Photobiomodulation Treatments Research Articles

Thermodynamic basis for comparative photobiomodulation dosing with multiple wavelengths to direct odontoblast differentiation.

Multiple wavelength devices are now available for photobiomodulation (PBM) treatments, but their dosimetry for individual or combinatorial use remains unclear. The present work investigated the effects of 447, 532, 658, 810, 980 and 1064 nm wavelengths on odontoblast differentiation at 10mW/cm2 using either equal treatment time for conventional fluence (300 seconds for 3J/cm2 ) or varying times to adjust for individual wavelength photon fluence (4.6p.J/cm2 ). Both 447 and 810 nm significantly increased alkaline phosphatase (ALP) activity, while 1064 nm showed reduced ALP activity at 3J/cm2 . However, ALP induction was significantly improved when equivalent photon fluence dosing was used. Other wavelengths did not show significant changes compared to untreated controls. The data suggest that accounting for wavelength-specific photon energy transfer during PBM dosing could improve clinical safety and efficacy.

Progress of Photobiomodulation for Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disease with global burden. The mechanisms and therapeutic effects of photobiomodulation (PBM) correspond to main mechanisms in the pathogenesis of PD. Numerous research results applying PBM for PD were published during the past two decades. Although several systematic review or review articles provided complete introduction, they are either mainly basic research or clinical research, and the year of the article publication is up to 2020. Comprehensive systematic review or review articles containing basic and clinical studies including those published articles is lacking. Hence, this systematic review aimed to include both basic and clinical studies published up to 2022. Results were obtained by retrieving articles from PubMed with the intersection of the articles derived from the terms of PBM synonyms and Parkinson’s disease followed by exclusion. Sixty-nine articles were included ultimately. Among them, 40 original articles were identified, which were composed of 31 basic research and 9 original articles of clinical research. Twenty-one review articles, a systematic review with focused content on PD, and 7 review articles with the term PD under general illustration of PBM were presented. Mechanisms regarding the therapeutic effects of PBM on the vitro studies were reviewed. Positive outcomes on motor symptoms after PBM treatments were shown in most in vivo and clinical studies. The immunohistochemical examination of in vivo studies reflect the therapeutic effects of PBM on the preservation even reverse of the pathogenic insults of PD on the in vitro studies. The most frequently used wavelength among original articles included was 670nm. Considering the acceptability of PBM for patients with PD, noninvasive transcranial PBM (tPBM) had crucial roles in respect to invasive intracerebral PBM. To match the penetration depth reaching deep brain target, Substantia nigra pars compacta, in human brains of patients with PD, the wavelength 810nm might match the need in the clinical setting of tPBM. More future clinical studies were needed. In conclusion, therapeutic approaches applying PBM for PD are promising. Recent studies revealed positive outcomes. Future clinical practices containing PBM are to be expected.

The Efficacy of Photobiomodulation Therapy in Improving Tissue Resilience and Healing of Radiation Skin Damage

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.

Photobiomodulation-Activated Latent Transforming Growth Factor-β1: A Critical Clinical Therapeutic Pathway and an Endogenous Optogenetic Tool for Discovery.

Objective: The central role of the TGF-β pathway in embryonic development, immune responses, tissue healing, and malignancies is well established. Prior attempts with small molecules, peptides, and regulatory RNAs have failed mainly due to off-target effects in clinical studies. This review outlines the evidence for selectively activating the endogenous, latent transforming growth factor (TGF)-β1 with photobiomodulation (PBM) treatments. Background: Light treatments play a central role in current-directed energy therapeutics in medicine. Therapeutic use of low-dose light treatments has been noted since the 1960s. However, the breadth of treatments and inconsistencies with clinical outcomes have led to much skepticism. This can be primarily attributed to a lack of understanding of the fundamental light-tissue interactions and optimization of clinical treatment protocols. Methods: Recent advances in molecular mechanisms and improved biophotonic device technologies have led to a resurgence of interest in this field. Results: Over the past two decades, our work has focused on outlining a direct molecular mechanism involving PBM-generated redox-mediated activation of endogenous latent TGF-β1. Conclusions: Despite its critical roles in these processes, the complexity and cross talk in this potent growth factor signaling network have prevented the development of directed targeted therapeutics. PBM treatments offer a novel therapeutic and discovery tool in this aspect, especially with the growing evidence for its roles in cancer immunotherapy and stem cell biology.

