seabuckthorn extract (SBTL-ALE) is known to possess antioxidant, anti-inflammation, and tissue-repair abilities. Current study aims to assess the effect of combination treatment of PBM 904 nm superpulsed laser and SBTL-ALE (2.5%) on repair of third-degree burn in rats. METHODS: Rats were randomized into five groups: uninjured, control, SBTL-ALE, 904 nm PBMT, and combination. A transdermal burn wound was induced on the dorsal side of rats of all groups except the uninjured group and respective treatment was applied for 7 days postwounding. RESULTS: Dual treatment increased wound area contraction compared to control and either treatment alone. Immunohistochemical analyses exhibited increased angiogenesis, dermal hydration, collagen synthesis, and maintained redox homeostasis as evidenced by enhanced expression (p < 0.05) of CD31, aquaporin3, collagen type 3, Nrf2, and HO1 in combination group compared with control. Conversely, pro-inflammatory and oxidative stress markers exhibited reduced (p < 0.05) TNF-α, IL-6, IL-1ß, NOS-2, ROS levels, and increased catalase activity in combined treatment. Furthermore, energy metabolizing enzymes viz. citrate synthase, CCO, and ATP contents were substantially (p < 0.05) increased, and LDH activity was reduced in the combination group. CONCLUSIONS: Dual treatment (PBMT + SBTL-ALE) prominently accelerates third-degree burn wound healing in rats, which could pave the path for multimode therapeutic strategies for the management of burns and dermal cosmetic care.

Effects of photobiomodulation therapy with red LED on inflammatory cells during the healing of skin burns.

The aim of this study was to evaluate the effects of red light emitting diode (LED) photobiomodulation therapy protocol on inflammatory cells during the healing of third-degree skin burns. Fifty Wistar rats were randomly divided into control group (CTRL) (n = 25) and red group (RED) (n = 25), with subgroups (n = 5) for each time of euthanasia (7, 14, 21, 28, and 32 days). Treatment animals were daily irradiated (630 nm ± 10 nm, 300 mW, 9 J/cm2 per point, 30 s, continuous emission mode) at the 4 angles of the wound (total: 36 J/cm2). After specimen removal, histological sections were stained with hematoxylin and eosin for quantitative analysis of the inflammatory infiltrate (neutrophils and lymphocytes) under light microscopy. Greater number of inflammatory cells was observed in irradiated groups when compared to CTRL at 7, 14, 21, and 28 days, but with statistically significant difference only at 14 days (p = 0.02). At 32 days, higher inflammatory cell value was observed in CTRL when compared to RED, but with no statistically significant difference (p = 0.91). The results suggest that red LED, according to the protocol used, modulates the number of inflammatory cells in the early stages of the healing of third-degree skin burns. Nevertheless, this low-intensity light therapy may not, be efficient in reducing the number of neutrophils and lymphocytes in advanced stages of the repair process of skin burns. Further studies with other therapy protocols are needed to assess the effects of this type of light on the inflammatory response of skin burns.

Effects of laser photobiomodulation on tgf-ß and vegf expression in burn wound: systematic review and meta-analysis in the animal model / Influencia de la fotobiomodulación por láser en la expresión de tgf-ß y vegf en heridas por quemadura: revisión sistemática y meta-análisis en modelo animal

SUMMARY: Laser photobiomodulation (laser PBM) is known to be able to accelerate burn wound healing in the animal model; however little evidence exists on the action of laser PBM on the expression of important proteins in wound healing in the animal model, such as VEGF and TGF-ß1. The aim of this study was to carry out a systematic review in order to analyse the effect of laser PBM on VEGF and TGF-ß expression during burn wound repair in the animal model. A systematic review was carried out of the EMBASE, PubMed/ MEDLINE and LILACS databases. The studies included were preclinical studies that analysed the action of laser PBM on the expression of VEGF and TGF-ß (1, 2, 3) during burn wound repair in the animal model. The SYRCLE risk of bias tool was used. Random effect models were used to estimate the combined effect. Increased VEGF expression was observed with the use of laser PBM at 4.93 J/cm2 per point in the first two weeks after induction of the burn wound, with greater size of effect in the second week (SDM = 5.72; 95% CI: 3.14 to 8.31, I2 = 0 %; very low certainty of evidence). We also observed that the effect of laser PBM on TGF-ß1 expression was greater than in the control in the first week (SDM = -0.45; 95% CI: -1.91 to 1.02, I2 = 51 %; very low certainty of evidence), but diminished in the third week after induction of the lesion (SDM = -2.50; 95% CI: 3.98 to -1.01, I2 = 0 %; very low certainty of evidence). Laser PBM has an effect on TGF-ß1 and VEGF expression, promoting burn wound repair in the animal model.

