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Monte Carlo techniques have been extensively used for planning laser-based clinical procedures such as photobiomodulation. However, the effects of several biological tissue characteristics regarding its morphological structure and physiological parameters have not been carefully addressed in many applications. Specifically, many questions remain concerning the effect of skin phototype and body mass index on the effectiveness of photobiomodulation for extraoral therapies. To address these questions, a Monte Carlo simulation model of the effects of body mass index-dependent skin structure on different Fitzpatrick skin types was developed, specifically tailored for the morphological characteristics of cheek tissue. The model describes the settings of a typical oral photobiomodulation treatment protocol for pain relief, namely the use of 660 nm and 808 nm laser wavelengths and a therapeutic dose of 2.0 J / cm 2 on the masseter muscle. The simulations were used to train a machine learning predictive model aimed at accelerating the treatment planning stage and assessing the importance of patient-specific parameters. A multiple-regression approach was adopted to predict muscle dose and treatment time for effective delivered dose. Body mass index had little effect on epidermal energy deposition, but an important impact on muscle dose parameters. Phototype also influenced muscle dose, but to a lesser extent than body mass index. The results of this study can be used to develop customized dosimetry phototherapy protocols to promote more effective and safe clinical outcomes. [ABSTRACT FROM AUTHOR]

This review aims to compare the effect of photobiomodulation therapy (PBMT) using visible and near-infrared diode laser wavelengths to that of the dry needling technique (DNT) on the management of orofacial pain in patients with Temporomandibular Disorder Myofascial Pain Syndrome (TMD/MPS) in term of effectiveness, speed of recovery, and lasting of treatment. A systematic search of multiple electronic databases was carried out to identify the relevant clinical trials published between 1 January 2010 and 1 January 2024. The included studies were limited to human subjects who had orofacial pain associated with Axis 1 of TMD/MPS, involving two genders with age >18 years and were treated either with photobiomodulation using diode laser with wavelengths ranging from 600 up to 1200 nanometer (nm), or with the dry needling (DN) technique (superficial SDN or deep DDN), as a non-pharmacological therapies to decrease the intensity of orofacial pain associated with TMD/MPS. The risk of bias for included studies was assessed using the Cochrane RoB tool (for randomized studies). Three distinct meta-analyses were performed to quantify the pooled effects of PBM and DN in the management of TMD/MPS myofascial pain and deactivation of myofascial trigger points (MTPs). The meta-analyses were performed using Review Manager (RevMan) 5.3 from Cochrane. The confidence interval (CI) was established at 95% and p-values of less than 0.05 (p < 0.05) were considered statistically significant. Statistical heterogeneity was assessed using I2. Qualitative data were extracted and summarized in tables for each group study, while quantitative data were reported as Mean and Standard Deviation (SD) values for assessment variables in each sub-group study. The results among groups were systematically evaluated to draw the final conclusion. A rigorous electronic and manual search revealed 4150 possible articles. Following the application of the inclusion and exclusion criteria, twelve eligible studies were included in the analysis. Both PBMT and DNT were found to be effective in controlling the myalgia pain and primary symptoms associated with TMD/MPS, as well as deactivating the MTPs. DNT was statistically superior in terms of recovery time while PBMT was the more effective long-term therapy. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a prevalent mental health condition affecting a significant portion of the population worldwide. This condition can impact individuals of all ages, including adolescents, leading to an impact on various aspects of their lives. Adolescence is a crucial phase of human development, characterized by several neurobiological changes. The onset of MDD during this period can result in damage not only to teenagers but also might have long-lasting implications for their future as adults. Notably, the onset of MDD in adolescents is often associated with various biomarkers, such as increased levels of inflammatory cytokines (e.g., IL-6, TNF-α), oxidative stress markers, and alterations in neurotransmitter levels, indicating a complex interplay of biological factors. Therefore, early intervention is essential for addressing MDD during this phase. Photobiomodulation therapy (PBMT) emerges as an innovative and promising approach that utilizes light, especially in the near-infrared (NIR) and red spectra, to trigger biological and therapeutic effects. Notably, targeting the skull and abdomen with PBMT might explore the bidirectional communication between the intestinal system and the central nervous system in a remote and/or systemic way. In this context, we present the rationale and design of an ongoing study aiming to assess the efficacy of PBMT on depressive symptoms and biomarkers associated with oxidative stress and mitochondrial function in adolescents with MDD. [ABSTRACT FROM AUTHOR]

Down syndrome (DS) is the leading genetic cause of intellectual disability globally, affecting about 1 in every 800 births. Individuals with DS often face various neuropsychiatric conditions alongside intellectual disabilities due to altered brain development. Despite the diverse phenotypic expressions of DS, typical physical characteristics frequently influence language development and acquisition. EEG studies have identified abnormal oscillatory patterns in individuals with DS. Emerging interventions targeting the enhancement of gamma (40 Hz) neuronal oscillations show potential for improving brain electrical activity and cognitive functions in this population. However, effective cognitive interventions for DS remain scarce. Extensive research indicates that transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light can penetrate deeply into the cerebral cortex, modulate cortical excitability, and enhance cerebral perfusion and oxygenation. Furthermore, t-PBM has been shown to improve cognitive functions such as language, attention, inhibition, learning, and memory, including working memory. This study presents the rationale and design of an ongoing randomized, sham-controlled clinical trial aimed at assessing the effectiveness of t-PBM using NIR light in enhancing the language abilities of individuals with DS. [ABSTRACT FROM AUTHOR]

