Investigating the Relevance of Cyclic Adenosine Monophosphate Response Element-Binding Protein to the Wound Healing Process: An In Vivo Study Using Photobiomodulation Treatment.

Monitoring inflammatory cytokines is crucial for assessing healing process and photobiomodulation (PBM) enhances wound healing. Meanwhile, cAMP response element-binding protein (CREB) is a regulator of cellular metabolism and proliferation. This study explored potential links between inflammatory cytokines and the activity of CREB in PBM-treated wounds. A total of 48 seven-week-old male SD rats were divided into four groups (wound location, skin or oral; treatment method, natural healing or PBM treatment). Wounds with a 6 mm diameter round shape were treated five times with an 808 nm laser every other day (total 60 J). The wound area was measured with a caliper and calculated using the elliptical formula. Histological analysis assessed the epidermal regeneration and collagen expression of skin and oral tissue with H&E and Masson's trichrome staining. Pro-inflammatory (TNF-α) and anti-inflammatory (TGF-ß) cytokines were quantified by RT-PCR. The ratio of phosphorylated CREB (p-CREB) to unphosphorylated CREB was identified through Western blot. PBM treatment significantly reduced the size of the wounds on day 3 and day 7, particularly in the skin wound group (p < 0.05 on day 3, p < 0.001 on day 7). The density of collagen expression was significantly higher in the PBM treatment group (in skin wound, p < 0.05 on day 3, p < 0.001 on day 7, and p < 0.05 on day 14; in oral wound, p < 0.01 on day 7). The TGF-ß/TNF-α ratio and the p-CREB/CREB ratio showed a parallel trend during wound healing. Our findings suggested that the CREB has potential as a meaningful marker to track the wound healing process.

Long-Term Outcome of Photobiomodulation Therapy for Refractory Diabetic Wound After Secretory Carcinoma of the Parotid Gland Surgery: A Case Report.

Objective: To evaluate the efficacy and safety of photobiomodulation therapy (PBMT) in the treatment of diabetic patients with refractory wound. Background: Refractory wound is one of the most challenging clinical complications of diabetes mellitus. Studies have shown that PBMT can promote wound healing in many ways. Methods: We reported a 55-year-old male patient with refractory diabetic wound after secretory carcinoma of the parotid gland surgery responding to 810 nm laser. Results: After PBMT, the refractory diabetic wound healed gradually without adverse events. During follow-up 5-years, the healed wound remained stable and showed no signs of recurrence. Conclusions: PBMT can be potentially considered as a therapeutic method in diabetic patients with refractory diabetic wound.

Photobiomodulation Can Prevent Medication-Related Osteonecrosis of the Jaw Formation in Tooth Extraction Site of Rat Model.

Objective: This study aims to explore the preventive potential of photobiomodulation (PBM) in bisphosphonate-related osteonecrosis of the jaw (BRONJ) using a rat model. Methods: An experimental rat model was established, exposing rats to zoledronic acid (ZA), a primary risk factor for BRONJ. An 810 nm diode laser was applied with parameters of 0.33 W/cm2 power density and 10 J/cm2 energy density for 30 sec. PBM was initiated 1 day pre-extraction and continued for 2 weeks. The impact of PBM on wound healing in both soft and hard tissues was evaluated post tooth extraction. Results: ZA exposure hindered wound healing in both soft and hard tissues after tooth extraction. PBM intervention effectively mitigated the adverse effects of ZA, promoting healing processes in both tissue types. This suggests the potential of PBM as a preventive strategy for BRONJ in patients on long-term bisphosphonate treatment. Moreover, PBM exhibited enhanced wound healing in normal rats, indicating its broader applicability beyond BRONJ cases. Conclusions: PBM shows promise in preventing and improving wound healing in BRONJ and normal cases. These findings underscore the significance of optimizing PBM parameters and suggest its potential clinical relevance as a preventive intervention for BRONJ and a promoter of wound healing.