RESUMEN: Es sabido que la fotobiomodulación por láser (FBM láser) puede acelerar el proceso de curación de heridas por quemadura en modelo animal, sin embargo aún se carece de mayor evidencia sobre la acción de la FBM láser en la expresión de proteínas importantes en el proceso de curación de heridas en modelo animal, como VEGF y TGF-ß1. Así, el objetivo de este estudio fue realizar una revisión sistemática a fin de analizar el efecto de la FBM láser sobre la expresión de VEGF, TGF-ß durante el proceso de reparación de heridas por quemadura en modelo animal. Se realizó una búsqueda sistemática en las bases de datos EMBASE, PubMed/MEDLINE y LILACS. Se incluyeron estudios preclínicos que analizaron la acción de la FBM láser en la expresión de VEGF, TGF-ß (1, 2, 3) durante el proceso de reparación de heridas por quemadura en modelo animal. Se utilizó la herramienta de riesgo de sesgo SYRCLE. Se utilizaron modelos de efectos aleatorios para estimar el efecto combinado. Observamos aumento de la expresión de VEGF con el uso de FBM láser 4.93 J/cm2 por punto, en las dos primeras semanas tras inducción de la herida por quemadura, con mayor tamaño de efecto en la segunda semana (SDM = 5,72; IC del 95%: 3,14 a 8,31, I2 = 0 %; certeza de la evidencia muy baja). También se observó el efecto de la FBM láser en la expresión del TGF- ß1 que fue mayor que el control en la primera semana (SDM = - 0,45; IC del 95%: -1,91 a 1,02, I2 = 51 %; certeza de la evidencia muy baja), disminuyendo en la tercera semana tras inducción de la lesión (SDM = -2,50; IC del 95%: -3,98 a -1,01; I2 = 0 %; certeza de la evidencia baja). La TFB por láser ejerce influencia en la expresión de TGF-ß1 y VEGF favoreciendo el proceso de reparación de heridas por quemadura en modelo animal.

Effects of Photobiomodulation and Split-Thickness Skin Grafting in the Prognosis of Wound Healing in Children with Deep Burn Ulcers.

Background: Split-thickness skin grafting (STSG) is a standard therapeutic technique in patients with extensive and deep ulcers. Hospitalization and surgery can result in complications, especially in children. Photobiomodulation (PBM) has been applied in a variety of conditions such as healing of surgical, venous, pressure, and diabetic wounds, but no clinical trial using this method for healing of burn ulcers in children was found on searching the literature. The aim of the study was to evaluate the effect of PBM on the outcome of burn ulcers in children. Materials and methods: Informed consent and protocols were reviewed according to Shahid Beheshti University of Medical Sciences' Medical Ethics Board (IR.SBMU.REC.1394.363) and the Iranian Registry of Clinical Trials (IRCT2016011726069N1). Forty children with deep burn ulcers, who were candidates for STSG, were divided into PBM and STSG groups. A 650-nm laser (power 150 mW, spot size 0.6 cm2, time 10 sec, and energy point 1.5 J) was used for irradiation over the burn area every other day until complete healing in the PBM group. STSG was performed in the STSG group. All other therapeutic care protocols were identical. Results: Thirty-nine children completed the study. The mean ulcer size in the two groups was similar before treatment (PBM = 60.72 cm2 ± 13.8 and STSG = 63.74 ± 7.6). In the PBM group, all wounds healed within 10-12 sessions. Analysis of the burn area was performed 1, 3, and 6 months after injury. There was a significant difference (t test) in the burn area after 6 months in the PBM group compared with the STSG group (t test; p > 0.001). Conclusions: This is the first study to compare PBM and STSG in burn ulcers in children. Results indicated that PBM was an effective alternative to STSG, significantly decreasing the rate of scar and hypertrophic scar formation. Potential mechanisms of PBM that may be involved in burn tissue repair are discussed.