Whole-organ transdermal photobiomodulation (PBM) of COVID-19: A 50-patient case study.

A nonrandomized 50‐person case study of COVID‐19‐positive patients was conducted employing (for the first time) a regimen of whole‐organ deep‐tissue transdermal dynamic photobiomodulation (PBM) as a primary (or exclusive) therapeutic modality in the treatment of coronavirus. Therapy sessions comprised algorithmically alternating red (650 nm) and near‐infrared (NIR; 850 nm) LEDs with an average irradiance of 11 mW/cm2 dynamically sequenced at multiple pulse frequencies. Delivered via 3D bendable polymeric pads maintaining orthogonal optical incidence to body contours over 1,000 cm2, a single 84‐minute session concurrently delivered 20 kJ to the sinuses and 15 kJ to each lung at skin temperatures below 42°C. Therapeutic outcomes observed include significant reductions in the duration and severity of disease symptoms. Acute conditions including fever, body aches (BA) and respiratory distress comprising paroxysmal coughing; lung congestion, dyspnea and hypoxia; sinus congestion; acute eye inflammation; and extreme malaise were eliminated in 41/50 patients within 4 days of commencing PBM treatments with 50/50 patients fully recovering within 3 weeks with no supplemental oxygen requirements. SpO2 concentrations improved as much as 9 points (average 2.5 points) across the entire study population. The PBM sessions required to completely resolve COVID‐19 conditions appears monotonically correlated to the time‐to‐treatment (TTTx)—the delay between the onset of a patient's symptoms and commencing PBM therapy. In contrast, acute inflammatory symptoms were resolved within 4 days irrespective of TTTx.

808-nm Photobiomodulation Affects the Viability of a Head and Neck Squamous Carcinoma Cellular Model, Acting on Energy Metabolism and Oxidative Stress Production

Photobiomodulation (PBM) is a form of low-dose light therapy that acts through energy delivery from non-ionizing sources. During the recent two decades, there has been tremendous progress with PBM acceptance in medicine. However, PBM effects on potential stimulation of existing malignant or pre-malignant cells remain unknown. Thus, the primary endpoint was to assess the safety of PBM treatment parameters on head and neck squamous cell carcinoma (HNSCC) proliferation or survival. The secondary endpoint was to assess any putative anti-cancer effects of PBM treatments. Cell viability, energy metabolism, oxidative stress, and pro- and anti-apoptotic markers expression were investigated on a Human Head and Neck Squamous Cell Carcinoma cellular model (OHSU-974 FAcorr cell line). PBM therapy was administered through the 810 nm diode laser (GaAlAs) device (Garda Laser, 7024 Negrar, Verona, Italy) at the powers of 0, 0.25, 0.50, 0.75, 1.00, or 1.25 W in continuous wave (CW) mode for an exposure time of 60 s with a spot-size of 1 cm2 and with a distance of 1.86 cm from the cells. Results showed that 810-nm PBM affected oxidative phosphorylation in OHSU-971 FAcorr, causing a metabolic switch to anaerobic glycolysis. In addition, PBM reduced the catalase activity, determining an unbalance between oxidative stress production and the antioxidant defenses, which could stimulate the pro-apoptotic cellular pathways. Our data, at the parameters investigated, suggest the safeness of PBM as a supportive cancer therapy. Pre-clinical and clinical studies are necessary to confirm the in vitro evidence.

Accelerated burn wound healing with photobiomodulation therapy involves activation of endogenous latent TGF-β1

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-β1 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-β 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-β dependent and independent signaling pathways. Finally, to investigate specific contributions of TGF-β1 signaling in these PBM-burn wound healing, we utilized a chimeric TGF-β1/β3 knock-in (TGF-β1Lβ3/Lβ3) mice. PBM treatments failed to activate the chimeric TGF-β1Lβ3/Lβ3 complex and failed to improve burn wound healing in these mice. These results suggest activation of endogenous latent TGF-β1 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.

Treatment of diabetic foot ulcers in a frail population with severe co-morbidities using at-home photobiomodulation laser therapy: a double-blind, randomized, sham-controlled pilot clinical study.

