Article

Light therapy by blue LED improves wound healing in an excision model in rats

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Low level light therapy (LLLT) is an attractive alternative to enhance wound healing. So far most studies are performed with red or infrared irradiation. However, we recently showed that blue light (470 nm) can significantly influence biological systems, improving perfusion by release of nitric oxide from nitrosyl complexes with haemoglobin in a skin flap model in rats. Here, we compared the effects of blue and red low level light by light-emitting diodes (LEDs) on in vivo wound healing in an excision wound model in rats. Circular excision wounds were surgically created on the dorsum of each rat. Excisions on either the left or right side were illuminated post-OP and on five consecutive days for 10 min by LED at 470 nm or 630 nm with an intensity of 50 mW/cm(2),while protecting the contralateral side from exposure. In the control group, neither side was illuminated. On day 7 post-OP, we analysed planimetric and histological parameters, as well as expression of keratin-1, keratin-10 and keratin-17 on mRNA level. Illumination substantially influenced wound healing. Blue light significantly decreased wound size on day 7, which correlated with enhanced epithelialisation. Light also affected mRNA expression. Both wavelengths decreased keratin-1 mRNA on day 7 post-OP, while keratin-10 mRNA level was elevated in both light treated group compared to control. Keratin-17 mRNA was also elevated in the red light group, but was unchanged in the blue light group. In contrast to previous studies, we showed that also blue light significantly influences wound healing. Furthermore, our data suggest that light therapy can play an important role in normotrophic wound healing by affecting keratin expression. Illumination would provide an easily applicable, safe and cost-effective treatment of surface wounds.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Low intensity, non-thermal irradiance does not generate heat [2]. This process is also referred to as photostimulation, phototherapy or photobiomodulation [3,4]. ...
... The biomodulatory effects of LLLT have been disseminated in a variety of in vitro studies using different cell types such as fibroblasts, lymphocytes, keratinocytes, macrophage, HeLa and stem cells [4]. It has been demonstrated that LLLT has the ability to modulate the process of tissue repair by prompting of cellular reaction such as migration, proliferation, apoptosis and cellular differentiation [5]. ...
... Light absorption may lead to photodissociation of the restrained nitric oxide from CCO, leading to the boost of enzyme activity, increasing electron transport, oxygen consumption, mitochondrial respiration and adenosine triphosphate (ATP) production. Thus, altering the mitochondria or redox state of the cell, LLLT can stimulate the activation of many intracellular signalling pathways and changes of cellular activities including proliferation, regeneration and cell survival [4,8]. ...
... Because blue light can affect wound healing positively [72], the effect of only blue light irradiation on wound healing was investigated. As shown in Fig. S6, after 15 days of cultivation, groups irradiated with blue light alone and PBS-only groups showed a healing ratio of 78.3 ± 3.1% and 76.6 ± 4.2%, respectively. ...
... No significant differences were observed because of the irradiation time. The wounds in the literature [72] were irradiated for five consecutive days for 10 min by LED at 470 nm with an intensity of 50 mW/cm 2 , while the wounds conducted in this study were treated with only blue light within 5 s after the removal of the wound skin. Therefore, there is almost no apparent effect of blue light on wound healing in this healing model. ...
Article
Uncontrollable bleeding and wound infection remain as the primary challenges for emergency surgical procedures, including deep and non-compressible bleeding in the clinic or on the battleground. To better control haemorrhaging immediately from irregularly shaped and non-compressible wounds, double-network adhesive hydrogels based on cellulose and 3,4-dihydroxyphenylalanine (DOPA)-cation copolymer were designed for wound healing. Due to the abundance of hydrogen bonding, π-π stacking, cation-π and electrostatic interactions in the double-network adhesives, the hydrogel with good biocompatibility presented tissue-like mechanical strength with Young’s modulus below 20 kPa. The catechol-cation cooperation effect enhances the wet adhesion of hydrogels to skin tissue surfaces. The blue-light-induced fast gelation networks provide rapid haemostasis ability of the hydrogels by sealing blood vessels. The quaternary ammonium cationic polymers have remarkable antibacterial properties and promote blood coagulation by erythrocyte and platelet aggregation. Furthermore, the hydrogel with 2.5% P(DOPMAm-co-MPTC) (AC/PDM2.5) exhibited better tissue adhesion strength than commercially available glue, better haemostatic capability than the gauze based on the mouse-tail amputation model, and higher performance compared to Tegaderm™ in the rat full-thickness skin defect model. These adhesive hydrogels with fast gelling, rapid haemostasis, biocompatibility and antibacterial activity offer great promising applications in wound healing.
... It is also called the integumentary system, with protection functions, water barrier, body temperature regulation, defense against microorganisms and salt excretion and vitamin D synthesis. It consists of three layers firmly adhered some to the others, which are termed the epidermis, dermis and hypodermis (1,2) . The dermis is the supporting layer of the epidermis, the most abundant type of tissue in the body. ...
... They observed that the irradiation caused by the blue LED had positive influences on the healing and the epithelization process, significantly reducing the wound size when compared to the control group. In addition, they also noticed positive effects on keratin, which plays an important role in the healing of normotrophic wounds (1) . Studies involving photobiomodualization with specific wavelengths provides a reinforcement in the rate of healing, as well as in the proliferation of specific cells and their mechanisms of action. ...
Article
Full-text available
Introduction: Drugs formulated as Resveratrol, associated with LED 627nm photobiomodulation, can increase the efficacy of active release, increased local circulation, cell proliferation and collagen synthesis, accelerating the healing process. Objective: To analyze the effects of 627nm LED photobiomodulation associated with Resveratrol on the tissue repair of induced wounds in Wistar rats. Methodology: We used 18 animals corresponding to the control groups, group LED 627nm with association to Resveratrol cream (GLed + Resv) 3 and 7 days. Results: Treatment with the use of LED associated with Resveratrol cream provided an efficient healing. In the statistical test, the significance level was observed between the groups of P <0.0156. In the multiple comparison between the pairs the Tukey’s test showed significance between the groups CG vs GLed627nm + Resv 7Day. Conclusion: The GLed + Resv group showed efficient inflammatory phase of healing, promoting a greater activation of fibroblasts and remodeling of the collagen fiber when compared to the control group.
... Groups 1 and 2 were obtained similar numbers in the evolution of the perimeter, but Group 2 (laser) showed increased hyperkeratosis (callus around the edges) and decreased hydration. In relation to epidermal injury, wound contraction and re-epithelialization from the wound edge, which is important in wound closure, is the proliferation of keratinocyte proliferation [28]. The study by Adamskaya N et al. [28] demonstrates that the laser therapy showed increased keratin tissue at the edges of the tissue and healing was still ongoing. ...
... In relation to epidermal injury, wound contraction and re-epithelialization from the wound edge, which is important in wound closure, is the proliferation of keratinocyte proliferation [28]. The study by Adamskaya N et al. [28] demonstrates that the laser therapy showed increased keratin tissue at the edges of the tissue and healing was still ongoing. The diabetic foot already suffered from increased keratin, leading the local hyperkeratosis (callus) that progresses to ulceration (perforating plantar disease), and required surgical removal procedure to pair definitive healing, allowing the use of adequate prostheses [4,9]. ...
... The biological effects promoted by this therapy in the repair process found in literature are related to the attenuation of the inflammatory response [4,8], increased proliferation of fibroblasts [9], stimulation of angiogenesis [7,10], increased synthesis of collagen [3,11], stimulus to re-epithelialization [12], and analgesic effects [13,14]. ...
... Sousa et al. [9] histologically evaluated fibroblastic proliferation in dorsal cutaneous wounds of rats daily treated with LED of three wavelength (red, green, and blue) for 7 days and observed that blue LED (460 ± 20 nm, 22 mW, 10 J/cm 2 ) Adamskaya et al. [12] investigated the in vivo effects of blue LED (470 nm, 1 W, 50 mW/cm 2 ) on cutaneous wounds of rats and found that light significantly reduced wound size within 7 days and strongly stimulated re-epithelialization. The findings in the present study suggest that re-epithelialization in treated animals was stimulated by LED in the first days, since re-epithelialization began in all wounds in animals from the BLUE group in 7 days. ...
Article
Full-text available
The aim of this study was to evaluate the effects of blue light-emitting diode (LED) on the healing process of third-degree skin burns in rats through clinical and histological parameters. Forty male Wistar rats were divided into two groups: control (CTR) (n = 20) and blue LED (BLUE) (n = 20), with subgroups (n = 5) for each time of euthanasia (7, 14, 21, and 28 days). LED (470 nm, 1 W, 12.5 J/cm² per point, 28 s) was applied at four points of the wound (total, 50 J/cm²). Feed intake was measured every other day. It was observed that there were no statistically significant differences in the Wound Retention Index (WRI) of the BLUE group in relation to CTR group (p > 0.05) at the evaluation times. After 14, 21, and 28 days, it was observed that the animals in the BLUE group consumed more feed than animals in the CTR group (p < 0.05). At 7 days, there was a statistically significant increase in the angiogenic index (AI) in BLUE (median: 6.2) when compared to CTR (median: 2.4) (p = 0.01) and all animals in BLUE had already started re-epithelialization. This study suggests that blue LED, at the dosimetry used, positively contributed in important and initial stages of the healing process of third-degree skin burns.
... ROS generation in retinal ganglion cells irradiated with 470 nm light for 2 h did not show a significant difference from that in a non-irradiated group (Huang et al., 2014). Previous studies (Adamskaya et al. 2011;Opländer et al. 2011) have shown that a long wavelength of blue light (480 nm) can enhance cell viability and proliferation of human dermal fibroblasts. Wang et al. (2016) have demonstrated that blue light can encourage osteoblastic differentiation of stem cells with intracellular calcium and lightgated ion channels. ...