Featured Application: Featured Application: The results presented inform a parametric wavelength at which photobiomodulation therapy of spinal cord injury could be most viable for clinical testing. This study compared the transcutaneous target level irradiances from the thoracic to lumbar segments of the interior spinal canal in three cadaver dogs, measured for light at four wavelengths (808 nm, 915 nm, 975 nm, and 1064 nm), common in photobiomodulation therapy (PBMT). Intra-spinal irradiances at nine sites spanning approximately 8 cm in length were measured using a flexible intra-spinal probe under surface application of continuous-wave (CW) light with powers ranging from 0.5 W to 2 W. Surface illumination was applied using an acupuncture treatment head in three modes: non-contact with skin removed, non-contact with skin intact, and contact with skin intact. During surface application, the treatment head was positioned over the spinal canal near the 13th vertebrae (T13, surface site 1), and approximately 4 cm (surface site 5) and 8 cm (surface site 9) caudal to T13. At each position of the treatment head, the light was multiplexed among the four wavelengths at the same power setting. In all three modes of surface application, the target level irradiance at the 1064 nm wavelength was significantly greater than that at the other three wavelengths (p ≤ 0.0017). At a surface irradiance of ~157 mW/cm2, corresponding to 0.5 W light applied with the treatment head directly in contact with the skin, the intra-spinal irradiance at 1064 nm reached 0.137 ± 0.095 mW/cm2. Obtaining a dosage of PBMT-associative wavelengths of this magnitude at the level of the spinal canal may guide focused research into the transcutaneous applicability of PBMT for spinal cord injuries. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a common cause of neurologic morbidity for which few effective therapies exist, especially during the chronic stage. A potential therapy for chronic TBI is transcranial photobiomodulation (tPBM). tPBM is a noninvasive neuromodulation technique that uses light to stimulate the cortex and increase blood flow and metabolism while also enhancing cognition and improving affect. There has been much work focusing on the efficacy of tPBM in acute TBI in small animals, but much less work has focused on chronic TBI. Patients with chronic TBI manifest microvascular injury, which may serve as a modifiable treatment target for tPBM. There is a need to study and improve tPBM, as the currently implemented protocols targeting microvascular injury have been relatively unsuccessful. This review includes 16 studies, which concluded that after tPBM application, there were improvements in neuropsychological outcomes in addition to increases in cerebral blood flow. However, these conclusions are confounded by differing tPBM parameters, small sample sizes, and heterogenous TBI populations. While these results are encouraging, there is a need to further understand the therapeutic potential of tPBM in chronic TBI. [ABSTRACT FROM AUTHOR]

In recent years, photobiomodulation (PBM) has attracted widespread attention for the treatment of various causes of pain and inflammation. Primary dysmenorrhea (PD) is a common gynecological condition characterized by severe menstrual pain, and the limited effectiveness and side effects of conventional treatments have highlighted the urgent need to develop and identify new adjunct therapeutic strategies. The present study from the perspective of light morphology aimed to bypass the heat risk limitation and evaluate the efficacy and safety of pulsed 630 nm PBM therapy for reducing pain associated with PD. The pulse light parameters were designed according to the transmittance of red light. In this randomized, cross-over design, sham-controlled study, 46 women with PD were included and randomly assigned to either pulsed 630 nm light therapy or white light sham control therapy. The intervention lasted for 20 min per day and was administered for 7 consecutive days before and during menstruation. The results showed that the pulsed 630 nm PBM treatment demonstrated a significant reduction in pain levels compared to the placebo treatment (p < 0.001), with 55.00% of active treatment participants experiencing a pain intensity differential concentration exceeding 50.00%. Moreover, participants reported an improved quality of life during the active treatment phase and generally preferred it as a more effective method for relieving PD. No adverse events or side effects were reported throughout the trial. Based on the results, pulsed 630 nm LED therapy showed significant relief of menstrual pain compared to white light placebo treatment and improved quality of life under certain circumstances. Therefore, this study proposes that pulsed red light PBM therapy may be a promising approach for future clinical treatment of PD. [ABSTRACT FROM AUTHOR]

Transcranial photobiomodulation (t-PBM) is an innovative, non-invasive treatment for depression. This study aimed to investigate the changes in individual depressive symptoms during t-PBM treatment and identify the symptoms that improved in those who responded to treatment. The research analyzed data from two trials, the Evaluation of Light-emitting diodes Therapeutic Effect in Depression-2 and -3, focusing on patients with major depressive disorder. The patients received t-PBM treatment on the F3 and F4 regions of the scalp over eight weeks, with symptoms assessed weekly using the Quick Inventory for Depression Symptomatology (QIDS). A response was defined as a 50% or greater reduction in the QIDS score at eight weeks from baseline. Out of the 21 patients analyzed, 4 responded at eight weeks. Neurovegetative symptoms, including sleep disturbances and change in appetite, improved in ≥50% of the patients who had these symptoms at baseline. However, core depressive symptoms, including a depressed mood and lack of energy, persisted in about 80–90% of the patients. The responders showed a more than 75% improvement in these core depressive symptoms. These findings suggest that t-PBM treatment may uniquely alleviate certain neurovegetative symptoms in depression, and the improvement in core depressive symptoms might be linked to a clinical response to this treatment. [ABSTRACT FROM AUTHOR]

This study compared the transcutaneous target level irradiances from the thoracic to lumbar segments of the interior spinal canal in three cadaver dogs, measured for light at four wavelengths (808 nm, 915 nm, 975 nm, and 1064 nm), common in photobiomodulation therapy (PBMT). Intra-spinal irradiances at nine sites spanning approximately 8 cm in length were measured using a flexible intra-spinal probe under surface application of continuous-wave (CW) light with powers ranging from 0.5 W to 2 W. Surface illumination was applied using an acupuncture treatment head in three modes: non-contact with skin removed, non-contact with skin intact, and contact with skin intact. During surface application, the treatment head was positioned over the spinal canal near the 13th vertebrae (T13, surface site 1), and approximately 4 cm (surface site 5) and 8 cm (surface site 9) caudal to T13. At each position of the treatment head, the light was multiplexed among the four wavelengths at the same power setting. In all three modes of surface application, the target level irradiance at the 1064 nm wavelength was significantly greater than that at the other three wavelengths (p ≤ 0.0017). At a surface irradiance of ~157 mW/cm2, corresponding to 0.5 W light applied with the treatment head directly in contact with the skin, the intra-spinal irradiance at 1064 nm reached 0.137 ± 0.095 mW/cm2. Obtaining a dosage of PBMT-associative wavelengths of this magnitude at the level of the spinal canal may guide focused research into the transcutaneous applicability of PBMT for spinal cord injuries.