To evaluate the safety and efficacy of an at-home photobiomodulation (PBM) device for the treatment of diabetic foot ulcers (DFUs) in a frail population with severe comorbidities. Prospective, randomized, double-blind, sham-controlled pilot study. Patients (age = 63 ± 11years, male:female 13:7) with insulin-dependent diabetes type 2, neuropathy, peripheral artery disease, significant co-morbidities, and large osteomyelitis-associated DFUs (University of Texas grade ≥ III) were randomized to receive active (n = 10) or sham (n = 10) at-home daily PBM treatments (pulsed near-infrared 808nmGa-Al-As laser, 250mW, 8.8J/cm2) for up to 12weeks in addition to standard care. The primary outcome was the %wound size reduction. The secondary was adverse events. With the numbers available, PBM-treated group had significantly greater %reduction compared to sham (area [cm2], baseline vs endpoint: PBM 10[20.3]cm2 vs 0.2[2.4]cm2; sham, 7.9 [12.0]cm2 vs 4.6 [13.8]cm2, p = 0.018 by Mann-Whitney U test). Wound closure > 90% occurred in 7 of 10 PBM-treated patients but in only 1 of 10 sham patients (p = 0.006). No adverse device effects were observed. Photobiomodulation at home, in addition to standard care, may be effective for the treatment of severe DFUs in frail patients with co-morbidities and is particularly relevant at these times of social distancing. Our preliminary results justify the conduction of a larger clinical trial. gov: NCT01493895.

Treatment of partial injury of the calcaneus tendon with heterologous fibrin biopolymer and/or photobiomodulation in rats.

The present study aimed to evaluate the new heterologous fibrin biopolymer associated, or not, with photobiomodulation therapy for application in tendon injuries, considered a serious and common orthopedic problem. Thus, 84 Rattus norvegicus had partial transection of the calcaneus tendon (PTCT) and were randomly divided into: control (CG); heterologous fibrin biopolymer (HFB); photobiomodulation (PBM); heterologous fibrin biopolymer + photobiomodulation (HFB + PBM). The animals received HFB immediately after PTCT, while PBM (660nm, 40 mW, 0.23J) started 24h post injury and followed every 24h for 7, 14, and 21days. The results of the edema volume showed that after 24h of PTCT, there was no statistical difference among the groups. After 7, 14, and 21days, it was observed that the treatment groups were effective in reducing edema when compared to the control. The HFB had the highest edema volume reduction after 21days of treatment. The treatment groups did not induce tissue necrosis or infections on the histopathological analysis. Tenocyte proliferation, granulation tissue, and collagen formation were observed in the PTCT area in the HFB and HFB + PBM groups, which culminated a better repair process when compared to the CG in the 3 experimental periods. Interestingly, the PBM group revealed, in histological analysis, major tendon injury after 7days; however, in the periods of 14 and 21days, the PBM had a better repair process compared to the CG. In the quantification of collagen, there was no statistical difference between the groups in the 3 experimental periods. The findings suggest that the HFB and PBM treatments, isolated or associated, were effective in reducing the volume of the edema, stimulating the repair process. However, the use of HFB alone was more effective in promoting the tendon repair process. Thus, the present study consolidates previous studies of tendon repair with this new HFB. Future clinical trials will be needed to validate this proposal.

In Vitro Evidences of Different Fibroblast Morpho-Functional Responses to Red, Near-Infrared and Violet-Blue Photobiomodulation: Clues for Addressing Wound Healing

Although photobiomodulation (PBM) has proven promising to treat wounds, the lack of univocal guidelines and of a thorough understanding of light–tissue interactions hampers its mainstream adoption for wound healing promotion. This study compared murine and human fibroblast responses to PBM by red (635 ± 5 nm), near-infrared (NIR, 808 ± 1 nm), and violet-blue (405 ± 5 nm) light (0.4 J/cm2 energy density, 13 mW/cm2 power density). Cell viability was not altered by PBM treatments. Light and confocal laser scanning microscopy and biochemical analyses showed, in red PBM irradiated cells: F-actin assembly reduction, up-regulated expression of Ki67 proliferation marker and of vinculin in focal adhesions, type-1 collagen down-regulation, matrix metalloproteinase-2 and metalloproteinase-9 expression/functionality increase concomitant to their inhibitors (TIMP-1 and TIMP-2) decrease. Violet-blue and even more NIR PBM stimulated collagen expression/deposition and, likely, cell differentiation towards (proto)myofibroblast phenotype. Indeed, these cells exhibited a higher polygonal surface area, stress fiber-like structures, increased vinculin- and phospho-focal adhesion kinase-rich clusters and α-smooth muscle actin. This study may provide the experimental groundwork to support red, NIR, and violet-blue PBM as potential options to promote proliferative and matrix remodeling/maturation phases of wound healing, targeting fibroblasts, and to suggest the use of combined PBM treatments in the wound management setting.

