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

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

Should open excisions and sutured incisions be treated differently? A review and meta-analysis of animal wound models following low-level laser therapy.

Although low-level laser therapy (LLLT) was discovered already in the 1960s of the twentieth century, it took almost 40 years to be widely used in clinical dermatology/surgery. It has been demonstrated that LLLT is able to increase collagen production/wound stiffness and/or improve wound contraction. In this review, we investigated whether open and sutured wounds should be treated with different LLLT parameters. A PubMed search was performed to identify controlled studies with LLLT applied to wounded animals (sutured incisions-tensile strength measurement and open excisions-area measurement). Final score random effects meta-analyses were conducted. Nineteen studies were included. The overall result of the tensile strength analysis (eight studies) was significantly in favor of LLLT (SMD = 1.06, 95% CI 0.66-1.46), and better results were seen with 30-79 mW/cm2 infrared laser (SMD = 1.44, 95% CI 0.67-2.21) and 139-281 mW/cm2 red laser (SMD = 1.52, 95% CI 0.54-2.49). The overall result of the wound contraction analysis (11 studies) was significantly in favor of LLLT (SMD = 0.99, 95% CI 0.38-1.59), and the best results were seen with 53-300 mW/cm2 infrared laser (SMD = 1.18, 95% CI 0.41-1.94) and 25-90 mW/cm2 red laser (SMD = 1.6, 95% CI 0.27-2.93). Whereas 1-15 mW/cm2 red laser had a moderately positive effect on sutured wounds, 2-4 mW/cm2 red laser did not accelerate healing of open wounds. LLLT appears effective in the treatment of sutured and open wounds. Statistical heterogeneity indicates that the tensile strength development of sutured wounds is more dependent on laser power density compared to the contraction rate of open wounds.

Effect of 670 nm laser photobiomodulation on vascular density and fibroplasia in late stages of tissue repair.

This study aimed to investigate the effects of gallium-aluminum-arsenium (GaAlAs) (670 nm) laser therapy on neoangiogenesis and fibroplasia during tissue remodelling. Forty male Wistar rats underwent cutaneous surgery and were divided into 2 experimental groups: the Control and Laser group (9 mW, 670 nm, 0.031 W/cm2 , 4 J/cm2 ). After 14, 21, 28, and 35 days, the animals were euthanised. Descriptive and quantitative analyses were performed in sections stained with haematoxylin-eosin and Sirius Red, respectively. The amounts of VEGF+ and CD31+ cells were evaluated by immunohistochemistry and histomorphometric analysis, respectively. Statistical analysis was performed using the Mann-Whitney, Friedman, and Spearman correlation test, P < 0.05. The collagen expression was significantly higher in the laser group compared with the control group on days 14 and 21 after the creation of the skin wound (P = 0.008; P = 0.016) and in the control group between 14 and 28 and 14 and 35 days (P = 0.001; P = 0.007). There were more blood vessels in three periods of the study only in the (Laser) treated group, with statistical significance at day 14 (P = 0.016). There was no statistically significant difference in VEGF+ cell count in the different experimental groups throughout the study, although a positive correlation was shown with the area of collagen on days 14 and 28 (P = 0.037). Laser treatment had a positive effect in the late course of healing, particularly with regards to collagen expression and the number of newly formed vessels. VEGF+ cells were present in both experimental groups, and VEGF appeared to influence fibroplasia in the treated group.

Clinical effectiveness of low-level laser treatment on peripheral somatosensory neuropathy.

Peripheral sensory neuropathy treatment is one of the common treatment problems and causes morbidity and mortality in people suffering from that. Although treatment depends on the underlying cause of the condition, nevertheless, in some cases, there is no cure for it, and it requires palliative and symptomatic treatment. In laboratory studies, low-level laser has been effective in the nerves protection and restoration. The aim of this article is to investigate the clinical efficacy of low-level laser on improvement of the peripheral somatosensory neuropathy. Search in the articles published up to 30 October 2015 (full text and abstracts) in databases PubMed (Medline), Cochrane library, Physiotherapy Evidence Database was performed. The studies of low-level laser trials on patients with peripheral neuropathy were carried out and evaluated in terms of the exclusion criteria. There are 35 articles among which 10 articles had the intended and required criteria. 1, 3, and 6 articles study the patients with diabetes, neuropathy caused by trauma, and carpal tunnel syndrome, respectively. In six studies, laser led to a reduction in sensory impairment and improvement of the physiological function of the sensory nerves. In these articles, lasers (Diode, GaAlAs, He-Ne) had wavelength range 660-860 nm, radiation power 20-250 mW, energy density 0.45-70 J/cm2. The intervention sessions range was 6-21 times and patient follow-up was 0-6 months. According to the results of these studies, low-level laser therapy can improve sensory function in patients with peripheral somatosensory neuropathy, although little research have not been done, laser treatment regimens are varied and do not recommend a specific treatment protocol. It seems it requires more research to sum up better, particularly in relation to diabetes.