Photobiomodulation, or Low-Level Laser Therapy, is a therapeutic technique that can be applied in tissue regenerative surgery. By stimulating the cellular compartment, photobiomodulation promotes cell proliferation, enabling tissue restoration after dental extractions, periodontal surgical treatments, or the management of traumatic oral injuries. On the other hand, Platelet-Rich Plasma (PRP) or Platelet-Rich Fibrin (PRF) therapy is particularly effective in providing a source of growth factors that enhance tissue healing. Authors carried out a Systematic Review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines by searching PubMed, Web of Science (WoS), Scopus, and Cochrane Library databases, using the combination of the following keywords: ("low laser therapy") AND ("growth factors") AND (dent* OR oral) and ("photobiomodulation") AND ("growth factors") AND (dent* OR oral). A total of 10 publications were deemed eligible for qualitative analysis. The evidence analyzed confirms that the use of photobiomodulation and PRP/PRF (alone or in combination) can stimulate tissue regeneration, allowing for a reduction in postoperative inflammation, wound healing, and new tissue formation. Moreover, these effects are strictly dependent on the intrinsic characteristics of the individual patient, the needs, and the clinical assessment of the practitioner who will appropriately direct the treatment. Furthermore, it is necessary to investigate with evidence-based methodologies (Evidence-based Medicine, EBM) which types of patients and/or lesions are more susceptible to treatment with these tools, as well as to understand the best ways of using (alone or in combination) these important and cutting-edge therapeutic options. [ABSTRACT FROM AUTHOR]

Alveolar bone repair is a complex and extremely important process, so that functions such as the mastication, occlusion and osseointegration of implants can be properly reestablished. Therefore, in order to optimize this process, many procedures have been used, such as grafting with biomaterials and the application of platelet-rich fibrin (PRF). Another method that has been studied is the use of photobiomodulation (PBM) with the use of low-level laser therapy (LLLT), which, through the absorption of photons by the tissue, triggers photochemical mechanisms in the cells so that they start to act in the search for homeostasis of the affected region. Therefore, the objective of this review was to analyze the use of LLLT as a possible auxiliary tool in the alveolar bone repair process. A search was carried out in scientific databases (PubMed/MEDLINE, Web of Science, Scopus and Cochrane) regarding the following descriptors: "low-level laser therapy AND alveolar bone repair" and "photobiomodulation AND alveolar bone repair". Eighteen studies were selected for detailed analysis, after excluding duplicates and articles that did not meet predetermined inclusion or non-inclusion criteria. According to the studies, it has been seen that LLLT promotes the acceleration of alveolar repair due to the stimulation of ATP production, activation of transcription and growth factors, attenuation of the inflammatory process and induction of angiogenesis. These factors depend on the laser application protocol, and the Gallium Aluminum Arsenide—GaAlAs laser, with a wavelength of 830 nm, was the most used and, when applications of different energy densities were compared, the highest dosages showed themselves to be more efficient. Thus, it was possible to conclude that PBM with LLLT has beneficial effects on the alveolar bone repair process due to its ability to reduce pain, the inflammatory process, induce vascular sprouting and, consequently, accelerate the formation of a new bone matrix, favoring the maintenance or increase in height and/or thickness of the alveolar bone ridge. [ABSTRACT FROM AUTHOR]

Orthodontics is constantly seeking innovation towards mechanical efficiency and better oral-related quality of life during treatment. This narrative review aims to discuss novel scientific reports about light therapies and how they can optimize different stages of orthodontic intervention: before, during, and after treatment. Recurrent conditions that can be treated with laser devices are the removal of carious tissue, dentin hypersensitivity, and temporomandibular disorders. Evidence reveals that laser procedures accelerate health recovery, enabling individuals to initiate orthodontic treatment. Along orthodontic procedure, photobiomodulation therapy, is indicated for analgesia after appliance activations, repair of traumatic ulcers, and acceleration of tooth movement. Moreover, antimicrobial photodynamic therapy is well-indicated for effective decontamination of oral infections such as herpetic lesions and peri-implantitis. Finally, high-intensity lasers are good allies in removing brackets and reconditioning red esthetics. There are many benefits to the use of light sources in the orthodontic routine: simplicity of technique, ease of handling devices, minimal invasiveness, and patient comfort during procedures. It is essential that professionals develop a critical overview of technological advances, offering safe and evidence-based therapies. Recent advances indicate that laser therapies improve patient experiences during orthodontic treatment and minimize the side effects of clinical interventions. [ABSTRACT FROM AUTHOR]

(1) Background: Thyroid tissue ablation with radioactive iodine (RAI) has been successfully used in the treatment of differentiated thyroid cancers. However, as a side effect, RAI may induce salivary gland (SG) hypofunction, which has been alternatively managed with photobiomodulation therapy (PBMT). In our study, we assessed the effects of RAI on the SGs and further analyzed whether PBMT can minimize tissue damage. (2) Methods: Balb/c mice were allocated into three groups, as follows: RI, submitted to RAI orally; RIL, similar to RI, but with PBMT for SG hypofunction; and C, control group. The animals were euthanized on days 0, 10, and 90 after RAI. (3) Results: A decrease in tri-iodothyronine (T3) and thyroxine (T4) serum levels was observed both in the RI and RIL groups. In addition, a decrease in SG weight and morphological alterations were shown in the RI group throughout the experimental period, as well as a significant increase in total protein and peroxidase concentrations, and catalase activity. On day 90, the RI group presented less collagen and fewer sodium/iodine channels, with higher rates of cell apoptosis. Pertechnetate (Na99mTcO4) uptake was also affected in the RI group in all experimental times. Interestingly, although the RIL group also presented some alterations regarding these parameters, they were not statistically different from those of the C group on day 90. (4) Conclusions: Our results provide evidence that RAI induces harmful effects on the SGs, which can be successfully managed with PBMT. [ABSTRACT FROM AUTHOR]