Effects of stimulating frequency of NIR LEDs light irradiation on forehead as quantified by EEG measurements

Near-infrared (NIR) light has been shown to produce a range of physiological effects in humans, however, there is still no agreement on whether and how a single parameter, like the flicker frequency of NIR light, affects the brain. An 810[Formula: see text]nm NIR LED was used as the stimulator. Fifty subjects participated in this experiment. Forty subjects were randomly divided into four groups. Each group underwent a 30-minute NIR LED radiation with four different frequencies (i.e., 0[Formula: see text]Hz, 5[Formula: see text]Hz, 10[Formula: see text]Hz and 20[Formula: see text]Hz, respectively) on the forehead. The remaining 10 subjects formed the control group, in which they underwent a 30-minute rest period without light radiation. EEG signals of all subjects during each test were recorded. Gravity frequency (GF), relative energy change, and sample entropy were analyzed. The experimental groups had larger GF values compared to the control group. Higher stimulation frequency would cause larger growth of GF ([Formula: see text], [Formula: see text]). The amplitude of alpha waves relative energy increased, while theta waves decreased remarkably in the experimental groups ([Formula: see text]), and the extent of increase/decrease was larger at higher stimulation frequency, compared to that of the control. Sample entropy of electrodes in the frontal areas were much larger than those in other brain areas in the experimental groups ([Formula: see text]). Larger frequency of the NIR LED light would cause more distinct brain activities in the stimulated areas. It indicates that NIR LED light may have a positive effect on modulating brain activity. These results may help improve the design of photobiomodulation treatments in the future.

Photobiomodulation Therapy to Mitigate Radiation Fibrosis Syndrome.

Objective: We evaluated the role of photobiomodulation (PBM) in radiation fibrosis syndrome (RFS). Background: Radiation therapy (RT) is an important treatment utilized in over half of newly diagnosed cancers. Despite its benefits, patients treated with RT may experience acute and chronic significant side effects depending on both treatment- and patient-related factors. RFS is an important long-term side effect of RT, which can adversely impact patient's quality of life and organ function. With improved oncologic outcomes and survival for cancer patients after radiation, there is an unmet need to address long-term side effects of RT, particularly RFS. Results: Photobiomodulation (PBM) using low energy, nonionizing light primarily in the visible (especially red) or near-infrared spectrum has been demonstrated to decrease acute side effects of radiation in rigorously conducted phase III randomized studies; however, its potential benefit in ameliorating chronic radiation side effects, particularly RFS remains to be investigated. Conclusions: This review summarizes the in vitro data, preclinical animal studies and clinical reports, which showcase the potential benefits of PBM treatments in preventing and reversing RFS.

Photobiomodulation plus Adipose-derived Stem Cells Improve Healing of Ischemic Infected Wounds in Type 2 Diabetic Rats