[Clinical application of photobiomodulation in trauma repair and medical aesthetics].

In recent years, with the deepening of researches on the molecular biological mechanisms of photobiomodulation (PBM), PBM has gradually been applied in clinical practice, providing effective treatment methods and approaches for various diseases. Compared with traditional photothermal therapy, PBM has the characteristics of good therapeutic effect, almost no adverse reaction, and simple operation, and its clinical efficacy is becoming increasingly significant. This article provides a detailed explanation on the mechanism of PBM, its application characteristics and development trends in trauma repair and medical aesthetics, in order to provide a theoretical basis for the extensively clinical application of this therapy.

Effects of Photobiomodulation Therapy on the Expression of Hypoxic Inducible Factor, Vascular Endothelial Growth Factor, and Its Specific Receptor: A Randomized Control Trial in Patients with Diabetic Foot Ulcer.

Background: Impaired angiogenesis is a significant factor contributing to delayed healing in diabetic foot ulcers (DFUs) due to inadequate oxygenation. Objective: This study aimed to investigate the impact of photobiomodulation (PBM) using a Ga-As laser on the release of serum hypoxia-inducible factor 1-α (HIF-1α), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2, and nitric oxide (NO) in diabetic patients with DFUs. Materials and methods: In this double-blind RCT, a total of 30 patients with grade II DFUs were enrolled. The patients were randomly divided into two groups: the PBM (n = 15) and the placebo (n = 15). In the PBM group, a Ga-As laser (904 nm, 2 J/cm2, 90 W) was given for 3 days/week for 4 weeks (11 sessions). In the placebo group, the power was turned off. Both groups received similar standard wound care. Before and after interventions, the levels of serum HIF-1α, VEGF, NO, and sVEGFR-2 were measured. In addition, the percentage decrease in the wound surface area (%DWSA) was measured. Results: Following the intervention, the results revealed that the PBM group had significantly lower levels of VEGF than the placebo group (p = 0.005). The %DWSA was significantly higher in the PBM group compared to the placebo group (p = 0.003). Moreover, VEGF showed a significant negative correlation with %DWSA (p < 0.001). Conclusions: The observed decrease in serum levels of VEGF and an increase in %DWSA, compared to the placebo group, suggests that PBM effectively improves angiogenesis. Furthermore, the significant correlation found between VEGF levels and %DWSA emphasizes the importance of evaluating wound surface in patients as a dependable indicator of enhanced wound angiogenesis. Clinical Trial Registration: NCT02452086.

Association of a Skin Dressing Made With the Organic Part of Marine Sponges and Photobiomodulation on the Wound Healing in an Animal Model.

The present study aims to characterize and to evaluate the biological effects of a skin dressing manufactured with the organic part of the Chondrilla caribensis marine sponge (called spongin-like collagen (SC)) associated or not to photobiomodulation (PBM) on the skin wound healing of rats. Skin dressings were manufactured with SC and it was characterized using scanning electron microscopy (SEM) and a tensile assay. In order to evaluate its biological effects, an experimental model of cutaneous wounds was surgically performed. Eighteen rats were randomly distributed into three experimental groups: control group (CG): animals with skin wounds but without any treatment; marine collagen dressing group (DG): animals with skin wounds treated with marine collagen dressing; and the marine collagen dressing + PBM group (DPG): animals with skin wounds treated with marine collagen dressing and PBM. Histopathological, histomorphometric, and immunohistochemical evaluations (qualitative and semiquantitative) of COX2, TGFß, FGF, and VEGF were done. SEM demonstrates that the marine collagen dressing presented pores and interconnected fibers and adequate mechanical strength. Furthermore, in the microscopic analysis, an incomplete reepithelialization and the presence of granulation tissue with inflammatory infiltrate were observed in all experimental groups. In addition, foreign body was identified in the DG and DPG. COX2, TGFß, FGF, and VEGF immunostaining was observed predominantly in the wound area of all experimental groups, with a statistically significant difference for FGF immunostaining score of DPG in relation to CG. The marine collagen dressing presented adequate physical characteristics and its association with PBM presented favorable biological effects to the skin repair process.