... Blue light has also shown angiogenic effects in previous studies. Adamskaya et al. (2011) have discovered that blue light irradiation on lesions can stimulate wound healing. It has been discovered that exposure to blue light can induce ocular disease with increases of neovascular factors attributed to abnormal secretion of pro-angiogenic factors of retinal pigmented epithelial cell (Scimone et al. 2020;Vila et al. 2017). ...
Article
Full-text available
Low-level light therapy (LLLT) is a safe and noninvasive technique that has drawn attention as a new therapeutic method to treat various diseases. However, little is known so far about the effect of blue light for LLLT due to the generation of reactive oxygen species (ROS) that can cause cell damage. We introduced a blue organic light-emitting diode (bOLED) as a safe and effective light source that could generate a low amount of heat and luminance compared to conventional light sources (e.g., light-emitting diodes). We compared phototoxicity of bOLED light with different light fluences to human adipose-derived stem cells (hADSC). We further explored molecular mechanisms involved in the therapeutic efficacy of bOLED for enhancing angiogenic properties of hADSC, including intracellular ROS control in hADSCs. Using optimum conditions of bOLED light proposed in this study, photobiomodulation and angiogenic properties of hADSCs were enhanced. These findings might open new methods for using blue light in LLLT. Such methods can be implemented in future treatments for ischemic disease. Graphical abstract
... Previous studies indicate that irradiation with blue light could enhance wound healing in vivo [24][25][26]. Despite this, we recently showed that irradiation with blue light reduced wound closure in vitro when keratinocytes were directly irradiated with blue light [27], which is in accordance with previous in vitro studies [28]. ...
... Previous studies indicate that irradiation with blue light could enhance wound healing in vivo [24][25][26], while several other studies described contrary results in in vitro settings [12,[27][28][29]. However, very little research is available addressing these opposite findings. ...
Article
Full-text available
Phototherapy is gaining more attention in the treatment of various diseases. Especially, blue light seems to be a promising approach for wound healing promotion due to its antimicrobial and immune-modulating properties. Despite this, there is only little research focusing on the immune-modulating properties of blue light and its possible effects on wound healing. Therefore, we investigated the effects of blue light irradiation on peripheral blood mononuclear cells (PBMC) and the influence on reepithelization in vitro. PBMCs were irradiated with DermoDyne® (DermoDyne HealthCare, Berlin, Germany) and effects on cell viability, cytokine expression, and scratch wound closure were evaluated afterwards. Irradiated cells showed a higher Interleukin-γ concentration while irradiation reduced resazurin concentration in a time-dependent manner. No differences in reepithelization were detectable when keratinocytes were treated with the supernatant of these blue light irradiated PBMCs. Blue light–mediated ex vivo stimulation of PBMCs does not cause faster reepithelization in an in vitro setting. Further research is needed to investigate the wound healing effects of phototherapy with blue light.
... Low-level laser therapy (LLLT) is known to increase collagen production, vasodilatation and nerve conduction velocity, and reduce bacterial growth, as well. [63,72,73] Animal studies have demonstrated potential beneficial effects of LLLT on wound healing. [72][73][74] A meta-analysis of seven RCTs including 194 patients reported that LLLT promoted a faster granulation formation with shorter wound closure time and alleviation of foot ulcer pain. ...
... [63,72,73] Animal studies have demonstrated potential beneficial effects of LLLT on wound healing. [72][73][74] A meta-analysis of seven RCTs including 194 patients reported that LLLT promoted a faster granulation formation with shorter wound closure time and alleviation of foot ulcer pain. [75] Although the ideal LLLT parameters for wound healing have not been established yet, an energy density between 5 and 24 J/cm 2 is considered to be the most effective range. ...
Article
Full-text available
Diabetes is one of the most common health problems worldwide. Diabetic foot wounds (DFWs) are hazardous complications of the disease. Patients are often referred to rehabilitation facilities at later stages of the diabetic complications, particularly after amputation surgery. There are potential benefits of rehabilitation practices in preventing and managing DFWs. Therefore, rehabilitation needs to be more involved in the management of DFWs and should be in all stages of diabetic care. In this review, we discuss literature data to bring rehabilitation perspective to the multidisciplinary management of DFWs.
... It has already been shown, that blue light, dependent on the wavelength, intensity (irradiance) and radiant exposure, has anti-inflammatory effects in keratinocytes [18] and suppresses dendritic cell activation [19]. In rodents blue light inhibits skin tumors [20] and improves wound healing [21]. But, in the context of DD, blue light is particularly interesting, because mitosis and proliferation of cultured cells could be inhibited [22]. ...
Article
Full-text available
Dupuytren’s contracture is a fibroproliferative disorder affecting the palmar fascia of the hand. Most affected are the ring fingers, and little fingers of middle-aged men. Symptomatic for this disease is the increased proliferation and differentiation of fibroblasts to myofibroblasts, which is accompanied by an elevated α-SMA expression. The present study evaluated the therapeutic benefit of blue light (λ = 453 nm, 38 mW/cm², continuous radiance, spot size 10–12 cm²) as well as the molecular mechanism mediating this effect. It could be determined that blue light significantly diminished the induced α-SMA protein expression in both normal palmar fibroblasts and Duypuytren’s fibroblasts. The beneficial effect mediated by this irradiance, radiant exposure and wavelength was associated with an elevated reactive oxygen species generation. Furthermore, the data underlines the potential usefulness of blue light irradiation as a promising therapy option for Dupuytren’s disease, especially for relapse prevention, and may represent a useful strategy to treat further fibrotic diseases, such as keloids, hypertrophic scarring, and scleroderma.
... The use of light therapy, both in the infrared and visible spectrum, positively impacts wound healing by increasing host cell proliferation, angiogenesis, granulation tissue formation and collagen synthesis [79,80]. In recent years, visible light, particularly blue light (wavelength 400-500 nm), has been studied for its antimicrobial and antibiofilm effects [81,82]. ...
Article
Full-text available
Chronic wounds are a major healthcare burden, with huge public health and economic impact. Microbial infections are the single most important cause of chronic, non-healing wounds. Chronic wound infections typically form biofilms, which are notoriously recalcitrant to conventional antibiotics. This prompts the need for alternative or adjunct ‘anti-biofilm’ approaches, notably those that account for the unique chronic wound biofilm microenvironment. In this review, we discuss the recent advances in non-conventional antimicrobial approaches for chronic wound biofilms, looking beyond standard antibiotic therapies. These non-conventional strategies are discussed under three groups. The first group focuses on treatment approaches that directly kill or inhibit microbes in chronic wound biofilms, using mechanisms or delivery strategies distinct from antibiotics. The second group discusses antimicrobial approaches that modify the biological, chemical or biophysical parameters in the chronic wound microenvironment, which in turn enables the disruption and removal of biofilms. Finally, therapeutic approaches that affect both, biofilm bacteria and microenvironment factors, are discussed. Understanding the advantages and limitations of these recent approaches, their stage of development and role in biofilm management, could lead to new treatment paradigms for chronic wound infections. Towards this end, we discuss the possibility that non-conventional antimicrobial therapeutics and targets could expose the ‘chink in the armor’ of chronic wound biofilms, thereby providing much-needed alternative or adjunct strategies for wound infection management.
... This resource consists of a semiconductor diode subjected to an electric current with a wavelength ranging from 400 to 470 nm, being the 405-nm light used in studies that aimed to test its fungicidal effect. To our knowledge, there is yet no standardized method for the use of this technique in terms of the application parameters for obtaining different effects and its use in the genital region, which is rarely mentioned in the literature [10,13,14]. ...
Article
Full-text available
Vulvovaginal candidiasis (VVC) is a frequent infection of the female genitourinary tract. It is considered the second most common genital infection in women, after bacterial vaginosis. VVC is treated with oral or topical azole derivatives. However, these agents may lead to adverse reactions and their chronic use might lead to resistance to antifungal agents. Given that the ultraviolet A/blue light-emitting diode (LED) is an electromagnetic radiation source with antimicrobial properties, it is hypothesized that this resource may be a non-drug alternative to the treatment of vulvovaginitis. A technical/experimental safety test was conducted to characterize the light source spectrum and temperature generation of the device, followed by a pilot study in a 52-year-old patient with a clinical diagnosis of VVC confirmed by culture and examination of fresh vaginal samples, owing to the presence of lumpy vaginal discharge and a complaint of pruritus. The vulva and vagina were exposed to 401 ± 5 nm ultraviolet A/blue LED irradiation in a single session, divided into two applications. A reassessment was performed 21 days after the treatment. The light-emitting device had a visible spectrum, in the violet and blue ranges, and a maximum temperature increase of 7 °C. During the reassessment, the culture was found to be negative for fungus, and the signs and symptoms of the patient had disappeared. A light-emitting device with a spectrum in the range of 401 ± 5 nm could potentially be an alternative treatment modality for women with VVC, as it led to the resolution of clinical and microbiological problems in our patient.
... Furthermore, the ability to precisely control the wavelength of light emitted through LEDs with the fabrication process can enable further advancements in areas previously inconceivable with traditional light sources. For instance, the use of blue LEDs (with a wavelength of 450-490 nm) in life science research has been shown to successfully inhibit the growth of skin tumours in the v-Ha-ras transgenic mouse [7] and improve wound healing in an excision model of rats [8]. In human biology research, it has the haemoglobin content of blood and then converted into heat, thus enabling the selective photocoagulation of superficial abrasions with reduced overall treatment time and scar formation [9]. ...