In this study, we sought to investigate the impact of photobiomodulation and adipose-derived stem cells (ADS), alone and in combination, on the maturation step of wound healing in an ischemic infected delayed healing wound model in rats with type 2 diabetes mellitus (DM2). We randomly divided 24 adult male rats into 4 groups (n = 6 per group). DM2 plus an ischemic delayed healing wound were induced in all rats. The wounds were infected with methicillin-resistant Staphylococcus aureus. Group 1 was the control (placebo) group. Group 2 received only photobiomodulation (890 nm, 80 Hz, 0.324 J/cm2, and 0.001 W/cm2). Group 3 received only the allograft ADS. Group 4 received allograft ADS followed by photobiomodulation. On days 0, 4, 8, 12, and 16, we performed microbiological examination (colony forming units, [CFU]), wound area measurement, wound closure rate, wound strength, and histological and stereological examinations. The results indicated that at day 16, there was significantly decreased CFU (Analysis of variance, p = 0.001) in the photobiomodulation + ADS (0.0 ± 0.0), ADS (1350 ± 212), and photobiomodulation (0.0 ± 0.0) groups compared with the control group (27250 ± 1284). There was significantly decreased wound area (Analysis of variance, p = 0.000) in the photobiomodulation + ADS (7.4 ± 1.4 mm2), ADS (11 ± 2.2 mm2), and photobiomodulation (11.4 ± 1.4 mm2) groups compared with the control group (25.2 ± 1.7). There was a significantly increased tensiometeric property (stress maximal load, Analysis of variance, p = 0.000) in the photobiomodulation + ADS (0.99 ± 0.06 N/cm2), ADS (0.51 ± 0.12 N/cm2), and photobiomodulation (0.35 ± 0.15 N/cm2) groups compared with the control group (0.18 ± 0.04). There was a significantly modulated inflammatory response in (Analysis of variance, p = 0.049) in the photobiomodulation + ADS (337 ± 96), ADS (1175 ± 640), and photobiomodulation (69 ± 54) treatments compared to control group (7321 ± 4099). Photobiomodulation + ADS gave significantly better improvements in CFU, wound area, and wound strength compared to photobiomodulation or ADS alone. Photobiomodulation, ADS, and their combination significantly hastened healing in ischemic methicillin-resistant Staphylococcus aureus infected delayed healing wounds in rats with DM2. Combined application of photobiomodulation plus ADS demonstrated an additive effect.

Impact of Photobiomodulation and Condition Medium on Mast Cell Counts, Degranulation, and Wound Strength in Infected Skin Wound Healing of Diabetic Rats.

Background: Numerous people suffer from diabetes mellitus (DM) and resultant diabetic foot ulcers (DFU), which lack effective treatment. Photobiomodulation (PBM) has accelerated wound healing in diabetic animals and patients in some studies. However, there is scant information on the number and activation state of skin mast cells (MCs) in PBM-treated diabetic wounds. Objective: We intend to assess the influence of the number of MCs and degranulation in the remodeling step of an infected wound model on wound strength and its microbial flora in a type 1 DM (T1DM) rat model by administration of PBM, condition medium (CM) derived from human bone marrow mesenchymal stem cells (hBMMSCs), and the combination of PBM+CM. Methods: We prepared CM by culturing hBMMSCs. T1DM was induced in 72 rats and, after 1 month, we created one excisional wound in each rat. All wounds were infected with methicillin-resistant Staphylococcus aureus (MRSA). We divided the rats into four groups: (n = 18): (i) control; (ii) PBM; (iii) CM, and (iv) PBM+CM. On days 4, 7, and 15, we conducted microbiological, tensiometrical, and stereological analyses. The type of MCs (T1MCs, T2MCs, or T3MCs) and total number of MCs (TOMCs) were counted by light microscopy. Results: On day 15, the PBM+CM, PBM, and CM groups had significantly increased wound strength compared with the control group. There was a significant decrease in colony-forming units (CFU) at all time points in the PBM+CM and PBM groups. The PBM+CM and PBM groups had more stable MCs (T1MCs), less significant degranulated MCs (T2MCs), less significant disintegrated MCs (T3MCs), and less significant TOMCs compared with the control group at all time points. Conclusions: PBM+CM and PBM treatments significantly increased the healing process in an ischemic and MRSA-infected wound model of T1DM rats. PBM+CM and PBM significantly decreased both TOMCs and their degranulation, and significantly decreased CFU.

A DOUBLE-MASKED, RANDOMIZED, SHAM-CONTROLLED, SINGLE-CENTER STUDY WITH PHOTOBIOMODULATION FOR THE TREATMENT OF DRY AGE-RELATED MACULAR DEGENERATION.