Alleviation of radiation combined skin injury in rat model by topical application of ascorbate formulation.

PURPOSE: This research endeavor was undertaken to elucidate the impact of an innovative ascorbate formulation on the regeneration process of full-thickness excision wounds in a rat model exposed to whole-body gamma irradiation, replicating conditions akin to combat or radiation emergency scenarios. MATERIALS AND METHODS: We established a comprehensive rat model by optimizing whole body γ-radiation doses (5-9 Gy) and full-thickness excision wound sizes (1-3 cm2) to mimic radiation combined injury (RCI). The developed RCI model was used to explore the healing potential of ascorbate formulation. The study includes various treatment groups (i.e., sham control, radiation alone, wound alone, radiation + wound, and radiation + wound + formulation). The ascorbate formulation was applied twice daily, with a 12-hour gap between each application, starting 1 hour after the initiation of the wound. The healing potential of the formulation in the RCI context was evaluated over 14 days through hematological, molecular, and histological parameters. RESULTS: The combination of a 5 Gy radiation dose and a 1 cm2 wound was identified as the optimal setting to develop the RCI model for subsequent studies. The formulation was used topically immediately following RCI, and then twice daily until complete healing. Treatment with the ascorbate formulation yielded noteworthy outcomes and led to a substantial reduction (p < .05) in the wound area, accelerated epithelialization periods, and an increased wound contraction rate. The formulation's localized healing response improved organ weights, normalized blood parameters, and enhanced hematopoietic and immune systems. A gene expression study revealed the treatment up-regulated TGF-ß and FGF, and down-regulated PDGF-α, TNF-α, IL-1ß, IL-6, MIP-1α, and MCP-1 (p < .05). Histopathological assessments supported the formulation's effectiveness in restoring cellular architecture and promoting tissue regeneration. CONCLUSION: Topical application of the ascorbate formulation in RCI resulted in a significant improvement in delayed wound healing, leading to accelerated wound closure by mitigating the expression of inflammatory responses.

Exploring the Safety and Efficacy of Organic Light-Emitting Diode in Skin Rejuvenation and Wound Healing.

PURPOSE: Photobiomodulation (PBM), encompassing low-energy laser treatment and light-emitting diode (LED) phototherapy, has demonstrated positive impacts on skin rejuvenation and wound healing. Organic light-emitting diodes (OLEDs) present a promising advancement as wearable light sources for PBM. However, the biological and biochemical substantiation of their skin rejuvenation and wound healing effects remains limited. This study aimed to ascertain the safety and efficacy of OLEDs as a next-generation PBM modality through comprehensive in vitro and in vivo investigations. MATERIALS AND METHODS: Cell viability assays and human ex vivo skin analyses were performed after exposure to OLED and LED irradiation to examine their safety. Subsequent evaluations examined expression levels and wound healing effects in human dermal fibroblasts (HDFs) using quantitative reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and wound healing assays post-irradiation. Additionally, an in vivo study was conducted using a ultra violet (UV)-irradiated animal skin model to explore the impact of OLED exposure on dermal collagen density and wrinkles, employing skin replica and tissue staining techniques. RESULTS: OLED irradiation had no significant morphological effects on human skin tissue, but caused a considerably higher expression of collagen than the control and LED-treated groups. Moreover, OLED irradiation reduced the expression levels of matrix metalloproteinases (MMPs) more effectively than did LED on HDFs. OLED irradiation group in HDFs had significantly higher expression levels of growth factors compared to the control group, but similar to those in the LED irradiation group. In addition, OLED irradiation on photo-aged animal skin model resulted in increased collagen fiber density in the dermis while reducing ultra violet radiation-mediated skin wrinkles and roughness, as shown in the skin replica. CONCLUSION: This study established comparable effectiveness between OLED and LED irradiation in upregulating collagen and growth factor expression levels while downregulating MMP levels in vitro. In the UV-irradiated animal skin model, OLED exposure post UV radiation correlated with reduced skin wrinkles and augmented dermal collagen density. Accelerated wound recovery and demonstrated safety further underscore OLEDs' potential as a future PBM modality alongside LEDs, offering promise in the realms of skin rejuvenation and wound healing.