Photobiomodulation Therapy in Burn Wound Healing: Systematic Review and Meta-Analysis of Preclinical Studies.

Background and objective: To determine the effectiveness of photobiomodulation therapy (PBMT) in the burn wound healing compared with the control or with the use of antibiotics, in animal models. Materials and methods: A systematic search was conducted in EMBASE, MEDLINE, and LILACS databases. Preclinical studies were included that analyzed the effectiveness of PBMT in the burn wound healing, which assessed wound contraction, angiogenesis, proliferation of fibroblasts, and collagen deposition. SYRCLE risk of bias tool was used. Random effects models were used to estimate the pooled effect. Results: Thirty-eight studies were included. PBMT favored wound contraction (mean difference = -11.47, 95% confidence interval -19.87 to -3.08, I2 = 0%; moderate certainty of evidence). PBMT also favored angiogenesis at doses between 11 and 20 J/cm2, and increased the collagenization rate. Conclusions: In animal models, PBMT favored wound contraction, angiogenesis, and collagen deposition in second- and third-degree burn wounds.

Accelerated burn wound healing with photobiomodulation therapy involves activation of endogenous latent TGF-ß1.

The severity of tissue injury in burn wounds from associated inflammatory and immune sequelae presents a significant clinical management challenge. Among various biophysical wound management approaches, low dose biophotonics treatments, termed Photobiomodulation (PBM) therapy, has gained recent attention. One of the PBM molecular mechanisms of PBM treatments involves photoactivation of latent TGF-ß1 that is capable of promoting tissue healing and regeneration. This work examined the efficacy of PBM treatments in a full-thickness burn wound healing in C57BL/6 mice. We first optimized the PBM protocol by monitoring tissue surface temperature and histology. We noted this dynamic irradiance surface temperature-monitored PBM protocol improved burn wound healing in mice with elevated TGF-ß signaling (phospho-Smad2) and reduced inflammation-associated gene expression. Next, we investigated the roles of individual cell types involved in burn wound healing following PBM treatments and noted discrete effects on epithelieum, fibroblasts, and macrophage functions. These responses appear to be mediated via both TGF-ß dependent and independent signaling pathways. Finally, to investigate specific contributions of TGF-ß1 signaling in these PBM-burn wound healing, we utilized a chimeric TGF-ß1/ß3 knock-in (TGF-ß1Lß3/Lß3) mice. PBM treatments failed to activate the chimeric TGF-ß1Lß3/Lß3 complex and failed to improve burn wound healing in these mice. These results suggest activation of endogenous latent TGF-ß1 following PBM treatments plays a key role in burn wound healing. These mechanistic insights can improve the safety and efficacy of clinical translation of PBM treatments for tissue healing and regeneration.

Role of 904 nm superpulsed laser-mediated photobiomodulation on nitroxidative stress and redox homeostasis in burn wound healing.