The LIGHTSITE I study investigated the efficacy and safety of photobiomodulation (PBM) treatment in subjects with dry age-related macular degeneration. Thirty subjects (46 eyes) were treated with the Valeda Light Delivery System, wherein subjects underwent two series of treatments (3× per week for 3-4 weeks) over 1 year. Outcome measures included best-corrected visual acuity, contrast sensitivity, microperimetry, central drusen volume and drusen thickness, and quality of life assessments. Photobiomodulation-treated subjects showed a best-corrected visual acuity mean letter score gain of 4 letters immediately after each treatment series at Month 1 (M1) and Month 7 (M7). Approximately 50% of PBM-treated subjects showed improvement of ≥5 letters versus 13.6% in sham-treated subjects at M1. High responding subjects (≥5-letter improvement) in the PBM-treated group showed a gain of 8 letters after initial treatment (P < 0.01) and exhibited earlier stages of age-related macular degeneration disease. Statistically significant improvements in contrast sensitivity, central drusen volume, central drusen thickness, and quality of life were observed (P < 0.05). No device-related adverse events were reported. Photobiomodulation treatment statistically improved clinical and anatomical outcomes with more robust benefits observed in subjects with earlier stages of dry age-related macular degeneration. Repeated PBM treatments are necessary to maintain benefits. These pilot findings support previous reports and suggest the utility of PBM as a safe and effective therapy in subjects with dry age-related macular degeneration.

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

To provide background and examine evidence for the therapeutic application of light energy treatments for wound healing. This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. 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. 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.

Effects of Home Photobiomodulation Treatments on Cognitive and Behavioral Function, Cerebral Perfusion, and Resting-State Functional Connectivity in Patients with Dementia: A Pilot Trial.

Objective: To examine the effects of transcranial and intranasal photobiomodulation (PBM) therapy, administered at home, in patients with dementia. Background: This study sought to replicate and build upon a previously published case series report describing improved cognitive function in five patients with mild-to-moderate dementia after 12 weeks of transcranial and intranasal near-infrared (NIR) PBM therapy. Materials and methods: Eight participants (mean age: 79.8 ± 5.8 years old) diagnosed with dementia by their physicians were randomized to 12 weeks of usual care (UC, n = 4) or home PBM treatments (n = 4). The NIR PBM treatments were administered by a study partner at home three times per week with the Vielight Neuro Gamma device. The participants were assessed with the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) subscale and the Neuropsychiatric Inventory (NPI) at baseline and 6 and 12 weeks, and with arterial spin-labeled perfusion magnetic resonance imaging (MRI) and resting-state functional MRI at baseline and 12 weeks. Results: At baseline, the UC and PBM groups did not differ demographically or clinically. However, after 12 weeks, there were improvements in ADAS-cog (group × time interaction: F1,6 = 16.35, p = 0.007) and NPI (group × time interaction: F1,6 = 7.52, p = 0.03), increased cerebral perfusion (group × time interaction: F1,6 = 8.46, p < 0.03), and increased connectivity between the posterior cingulate cortex and lateral parietal nodes within the default-mode network in the PBM group. Conclusions: Because PBM was well tolerated and associated with no adverse side effects, these results support the potential of PBM therapy as a viable home treatment for individuals with dementia.

Photobiomodulation (PBM) Provides a Prompt and Near-Resolution Response to Advanced Oral Chronic Graft-Versus-Host Disease (cGVHD) after Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)