Advances in far-infrared research: therapeutic mechanisms of disease and application in cancer detection.

Far infrared (FIR) irradiation is commonly used as a convenient, non-contact, non-invasive treatment for diseases such as myocardial ischemia, diabetes, and chronic kidney disease. In this review, we focus on reviewing the potential therapeutic mechanisms of FIR and its cutting-edge applications in cancer detection. Firstly, we searched the relevant literature in the last decade for systematic screening and briefly summarized the biophysical properties of FIR. We then focused on the possible mechanisms of FIR in wound healing, cardiovascular diseases, and other chronic diseases. In addition, we review recent applications of FIR in cancer detection, where Fourier transform infrared spectroscopy and infrared thermography provide additional diagnostic methods for the medical diagnosis of cancer. Finally, we conclude and look into the future development of FIR for disease treatment and cancer detection. As a high-frequency non-ionizing wave, FIR has the advantages of safety, convenience, and low cost. We hope that this review can provide biological information reference and relevant data support for those who are interested in FIR and related high-frequency non-ionizing waves, to promote the further application of FIR in the biomedical field.

Use of adipose derived stem cells accelerates the healing process in third-degree burns.

INTRODUCTION: Burns are defined as a traumatic injury, usually of thermal origin, that affects the epithelial and adjacent tissue and is classified according to the depth reached. Tissue repair involved in this type of injury is often a challenge both due to its severity and the multiplicity of complications. Regenerative medicine has focused on the use of low-level laser photobiomodulation therapy (LLLT) and adipose-derived stem cells (ADSC), especially in the early stages of the process, to promote better healing and shorten repair time. Therefore, aim of this study was to evaluate the action of LLLT (660 nm) and ADSC in the repair process of burned skin tissue and investigate the association of the techniques (LLLT and ADSC). MATERIALS AND METHODS: An in vivo study was carried out using 96 rats (Wister) with a scald burn model at a temperature of 95ºC, exposing the animal's back for 14 s. Animals were randomized into seven groups and three periods, five, 14 and 21 days. The groups included GC: Control group, ADSC-: Group treated with CD49d negative cells, ADSC+ : Group treated with positive CD49d cells, CULT: Group treated with conventional isolation cells, LLLT: Group treated only with LLLT Low Power Laser, ADSC-LLLT: Group treated with CD49d negative cells and LLLT. ADSC+LLLT: Group treated with positive CD49d cells and LLLT. The groups treated with LLLT (660 nm; 5 J/cm2) received irradiation three times a week, on alternate days for five, 14 and 21 days, according to the time of biopsy. ADSC-treated groups received one to three applications of the cells in a total volume of 1000 µL starting soon after the surgical debridement of the burn. Photographic monitoring was carried out at 5, 14 and 21 days after the beginning of the experiment to assess the degree of lesion contraction. Macroscopic, morphometric and histopathological analyzes were performed. RESULTS: We showed significant re-epithelialization as well as an improvement in the healing process in the ADSC+, LLLT and ADSC+LLLT groups. We observed effects in the reduction of the inflammatory phase, increase in angiogenesis, decrease in oedema, greater collagen deposition, and better organization of the extracellular matrix compared to the other treatments. Moreover, the immunomagnetic separation of ADSC cells through the expression of the CD49d protein proved to be a useful means to obtain a more homogeneous population of cells with a role in tissue regeneration compared to the ADSC- and CULT groups. CONCLUSION: In conclusion, the association of ADSC+ with LLLT was effective in accelerating the burn repair process, stimulating cell proliferation and formation of more normal skin tissue.