[Antibiotic Resistance of Microbial Isolates from Long-Term Healing Wounds Exposed to Light of Various Wave Lengths].

The data on inhibition of the growth of microorganisms of a characteristic spectrum and antibiotic resistance isolated from long-term healing wounds by light of various wave ranges are presented. The growing cultures on blood agar were exposed to polarized light, red and infrared, ultraviolet of medium- and short-wave continuous modes accustomed in physiotherapy of wounds.The effect of light in some way induced inhibition of the growth, but complete recovery was stated only after the use of ultraviolet light when confirmed quantitatively in terms of the CFU.

The energy density of laser light differentially modulates the skin morphological reorganization in a murine model of healing by secondary intention.

This study investigates the influence of gallium-arsenide (GaAs) laser photobiostimulation applied with different energy densities on skin wound healing by secondary intention in rats. Three circular wounds, 10 mm in diameter, were made on the dorsolateral region of 21 Wistar rats weighting 282.12 ± 36.08 g. The animals were equally randomized into three groups: Group SAL, saline solution 0.9%; Group L3, laser GaAs 3 J/cm(2); Group L30, laser GaAs 30 J/cm(2). Analyses of cells, blood vessels, collagen and elastic fibres, glycosaminoglycans and wound contraction were performed on the scar tissue from different wounds every 7 days for 21 days. On day 7, 14 and 21, L3 and L30 showed higher collagen and glycosaminoglycan levels compared to SAL (P < 0.05). At day 21, elastic fibres were predominant in L3 and L30 compared to SAL (P < 0.05). Type-III collagen fibres were predominant at day 7 in both groups. There was gradual reduction in these fibres and accumulation of type-I collagen over time, especially in L3 and L30 compared with SAL. Elevated density of blood vessels was seen in L30 on days 7 and 14 compared to the other groups (P < 0.05). On these same days, there was higher tissue cellularity in L3 compared with SAL (P < 0.05). The progression of wound closure during all time points investigated was higher in the L30 group (P < 0.05). Both energy densities investigated increased the tissue cellularity, vascular density, collagen and elastic fibres, and glycosaminoglycan synthesis, with the greater benefits for wound closure being found at the density of 30 J/cm(2).

Fractional CO2 laser is as effective as Q-switched ruby laser for the initial treatment of a traumatic tattoo.

BACKGROUND AND OBJECTIVE: Q-switched laser treatments are considered the standard method for removing both regular and traumatic tattoos. Recently, the removal of tattoo ink using ablative fractional lasers has been reported. Ablative fractional CO2 laser and q-switched ruby laser treatments were used in a split-face mode to compare the safety and efficacy of the two types of laser in removing a traumatic tattoo caused by the explosion of a firework. STUDY DESIGN/PATIENTS AND METHODS: A male patient suffering from a traumatic tattoo due to explosive deposits in his entire face was subjected to therapy. A series of eleven treatments were performed. The right side of the face was always treated using an ablative fractional CO2 laser, whereas the left side was treated only using a q-switched ruby laser. RESULTS: After a series of eleven treatments, the patient demonstrated a significant lightening on both sides of his traumatic tattoo, with no clinical difference. After the first six treatments, the patient displayed greater lightening on the right side of his face, whereas after another five treatments, the left side of the patient's face appeared lighter. No side effects were reported. CONCLUSIONS: In the initial stage of removing the traumatic tattoo, the ablative fractional laser treatment appeared to be as effective as the standard ruby laser therapy. However, from the 6th treatment onward, the ruby laser therapy was more effective. Although ablative fractional CO2 lasers have the potential to remove traumatic tattoos, they remain a second-line treatment option.

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

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

The effect of monochromatic infrared energy on diabetic wound healing.