Article
Full-text available
Light-emitting diodes (LEDs) are solid-state devices that are highly energy efficient, fast switching, have a small form factor, and can emit a specific wavelength of light. The ability to precisely control the wavelength of light emitted with the fabrication process enables LEDs to not only provide illumination, but also find applications in biology and life science research. To enable the new generation of LED devices, methods to improve the energy efficiency for possible battery operation and integration level for miniaturized lighting devices should be explored. This paper presents the first case of the heterogeneous integration of gallium nitride (GaN) power devices, both GaN LED and GaN transistor, with bipolar CMOS DMOS (BCD) circuits that can achieve this. To validate this concept, an LED driver was designed, implemented and verified experimentally. It features an output electrical power of 1.36 W and compact size of 2.4 × 4.4 mm 2. The designed fully integrated LED lighting device emits visible light at a wavelength of approximately 454 nm and can therefore be adopted for biology research and life science applications.
... In this study we examined the potential of a short wavelength in the visible light region (405 nm provided by a violet-blue LED) to activate an antibacterial photodynamic reaction with four PSs. Since Akasaki et al. first developed the blue LED [13] it has been used not only for display purposes but also in various medical fields [14][15][16][17]. Blue LEDs are used in dentistry for detecting early caries lesion [18] and matured dental plaque based on autofluorescence [19]. ...
... Similar wavelengths of FIR radiation and vibration frequency characteristics of human body allow FIR heat to penetrate 2.5cm deep under the skin, to the muscles, blood vessels, lymphatic glands, and nerves [2]. Even low-intensity light significantly influences wound healing [3]. The function of infrared sauna and infrared radiator is based on the vibrational effect of FIR radiation [4,5]. ...
Article
Full-text available
Despite increased evidence of bio-activity following far-infrared (FIR) radiation, susceptibility of cell signaling to FIR radiation-induced homeostasis is poorly understood. To observe the effects of FIR radiation, FIR-radiated materials-coated fabric was put on experimental rats or applied to L6 cells, and microarray analysis, quantitative real-time polymerase chain reaction, and wound healing assays were performed. Microarray analysis revealed that messenger RNA expressions of rat muscle were stimulated by FIR radiation in a dose-dependent manner in amount of 10% and 30% materials-coated. In 30% group, 1,473 differentially expressed genes were identified (fold change [FC] > 1.5), and 218 genes were significantly regulated (FC > 1.5 and p < 0.05). Microarray analysis showed that extracellular matrix (ECM)-receptor interaction, focal adhesion, and cell migration-related pathways were significantly stimulated in rat muscle. ECM and platelet-derived growth factor (PDGF)-mediated cell migration-related genes were increased. And, results showed that the relative gene expression of actin beta was increased. FIR radiation also stimulated actin subunit and actin-related genes. We observed that wound healing was certainly promoted by FIR radiation over 48 h in L6 cells. Therefore, we suggest that FIR radiation can penetrate the body and stimulate PDGF-mediated cell migration through ECM-integrin signaling in rats.
... Several groups have, however, tested wavelengths within the white spectrum. Adamskaya and colleagues 84 reported that blue light (470 nm) accelerates wound healing in a rat model, improving blood flow by inducing the release of NO; Fushimi and colleagues 85 reported that red (638 nm) and green (518 nm) light accelerate wound healing and Yuan and colleagues 86 observed that blue light (424 nm) protects liver and kidney tissue from ischemiareperfusion damage. This evidence is limited but does suggest that broad-spectrum daylight, at appropriate low doses, induces tissue resilience. ...
Article
Full-text available
This review brings together observations on the stress-induced regulation of resilience mechanisms in body tissues. It is argued that the stresses that induce tissue resilience in mammals arise from everyday sources: sunlight, food, lack of food, hypoxia and physical stresses. At low levels, these stresses induce an organised protective response in probably all tissues; and, at some higher level, cause tissue destruction. This pattern of response to stress is well known to toxicologists, who have termed it hormesis. The phenotypes of resilience are diverse and reports of stress-induced resilience are to be found in journals of neuroscience, sports medicine, cancer, healthy ageing, dementia, parkinsonism, ophthalmology and more. This diversity makes the proposing of a general concept of induced resilience a significant task, which this review attempts. We suggest that a system of stress-induced tissue resilience has evolved to enhance the survival of animals. By analogy with acquired immunity, we term this system ‘acquired resilience’. Evidence is reviewed that acquired resilience, like acquired immunity, fades with age. This fading is, we suggest, a major component of ageing. Understanding of acquired resilience may, we argue, open pathways for the maintenance of good health in the later decades of human life.
... 21 LED has been used due to their applicability in clinical and experimental studies and is also investigated as a potential light source in research with biomodulatory effects. 22 The application of low-intensity light fluencies at appropriate time intervals promotes and stimulates the cell proliferation, differentiation, migration activity maintaining the viability without causing damage or stress to the cell. 23 However, when in elevated fluencies, photoinhibition activity can be found but it depends on the wavelength of light used. ...
Article
Full-text available
Development of biomaterials’ substitutes and/or equivalents to mimic normal tissue is a current challenge in tissue engineering. Thus, three-dimensional cell culture using type I collagen as a polymeric matrix cell support designed to promote cell proliferation and differentiation was employed to create a dermal equivalent in vitro, as well to evaluate the photobiomodulation using red light. Polymeric matrix cell support was prepared from porcine serous collagen (1.1%) hydrolyzed for 96 h. The biomaterial exhibited porosity of 95%, a median pore of 44 µm and channels with an average distance between the walls of 78 ± 14 µm. The absorption of culture medium was 95%, and the sponge showed no cytotoxicity to Vero cells, a non-tumor cell line. Additionally, it was observed that irradiation with light at 630 nm (fluency 30 J cm⁻²) leads to the cellular photobiomodulation in both monolayer and human dermal equivalent (three-dimensional cell culture system). It was also verified that the cells cultured in the presence of the polymeric matrix cell support, allows differentiation and extracellular matrix secretion. Therefore, the results showed that the collagen sponge used as polymeric matrix cell support and the photobiomodulation at 630 nm are efficient for the production of a reconstructed human dermal equivalent in vitro.
... These data are similar to those found in the literature (Table 1). In a study to compare the effect of low-intensity laser on circular wounds in rats, it was concluded that low-intensity laser treatment is easy to apply, safe and cost effective for surface wounds [24]. The present study also made surgically performed circular wounds in the dorsum of rats and found that low-intensity laser was successful for this type of injury, which corroborates the data found in the mentioned study ( Table 2). ...
... In this study we examined the potential of a short wavelength in the visible light region (405 nm provided by a violet-blue LED) to activate an antibacterial photodynamic reaction with four PSs. Since Akasaki et al. first developed the blue LED [13] it has been used not only for display purposes but also in various medical fields [14][15][16][17]. Blue LEDs are used in dentistry for detecting early caries lesion [18] and matured dental plaque based on autofluorescence [19]. ...
Article
Full-text available
Effective methods for managing the oral microbiome are necessary to ensure not only the oral but also the systemic health of a human body. The purpose of this study was to determine the sensitivity of four photosensitizers (PSs) to blue light in six representative oral bacterial species that cause intraoral diseases. The following six strains were investigated: Actinomyces israelii, Enterococcus faecium, Fusobacterium nucleatum, Lactobacillus gasseri, Streptococcus mutans, Veillonella parvula. PS stock solutions (1 mg/ml) were prepared by dissolving curcumin and protoporphyrin-IX in dimethyl sulfoxide, and resazurin and riboflavin in distilled water. The inoculation of 20 ml of a bacterial suspension cultured for 24 hours was mixed with 1,980 ml of each test solution, and then a light source was placed in front of the mixture. The irradiation wavelength was 405 nm and its applied energy was 25.3 J. The independent-samples t-test and one-way analysis of variance within groups were performed to compare the antibacterial effects in the four PSs. The antibacterial susceptibility when using different PSs and visible blue-light irradiation differed between the bacterial strains. Antibacterial photodynamic therapy that includes light exposure and PSs can be used to control the oral bacteria strains related to oral disease.
... 11 In particular, the specific range of light frequencies between 400 and 450 nm (Blue Light) has proved to be effective in many applications such as the reduction of the bacterial load; 12-14 the treatment of skin diseases such as acne, 12,15,16 psoriasis, 17,18 and eczema; 19 and for the treatment of skin lesions. [20][21][22] Further evidence shows that PBMT with Blue Light has an antiinflammatory potential as it inhibits the pathways involved in the inflammatory response 23 and is able to reduce the release of proinflammatory cytokines. 24 This article reports the observations made on three patients suffering from ulcers of the lower limbs who were treated with PBMT using Blue light emitting diodes (LEDs) irradiation in specific wavelengths (410-430 nm), in addition to the standard treatment at a private clinic. ...
Article
Full-text available
Giovanni Mosti,1 Stefano Gasperini2 1Barbantini Clinic, Lucca, Italy; 2Medical Advisor, Pisa, Italy Abstract: Chronic skin lesions are an important medical health problem. Chronic skin lesions are associated with high costs for the National Health Service and reduced quality of life for the patient. The availability of means to reduce the healing time of skin ulcers is a medical and public health priority. Within this context, for patients suffering from skin ulcers, great attention has been given to the use of particular frequencies of the light spectrum that have shown beneficial effects on both ulcer cleansing and healing stimulation. This article reports the observations made on three patients suffering from ulcers of the lower limbs who were treated with Photobiomodulation therapy using Blue Light in addition to the standard treatment at a private clinic. The results were encouraging and have prompted us to participate in a protocol of a multicenter randomized study on a significant number of patients. Keywords: photobiomodulation, blue light emitting diodes, wound healing, chronic leg skin lesion
... For the treatment of bacterial implications, it turned out that addition of external photosensitizers is not implicitly necessary. Most bacterial species seem to have sufficient amounts of internal photosensitizing molecules that disinfection through irradiation is possible without any supplements making this technology advantageous for a multiplicity of application fields like medical wound care [7][8][9] or inhibiting contaminations in the food industry 10 . While in PDT the photosensitizer and the wavelength of irradiation are artificially matched often by modifying the molecule itself to gain the greatest impact possible, the bactericidal effect is based and therefore dependent on the endogenous photosensitizer so that wavelength characteristics must be adapted. ...