Oral mucositis (OM) is a debilitating adverse event in patients undergoing treatment for cancer. This study aimed to evaluate the therapeutic effect of a novel handheld photobiomodulation therapy (PBMT) device on chemoradiation therapy (CRT)-induced OM in patients with head and neck cancer. Head and neck cancer patients undergoing CRT who developed moderate-to-severe OM during treatment were enrolled. After PBMT and at 2 and 4 weeks after PBMT, the mean value of OM grade decreased significantly from 2.63 to 2.13, 1.31, and 0.75, respectively (p < 0.05, p < 0.001, and p < 0.001). Moreover, we observed significant improvement in health-related quality of life (HRQoL) after PBMT compared to baseline through a validated questionnaire; EORTC QLQ-C30. In the present study, the use of this PBMT device in the management of CRT-induced OM in patients with head and neck cancer was generally well tolerated and resulted in the improvement of OM. However, evidence supporting its use remains lacking owing to limitations such as the small number of participants and lack of a control group. Therefore, further mechanistic studies and large-scale randomized controlled trials are needed to confirm the effectiveness of PBMT in the treatment of CRT-induced OM, as shown in our results. [ABSTRACT FROM AUTHOR]

We report on the rationale and design of an ongoing National Institute of Mental Health (NIMH) sponsored R61-R33 project in major depressive disorder (MDD). Current treatments for MDD have significant limitations in efficacy and side effect burden. There is a critical need for device-based treatments in MDD that are efficacious, well-tolerated, and easy to use. This project focuses on the adjunctive use of the transcranial photobiomodulation (tPBM) with near-infrared (NIR) light for the treatment of MDD. tPBM with NIR light penetrates robustly into the cerebral cortex, stimulating the mitochondrial respiratory chain, and also significantly increases cerebral blood flow (CBF). In the R61 phase, we will conduct target engagement studies to demonstrate dose-dependent effects of tPBM on the prefrontal cortex (PFC) CBF, using the increase in fMRI blood-oxygenation-level-dependent (BOLD) signal levels as our Go/No-go target engagement biomarker. In the R33 phase, we will conduct a randomized clinical trial of tPBM vs. sham in MDD to establish the target engagement and evaluate the association between changes in the biomarker (BOLD signal) and changes in clinical symptoms, while also collecting important information on antidepressant effects, safety, and tolerability. The study will be done in parallel at New York University/the Nathan Kline Institute (NYU/NKI) and at Massachusetts General Hospital (MGH). The importance of this study is threefold: 1. it targets MDD, a leading cause of disability worldwide, which lacks adequate treatments; 2. it evaluates tPBM, which has a well-established safety profile and has the potential to be safe in at-home administration; and 3. it uses fMRI BOLD changes as a target engagement biomarker. If effects are confirmed, the present study will both support short-term clinical development of an easy to scale device for the treatment of MDD, while also validating a biomarker for the development of future, novel modulation strategies. [ABSTRACT FROM AUTHOR]

Photobiomodulation (PBM) has been clinically used for the prevention and treatment of oral mucositis (OM). The effect of red and near-infrared wavelengths on OM repair is still misunderstood. The aim of this study was to compare the clinical effect and tissue changes caused by 660 nm and 780 nm exposure in an experimental model of OM. Rats were submitted to gamma irradiation for induction of OM lesions and treated with 660 nm or 780 nm lasers with the same dosimetry parameters (30 mW, 7.5 J/cm2, 10 s, spot size = 0.04 mm, irradiation every two days). Clinical assessment of OM severity and histopathological analyses was performed after 8, 14, and 20 days of the ionizing radiation. OM severity was reduced in the PBM groups, especially when the red laser was used. The histopathological pattern was similar between the PBM groups, showing advanced re-epithelization and more pronounced angiogenesis and collagen deposition compared to the control. The 660 nm group showed a greater collagen matrix area than the 780 nm group at 14 days. In conclusion, PBM at 660 nm and 780 nm improved the repair of ionizing radiation-induced OM. Both wavelengths activated the angiogenesis and collagen deposition, but these tissue effects were more pronounced when 660 nm was used. [ABSTRACT FROM AUTHOR]

The aim of this randomized, controlled split-mouth clinical trial was to assess the effect of LLLT on wound healing after modified coronally advanced flap (MCAF) procedure for treatment of isolated recession-type defects. Fifteen patients with isolated bilaterally symmetrical gingival recessions (Miller's Class I or Class II, or a combination of both) were enrolled in this study. After a modified, coronally advanced flap technique was implemented, a diode laser (810 nm) with a power of 120 mW irradiated the inner surface of the flap and the outer surface of the flap (low-level laser therapy—LLLT) after suturing for 5 min. This was repeated for the following four consecutive days. Descriptive statistics, a Kruskal–Wallis test and a Mann–Whitney test were performed to analyze the data. A p-value of less than 0.05 was considered statistically significant. The mean recession depth decreased from 3.33 ± 0.9 mm (baseline) to 0.2 ± 0.3 mm (3 months) and 0.4 ± 0.2 mm (6 months) in the test group. The mean recession width decreased from 3.8 ± 0.7 mm (baseline) to 0.2 ± 0.3 mm (3 months) and 0.5 ± 0.3 mm (6 months) in the test group. Due to minimal pain and discomfort, patient acceptability was quite high. [ABSTRACT FROM AUTHOR]