BACKGROUND: Burn wound healing is delayed due to several critical factors such as sustained inflammation, vascular disorder, neuropathy, enhanced proteolysis, infection, and oxidative stress. Burn wounds have limited oxygen supply owing to compromised blood circulation. Hypoxic burn milieu leads to free radicals overproduction incurring oxidative injury, which impedes repair process causing damage to cell membranes, proteins, lipids, and DNA. Photobiomodulation (PBM) with 904 nm superpulsed laser had shown potent healing efficacy via attenuating inflammation while enhancing proliferation, angiogenesis, collagen accumulation, and bioenergetic activation in burn wounds. METHODS: This study investigated the effects of 904 nm superpulsed laser at 0.4 mW/cm2 average power density, 0.2 J/cm2 total energy density, 100 Hz frequency, and 200 ns pulse width for 10 min daily for seven days postburn injury on nitroxidative stress, endogenous antioxidants status, and redox homeostasis. RESULTS: Photobiomodulation treatment significantly decreased reactive oxygen species, nitric oxide, and lipid peroxidation levels as compared to non-irradiated control. Further, protective action of PBM against protein oxidative damage was evidenced by reduced protein carbonylation and advanced oxidation protein product levels along with significantly enhanced endogenous antioxidants levels of SOD, catalase, GPx, GST, reduced glutathione, and thiol (T-SH, Np-SH, P-SH). Biochemical changes aid in reduction of oxidative stress and maintenance of redox homeostasis, which further well corroborated by significantly up-regulated protein expression of Nrf 2, hemeoxygenase (HO-1), and thioredoxin reductase 2 (Txnrd2). CONCLUSION: Photobiomodulation with 904 nm superpulsed laser led to reduction of nitroxidative stress, induction of endogenous antioxidants, and maintenance of redox homeostasis that could play a vital role in augmentation of burn wound healing.

Photobiomodulation of red and green lights in the repair process of third-degree skin burns.

The aim of this study was to evaluate the photobiomodulation of red and green lights in the repair process of third-degree skin burns in rats through clinicopathological and immunohistochemical parameters. Sixty male Wistar rats were divided into three groups: control (CTRL) (n = 20), red LED (RED) (n = 20), and green LED (GREEN) (n = 20), with subgroups (n = 5) for each time of euthanasia (7, 14, 21, and 28 days). Daily applications in RED (λ630 ± 10 nm, 300 mW) and GREEN groups (λ520 ± 30 nm, 180 mW) were performed at four points of the wound (total 36 J/cm2 in RED and 240 J/cm2 in GREEN). After euthanasia, the wound retraction index (WRI) was evaluated. In histological sections, the re-epithelialization degree, the angiogenic index (AI), and the amount of myofibroblasts in wounds were analyzed. At 14 and 21 days, the RED group induced higher re-epithelialization and WRI compared to CTRL (p > 0.05) and GREEN groups (p < 0.05). At 7 and 14 days, greater AI were observed in the GREEN group, with significant difference in relation to CTRL group at 7 days (p < 0.05). At 21 and 28 days, a trend was observed for greater amount of myofibroblasts in the GREEN group, with significant difference in relation to CTRL group at 21 days (p < 0.05). The results suggest greater potential of the green light to stimulate angiogenesis in the initial periods and myofibroblastic differentiation in the final periods of the repair of third-degree skin burns. Red light may stimulate further re-epithelialization and wound retraction, especially in advanced repair phases.

Low dose radiation attenuates inflammation and promotes wound healing in a mouse burn model.

BACKGROUND: Burn injuries are devastating traumas that functionally affect a variety of organ systems. As intensive inflammatory responses induced by burns can lead to multiple organ failures and impaired skin regeneration increases risk of infectious complex, multimodal therapeutic approaches are needed. OBJECTIVES: To investigate the role of low dose radiation (LDR) treatment for regulation of excessive inflammation and wound healing after burn injury. METHODS: Mouse burn model was established by generating third-degree burn injury in dorsal skin and local LDR less than 100 mGy was delivered to the mice. After 3 or 12 days after burn injury, systemic inflammation in liver, lung, spleen, and kidney and skin wound healing were assessed. For investigation of molecular mechanisms, HaCaT keratinocytes were administrated with serum from mice with burn injury and alteration of viability and cornification biomarkers are assessed. RESULTS: In a mouse burn model, expression of proinflammatory cytokines, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α, were downregulated by LDR in major organs and wound healing capacity was increased by LDR. In skin tissue, we observed the alleviation of reactive oxygen species generation and increased antioxidant gene expression by LDR. In addition, we found that treatment of serum from mice with burn injury and LDR increased proliferation and cornification in HaCaT cells through activation of focal adhesion kinase signaling pathway. CONCLUSION: LDR could reduce proinflammatory signaling pathway and increase skin wound healing after burn injury. Therefore, the present study suggested LDR as a novel treatment for burn injury patients.

Photobiomodulation associated to cellular therapy improve wound healing of experimental full thickness burn wounds in rats.