... While there is much less of a precedent for the use of violet (or blue) light to treat ulcers, it is important to consider that blue light is more photochemically active than red light and causes more reactive oxygen species generation (34). Blue light has been shown to increase perfusion through stimulation of local nitric oxide (NO) release, with relaxation of vascular smooth muscle, and to increase wound healing in a skin excision model (35,36). ...
Article
Full-text available
Background: Locally acting, well-tolerated treatments for systemic sclerosis (SSc) digital ulcers (DUs) are needed. Objectives: Our primary aim was to investigate the safety, feasibility and tolerability of a novel low level light therapy (LTTT). A secondary aim was to tentatively assess efficacy. Methods: A custom-built device comprising infrared (850nm), red (660nm) and violet (405nm) LEDs was utilised. DUs were irradiated with 10J/cm² twice weekly for three weeks, with follow-up at weeks 4&8. Any safety concerns were documented. Patient opinion on time to deliver, feasibility and pain visual analogue score (0-100,100 most severe) was collected. Patient and clinician DU global assessment VAS were documented. DUs were evaluated by laser Doppler perfusion imaging pre- and post-irradiation. Results: 14 DUs in 8 patients received a total of 46 light exposures, with no safety concerns. All patients considered LTTT ‘took just the right amount of time’ and was ‘feasible’, with a low associated mean pain VAS of 1.6 (SD 5.2). Patient and clinician global digital ulcer VAS improved during the study (mean change -7.1 and -5.2, respectively, both P= <0.001). DU perfusion significantly increased post-irradiation. Conclusions: LTTT for DUs is safe, feasible and well tolerated. There was an early tentative suggestion of treatment efficacy.
... Other effects include increased: antioxidant enzymes catalase and superoxide dismutase ( Martins et al., 2016) and mitochondrial NO synthase activity, release of NO, also a potent vasodilator ( Adamskaya et al, 2011), and the production of reactive oxygen species (ROS). ROS plays an important role in cell signaling, cell cycle progression regulation, enzyme activation, and nucleic acid and protein synthesis (Holmström and Finkel, 2014). ...
Article
Full-text available
Research into photobiomodulation reveals beneficial effects of light therapy for a rapidly expanding list of medical conditions and illnesses. Although it has become more widely accepted by the mainstream medicine, the effects and mechanisms of action appear to be poorly understood. The therapeutic benefits of photobiomodulation using low-energy red lasers extend far beyond superficial applications, with a well-described physics allowing an understanding of how red lasers of certain optimum intensities may cross the cranium. We now have a model for explaining potential therapeusis for applications in functional neurology that include stroke, traumatic brain injury, and neurodegenerative conditions in addition to the currently approved functions in lipolysis, in onychomycosis treatment, and in pain management.
... Interestingly, the Pi-mCherry line also displayed some increased growth when cultured under blue light. It has been previously reported that blue and/or green light may have antioxidant effects (Comorosan et al., 2009), have protective effects on protein subjected to UV irradiation (Espinoza and Mercado-Uribe, 2017), and initiate biophysical processes in cells such as increased wound healing and cell proliferation (Adamskaya et al., 2011;Rohringer et al., 2017). ...
Article
Full-text available
The MYC oncogene has been studied for decades, yet there is still intense debate over how this transcription factor controls gene expression. Here, we seek to answer these questions with an in vivo readout of discrete events of gene expression in single cells. We engineered an optogenetic variant of MYC (Pi-MYC) and combined this tool with single-molecule RNA and protein imaging techniques to investigate the role of MYC in modulating transcriptional bursting and transcription factor binding dynamics in human cells. We find that the immediate consequence of MYC overexpression is an increase in the duration rather than in the frequency of bursts, a functional role that is different from the majority of human transcription factors. We further propose that the mechanism by which MYC exerts global effects on the active period of genes is by altering the binding dynamics of transcription factors involved in RNA polymerase II complex assembly and productive elongation.
... Previous literature supports our findings, as LED treatment potentiate wound healing by enhancing angiogenesis, irrespective of the wavelength [60]. At cellular level, it is reported that blue light can significantly influence biological systems, improving perfusion by releasing nitric oxide, which is known to regulate angiogenesis [61,62]. Phototherapy is also reported to promote the tissue repair processes of wounds by increasing the quantity of collagen fibers [63]. ...
Article
Wound healing, being a dynamic process consisting of hemostasis, inflammation, proliferation, and remodeling, involves the complicated interplay of various growth mediators and the cells associated repair system. Current wound healing therapies usually fail to completely regain skin integrity and functionality. Traditionally, curcumin is considered a potent natural wound healing agent as it possesses antibacterial, antioxidant, and anti-inflammatory properties. It is also known that zinc oxide (ZnO) nanoparticles (NPs) have photocatalytic properties, including the generation of reactive oxygen species. ZnO nanoaprticles are also Food and Drug Administration (FDA) approved as safe substances. While ZnO oxide requires illumination with ultraviolet light to become photocatalytically active, dye-sensitized ZnO can be activated by illumination with visible light. In the present study, we explored the wound healing potential of ZnO nanoparticles sensitized with curcumin (Cu+ZnO Nps) and illuminated with visible (blue) light generated by an array of high power LEDs. We studied the antibacterial effect of our conjugates by percentage reduction in bacterial growth and biofilm formation. The wound healing potential was analyzed by percentage wound contraction, biochemical parameters, and histopathological analysis of the wounded site. Additionally, angiogenesis and wound associated cytokines was evaluated by immunohistochemistry of CD31 and gene expression analysis of IL-1β, TNF-α, and MMP-9 after 16 days of post-wound treatment, respectively. Our study suggests that the therapeutic effect of Cu+ZnO NPs with LED illumination increases its wound healing potential by producing an antibacterial and anti-inflammatory effect. Moreover, the treatment strategy of using a nano formulation in combination with LED illumination further increases its efficacy. It was concluded that the anti-inflammatory and bactericidal effects of the LED illuminated Cu+ZnO Np showed accelerated wound healing with increased wound contraction, collagen deposition, angiogenesis, and re-epithelialization.
... On bacteria, photobiomodulation by exposure to these radiations emitted by low power lasers is thought to increase cell proliferation in cultures at optimal [3] and harmful or stressful conditions [4,5]. Otherwise, exposure to radiations in blue spectrum emitted by LEDs, for example, is significantly able to affect bacterial growth, producing an inhibitory effect [6][7][8] and speeding up healing and clearing of infected wounds [9][10][11]. Bacteria are in stressful conditions in infected tissue injuries [12], it being possible that the infection could worsen in tissue injuries if bacterial proliferation is induced by photobiomodulation. ...
Article
Full-text available
Radiations emitted by low power radiation sources have been applied for therapeutic proposals due to their capacity of inactivating bacteria and cancer cells in photodynamic therapy and stimulating tissue cells in photobiomodulation. Exposure to these radiations could increase cell proliferation in bacterial cultures under stressful conditions. Cells in infected or not infected tissue injuries are also under stressful conditions and photobiomodulation-induced regenerative effect on tissue injuries could be related to effects on stressed cells. The understanding of the effects on cells under stressful conditions could render therapies based on photobiomodulation more efficient as well as expand them. Thus, the objective of this review was to update the studies reporting photobiomodulation on prokaryotic and eukaryotic cells under stress conditions. Exposure to radiations emitted by low power radiation sources could induce adaptive responses enabling cells to survive in stressful conditions, such as those experienced by bacteria in their host and by eukaryotic cells in injured tissues. Adaptive responses could be the basis for clinical photobiomodulation applications, either considering their contraindication for treatment of infected injuries or indication for treatment of injuries, inflammatory process resolution, or tissue regeneration.
... 6,8,18 Although fewer pieces of evidence have been gathered about the action mechanism of noncoherent light, LED therapy may promote a bio-stimulative effect upon irradiated cells. 6,17,[19][20][21] In the past few years, the published literature on the subject has shown positive, preventive and curative effects of LED therapy on chemotherapy and/or head and neck radiotherapy-induced OM. Furthermore, some authors have observed an immediate pain relief in pediatric patients who underwent a bone marrow transplant and were submitted to LED therapy. ...
Article
Full-text available
Introduction: Oral mucositis (OM) has been considered one of the most feared collateral effects of oncological treatments. Some therapies have been used, such as light-emitting diode (LED), with promising results, but with no sufficient evidence in the literature. Objective: Our study aimed to evaluate, by clinical and histological analysis, the effect of LED on the treatment of chemotherapy-induced OM (CIOM) in an animal model. Methods: Twenty male hamsters were equally distributed to two groups: control (C), which received anesthesia and CIOM induction; and LED (L), which received anesthesia, CIOM induction, and LED treatment (635 nm, 120 mW, 0.48 J). The clinical analysis was performed through two specific scales for OM analysis on days 5, 7 and 10 of the experiment. In addition, the injured area of all hamsters check pouch mucosa was removed and processed for histological analysis on the last experimental day. Results: After statistical analysis, group L showed less severity of OM when compared with the C group (P <0.05); beyond that, both healed completely on day 10. Conclusion: Our results suggested that the phototherapy with LED had a positive effect on accelerating repair, reducing the severity of CIOM.
... Blue light is colored light with a wavelength ranging between 400 and 500 nm (5). Due to its fruitful broad-spectrum antibacterial effect (6)(7)(8), LED blue-light irradiation has been used for the treatment of skin diseases and wound sterilization (9)(10)(11). Various studies have revealed that blue light also plays a role in regulating physiological functions in vivo, e.g., it improves cognitive performance (12), promotes cell proliferation and differentiation (13,14), and even inhibits tumor cell growth and metastasis (15,16). ...