Light and lasers, as high-tech devices whose medical potential has yet to be fully discovered, have made important contributions to medicine, even in the current pandemic. The main aim of this review was to investigate how light was applied as a therapeutic tool during a crisis triggered by COVID-19. Another goal was to encourage scientists and industry to quickly design new at-home photobiomodulation therapy (PBMT) and/or antimicrobial photodynamic therapy (aPDT) easy to use systems to end this pandemic, especially for those who believe in high-tech but would never get vaccinated. This review revealed that PBMT has been successfully applied as adjunct therapy, in combination with conventional medical treatment, and as a pioneering action in SARS-CoV-2 infection, demonstrating significant improvements in airway inflammation and general clinical condition of patients, a faster recovery, avoiding intensive care unit (ICU) hospitalization, mechanical ventilation, mortality, and overcoming long-term sequelae. Application in only a limited number of cases strongly suggests the need for future randomized, placebo-controlled clinical trials to objectively determine the action and effects of PBMT in COVID-19. Implementation of unparalleled theragnostics methods and light-based techniques for disinfection of spaces, air, skin, mucosae, and textures to decrease the load of SARS-CoV-2 virus would save lives, time, and money. In this ongoing and challenging search for the seemingly intangible end of this pandemic, a non-invasive, easily accessible, safe, and side-effect-free adjuvant method appears to be PBMT, alone or in synergistic combination with aPDT, which has been shown to work in COVID-19 and opens unprecedented potential for use as home self-treatment to end the pandemic. [ABSTRACT FROM AUTHOR]

The use of light in the red and near-infrared light spectrum influences cell viability and proliferation in both cell and animal experimental models. In wounded models, photobiomodulation (PBM) at various laser parameters may stimulate or inhibit the tissue repair process by affecting cells important to healing. Connective tissue cells include osteocytes and osteoblasts in bone, chondrocytes and chondroblasts in cartilage, and tenocytes and tenoblasts in tendons. PBM, at various wavelengths, energy densities and power output, has various effects on cell viability, proliferation, migration and gene expression. This narrative review will briefly encapsulate the effectiveness of PBM on connective tissue cells, and its possible role in tissue repair. Relevant journal articles were obtained through PubMed and Google Scholar. [ABSTRACT FROM AUTHOR]

Alveolar bone repair is a complex and extremely important process, so that functions such as the mastication, occlusion and osseointegration of implants can be properly reestablished. Therefore, in order to optimize this process, many procedures have been used, such as grafting with biomaterials and the application of platelet-rich fibrin (PRF). Another method that has been studied is the use of photobiomodulation (PBM) with the use of low-level laser therapy (LLLT), which, through the absorption of photons by the tissue, triggers photochemical mechanisms in the cells so that they start to act in the search for homeostasis of the affected region. Therefore, the objective of this review was to analyze the use of LLLT as a possible auxiliary tool in the alveolar bone repair process. A search was carried out in scientific databases (PubMed/MEDLINE, Web of Science, Scopus and Cochrane) regarding the following descriptors: “low-level laser therapy AND alveolar bone repair” and “photobiomodulation AND alveolar bone repair”. Eighteen studies were selected for detailed analysis, after excluding duplicates and articles that did not meet predetermined inclusion or non-inclusion criteria. According to the studies, it has been seen that LLLT promotes the acceleration of alveolar repair due to the stimulation of ATP production, activation of transcription and growth factors, attenuation of the inflammatory process and induction of angiogenesis. These factors depend on the laser application protocol, and the Gallium Aluminum Arsenide—GaAlAs laser, with a wavelength of 830 nm, was the most used and, when applications of different energy densities were compared, the highest dosages showed themselves to be more efficient. Thus, it was possible to conclude that PBM with LLLT has beneficial effects on the alveolar bone repair process due to its ability to reduce pain, the inflammatory process, induce vascular sprouting and, consequently, accelerate the formation of a new bone matrix, favoring the maintenance or increase in height and/or thickness of the alveolar bone ridge.

Our objective was to assess the effect of low-level laser therapy (LLLT) administered using a diode laser on the growth processes of human fibroblast cells involved in wound healing. Initially, studies were conducted using a diode laser at wavelengths of 633, 520, and 450 nm with an irradiance of 3 mW/cm2. The distance between the light source and culture plate was 3 cm. The mechanism(s) of action of the diode laser illumination on human fibroblast cells were studied by examining different wavelengths to determine the relevant light parameters for optimal treatment. In addition, the percentages of fibroblast-mediated procollagen and matrix metallopeptidase (MMP)-1, -2, and -9 production were compared. In the clinical study, the changes in basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and fibroblast collagen production were assessed in 60 patients with complicated wounds who received LLLT (633 nm). No statistically significant difference was observed between red light versus green and blue light in the viability analysis. In addition, the effects of LLLT on the cell cultures of fibroblast cells in vitro demonstrated a decrease in the relative expression of MMP-1, -2, and -9 while using light with a wavelength of 633 nm. In the clinical study, 633 nm diode laser LLLT at 2–8 J/cm2 was administered to 60 patients with complicated wounds; all patients showed increased levels of bFGF and VEGF and the occurrence of collagen synthesis. Our studies demonstrated that LLLT might affect fibroblast cell growth processes involved in wound healing. [ABSTRACT FROM AUTHOR]

The periapical local anesthetic injection may be associated with fear of needles and pain administration. Dental topical anesthetic agents can help to reduce pain perception; however, adverse events can occur. To investigate the efficacy of 1064-nm photobiomodualtion (PBM) in inducing mucosal anesthesia delivered with a flat-top hand-piece compared to 20% Benzocaine topical anesthetic gel, sixty healthy patients were randomly allocated (1:1) to either 20% benzocaine topical gel + placebo laser (T group) or PBM + placebo gel (L group). The 1064-nm Nd:YAG laser was employed and is associated with a novel flat-top hand piece. The applied operational parameters were 0.5 W, 10 Hz, 100 µs pulse width, and 30 J/cm2 for one-minute single application time. The enrolled subjects were asked to assess pain intensity at the time of anesthetic injection with a Visual Analog Scale. Taking into consideration taste, undesirable numbness, and overall satisfaction, the patients were asked to rate their experiences according to a verbal rating scale. Statistical analysis showed no statistically significant difference between the T and L Groups for pain ratings (p = 0.0596). The L Group displayed significantly higher ratings than T Group for taste, undesirable numbness, and overall satisfaction (p < 0.001). The 1064-nm PBM delivered by flat-top hand piece is effective in inducing mucosal anesthesia, eliminating the adverse side-effects of the conventional topical anesthetic gel. [ABSTRACT FROM AUTHOR]