The Impact of Blue Light Irradiation on Keratinocytes in Vitro.

BACKGROUND: This study examined the effects of irradiation with blue light on HaCaT keratinocytes. As irradiation with blue light is known to be antimicrobial, it offers a promising alternative therapy for contaminated wounds. There is evidence that red light promotes wound healing, but the potential benefits of irradiation with blue light have not yet been adequately investigated. METHODS: The rate of wound closure in sterile and contaminated cells was measured using an in vitro scratch assay wound-healing model. Additionally, cell viability after treatment was determined using a Sulforhodamine B (SRB) assay. RESULTS: In both the sterile and contaminated groups, treated cells showed delayed wound closure when compared with cells not irradiated with blue light. Additionally, treatment with blue light resulted in poorer viability in the treatment groups. CONCLUSION: Although irradiation with blue light may offer a promising alternative therapy for reducing bacterial colonization, our data indicate that re-epithelization may be negatively influenced by blue light. Further research is needed to clarify possible wound healing applications.

Acoustic evaluation of photobiomodulation effect on in vitro human blood samples.

Although positive photobiomodulation response on wound healing, tissue repair, and therapeutic treatment has been widely reported, additional works are still needed to understand its effects on human blood. This research carried out acoustic measurements using A-scan (GAMPT) ultrasonic techniques to elucidate the photobiomodulation effects on in vitro human blood samples as therapeutic treatment measures. The human blood samples were irradiated using a 532-nm laser with different output laser powers (60 and 80 mW) at various exposure times. The ultrasonic velocity measured in the human blood samples after laser irradiation showed significant changes, most of which were within the acceptance limit for soft tissues (1570 [Formula: see text] 30 m/s). Abnormal cells (echinocyte and crenation) were observed due to excessive exposure during laser treatment.

Concise review of non-invasive physical plasma as a promising treatment option for radiation injuries of the skin.

Radiation injury has a complex pathophysiology and can result in long-term impediment of the dermal barrier function. Historically, its treatment has been no different to that of thermal burns and it is not always possible to prevent an unpredictable and uncontrolled extension of the radiation-induced reactions. Non-invasive physical plasma (NIPP), a highly energised gas encompassing a combination of various reactive species, positively affects the key players involved in wound healing and proves to be a promising treatment option for chronic wounds and inflammatory skin disorders. Recent clinical evidence also suggests preliminary efficacy in radiation injury following therapeutic irradiation as a part of cancer therapy. Further research is warranted to also investigate the clinical value of NIPP in the context of unplanned or accidental radiation exposure, either as a topical treatment or possibly as an intraoperative procedure, to potentially improve the dermatological outcome and reduce symptoms in radiation victims.

Photomodulative effects of low-level laser therapy on tracheal fenestration developed in in vivo model.

The effect of low-level laser therapy (LLLT) on variable mucosal lesions in the upper aerodigestive tract has been reported. However, the effect of LLLT on tracheostomy sites or tracheal fenestration is rarely reported. In this study, we evaluate the effect of LLLT performed using 635 nm laser light based on a cylindrical diffuser and an animal model with tracheal fenestration. An animal model of tracheal fenestration is developed by suturing the trachea to the skin after performing a vertical tracheostomy from the second to the fifth tracheal ring of Wistar rats (male, body weight 200-250 g). LLLT (spot size: 2 cm2) is conducted once daily for five days using a handheld cylindrical device. Twenty-four rats are randomly assigned to a no-therapy or LLLT group with an energy density of 20 J/cm2. Histological analysis is performed at 7 and 14 days after tracheal fenestration. Irradiation at the tracheal fenestration site with an energy density of 20 J/cm2 improves the wound healing, as shown at 2 weeks after tracheostomy. Histological analysis shows significantly decreased acute inflammation and granulation tissue, as well as better cartilage regeneration and less tracheal wall thickening. Therefore, LLLT demonstrates therapeutic potential for preventing tracheal stenosis and granuloma after tracheostomy.