Article
Full-text available
Monochromatic light is widely used in industry, medical treatment, and animal husbandry. Green-blue light has been found to stimulate the proliferation of satellite cells and the results of studies on the effects of blue light on poultry vary widely. It would be worthwhile to study the effect of blue light on poultry growth and how exposure to blue light affects metabolism and the intestinal microbiota. In this study, we irradiated Cherry Valley ducks with 460 nm wavelength light (blue light) for 3 weeks to explore the effects of blue light in comparison to those of white light (combined wavelength light) on animal growth and development. Our results showed that, under exposure to blue light, the body weight and average daily feed intake of ducks were decreased, but the leg muscle and relative length of the intestine were increased. Exposure to blue light chiefly enhanced the anti-inflammatory and antioxidant capacities of the animal and decreased lipid levels in serum and liver. Metabolomic analysis revealed that blue light heightened cysteine and methionine metabolism, and increased serum taurine and primary bile acid levels, as well as up-regulating the metabolites L-carnitine and glutamine. Treatment with blue light significantly increased the beta diversity of intestinal microbiota and the relative abundances of bile acid hydrolase-producing bacteria, especially Alistipes. These changes promote the synthesis of secondary bile acids to further enhance lipid metabolism in the host, thereby reducing cholesterol accumulation in ducks. These results should help us better understand the effects of exposure to blue light on metabolite levels and the intestinal microbiota, and suggest that it may be possible to use colored light to control the development of livestock and poultry.
... The red laser has deeper penetration into the tissue so that it has a significant effect on wound healing. Blue laser usually used for antimicrobial therapy [13,14], but it is Fig. 6 The outline of the PBM process for wound healing also able to show a positive effect on wound healing even though has lower penetration into the tissue [47]. The other studies indicated the effect of blue light on NO metabolism, an important mediator in wound healing [35]. ...
Article
Full-text available
Purpose This study aims to examine the effects of red 649 nm 4 J/cm ² and blue 403 nm 8 J/cm ² diode laser treatment for post-extraction wounded healing in rats through histopathological and immunohistochemical analysis. Methods Samples of 54 Wistar rats were divided into six groups: C- control group without treatment; C + wounded group without treatment; TB wound group with Povidone-iodine treatment; TD wounded group with doxycycline treatment; TLB wounded group with 403 nm diode laser treatment; and TLR wounded group with 649 nm diode laser treatment. Mandibular samples were observed for the number of lymphocytes and fibroblasts cells, new blood vessels formation, Interleukin 1β, and Collagen 1α expression level. Results Based on the histopathological test results, red laser diode treatment significantly increased the number of lymphocyte, fibroblast cells and the formation of new blood vessels. Meanwhile, immunohistochemical tests showed an increase in the expression of the Colagen-1α protein which plays a role in the formation of collagen for new tissues formation after damage, as well as a decrease in Interleukin-1β expression level. Blue laser is also able to show a positive effect on wound healing even though its penetration level into the tissue is lower compared to red laser. Conclusion The red diode laser 649 nm has been shown to accelerate the process of proliferation in wound healing post molar extraction based on histopathological and immunohistochemical test results.
... Light-emitting diodes (LEDs)-based therapy/phototherapy has been widely reported their use in several aspects including acne, rosacea, ageing and wound healing. [16][17][18][19] The majority studies, however, were performed in the red or infrared spectrum. ...
Article
Full-text available
Osteosarcoma (OS) is the most common primary malignant bone tumour in adolescence. Lately, light-emitting diodes (LED)-based therapy has emerged as a new promising approach for several diseases. However, it remains unknown in human OS. Here, we found that the blue LED irradiation significantly suppressed the proliferation, migration and invasion of human OS cells, while we observed blue LED irradiation increased ROS production through increased NADPH oxidase enzymes NOX2 and NOX4, as well as decreased Catalase (CAT) expression levels. Furthermore, we revealed blue LED irradiation-induced autophagy characterized by alterations in autophagy protein markers including Beclin-1, LC3-II/LC3-I and P62. Moreover, we demonstrated an enhanced autophagic flux. The blockage of autophagy displayed a remarkable attenuation of anti-tumour activities of blue LED irradiation. Next, ROS scavenger N-acetyl-L-cysteine (NAC) and NOX inhibitor diphenyleneiodonium (DPI) blocked suppression of OS cell growth, indicating that ROS accumulation might play an essential role in blue LED-induced autophagic OS cell death. Additionally, we observed blue LED irradiation decreased EGFR activation (phosphorylation), which in turn led to Beclin-1 release and subsequent autophagy activation in OS cells. Analysis of EGFR colocalization with Beclin-1 and EGFR-immunoprecipitation (IP) assay further revealed the decreased interaction of EGFR and Beclin-1 upon blue LED irradiation in OS cells. In addition, Beclin-1 down-regulation abolished the effects of blue LED irradiation on OS cells. Collectively, we concluded that blue LED irradiation exhibited anti-tumour effects on OS by triggering ROS and EGFR/Beclin-1-mediated autophagy signalling pathway, representing a potential approach for human OS treatment.
... Lee et al. [8] investigated the clinical efficacy of blue light (415 ± 5 nm, 40 mW/cm 2 ) and red light (633 ± 6 nm, 80 mW/cm 2 ) combination to treat acne vulgaris. The influences of blue light, with wavelength length of 470 nm at 50 mW/cm 2 , on biological systems and keratin expression in an excision wound model of rats were shown [9] . Additionally, blue LED therapy (450 nm, irradiance 50 mW/cm 2 ) also indicated a significant improvement in tissue perfusion and angiogenesis in the subepidermal layer [10] . ...
Article
Full-text available
The biological effects of a light-emitting diode (LED) light therapy device are determined by irradiation parameters, mainly wavelength and power density. However, using a battery to provide power causes a problem in the variation of LED power density during battery discharge. As a result, maintaining a stable LED power density, along with extending battery life and operating time, are the primary concerns in designing a LED light therapy device. The present study aims to introduce a LED light therapy device design with different LED color power density control. A Fuzzy logic, based on the relationship between LED power density and operating time, was proposed to control constant power density in this design. The experimental results demonstrate that by using the designed controller, the LED light therapy device’s power3 density (40 mW/cm2, 50 mW/cm2, 60 mW/cm2 for red, blue, and green light, respectively) can be controlled. The newly designed LED light therapy device could be considered an advanced version with energy savings and stabilized LED power emitting property under a broad range voltage variation.
... Blue light, as a part of the visible light spectrum, is commonly described within the range of 380 to 495 nm, including violet to green wavelengths, and these specific wavelengths are also reported to have opposite biological effects. For instance, blue light phototherapy is widely used for treatment of skin diseases such as acne [17][18][19], psoriasis [20], atopic dermatitis [21], or eczema [22] and for wound healing [23]. Indeed, it is known that skin exposure to blue light results in antibacterial [24], antimicrobial [25], and anti-inflammatory [26] effects leading to the increasingly important development of photobiomodulation therapies. ...
Article
Full-text available
Background: The purpose of this study was to elucidate why some potentially damaging and beneficial effects were obtained following blue light exposures on skin. Materials and methods: Light-emitting diode (LED) devices containing 415 and 470 nm bulbs were used on normal human keratinocytes, skin biopsies and subjects with acne. Reactive oxygen species (ROS) evaluation was performed after a course of blue LED light exposures. A comparison between very small bandwidth centered at 415 nm and a combination of (415 + 470 nm) wavelengths was also carried out regarding the effects on ROS production. The effects on other targets such as opsin1 short wavelength (OPN1 SW) photoreceptor, fibrillin-1 dermal component, LL37 antimicrobial peptide and interleukin-8 (IL-8) proinflammatory cytokine were then explored. Finally, clinical pictures of acne signs were also investigated after blue LED exposures. Results: Dose dependent increases of ROS production were obtained on keratinocytes exposed to increasing 415 nm LED exposures. However, a ROS decreasing first phase was observed on keratinocytes exposed to 415 + 470 nm LED exposures. Moreover, comparing the same doses of 415 nm wavelength and (415 + 470 nm) wavelength combination, 415 nm alone is more damaging than the 415 + 470 nm exposures. In case of increase in ROS, decrease in OPN1 SW photoreceptor and fragmentation of fibrillin-1 dermal fiber were observed. When conditions of ROS decrease were experienced, an increase in LL37 antimicrobial peptide and a modulation of IL-8 inflammatory response were noted, suggesting improvement in acne signs. Clinical results confirmed the benefits on inflammatory lesions on subjects with acne. Conclusion: Blue lights can induce beneficial and adverse effects, depending on the dose and on the spectrum width of the exposure.
... Іншими авторами показано, що червоне світло з довжиною хвилі 460-620 нм підвищує біологічну активність ферментів [25]. Зміна активності молекул призводить до вироблення цитокінів, що впливають на тонус судин, модулюють каскад арахідонової кислоти, перекисне окиснення ліпідів, і змінює характер імунних реакцій [3,25]. ...
Article
Treatment of inflammatory and septic conditions is a serious problem due to the existing antibiotic resistance. It is necessary to find new treatments using biological and physical factors that affect the course of inflammatory reactions in chronic processes. It is important to understand the mechanisms of interaction of light photons with cellular acceptors, which provide reactivity and resistance. The aim – is to evaluate the low-intensity light effect of the red range spectrum (λ =630-660 nm) on the course of the inflammatory process in experimental animals with LPS-induced peritonitis. Animals were divided into 3 groups: A – intact animals; B – animals with peritonitis induced by intraperitoneal administration of LPS; C – animals with LPS-induced peritonitis after repeated exposure to red light. Irradiation of the abdominal wall was performed with LED matrices Korobov A. – Korobov V. "Barva-Flex/24FM", which emit in the red region of the spectrum. Methods of light microscopy (study of the barrier function in oxygen-independent phagocytosis of neutrophils, estimation of the lymphocytotoxicity degree in the Terasaki test) and spectrophotometry (determination of the concentration of circulating immune complexes) were used. In animals after induction of peritonitis (group B) was observed inhibition of phagocytosis, which manifested itself in reduced adhesion and endocytosis of antigens by neutrophils compared with intact animals. The use of light exposure of the red range spectrum (group C) significantly activated phagocytic cells and reduced the degree of lymphocytotoxicity and the concentration of circulating immune complexes at different stages of the inflammatory process. Thus, the action of red light contributed to the normalization of immunoresistance in animals, thereby reducing antigenic load by activating infiltration and exudation stages of the inflammatory process and induction of regenerative processes after repeated irradiation at the end of the experiment.