Introduction: Mood and anxiety disorders are a prevalent and significant leading cause of years lived with a disability worldwide. Existing antidepressants drugs are only partially effective, having burdensome side effects. One-third of patients do not achieve remission after several adequate antidepressant trials, and relapses of depression are frequent. Psychotherapies for depression are limited by the lack of trained professionals, and further by out-of-pocket prohibitive costs. Existing FDA-approved, device-based interventions are either invasive or only administered in the office. Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light may be a promising treatment option for mood and anxiety disorders. Due to its low cost, and ease of self-administration, t-PBM has the potential to become widely accessible. The safety profile of t-PBM is a relevant factor for widespread use and administration. Aim: To further investigate the t-PBM safety profile, this study aims to evaluate the tolerability and safety of t-PBM for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). Method: We completed a systematic analysis of the side effects from repeated sessions of t-PBM in three studies: an open-label study for GAD (LIGHTEN GAD) and two randomized control studies for MDD (ELATED-2; ELATED-3). Overall, 80 subjects were studied. Result: Our results show that a low dose of NIR per t-PBM session can be administered with increasing frequency (up to daily sessions) and for several weeks (up to 12 weeks) without a corresponding increase in the occurrence or severity of adverse events. Additionally, there were no significant predictors for the variance in the number of reported adverse events (such as age, sex or diagnosis). Conclusion: The literature indicates that higher dosages of transcranial NIR could lead to greater antidepressant and anxiolytic effects; this study did not find any correlation between the increasing number of t-PBM sessions and the occurrence of adverse events. [ABSTRACT FROM AUTHOR]

This study verifies the acute dose response effect of photobiomodulation (PBM) by light emitting diodes (LEDs) on hemodynamic and metabolic responses in individuals with type 2 diabetes mellitus (T2DM). Thirteen participants with T2DM (age 52 ± 7 years) received PBM by a light-emitting diode array (50 GaAIAs LEDs, 850 ± 20 nm, 75 mW per diode) on the rectus and oblique abdomen, quadriceps femoris, triceps surae, and hamstring muscle areas, bilaterally, using different energy treatments (sham, 75, 150, 300, 450, and 600 Joules) in random order with a washout of at least 15 days apart. The PBM by LEDs statistically decreased plasma glucose levels (primary outcome) in 15 min after application of the 75 and 450 J irradiation protocol, reduced blood lactate levels 15 min after application of the 75, 450, and 600 J irradiation protocol, increased cardiac output ( Q ˙ ) and cardiac index (CI) in the 1st minute after application of the 75 and 300 J irradiation protocol, and reduced Q ˙ and heart rate (HR) in the 15 min after application of the 300 J and 600 J irradiation protocol, respectively. For hemodynamic variables, including Q ˙ , total peripheral resistance (TPR), and HR, we observed that the ideal therapeutic window ranged between 75 and 300 J, while for metabolic variables, glucose and lactate, the variation was between 450 and 600 J. [ABSTRACT FROM AUTHOR]

Despite the literature providing compelling evidence for the medical efficacy of photobiomodulation (PBM) therapy, its consistency in terms of accuracy and standardization needs improving. Identification of new technology and reliable and ethical biological models is, therefore, a challenge for researchers working on PBM. We tested the reliability of PBM irradiation through a novel delivery probe with a flat-top beam profile on the regenerating amphioxus Branchiostoma lanceolatum. The caudalmost 9 ± 1 myotomes, posterior to the anus, were excised using a sterile lancet. Animals were randomly split into three experimental groups. In the control group, the beam area was bounded with the 635-nm red-light pointer (negligible power, <0.5 mW) and the laser device was coded to irradiate 810 nm and 0 W. In Group laser-1, the beam area was bounded with the same 635-nm red-light pointer and irradiated at 810 nm, 1 W in CW for 60 s, spot-size 1 cm2, 1 W/cm2, 60 J/cm2, and 60 J; irradiation was performed every day for two weeks. In Group laser-2, the beam area was bounded with the same 635-nm red-light pointer and irradiated at 810 nm, 1 W in CW for 60 s, spot-size 1 cm2, 1 W/cm2, 60 J/cm2, and 60 J; irradiation was performed on alternate days for four weeks. We observed that PBM improved the natural wound-healing and regeneration process. The effect was particularly evident for the notochord. Daily irradiation better supported the regenerative process. [ABSTRACT FROM AUTHOR]

Low-level laser therapy (LLLT) has become an important part of the therapeutic process in various diseases. However, despite the broad use of LLLT in everyday clinical practice, the full impact of LLLT on cell life processes has not been fully understood. This paper presents the current state of knowledge concerning the mechanisms of action of LLLT on cells. A better understanding of the molecular processes occurring within the cell after laser irradiation may result in introducing numerous novel clinical applications of LLLT and potentially increases the safety profile of this therapy. [ABSTRACT FROM AUTHOR]

Photobiomodulation (PBM) has demonstrated positive effects on the muscle repair process. The aim of the study was to evaluate the effects of infrared PBM using different light sources—low-level laser (LLL) at 780 nm (40 or 70 mW, 10 J/cm2, 0.4 J) or LED at 850 nm (40 or 70 mW, 0.13 J/cm2, 0.4 J)—and dosimetric parameters on the proliferation and migration of muscle cells. The results showed that LLL 40 mW and 70 mW, with the same radiation exposure, led to an increase in proliferation after 24 h, but no differences at 48 and 72 h. Cells irradiated with LED 70 mW exhibited an increase in proliferation in comparison to the control group and 40mW after 24 and 48 h, but not at 72 h. Moreover, cell migration was greater in comparison to the control after 6 and 24 h, and no differences were found at 12 h when LLL was used with an output power of 70 mW. Furthermore, no differences were found at 6 and 12 h with the 70 mW output power-LED, but an increase was observed in the cell migration after 24 h. In conclusion, PBM using different light sources and dosimetric parameters was able to modulate the proliferation of C2C12 myoblasts, but only PBM at 70 mW was able to modulate the migration of these cells. [ABSTRACT FROM AUTHOR]