The associations between diode laser (810 nm) therapy and chronic wound healing and pain relief: Light into the chronic wound patient's life.

Chronic wounds have become one of the major issues in medicine today, the treatments for which include dressing changes, negative pressure wound therapy, hyperbaric oxygen, light irradiation, surgery and so forth. Nevertheless, the application of diode lasers in chronic wounds has rarely been reported. This retrospective cohort study aimed to evaluate the therapeutic effect of diode laser (810 nm) irradiation on chronic wounds. Eighty-nine patients were enrolled in the study. The control group (41 patients) received traditional dressing change therapy, while the diode laser treatment group (48 patients) were patients received additional treatment with diode laser (810 nm) irradiation for 10 min at each dressing change. Wound healing time was compared between two groups, while the pain relief index was creatively introduced to evaluate the effect of relieving wound pain, which was calculated by the difference in pain scores between the first and last dressing changes divided by the number of treatment days. The wound healing time of the diode laser treatment group was 22.71 ± 8.99 days, which was significantly shorter than that of the control group (37.44 ± 23.42 days). The pain relief index of the diode laser treatment group was 0.081 ± 0.055, which was significantly increased compared with that of the control group (0.057 ± 0.033). Our findings suggest that diode laser irradiation has the potential to promote healing in chronic wounds and relieve wound pain.

Mitochondria and light: An overview of the pathways triggered in skin and retina with incident infrared radiation.

Slightly more than half of the solar radiation that passes through the atmosphere and reaches the Earth's surface is infrared. Over the past few years, many papers have been published on the possible positive effects of receiving this part of the electromagnetic spectrum. In this article we analyse the role of mitochondria in the supposed effects of infrared light based on the published literature. It is claimed that ATP synthesis is stimulated, which has a positive effect on the skin by increasing fibroblast proliferation, anchorage and production of collagen fibres, procollagen, and various cytokines responsible for the wound healing process, such as keratinocyte growth factor. Currently there are infrared light emitting equipment whose manufacturers and the centres where this service or treatment is offered claim that they are used for skin rejuvenation among other positive effects. Based on the literature review, it is necessary to deepen the scientific study of the mechanism of absorption of infrared radiation through the skin to better understand its possible positive effects, the risks of overexposure and to improve consumer health protection.

The effects of low power laser light at 661 nm on wound healing in a scratch assay fibroblast model.

Wound treatment, especially for chronic and infected wounds, has been a permanent socio-economical challenge. This study aimed to investigate the ability of red light at 661 nm to accelerate wound healing an in vitro wound model using 3T3 fibroblasts. The purpose is further specified in clarifying the mechanisms of wound closure by means of intracellular ROS production, proliferation and migration of cells, and cellular orientation. Illumination effects of red light from a diode laser (661 nm) at different doses on 3T3 cell viability was assessed via MTT assay and tested in a scratch wound model. Wound closure rates were calculated by image analysis at 0, 24, and 48 h after laser treatment. ROS production was monitored and quantified immediately and 24 h after the treatment by fluorescence microscopy. Cellular orientation was quantified by image analysis. No phototoxic energy doses used and increased cell viability in most of the groups. Scratch assay revealed an energy interval of 3 - 4.5 J/cm2 that promote higher wound healing rate 24 h post treatment. An increase in ROS production was also observed 24 h post irradiation higher in the group with the highest wound healing rate. Also, cellular orientation toward the margin of the wound was observed and quantified after irradiation. Low power laser light at 661 nm activated both the migration and proliferation in the in vitro model used, providing evidence that it could also accelerate wound healing in vivo. Also, ROS production and cellular orientation seem to play an important role in wound healing process.