... Also, it has been suggested that proteins and enzymes containing riboflavin and porphyrins act as photoreceptors for blue-violet wavelengths [14,15]. Blue laser or LED light sources have shown biomodulatory properties like wound healing and expression of chodrogenic mRNA by prechondrogenic cells [16,17]. For lasers that have high absorption coefficients (μ a > 1000 cm − 1 ) in hydroxyapatite like CO 2 and Er : YAG lasers, the absorption will be restricted to the first few micrometers of the surface of enamel where temperature can reach 1000°C. ...
Article
Full-text available
Objective: This in vitro study is aimed at investigating the caries preventive effectiveness of 445 nm diode laser in combination with topical fluoridation. Materials and methods: A total of 30 caries-free bovine teeth were used in this study. Eighteen teeth were covered with nail varnish except four windows on the labial surface. The windows were assigned to no treatment/control (C), laser (L) (0.3 W, 60 s, and 90 J/cm2), fluoride (F), and fluoride followed by laser (FL) treatment groups. Artificial caries lesions were created, and the teeth were sectioned and investigated under polarized light microscopy for quantitative measurement of the resulted lesion depth. Ten teeth were used for surface temperature measurement and two teeth for scanning electron microscopy (SEM). Extra twelve human molars were used for the intrapulpal temperature measurement. The absorbance of fluoride at 445 nm was measured. Results: The means of lesion depth for the C, L, F, and FL groups were 123.48 (±21.93), 112.33 (±20.42), 99.58 (±30.68), and 89.03 (±30.38) μm, respectively. The pairwise differences of the L, F, and FL groups compared with the C group were significant (p < 0.05). The differences between groups were tested: FL versus L p=0.02, F versus L p=0.16, and FL versus F p=0.91, and the difference of the F versus FL was not significant (p=0.91). Temperature increment at the enamel surface and pulp roof were ∆T = 16.67 (±4.11) and 2.12 (±0.66)°C, respectively. The topical fluoride absorbance at 445 nm is five orders higher than that at 810 nm. SEM shows that after laser irradiation the enamel surface was intact and without thermal damage. Conclusions: The 445 nm laser irradiation may be useful for caries prevention, and its effectiveness is lower than those previously achieved using the argon ion laser.
Article
Background Light-emitting diodes (LEDs) in the visible or near-infrared spectrum have been reported to promote wound healing. However, despite being frequently proposed in daily clinical practice, the efficacy of photobiomodulation treatment after a laser procedure relies on very limited clinical data. Objective To compare the relative efficacy of LED versus placebo treatment in decreasing erythema and transepidermal water loss (TEWL) after a fractional CO2 session. Methods We conducted an open prospective intraindividual randomized controlled study with 10 healthy volunteers. An ablative fractional laser was performed on the seven forearm areas. Three consecutive daily sessions of LED (590, 630, and 850 nm [two tested irradiances each] and placebo) were applied after randomization. Physical measures (colorimetry, TEWL), photography, and clinical evaluation were performed on Days 1, 2, 3, 7, and 21. The main criterion of evaluation was the variation of parameter a* (erythema) at 72 hours for each LED parameter compared to placebo treatment. Results No significant differences in the variation of the parameter a* or any of the other studied parameters were found for the different LEDs compared to the placebo area. Conclusion Photobiomodulation failed to improve healing after laser ablation compared to placebo.
Article
A highly interesting source for adult stem cells is adipose tissue, from which the stromal vascular fraction (SVF) ‐ a heterogeneous cell population including the adipose‐derived stromal/stem cells (ASC) ‐ can be obtained. To enhance the regenerative potential of freshly isolated SVF cells low level light therapy (LLLT), was used. The effects of pulsed blue (475 nm), green (516 nm) and red light (635 nm) from light‐emitting diodes (LEDs) applied on freshly isolated SVF were analyzed regarding cell phenotype, cell number, viability, adenosine triphosphate content, cytotoxicity and proliferation, but also osteogenic, adipogenic and pro‐angiogenic differentiation potential. The colony‐forming unit fibroblast assay revealed a significantly increased colony size after LLLT with red light compared to untreated cells, whereas the frequency of colony forming cells was not affected. LLLT with green and red light resulted in a stronger capacity to form vascular tubes by SVF when cultured within 3D fibrin matrices compared to untreated cells, which was corroborated by increased number and length of the single tubes and a significantly higher concentration of vascular endothelial growth factor. Our study showed beneficial effects after LLLT on the vascularization potential and proliferation capacity of SVF cells. Therefore, LLLT using pulsed LED light might represent a new approach for activation of freshly isolated SVF cells for direct clinical application.
Book
In this book, the authors have provided the latest and most in-depth information on one of clinical medicine's most useful tools: Low-Level Laser Therapy (LLLT). Written by over a dozen experts from five continents, from Jerusalem to Johannesburg and San Diego to Sao Paolo, the breadth of knowledge provided herein expands not only the globe, but many medical fields. LLLT is an inexpensive, easily employed therapeutic strategy that has validated clinical utility in dermatology, oncology, dentistry, veterinary field, wound healing and many other medical arenas. This book provides the most up-to-date information on recent clinical trials as well as catalogs the optimal therapeutic settings for a myriad of disease states. In the past, biochemical mechanisms associated with LLLT therapy have not been well-described; however, this book provides comprehensive and simple biochemical processes pieced together from theories provided by the most recent and reputable publications. The mechanisms involved in the numerous diseases covered by each chapter are also included herein. Low-Level Laser Therapy: History, Mechanisms, and Clinical Uses captures the incredible dynamic usefulness of this simple technology while also listing the therapeutic settings that have been deemed the most effective for dozens of medical ailments. Whether you are a student of medicine or a clinical practitioner, this book will serve as a helpful guide on how LLLT could play a role in the care you or your team provides on a daily basis.
Article
Physical wounds in fish can devastate bodily homeostasis, increase the likelihood of secondary infections, and cause massive economic damage. Due to the importance of skin as a primary physical barrier, the strategy of promptly healing physical wounds to reduce further negative consequences has attracted a great deal of attention. The purpose of this study was to accelerate physical wound healing in the flounder using LED technology, which can be applied to thousands of fish at the same time at a reasonable economic cost. The fish epithelial cell line (Epithelioma papulosum cyprini; EPC) was used to verify the proliferative effects of LED irradiation at wavelengths of 465, 520, and 640 nm at 0, 10, 20, 40, and 80 μ·mol·m⁻²·s⁻¹. Also, desquamated wounds were made to flounder with a razor, and the wounds were exposed to LED light at 520 and 640 nm, as well as ambient light as a control, in 12-h light/ dark cycles for seven or 28 days. The results showed that 520 and 640 nm LED treatment stimulated EPC cell proliferation, while the no-LED and 465 nm LED conditions had no effect. After the injuries, the mortality rate of fish exposed to 520 nm LED was markedly lower than those of the control (ambient light) and 640 nm-treated group. Also, the highest re-generated epithelium thickness (1-day post-injury (dpi)) and thicker collagen and connective tissue (7 dpi) were observed in the 520 nm group, along with high expression of IL-1, HSP70, TNF-α, and MMP-13. Likewise, significantly faster wound closure rates were observed with ample recovered muscle layers in the 520 nm treatment group at 21 and 28 dpi. These results show that 520 nm LED treatment is a very effective alternative method of aiding recovery from physical injuries, and is an eco-friendly method that can easily be applied in aquaculture.
Article
Background: Light-emitting diode (LED) has been used for wound healing because of its stimulatory effects on fibroblast proliferation, matrix synthesis, angiogenesis, and downmodulation of inflammatory reactions. Objective: The aim of the authors' study was to investigate the effects of red LED (wavelength 633 nm) photomodulation on lower extremity surgical defects left to heal by secondary intention. Materials and methods: Fourteen subjects with surgical defects of the lower leg were irradiated with a 633 ± 3-nm light source for 20 minutes (105 mW/cm, 126 J/cm) at 4 weekly sessions. Results: The number of days required for wounds to heal was greater in the treatment group (63.2 ± 12.2 days) than in the control group (48.67 ± 11.1 days), although this difference was not statistically significant (p = .07). The percentage of the original wound remaining was not statistically different between treatment and control groups between Weeks 1 and 2 (p = .71) and Weeks 3 and 4 (p = .56). It was significant between Weeks 2 and 3 (p = .01). Conclusion: This study revealed that red LED photomodulation at a wavelength of 633 nm did not result in clinical improvement in wound healing of surgical defects on the lower extremities.