Adipose derived stromal vascular fraction (SVF) is a method of cell therapy potentially applicable for treatment of full thickness burns. Here we investigated if the association of photobiomodulation (PBM) with SVF therapy could improve wound healing in experimentally induced full thickness burn wounds in rats compared to the topical agent 2% silver sulfadiazine in a dose-dependent manner. Sixty-six male Wistar rats were divided in 4 groups containing 5 animals each which received the following treatments: 2% sulfadiazine (SD), SVF, SVF plus PBM at 30 mW (SVFL30), and SVF plus PBM at 100 mW (SVFL100). Two donor animals were used for each experimental series with 3, 7 and 30 days. Digital photography, microscopic analysis with Hematoxilin and Eosin (H&E), quantification of collagen type I by picrosirius red staining analysis and wound contraction evaluation were performed in order to quantify the results. At day 3 SVF alone or combined with PBM promoted increased early inflammatory response compared to SD. At day 7 SVFL30 and SVFL100 enhanced inflammatory cells infiltration, angiogenesis and fibroblast content compared to SVF and SD groups. At day 30 collagen concentration and wound contraction were higher in SVFL30 when compared to the other groups. In conclusion PBM promotes a synergistic outcome with SVF therapy with a dose dependent effect potentializing wound healing of experimental full thickness burns in rats through amplification of early inflammatory response, enhanced angiogenesis, fibroblast content, accentuated wound contraction and collagen concentration.

Photobiomodulation Therapy for Wound Care: A Potent, Noninvasive, Photoceutical Approach.

GENERAL PURPOSE: To provide background and examine evidence for the therapeutic application of light energy treatments for wound healing. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After completing this continuing education activity, you should be better able to:1. Explain the basics of lasers, light-emitting diodes, and light-tissue interactions as they apply to photobiomodulation therapy.2. Summarize the results of the authors' literature review of the evidence regarding the therapeutic applications of photobiomodulation treatments for wound healing. ABSTRACT: To provide background and examine evidence for the therapeutic applications of light energy treatments for wound healing.A search was performed in PubMed for peer-reviewed scientific articles published in the last 5 years using the search terms "photobiomodulation therapy" and "low-level laser therapy," and these terms combined with "wound," using a "human species" filter. This search yielded 218 articles on photobiomodulation therapy or low-level laser therapy and wounds. Of these, only articles on in vivo wound care using light treatments were specifically included in this review (n = 11).The wound healing effects of low-dose laser treatments were first described over 50 years ago. Various doses ranging from 0.1 to 10 J/cm and wavelengths ranging from 405 to 1,000 nm appear to provide therapeutic benefits for a broad range of chronic wounds. A range of light energy sources from LEDs to lasers have been used and have specific advantages and limitations. There is a lack of consensus on standardized treatment parameters such as wavelengths, dose, and therapeutic outcomes in the reviewed studies, preventing direct comparison and clinical protocol recommendation. An expert opinion based on ongoing research studies and reported literature is offered.Noninvasive, economical, and multipurpose light devices are an attractive tool for wound management. However, there is an urgent need in the wound care community to develop optimal clinical protocols for use based on well-designed, rigorous clinical research studies.

Effect of blue LED on the healing process of third-degree skin burns: clinical and histological evaluation.

The aim of this study was to evaluate the effects of blue light-emitting diode (LED) on the healing process of third-degree skin burns in rats through clinical and histological parameters. Forty male Wistar rats were divided into two groups: control (CTR) (n = 20) and blue LED (BLUE) (n = 20), with subgroups (n = 5) for each time of euthanasia (7, 14, 21, and 28 days). LED (470 nm, 1 W, 12.5 J/cm2 per point, 28 s) was applied at four points of the wound (total, 50 J/cm2). Feed intake was measured every other day. It was observed that there were no statistically significant differences in the Wound Retention Index (WRI) of the BLUE group in relation to CTR group (p > 0.05) at the evaluation times. After 14, 21, and 28 days, it was observed that the animals in the BLUE group consumed more feed than animals in the CTR group (p < 0.05). At 7 days, there was a statistically significant increase in the angiogenic index (AI) in BLUE (median: 6.2) when compared to CTR (median: 2.4) (p = 0.01) and all animals in BLUE had already started re-epithelialization. This study suggests that blue LED, at the dosimetry used, positively contributed in important and initial stages of the healing process of third-degree skin burns.