Postoperative complications and oncologic outcomes after multimodal therapy of localized high risk soft tissue sarcoma.

BACKGROUND: Standard therapy for localized high-risk soft tissue sarcoma includes surgical resection and neoadjuvant or adjuvant radiation therapy (± chemotherapy and locoregional hyperthermia). No difference in oncologic outcomes for patients treated with neoadjuvant and adjuvant radiation therapy was reported, whereas side effect profiles differ. The aim of this analysis was to analyse oncologic outcomes and postoperative complications in patients treated with multimodal treatment. METHODS: Oncologic outcomes and major wound complications (MWC, subclassified as wound healing disorder, infection, abscess, fistula, seroma and hematoma) were evaluated in 74 patients with localized high-risk soft tissue sarcoma of extremities and trunk undergoing multimodal treatment, and also separately for the subgroup of lower extremity tumors. Clinical factors and treatment modalities (especially neoadjuvant vs. adjuvant radiotherapy) were evaluated regarding their prognostic value and impact on postoperative wound complications. RESULTS: Oncologic outcomes were dependent on number of high risk features (tumor size, depth to superficial fascia and grading), but not on therapy sequencing (however with higher risk patients in the neoadjuvant group). Different risk factors influenced different subclasses of wound healing complications. Slightly higher MWC-rates were observed in patients treated with neoadjuvant therapy, compared to adjuvant radiotherapy, although only with a trend to statistical significance (31.8% vs. 13.3%, p = 0.059). However, except for wound infections, no significant difference for other subclasses of postoperative complications was observed between neoadjuvant and adjuvant therapy. Diabetes was confirmed as a major risk factor for immune-related wound complications. CONCLUSION: Rates of major wound complications in this cohort are comparable to published data, higher rates of wound infections were observed after neoadjuvant radiotherapy. Tumor localization, patient age and diabetes seem to be major risk factors. The number of risk factors for high risk soft tissue sarcoma seem to influence DMFS. Neoadjuvant treatment increases the risk only for wound infection treated with oral or intravenous antibiotic therapy and appears to be a safe option at an experienced tertiary center in absence of other risk factors.

Investigating the effects of low intensity visible light on human keratinocytes using a customized LED exposure system.

Photobiomodulation (PBM) refers to the use of light to modulate cellular processes, and has demonstrated utility in improving wound healing outcomes, and reducing pain and inflammation. Despite the potential benefits of PBM, the precise molecular mechanisms through which it influences cell behavior are not yet well understood. Inconsistent reporting of key light parameters has created uncertainty around optimal exposure profiles. In addition, very low intensities of light, < 0.1 J/cm2, have not been thoroughly examined for their use in PBM. Here, we present a custom-made compact, and modular LED-based exposure system for studying the effects of very low-intensity visible light (cell proliferation, migration, ROS production, and mitochondrial membrane potential) of three different wavelengths in a parallel manner. The device allows for six repeats of three different exposure conditions plus a non-irradiated control on a single 24-well plate. The immortalised human keratinocyte cell line, HaCaT, was selected as a major cellular component of the skin epidermal barrier. Furthermore, an in vitro wound model was developed by allowing the HaCaT to form a confluent monolayer, then scratching the cells with a pipette tip to form a wound. Cells were exposed to yellow (585 nm, 0.09 mW, ~ 3.7 mJ/cm2), orange (610 nm, 0.8 mW, ~ 31 mJ/cm2), and red (660 nm, 0.8 mW, ~ 31 mJ/cm2) light for 10 min. 48 h post-irradiation, immunohistochemistry was performed to evaluate cell viability, proliferation, ROS production, and mitochondrial membrane potential. The results demonstrate increased proliferation and decreased scratch area for all exposure conditions, however only red light increased the mitochondrial activity. Oxidative stress levels did not increase for any of the exposures. The present exposure system provides opportunities to better understand the complex cellular mechanisms driven by the irradiation of skin cells with visible light.

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.