Article
Objective:: Fluorescence biomodulation (FB), a form of photobiomodulation (PBM) that is also known as low energy level light (LELL), has become an increasingly used clinical tool to induce wound healing in wounds that remain recalcitrant to treatment. In a real-life clinical setting, the aim of the EUREKA (EvalUation of Real-lifE use of Klox biophotonic system in chronic wound mAnagement) study was to confirm the efficacy and safety of LumiHeal, a system based on FB, in the treatment of chronic wounds such as venous leg ulcers (VLUs), diabetic foot ulcers (DFUs) and pressure ulcers (PUs). The effects of this FB system on the modulation of wound healing in chronic ulcers through FB induction were previously examined in an interim analysis of this study. Method:: A multicenter, prospective, observational, uncontrolled trial in 12 clinical sites in Italy. The wound was cleansed with saline and a 2mm thick layer of a chromophore gel was applied to the affected area in a biweekly regimen. The area was then illuminated with the LED activator for five minutes at a distance of 5cm. Treatment was used in combination with standard of care specific to each type of chronic wound (VLU, DFU, PU). Wound area evaluation was assessed using the Silhouette Imaging System and quality of life (QoL) with the Cardiff Wound Impact Schedule (CWIS). A seven-point evaluation of the clinicans' view was also examined. Results:: We enrolled 100 subjects, with the final analysis including 99 patients/ulcers consisting of 52 VLUs, 32 DFUs and 15 PUs. Total wound closure at the end of the study was achieved in 47 patients by aetiology: 26 VLUs (50% of VLUs); 16 DFUs (50% of DFUs); and five PUs (33.3% of PUs). The mean wound area regression at last study assessment was significant for VLUs (41.0%; p<0.001) and DFUs (52.4%; p<0.001). After four weeks of treatment, it was possible to significantly predict if the ulcer would respond (defined as a decrease of wound size) to the study treatment. Adherence was high (95.2%) and no related serious adverse events were reported during the study. QoL significantly improved, with an increase of 15.4% of the total score, using the CWIS (p<0.001). Conclusion:: The study confirmed a positive efficacy profile of the FB system in inducing the wound healing process in three different types of hard-to-heal chronic wounds. The treatment was shown to be safe and well tolerated by the patients, with a significant improvement in patient QoL. This approach offers an effective modality for the treatment of hard-to-heal chronic ulcers.
Article
Bacterial cellulose (BC) is a bio-derived polymer, and it has been considered as an excellent candidate material for tissue engineering. In this study, a crossed groove/column micropattern was constructed on spongy, porous BC using low-energy CO2 laser photolithography. Applying the targeted immobilization of a tetrapeptide consisting of Arginine-Glycine-Aspartic acid-Serine (H-Arg-Gly-Asp-Ser-OH, RGDS) as a fibronectin onto the column platform surface, the resulting micropatterned BC (RGDS-MPBC) exhibited dual affinities to fibroblasts and collagen. Material characterization of RGDS-MPBC revealed that the micropattern was built by the column part with size of ~100 × 100 μm wide and ~100 μm deep, and the groove part with size of ~150 μm wide. Hydrating the MPBC did not result in the collapse of the integrity of the micropattern, suggesting its potential application in a highly hydrated wound environment. Cell culture assays revealed that the RGDS-MPBC exhibited an improved cytotoxicity to mouse fibroblasts L929, as compared to the pristine BC. Meanwhile, it was observed that the RGDS-MPBC was able to guide the ordered aggregation of human skin fibroblast (HSF) cells on the column platform surface, and no HSF cells were found in the groove channels. Over time, it was found that a dense network of collagen was gradually established across the groove channels. Furthermore, the in-vivo animal study preliminarily demonstrated the scar-free healing potential of the micropatterned BC materials. Therefore, this RGDS-MPBC material exhibited its advantages in guiding cell migration and collagen distribution, which could present a prospect in the establishment of “basket-woven” organization of collagen in normal skin tissue against the formation of dense, parallel aggregation of collagen fibers in scar tissue toward scar-free wound healing outcome.
Conference Paper
Full-text available
Due to ubiquitous display technology, we are increasingly exposed to screens from television, computers, and smartphones. The main components of these screens are blue Light Emitting Diodes (LEDs) combined with lower-energy phosphors. Blue light is a High Energy Visible (HEV) light with a wavelength ranging between 400 nm and 495 nm that could significantly influence biological systems and act on our health. However, blue light seems to have a more nuanced effect. Several publications reported blue light exposure as being beneficial. For instance, it seems able to improve in-vivo wound healing by affecting keratin gene expression. On the other hand, authors have also shown that exposure to blue light can disrupt the circadian rhythm and induce hyper-pigmentation and oxidative stress in the skin. Interestingly, studies published in 2017 suggested that blue light may also contribute to skin aging similar to UVA. The latter can penetrate the dermis and largely participate to oxidative stress which in turn contributes to the photoaging process. Increasing evidence suggests that these opposite effects of blue light may be dependent on the wavelength and dose applied. To study this ambivalence, we developed a new device able to deliver various doses at 3 wavelengths of the blue light spectrum: 447 nm, 457 nm, and 462 nm. In this study, we evaluated the effect of blue light on skin cells using wound healing assay and cellular oxidative stress using in-vitro and ex-vivo CellROX staining. Then, we decrypted the effect of oxidative stress on genes involved in several skin-aging dependent pathways such as matrix remodelling and melanogenesis. First, we showed that irradiation of blue light at 462 nm at various doses has a positive effect on skin pathways. Furthermore, a dose corresponding to an LED screen exposition rate of 4h a day over one month is able to reduce CellROX staining in skin explant, suggesting a reduction of Reactive Oxygen Species (ROS) production. Moreover, blue light at 462 nm statistically improved keratinocyte migration in wound healing assays. Oppositely, we observed that blue light at 447 nm - at an equivalent dose of exposition - increased CellROX staining in primary keratinocytes. These observations suggest the ability of this wavelength to increase oxidative stress in keratinocytes. A gene screening analysis of several pathways highlighted that this oxidative stress mainly occurs at mitochondrial level but also influences matrix remodelling and melanogenesis. Altogether, our findings indicated that the ambivalence of blue light effects may be dependent on the wavelength applied. Thus, at 462 nm, blue light seems to have a positive effect on skin by reducing oxidative stress and can play an important role in wound healing. However, blue light at 447 nm displays negative effects which seem to include the induction of oxidative stress associated with mitochondria but also with the modulation of matrix remodelling and melanogenesis.
Article
Background: Random skin flap ischemic necrosis is a serious challenge in reconstructive surgery. Photobiomodulation is a noninvasive effective technique to improve microcirculation and neovascularization. Photobiomodulation with red or blue light has been separately proven to partially prevent skin flap necrosis, but the synergistic effect of red and blue light not been elucidated. Our experiment evaluated the impact of postconditioning with red-blue light therapy on the viability of random flaps. Methods: Thirty Sprague-Dawley male rats (male, 12 weeks) with a cranially based random pattern skin flap (3 × 8 cm) were divided into 3 groups: control group, red light group, and red-blue light group. On postoperative day 7, flap survival was observed and recorded using transparent graph paper, flaps were obtained and stained with hematoxylin and eosin, and microvessel density was measured. Micro-computed tomography was used to measure vascular volume and vascular length. On days 0, 3, and 7 after surgery, blood flow was measured by laser Doppler. To investigate the underlying mechanisms, the amount of nitric oxide (NO) metabolites in the flap tissue was assessed on days 3, 5, and 7 after surgery. Results: The mean percentage of skin flap survival was 59 ± 10% for the control group, 69 ± 7% for the red light group, and 79 ± 9% for the red-blue light group (P < 0.01). The microvessel density was 12.3 ± 1.2/mm for the control group, 31.3 ± 1.3/mm for the red light group, and 36.5 ± 1.4/mm for the red-blue light group (P < 0.01). Both vascular volume and total length in the red-blue light group showed significantly increased compared with the red light and control group (P < 0.01). Blood flow in the red-blue light treated flap showed significantly increased at postsurgery days 3 and 7 compared with the red light and control group (P < 0.01). The level of the NO metabolites was significantly increased in flap tissues belonging to the red-blue light group compared with the other 2 groups (P < 0.01). Conclusions: This study showed that postconditioning with red-blue light therapy can enhance the survival of random skin flap by improving angiogenesis and NO releasing.
Article
Searching for pathogenetically justified, non-invasive methods of treatment that contribute to the normalisation of local immune factors is a priority state task. One method of pathogenetic therapy is the use of the incoherent monochromatic blue light of the optical range. The use of the incoherent monochromatic blue light of the optical range leads to the normalisation of cellular and humoral factors of innate immunity. This, in turn, contributes to the resolution of clinical manifestations of inflammation of different etiologies.
Chapter
The advances seen with recent stem cell technology are among the world’s ultimate scientific breakthroughs. Novel strategies allowing treatment of many pathological conditions also pave the way for the development of new innovative regenerative therapies including soft tissue regeneration and wound healing. Autologous adipose-derived stem cells have gained remarkable momentum in clinical practice over the past several years due to its potential applications in reconstructive surgery, cosmetic and dermatologic surgery. A new therapeutic standard has emerged which has changed the way debilitating diseases may be treated in the future. Stem cell therapy has vast potential to alleviate human distress and to provide a solution for conditions with no current medical treatment or cure. The future direction of stem cells is a revolutionary approach to improve esthetic enhancements such as skin rejuvenation, autologous fat transfer and targeting indications that involve functional restoration of defective tissues.
Article
Background: The Photobiomodulation (PBM) effect has been applied to various clinical therapy for a long time. However, the mechanism related to the PBM effect in terms of wavelengths has been lack of in-depth study, except that ultraviolet radiation has attracted much attention due to its strong cell killing effect. Purpose: To clarify the principle behind PBM and the main mechanism of improvement. Methods: To carry on this study, we created light equipment using three LED chips, which emit 390 nm ultraviolet radiation, 415 nm blue light and 660 nm red light, respectively. We choose human fibroblasts (HF) to be irradiated by three different wavelengths for PBM test. In this study, we used cell counting kit (CCK-8) test to show the cell proliferation roughly and reported on a systematic RNA sequencing (RNA-seq) analysis at transcriptional expression levels from HF, which accepted PBM of different wavelengths of light. Results: We found that 415 nm blue light inhibited cell proliferation and 660 nm red light stimulated cell proliferation while 390 nm ultraviolet radiation has little influence on cell proliferation. Furthermore, RNA-seq results showed that CSF1R, PPP3CC, ITGAL, ITGAM, IL2RB and several other differentially expressed genes (DEGs) are involved in the cell proliferation. Relative DEGs values for matrix metalloproteinases (MMPs) gene family has shown a great difference in blue and red light radiation especially on MMP25, MMP9, MMP21 and MMP13. Conclusion: Taken together, the results provide a valuable resource to describe the variation of HFs under PBM of different light at gene level.