Effects and parameters of the photobiomodulation in experimental models of third-degree burn: systematic review.

This systematic review was performed to identify the role of photobiomodulation therapy in experimental models of third-degree burns used to induce oxidative stress. EMBASE, PubMed, and CINAHL databases were searched for studies published between January 2003 and January 2018 on the topics of photobiomodulation therapy and third-degree burns. Any study that assessed the effects of photobiomodulation therapy in animal models of third-degree burns was included in the analysis. A total of 17 studies were selected from 1182 original articles targeted on photobiomodulation therapy and third-degree burns. Two independent raters with a structured tool for rating the research quality critically assessed the articles. Although the small number of studies limits the conclusions, the current literature research indicates that photobiomodulation therapy can be an effective short-term approach to accelerate the healing process of third-degree burns, to increase and modulate the inflammatory process, to accelerate the proliferation of fibroblasts, and to enhance the quality of the collagen network. However, differences still exist in the terminology used to describe the parameters and the dose of photobiomodulation therapy.

Therapeutic applications of polarized light: Tissue healing and immunomodulatory effects.

As the population grows and ages, non-pharmaceutical options for the treatment and management of wounds, disease and injury are required to ensure adequate care. Polarized light therapy (PLT) utilizes visible-spectrum polarized light for a number of clinical applications. The advantage of polarized light is that it is able to penetrate the skin to a depth of up to 5 cm, reaching deeper tissues involved in wound healing. PLT has been shown to accelerate the healing process for ulcers, surgical wounds and dermal burns as well as a small number of musculoskeletal injuries. As research into the histological and physiological effects of PLT is largely absent, studies related to other light therapy modalities, largely low-level laser therapy, may pave the way to identify putative mechanisms by which PLT might exert its effects. Changes to cell signalling and secretion of substances required for wound healing have been identified in response to phototherapies. The reviewed literature suggests that PLT may be efficacious in some wound and injury healing contexts, though a gap in the literature exists regarding its mechanisms of action. Future studies should fully explain the therapeutic effects of PLT and the physiological mechanisms underpinning them.

Combination of medicinal honey and 904 nm superpulsed laser-mediated photobiomodulation promotes healing and impedes inflammation, pain in full-thickness burn.

Burn wound is a complex multi-factorial pathophysiology producing excruciating pain and psychological discomfort among patients, which imposes a major burden on the healthcare system. Multi-target therapy focuses on augmented healing by regulating different phases of tissue repair. Recently, photobiomodulation (PBM)-induced wound healing has achieved profound impetus as a non-invasive, drug-free biophysical therapeutic approach. On the other hand, medicinal honey known to possess antibacterial and immunomodulatory properties and is being used as an effective treatment option for infected wounds. The present study aimed to determine whether the combination of medicinal honey and PBM using superpulsed 904 nm laser treatment could additively accelerate full-thickness burn wound repair in rats. Animals were randomly allocated into 4 experimental groups: control (C), PBM superpulsed 904 nm laser treated (PBMT), honey treated (HT) and combined treatment (CT). The dual treatment exhibited an enhanced wound area contraction and hexosamine content as compared to the other groups. Histopathological analysis revealed increased cellular proliferation, extracellular matrix accumulation and decreased inflammation in the CT group. Further, the CT group demonstrated synergistically attenuated inflammation, pain and enhanced cell adhesion, migration as evidenced by significantly reduced protein expression of TNF-α, NF-κB, IL-1ß, COX-2, substance-P receptor and up-regulation of fibronectin, respectively as compared with the other groups. Thus, the findings of present study signify that the combination of medicinal honey and PBMT accelerates the repair process of burn wounds. The study showed that therapeutic efficacy of 904 nm superpulsed laser-mediated PBM augments in the presence of medicinal honey by enhancing cellular proliferation and attenuation of inflammation and pain in burn wound healing.