This study examined the effect of monochromatic infrared energy (MIRE) on diabetic wound healing. Fifteen diabetic rats were given MIRE intervention on their skin wounds located on the dorsum and compared with 15 control diabetic rats. Assessments were conducted for each group at weeks 1, 2 and 4 post wounding (five rats at each time point) by calculating the percentage of wound closures (WCs) and performing histological and immunohistochemical staining on sections of wound tissue. Evaluations of WCs and histological examinations of reepithelialisation, cellular content and granulation tissue formation showed no significant difference between the MIRE and the control group at each time point. Through semi-quantitative immunohistochemical staining, the deposition of type I collagen in the MIRE group was found to have improved when compared with the control group at the end of week 2 (P = 0.05). No significant differences in the myofibroblast population were detected between the two groups. In conclusion, MIRE appeared to promote collagen deposition in the early stage of wound healing in diabetic rats, but the overall wound healing in the MIRE group was not significantly different from that of the control group.

Pulsed radio frequency energy in the treatment of painful chronic cutaneous wounds: a report of two cases.

SETTING: Chronic cutaneous wounds may cause considerable pain, often affecting patient compliance with necessary treatment protocols. PATIENTS: Two patients are presented who were unable to comply with compression therapy because of severe wound pain. INTERVENTION: Adjunctive pulsed radio frequency energy was administered for 30 minutes twice daily through an applicator pad placed directly on the dressing over the wound area. RESULTS: Both patients reported immediate, marked pain reduction, allowing compression therapy. The ulcers healed completely within 3 weeks for patient 1 and 28 weeks for patient 2. CONCLUSIONS: Further investigation into the efficacy of pulsed radio frequency energy for the treatment of painful wounds is warranted.

[Effect of the photosensitizers pheophorbid a and protoporphyrin IX on skin wound healing by the action of low-intensity laser irradiation].

The effect of photosensitizer with subsequent He-Ne (632.8 nm; 3 mW/cm2) laser irradiation on experimental skin wound healing has been studied. Pheophorbid a and protoporphyrin IX were used as photosensitizers. It was found that the application of the photosensitizer and subsequent laser irradiation, first, decreased the amount and the functional activity of leukocyte in wound excudate and, second, inhibited the SOD-activity, compared to that of the control group. Moreover, pheophorbide a and protoporphyrin practically did not affect the total healing period but decreased the length of the inflammation stage. It was supposed that these effects are related to the generation of reactive oxygen species during irradiation.

[Muscle regeneration and the state of the thymus in adult rats under laser irradiation and alloplasty of the gastrocnemius muscles and diaphragm of newborn rats].

The regeneration of gastrocnemius muscles of adult rats under implantation conditions in areas of muscle tissue damage in newborn rats has been studied. Alloplasty was performed using minced gastrocnemius and diaphragm muscles, which differs at birth in animals by degree of differentiation. The rat-recipient area of alloplasty was subjected to He-Ne laser radiation before operation, with the aim of reducing the immune response to allogenic muscle tissue. It has been shown that the number of regenerating myofibers produced in implanted gastrocnemius muscles is more than in alloplants from diaphragms. However, the formation of cartilage, bone, and adipose tissue foci were observed in the alloplastic region throughout the whole regeneration period. After implantation of minced diaphragm muscles, cartilage nodes were observed only in 7-day regenerates. At the end of observation, in the first instance, the area of muscle trauma in adult rat muscles was replaced by adipose tissue, even in the case of initial laser irradiation. During the implantation of diaphragm muscles, the area of trauma was filled with regenerating muscle tissue.

The Effects of Ultraviolet C Irradiation in the Treatment of Chronic Wounds: A Retrospective, Descriptive Study.

Although there is evidence supporting the bactericidal effects of ultraviolet C (UVC) in chronic wounds, clinical studies examining the effects of UVC on wound healing are limited. PURPOSE: The objective of this single-center, retrospective, descriptive study was to evaluate the effect of UVC as an adjunct modality to standard wound care. METHODS: Data from January 1, 2015, through August 30, 2015, from all patients receiving UVC treatment and wound etiology-appropriate standard care provided twice weekly at a wound care center and lymphedema clinic were extracted from the electronic health records. Demographic (age, gender) and clinical wound data (duration, type, initial and final dimensions, number of UVC treatments, time to healing, healed versus not healed, and adverse events) were extracted, deidentified, and analyzed using descriptive and chi-squared analysis and analysis of variance. Wound type categories with small sample sizes were combined for analysis. RESULTS: Among the 127 patients studied (64 women [50.4%], average age 69 ± 15.0 years; and 63 men [49.6 %], average age 61 ± 15.8 years; P = .03), 224 wounds received UVC treatment. Initial average wound area was 24.1 ± 121.8 cm², and the most common type of wound was venous (58, 25.9%), followed by neuropathic/diabetic foot ulcer and traumatic wounds (43 each, 19.2% each). Mean wound duration was 57.7 ± 63 days; overall average patient age was 64.8 ± 15.9 years. Average number of treatments of 11.9 ± 13.4, and average time to healing was 45.2 ± 44.4 days. A total of 127 patients with 161 wounds (71.9%) healed after an average of 45 (range 4-260) days, including 36 venous leg ulcers (62.1%) and 33 neuropathic wounds/diabetic foot ulcers (76.7%). No adverse events were recorded. CONCLUSION: UVC may be an effective adjuvant treatment modality when used with standard care in the treatment of chronic wounds. Prospective studies are needed to ascertain the effectiveness and efficacy of UVC in the treatment of chronic wounds.