This study aims to point out the correlation between photobiomodulation (PBM) targets and effects and management of temporomandibular disorders (TMDs) pain using diode lasers with infrared wavelengths ranging from 780 up to 980 nanometers (nm). A systematic search of multiple electronic databases was done to identify the clinical trials published between 1st January 2010 and 18th December 2021. The included studies were limited to human subjects who had TMD pain, involving two genders with age > 18 years, and were treated with PBM using a diode laser (780–980 nm) as a non-pharmacological therapy to decrease the intensity of the pain associated to TMDs. The risk of bias for included studies was assessed using the Cochrane RoB tool (for randomized studies). The methodologic quality was rated using the Delphi list. The findings suggest that PBM is an effective tool in alleviating TMDs' pain and increasing the range of movement in patients with Axis 1 of TMDs. However, TMDs' pain related to underlying pathology cannot be solely treated by PBM. The causative factors must be treated first. Studies displaying the highest quality Delphi score may represent a suggested PBM therapy protocol to follow for TMDs pain management. [ABSTRACT FROM AUTHOR]

The optical power density in biotissue is an important issue for photobiomodulation (PBM) clinical applications. In our previous study, the maximal dose and the power density distributions of 830 nm lasers under human skin could be exactly calculated and measured. In this work, the laser power density in tissue can be changed by adjusting the focal point of the lens. From the experimental results, it is evident that the power densities on the attached gingiva and the surrounding tissues can be improved. Thus, the dose of a near-infrared (NIR) laser in the target tissue can be increased with a suitable lens. Most importantly, focusing lasers on deeper tissue can avoid any damage to the skin. This study provides a dose optimization method on the target tissue, and the results can be applied to clinical applications, especially laser acupuncture (LA). [ABSTRACT FROM AUTHOR]

The contact of blood with the bioincompatible membranes of the dialyzer, which is part of the extracorporeal circuit during hemodialysis (HD), causes upregulation of various cellular and non-cellular processes, including massive generation and release of reactive oxygen species (ROS), (which is one of the primary causes of anemia in chronic renal failure). We hypothesize that near-infrared (NIR) radiation possesses antioxidant properties and is considered to protect the red blood cell (RBC) membrane by enhancing its resilience to negative pressures. Our experimental setup consisted of an HD machine equipped with a dialyzer with a polyamide membrane; whole bovine blood was examined in vitro in blood-treated circulation. Blood samples were taken at 0, 5, 15, and 30 min during the HD therapy. We also assessed osmotic fragility, hematocrit, hemolysis, and oxidative stress as a concentration of reactive thiobarbituric acid substances (TBARS). Our results have shown that RBC membrane peroxidation increased significantly after 30 min of circulation, whereas the TBARS level in NIR-treated blood remained relatively steady throughout the experiment. The osmotic fragility of NIR-irradiated samples during dialysis was decreased compared to control samples. Our studies confirm that in vitro, blood photobiomodulation using NIR light diminishes oxidative damage during HD and can be considered a simultaneous pretreatment strategy for HD. [ABSTRACT FROM AUTHOR]

Sexual dysfunction (SD) is frequently encountered in patients suffering from depression. There is a bidirectional relationship between various types of SD and depression, so the presence or treatment of one condition may exacerbate or improve the other condition. The most frequent sexual problem in untreated depressed patients is declining sexual desire, while in treated depressed patients it is difficulties with erection/ejaculation and with orgasm. Numerous classes of neuropsychiatric medications, commonly used in depressed patients—such as antidepressant, antipsychotic, alpha sympathetic, and opioid drugs—may cause SD. Photobiomodulation (PBM) therapy, also called low-level light/laser therapy, is a novel neuromodulation technique for neuropsychiatric conditions, such as depression. Transcranial PBM (tPBM) targets the cellular metabolism—through the mitochondrial respiratory enzyme, cytochrome c oxidase—and has numerous cellular and physiological beneficial effects on the central nervous system. This paper represents a comprehensive review of the application of tPBM to SD, coexisting with depression or induced by antidepressant medications. [ABSTRACT FROM AUTHOR]

Periodontitis is an inflammatory condition of the soft and hard tooth-supporting tissues, representing the first cause of tooth loss. In addition to standard mechanical debridement (Scaling and Root Planing, SRP), further approaches have been proposed as adjuncts. The aim of the present randomized clinical trial is to compare the efficacy of ozone or photobiomodulation (PBM) therapy in addition to SRP to treat periodontal disease. According to a split-mouth design, 240 pathological sites, corresponding to 30 periodontal patients, were randomly divided according to the professional oral hygiene protocol performed at baseline (T0) and after 1 (T1), 2 (T2), 3 (T3), 4 (T4), 5 (T5), and 6 (T6) months. A total of 120 sites underwent an ozonized water administration (ozone group), whereas the other 120 sites were treated with photobiomodulation (PBM group), both in addition to SRP. At every timepoint, the following clinical indexes were assessed: Probing Pocket Depth (PPD) (measured on six sites per element), Plaque Index (PI), and Bleeding on Probing (BOP). As regards PPD, significant intergroup differences were noticed from T5, with significantly lower values in the PBM group (p < 0.05), where values further decreased at T6 (p < 0.05). Both PI and BoP generally decreased from baseline to T6 in both groups; a significant difference was found between T0 and T1 among the groups (p < 0.05), with a progressively higher reduction in the PBM group among the time frames of the study, despite intergroup comparisons not being significant (p > 0.05). Both ozone and PBM appear to be effective adjuvant treatments to SRP, obtaining a slightly better outcome for the latter in the long term, with significant differences at T5 and T6 for PPD. However, because of the absence of standardized protocols for PBM considering both therapeutic and research purposes, no definitive conclusions can be reached, and further studies are required. [ABSTRACT FROM AUTHOR]