Background cGVHD is a major complication after allo-HSCT. The oral cavity is frequently affected and may present with painful ulcerations, intraoral discomfort, and limitation to oral intake. While systemic corticosteroids remain first line therapy for moderate/ severe cGVHD, topical and intralesional immunosuppressant (IS)-based therapies have been used with modest effect. PBM, a non-invasive light therapy, appears to promote tissue recovery via direct absorption of cytochrome C oxidase and activation of TGF-β1, and has been used for the prevention and treatment of radiation-induced mucositis in head & neck cancer. However, the effect of PBM therapy in oral cGVHD is currently unknown. Methods We evaluated 7 patients (median age 47) who underwent allo-HSCT (7 PBSC grafts) after myeloablative (n = 3) and reduced (n = 4) conditioning between 09/2015-05/2017. Patients developed moderate (n = 2) or severe (n = 5) oral cGVHD and received PBM (2x/week for 3 weeks) after failure to improve with topical corticosteroid and/or topical tacrolimus therapy +/- intralesional triamcinolone injections and systemic IS. Thor® laser LX2 with wavelengths of 660 nm (visible-red) and 810 nm (near-infrared) was applied extra-orally. The psychometric questionnaire for pain rating (Visual Analogue Scale [VAS], scale 0-10), and oral GVHD (OGVHD) score (severity of erythema, lichenoid changes, ulcers and mucoceles, scale 0-15) were used weekly for the assessment of therapeutic response. Results The baseline oral cGVHD evaluation revealed high VAS (median 7, range 3-8) and OGVHD (median 9, range 6-9) scores. Patients had affected oral cavity that included lichen planus-like changes, ulcers, mucositis, gingivitis, and/or erythema (Fig. 1A-B). The first therapeutic response assessment was obtained 1 week after initiation of therapy and showed improvement in pain by VAS score (median 3). Subsequent assessments were obtained for the duration of PBM therapy and showed overall improvement in the pain scale and healing of the oral cavity (Fig. 1C-D, 2A-B). At the end of treatment, the median VAS score was 2 (range 1-2) and OGVHD was 3 (range 1-4). Treatment was well tolerated, and all patients received the intended number of PBM treatments in the planned period of 3 weeks. No adverse events were reported as related to PBM. Conclusions Advanced oral cGVHD achieved near-complete resolution of pain and oral cavity lesions after PBM therapy. Notable, patients who previously failed to respond to upfront topical and systemic IS treatment achieved high therapeutic response with PBM. Improvement in pain scale was observed 1 week after starting therapy and healing of the oral cavity was observed at 2 weeks. This non-IS treatment appears feasible, safe and promising in oral cGVHD. A prospective study is needed to confirm these preliminary findings.

Red (635 nm), Near-Infrared (808 nm) and Violet-Blue (405 nm) Photobiomodulation Potentiality on Human Osteoblasts and Mesenchymal Stromal Cells: A Morphological and Molecular In Vitro Study.

Photobiomodulation (PBM) has been used for bone regenerative purposes in different fields of medicine and dentistry, but contradictory results demand a skeptical look for its potential benefits. This in vitro study compared PBM potentiality by red (635 ± 5 nm) or near-infrared (NIR, 808 ± 10 nm) diode lasers and violet-blue (405 ± 5 nm) light-emitting diode operating in a continuous wave with a 0.4 J/cm2 energy density, on human osteoblast and mesenchymal stromal cell (hMSC) viability, proliferation, adhesion and osteogenic differentiation. PBM treatments did not alter viability (PI/Syto16 and MTS assays). Confocal immunofluorescence and RT-PCR analyses indicated that red PBM (i) on both cell types increased vinculin-rich clusters, osteogenic markers expression (Runx-2, alkaline phosphatase, osteopontin) and mineralized bone-like nodule structure deposition and (ii) on hMSCs induced stress fiber formation and upregulated the expression of proliferation marker Ki67. Interestingly, osteoblast responses to red light were mediated by Akt signaling activation, which seems to positively modulate reactive oxygen species levels. Violet-blue light-irradiated cells behaved essentially as untreated ones and NIR irradiated ones displayed modifications of cytoskeleton assembly, Runx-2 expression and mineralization pattern. Although within the limitations of an in vitro experimentation, this study may suggest PBM with 635 nm laser as potential effective option for promoting/improving bone regeneration.

Improved Wound Remodeling Correlates with Modulated TGF-beta Expression in Skin Diabetic Wounds Following Combined Red and Infrared Photobiomodulation Treatments.

Diabetic wounds are a major cause of morbidity among patients with poorly controlled blood glucose levels. Conventional empirical wound care strategies have shown limited efficacy, and there is an urgent need to develop novel therapeutic strategies. Photobiomodulation treatments have shown positive therapeutic effects in several cell culture and animal models. In this study, we examined wound healing in diabetic rats following treatments with two laser wavelengths, namely red (660 nm) and infrared (808 nm) individually and in combination as compared to routine wound dressings. Immunostaining for TGF-β expression was performed at various times postwounding. We noted that the combination of red and infrared laser treatments correlated with decreased TGF-β1 levels at late stages in healing. There was no statistical significance with any treatments at an earlier time point. This study emphasizes the role of appropriate laser treatment protocols in modulating wound healing and remodeling responses.