Role of the PI3K/AKT (mTOR and GSK3ß) signalling pathway and photobiomodulation in diabetic wound healing.

Activated phosphatidylinositol 3 kinase/Protein kinase B (PI3K/AKT) signalling with increased or reduced mTOR and GSK3ß activity influences the wound repair process. Diabetic wounds, usually ulcerated, are characterised by reduced growth factors and cellular performance. The occurrence of diabetic ulcers is linked to peripheral arterial disease, neuropathy, and wound contamination. Lasers or light emitting diodes (LEDs) provide photon energy with therapeutic benefits (Photobiomodulation-PBM), and has been broadly commended to quicken diabetic wound healing. PBM is efficient in the visible red and near-infrared electromagnetic spectrum, and fluencies ranging from 2 to 6 J/cm2. However, cellular and molecular mechanisms induced by PBM are not fully understood. In this review we discuss PBM and the PI3K/AKT pathway with specific focus on the mTOR and GSK3ß downstream activity in diabetic wound healing.

Influence of laser photobiomodulation upon connective tissue remodeling during wound healing.

The modulation of collagen fibers during experimental skin wound healing was studied in 112 Wistar rats submitted to laser photobiomodulation treatment. A standardized 8mm-diameter wound was made on the dorsal skin of all animals. In half of them, 0.2ml of a silica suspension was injected along the border of the wound in order to enhance collagen deposition and facilitate observation. The others received saline as vehicle. The treatment was carried out by means of laser rays from an aluminum-gallium arsenide diode semiconductor with 9mW applied every other day (total dose=4J/cm2) on the borders of the wound. Tissue sections obtained from four experimental groups representing sham-irradiated animals, laser, silica and the association of both, were studied after 3, 7, 10, 15, 20, 30 and 60 days from the laser application. The wounded skin area was surgically removed and submitted to histological, immunohistochemical, ultrastructural, and immunofluorescent studies. Besides the degree and arrangement of collagen fibers and of their isotypes, the degree of edema, the presence of several cell types especially pericytes and myofibroblasts, were described and measured. The observation of Sirius-red stained slides under polarized microscopy revealed to be of great help during the morphological analysis of the collagen tissue dynamic changes. It was demonstrated that laser application was responsible for edema regression and a diminution in the number of inflammatory cells (p<0.05). An evident increase in the number of actin-positive cells was observed in the laser-treated wounds. Collagen deposition was less than expected in silica-treated wounds, and laser treatment contributed to its better differentiation and modulation in all irradiated groups. Thus, laser photobiomodulation was able to induce several modifications during the cutaneous healing process, especially in favoring newly-formed collagen fibers to be better organized and compactedly disposed.

Effects of Photobiomodulation on Degranulation and Number of Mast Cells and Wound Strength in Skin Wound Healing of Streptozotocin-Induced Diabetic Rats.