The increased precision, efficacy, and safety of radiation brachytherapy has tremendously improved its popularity in cancer care. However, an unfortunate side effect of this therapy involves localized skin damage and breakdown that are managed palliatively currently. This study was motivated by prior reports on the efficacy of photobiomodulation (PBM) therapy in improving tissue resilience and wound healing. We evaluated the efficacy of PBM therapy on 36 athymic mice with 125I seed (0.42 mCi) implantation over 60 days. PBM treatments were performed with either red (660 nm) or near-infrared (880 nm, NIR) LEDs irradiance of 40 mW/cm2, continuous wave, fluence of 20 J/cm2 once per week. Animals were evaluated every 7 days with digital imaging, laser Doppler flowmetry, thermal imaging, µPET-CT imaging using 18F-FDG, and histology. We observed that both PBM treatments—red and NIR—demonstrated significantly less incidence and severity and improved healing with skin radionecrosis. Radiation exposed tissues had improved functional parameters such as vascular perfusion, reduced inflammation, and metabolic derangement following PBM therapy. Histological analysis confirmed these observations with minimal damage and resolution in tissues exposed to radiation. To our knowledge, this is the first report on the successful use of PBM therapy for brachytherapy. The results from this study support future mechanistic lab studies and controlled human clinical studies to utilize this innovative therapy in managing side effects from radiation cancer treatments.

The increased precision, efficacy, and safety of radiation brachytherapy has tremendously improved its popularity in cancer care. However, an unfortunate side effect of this therapy involves localized skin damage and breakdown that are managed palliatively currently. This study was motivated by prior reports on the efficacy of photobiomodulation (PBM) therapy in improving tissue resilience and wound healing. We evaluated the efficacy of PBM therapy on 36 athymic mice with 125I seed (0.42 mCi) implantation over 60 days. PBM treatments were performed with either red (660 nm) or near-infrared (880 nm, NIR) LEDs irradiance of 40 mW/cm2, continuous wave, fluence of 20 J/cm2 once per week. Animals were evaluated every 7 days with digital imaging, laser Doppler flowmetry, thermal imaging, µPET-CT imaging using 18F-FDG, and histology. We observed that both PBM treatments—red and NIR—demonstrated significantly less incidence and severity and improved healing with skin radionecrosis. Radiation exposed tissues had improved functional parameters such as vascular perfusion, reduced inflammation, and metabolic derangement following PBM therapy. Histological analysis confirmed these observations with minimal damage and resolution in tissues exposed to radiation. To our knowledge, this is the first report on the successful use of PBM therapy for brachytherapy. The results from this study support future mechanistic lab studies and controlled human clinical studies to utilize this innovative therapy in managing side effects from radiation cancer treatments. [ABSTRACT FROM AUTHOR]

Periodontal disease is the most common oral chronic inflammatory disease in humans. Recent studies have indicated that red light Photobiomodulation (PBM) could inhibit cell inflammation effectively, but the effect of different doses of PBM on the treatment of inflammation has to be improved. Thus, this study was aimed to investigate the effects of various doses of PBM (630 ± 30 nm, (1) 5 mW/cm2, 1 J/cm2, 200 s; (2) 5 mW/cm2, 3 J/cm2, 600 s; (3) 5 mW/cm2, 9 J/cm2, 1800 s; (4) 5 mW/cm2, 18 J/cm2, 3600 s; (5) 5 mW/cm2,36 J/cm2, 7200 s) on the anti-inflammatory response of human gingival fibroblasts. Our results suggested that PBM (630 ± 30 nm) with doses of 18 J/cm2 and 36 J/cm2 could significantly inhibit the production of inflammatory cytokines such as Prostaglandin E2 (PGE2) and IL-8, presumably due to the fact that a high dose of PBM treatment could reduce intracellular Reactive oxygen species (ROS) in human gingival fibroblasts, thus reducing the expression of COX-2 enzyme. In addition, it was found that treatment with different doses of PBM (630 ± 30 nm) did not result in reduced mitochondrial membrane potential and mitochondrial dysfunction in human gingival fibroblasts. Our study provides a theoretical reference for the selection of PBM parameters and the application of PBM in the clinical treatment of periodontitis. [ABSTRACT FROM AUTHOR]

Diminished facial movement and marked facial asymmetry can lead to a consistent psychological burden. Bell′s palsy (BP) is one of the most common causes of facial nerve illness, which comes with unilateral acute facial paresis. Nowadays, no clear guidelines for treating BP are available. We carried out a case series study to test the efficacy of photobiomodulation (PBM) therapy in patients with BP non-responsive to standard treatment. The study was experimentally performed at the Department of Surgical and Diagnostic Sciences, University of Genoa (Genoa, Italy), in accordance with case report guidelines. Patients were referred to our department by colleagues for evaluation to be included in the case series because no consistent improvement was observed at least 3 months from the diagnosis of BP. All the patients interrupted their pharmacological therapy before the initiation of PBM therapy. PBM therapy (808 nm, 1 W irradiated in continuous-wave for 60 s on spot-size 1 cm2; 1 W/cm2; 60 J/cm2; and 60 J) was administered every 2 days until complete resolution. Evaluation of the House-Brackmann scale was performed before and after treatments. Fourteen patients were screened as eligible for the study. Patients were Caucasians (36% females and 64% males) with a mean age ± standard deviation of 56.07 ± 15.21 years. Eleven patients out of 14, who experienced BP a maximum of 6 months, completely recovered through PBM. The three patients that did not show improvement were those who had experienced BP for years. PBM could be a supportive therapy for the management of BP in patients non-responsive to standard treatment. However, randomized controlled trials are necessary to sustain our encouraging results, exclude bias, and better explain the boundary between the time from diagnosis and the recovery of BP through PBM therapy. [ABSTRACT FROM AUTHOR]

Up to now it has not yet been scientifically proven whether the technical methods of photonics in the field of photobiomodulation (PBM), photodynamic therapy (PDT), and laser acupuncture in connection with COVID-19 have achieved effective medical success. As part of this short technical note, an overview of the current scientific status is given and new equipment from our own research area is briefly presented. Although there are still many unanswered questions, it seems to be emerging that PBM and PDT in connection with the corresponding photosensitizers may make it appear worthwhile to perform experimental and clinical studies, primarily as so-called home therapy studies. In any case, the technical requirements for this are already in progress. [ABSTRACT FROM AUTHOR]