BACKGROUND: A lack of effective treatments still exists for patients suffering from diabetes mellitus. Photobiomodulation is proved as a beneficial therapeutic modality for wounds. OBJECTIVE: The aim of this study is to examine the effect of degranulation of mast cells and total number of mast cells in the remodeling step of an ischemic model of wound healing under the influence of photobiomodulation and conditioned medium (CM) from human bone marrow-derived mesenchymal stem cells (hBM-MSCs-CM), or CM, administered alone and or in combination. MATERIALS AND METHODS: Initially, type 1 diabetes mellitus was induced in 72 male adult rats. Then, after a month, one incision was made on the back of each rat. Subsequently, the rats were divided into four groups. The first group was considered as the control (placebo) group, the second group received CM, the third group received photobiomodulation, and the fourth group received photobiomodulation+CM. On days 4, 7, and 15, samples were extracted from the wound for histological and tensiometric examinations. The total number of mast cells, including the three types of mast cells, was counted by the stereological methods. The tensiometric properties of the repairing tissue were examined. RESULTS: The administration of photobiomodulation and CM, alone or in combination, significantly increased the tensiometric properties within the healing wounds. Histologically, photobiomodulation+CM, CM, and photobiomodulation groups showed a significant decrease in the three types of mast cells and in the total number of mast cells compared with the control group on day 15. CONCLUSIONS: We conclude that photobiomodulation and CM alone and or in combination significantly accelerated the healing process in a rat with a diabetic and ischemic wound, and significantly decreased the total number of mast cells and degranulation of mast cells. We suggest that the increased number of type 2 mast cells in the control group adversely affected the tensiometric properties of wounds in this group.

Effects of laser therapy in CO2 laser wounds in rats.

OBJECTIVE: The aim of this study was to assess the effects of laser therapy and its possible dose dependency on the healing of CO2 laser surgical wounds. BACKGROUND DATA: Several reports from our group and others have indicated that light therapies may improve healing, depending on wavelength, dose, intensity of the light, and both local and systemic conditions. METHODS: Circular surgical wounds were created on the dorsum of Wistar rats, which were separated into three groups (A, B, and C). Group A acted as control and had no additional treatment. Groups B and C were irradiated with GaAlAs lambda685-nm laser light, either with 20 J/cm2 (Group B) or 40 J/cm2 (Group C). The animals were humanely killed at the end of the experimental period; specimens were taken and routinely processed to wax and stained with Hematoxylin and Eosin, Sirius Red, and alpha-Smooth Muscle Actin (alphaSMA). RESULTS: Laser-irradiated groups showed a healing process characterized by a more prominent fibroblastic proliferation, with young fibroblasts actively producing collagen; no myofibroblasts were found. No statistically significant differences were observed when the different doses were compared. CONCLUSION: It may be concluded that, using this methodology, laser therapy has a positive effect in wound healing produced by CO2 laser, and the dose has no influence on the treatment.

[Structure peculiarities of muscle regenerates and state of thymus under He-Ne laser therapy in different periods after muscle trauma].

We studied the gastrocnemius muscle regeneration and the reactive changes in thymus of rats under different regimens of He-Ne laser therapy of both operated legs (632.8 nm; 2.5-3.0 mW/cm(2) ). Laser radiation (10 exposures by 3 min within 1-15 days after muscle trauma, 4.5-5.4 J/cm(2) total dose per each leg) stimulated inflammatory reaction, muscle healing and favored preservation of muscle tissue in regenerates. The changes in thymus mass, its histological structure, size of cortex and thymocite mitotic index pointed to the increase of the functional load on thymus and delay of its recovery. The same dose of laser therapy of muscles within 16-30 days after trauma led to the increase of muscle tissue sclerotization in regenerates. The reactive changes in thymus were less pronounced. Threefold decrease of laser dose (10 exposures by 1 min for 1-15 days, 1.5-1.8 J/cm(2)) suppressed inflammatory reaction, impaired the muscle regeneration. The increase of functional activity in thymus was not observed.

Effect of external beam irradiation on neointimal hyperplasia after experimental coronary artery injury.

Human coronary artery restenosis after percutaneous revascularization is a response to mechanical injury. Smooth muscle cell proliferation is a major component of restenosis, resulting in obstructive neointimal hyperplasia. Because ionizing radiation inhibits cellular proliferation, this study tested in a porcine coronary injury model the hypothesis that the hyperplastic response to coronary artery injury would be attenuated by X-irradiation. Deep arterial injury was produced in 37 porcine left anterior descending coronary artery segments with overexpanded, percutaneously delivered tantalum wire coils. Three groups of pigs were irradiated with 300-kV X-rays after coil injury: Group I (n = 10), 400 cGy at 1 day; Group II (n = 10), 400 cGy at 1 day and 400 cGy at 4 days and Group III (n = 9), 800 cGy at 1 day. Eight pigs in the control group underwent identical injury but received no radiation. Treatment efficacy was histologically assessed by measuring neointimal thickness and percent area stenosis. Mean neointimal thickness in all irradiated groups was significantly higher than in the control groups and thickness was proportional to X-ray dose. X-irradiation delivered at these doses and times did not inhibit proliferative neointima. Rather, it accentuated the neointimal response to acute arterial injury and may have potentiated that injury.