Article
Background : Mitomycin-C (MMC) has been used for treating stricture. Topical MMC has been proven to inhibit fibroblasts proliferation and reduce the number of fibroblasts. Myofibroblasts are originally from fibroblasts. The scarring potential of myofibroblasts has been documented in many anatomical sites. The purpose of this study is to analyze the effect of topical MMC on myofibroblasts in healing anoplasty wounds in Wistar rats. Methods : An anoplasty procedure was performed on Wistar rats (n=30) that were subsequently randomly placed into two equal groups; i.e., control and treated groups. In the treated group, topical mitomycin-C was applied to the wound following the anoplasty procedure. Five rats in each group were weekly sacrificed. The myofibroblasts in tissue samples were identified by immunohistochemical analysis of alpha-smooth muscle actin. The total of myofibroblasts was evaluated by scoring methods. The Mann-Whitney test was used to analyze the statistical significance of differences, and p values below 0.05 were considered to be significant. Results : The median myofibroblasts scores in the first week for the treated and control groups were 5 and 9, respectively. In the second and third week, the median myofibroblasts scores were 6 for both groups. Statistical evaluations revealed significant differences between the groups only in the first week (p=0.007). Conclusions : Topical MMC reduced the myofibroblasts in the first week of healing anoplasty wounds in Wistar rats.
Article
Low Level Light Therapy (LLLT) within the visible blue spectrum (400-470 nanometers) is a well-documented therapeutic alternative to combat multidrug resistant organism infections through the generation of reactive oxygen species (ROS). However, one shortcoming of LLLT is that many studies deliver therapy through high powered lasers and lamps. High powered light sources not only require specialized staff to operate, but they also deliver the total light dose (fluence) at an exceptionally high intensity, or irradiance, which could consequently deplete the oxygen supplies required to promote LLLT’s bactericidal properties. To overcome these faults, low-irradiance LLLT, or delivering the same total fluence of LLLT over an extended period of time with decreased irradiance was evaluated in vitro. To further explore this alternative approach, the bactericidal effects of low-irradiance (10.44 mW/cm2) LLLT using wavelengths of 405-nm, 422-nm and 470-nm were studied on methicillin-resistant Staphylococcus aureus (MRSA) cultures. Among these wavelengths, it was determined that 405-nm LLLT provided the most effective reduction of bacterial load at the lowest total fluence (75 J/cm2) (94.50% reduction). The bactericidal effects of 405-nm low-irradiance LLLT were then further studied by treating MRSA cultures to 75 J/cm2 LLLT while using irradiances of 5.22 mW/cm2 and 3.48 mW/cm2. It was concluded that there was a greater reduction of MRSA bacterial load when samples were exposed to irradiances of 5.22 mW/cm2 (95.71% reduction) and 3.48 mW/cm2 (99.63% reduction). This study validates the bactericidal properties of low-irradiance LLLT on MRSA, and subsequent studies should be completed to optimize its full therapeutic potential.
Article
Full-text available
Photobiomodulation (PBM) describes the application of light at wavelengths ranging from 400-1100nm to promote tissue healing, reduce inflammation and promote analgesia. Traditionally, red and near-infra red (NIR) light have been used therapeutically, however recent studies indicate that other wavelengths within the visible spectrum could prove beneficial including blue and green light. This review aims to evaluate the literature surrounding the potential therapeutic effects of PBM with particular emphasis on the effects of blue and green light. In particular focus is on the possible primary and secondary molecular mechanisms of PBM and also evaluation of the potential effective parameters for application both in vitro and in vivo. Studies have reported that PBM affects an array of molecular targets, including chromophores such as signalling molecules containing flavins and porphyrins as well as components of the electron transport chain. However, secondary mechanisms tend to converge on pathways induced by increases in reactive oxygen species (ROS) production. Systematic evaluation of the literature indicated 72% of publications reported beneficial effects of blue light and 75% reported therapeutic effects of green light. However, of the publications evaluating the effects of green light, reporting of treatment parameters was uneven with 41% failing to report irradiance (mW/cm²) and 44% failing to report radiant exposure (J/cm²). This review highlights the potential of PBM to exert broad effects on a range of different chromophores within the body, dependent upon the wavelength of light applied. Emphasis still remains on the need to report exposure and treatment parameters, as this will enable direct comparison between different studies and hence enable the determination of the full potential of PBM.
Article
Full-text available
The primary function of the skin is to serve as a protective barrier against the environment. Loss of the integrity of large portions of the skin as a result of injury or illness may lead to major disability or even death. Every year in the United States more than 1.25 million people have burns1 and 6.5 million have chronic skin ulcers caused by pressure, venous stasis, or diabetes mellitus.2 The primary goals of the treatment of wounds are rapid wound closure and a functional and aesthetically satisfactory scar. Recent advances in cellular and molecular biology have greatly expanded our understanding . . .
Article
Full-text available
Background In medicine, lasers have been used predominantly for applications, which are broadly termed low level laser therapy (LLLT), phototherapy or photobiomodulation. This study aimed to establish cellular responses to Helium-Neon (632.8 nm) laser irradiation using different laser fluences (0.5, 2.5, 5, 10, and 16 J/cm2) with a single exposure on 2 consecutive days on normal and wounded human skin fibroblasts.Materials and Methods Changes in normal and wounded fibroblast cell morphology were evaluated by light microscopy. Changes following laser irradiation were evaluated by assessing the mitochondrial activity using adenosine triphosphate (ATP) luminescence, cell proliferation using neutral red and an alkaline phosphatase (ALP) activity assay, membrane integrity using lactate dehydrogenase (LDH), and percentage cytotoxicity and DNA damage using the Comet assay.ResultsMorphologically, wounded cells exposed to 5 J/cm2 migrate rapidly across the wound margin indicating a stimulatory or positive influence of phototherapy. A dose of 5 J/cm2 has a stimulatory influence on wounded fibroblasts with an increase in cell proliferation and cell viability without adversely increasing the amount of cellular and molecular damage. Higher doses (10 and 16 J/cm2) were characterized by a decrease in cell viability and cell proliferation with a significant amount of damage to the cell membrane and DNA.Conclusions Results show that 5 J/cm2 stimulates mitochondrial activity, which leads to normalization of cell function and ultimately stimulates cell proliferation and migration of wounded fibroblasts to accelerate wound closure. Laser irradiation can modify cellular processes in a dose or fluence (J/cm2) dependent manner. Lasers Surg. Med. 38:74–83, 2006. © 2006 Wiley-Liss, Inc.
Article
Full-text available
In this study, we examined the hypothesis that laser photostimulation can facilitate healing of impaired wounds in experimental diabetes using a rat model. Diabetes was induced in male rats by streptozotocin injection and two 6 mm diameter circular wounds were created on either side of the spine. The left wound of each animal was treated with a 632.8 nm He:Ne laser at a dose of 1.0 J/cm2 for five days a week until the wounds closed (three weeks). Measurements of the biomechanical properties of the laser-treated wounds indicated there was a marginal increase in maximum load (16%), stress (16%), strain (27%), energy absorption (47%) and toughness (84%) compared to control wounds of diabetic rats. Biochemical assays revealed that the amount of total collagen was significantly increased in laser treated wounds (274 +/- 8.7 microg) over the control wounds (230 +/- 8.4 microg). Sequential extractions of collagen from healing wounds showed that laser treated wounds had significantly greater concentrations of neutral salt soluble (15%) and insoluble collagen (16%) than control wounds, suggesting accelerated collagen production in laser treated wounds. There was an appreciable decrease in pepsin soluble collagen (19%) in laser treated wounds over control wounds, indicating higher resistance to proteolytic digestion. In conclusion, the biomechanical and biochemical results collectively suggest that laser photostimulation promotes the tissue repair process by accelerating collagen production and promoting overall connective tissue stability in healing wounds of diabetic rats.
Article
Full-text available
Greater interest in wound healing is needed to ensure higher standards of basic care. Precise identification of the systemic, local, and molecular factors underlying the wound healing problem in individual patients should allow better tailored treatment. Allogeneic skin grafting and bioengineered skin equivalents are being used successfully in patients with venous leg ulcers and diabetic patients with foot ulcers.
Article
Full-text available
The biological effects of far-infrared ray (FIR) on whole organisms remain poorly understood. The aim of our study was to investigate not only the hyperthermic effect of the FIR irradiation, but also the biological effects of FIR on wound healing. To evaluate the effect of FIR on a skin wound site, the speed of full-thickness skin wound healing was compared among groups with and without FIR using a rat model. We measured the skin wound area, skin blood flow, and skin temperature before and during FIR irradiation, and we performed histological inspection. Wound healing was significantly more rapid with than without FIR. Skin blood flow and skin temperature did not change significantly before or during FIR irradiation. Histological findings revealed greater collagen regeneration and infiltration of fibroblasts that expressed transforming growth factor-beta1 (TGF-beta1) in wounds in the FIR group than in the group without FIR. Stimulation of the secretion of TGF-beta1 or the activation of fibroblasts may be considered as a possible mechanisms for the promotive effect of FIR on wound healing independent of skin blood flow and skin temperature.
Article
Full-text available
The influence of daily energy doses of 0.03, 0.3 and 0.9 J of He-Ne laser irradiation on the repair of surgically produced tibia damage was investigated in Wistar rats. Laser treatment was initiated 24 h after the trauma and continued daily for 7 or 14 days in two groups of nine rats (n=3 per laser dose and period). Two control groups (n=9 each) with injured tibiae were used. The course of healing was monitored using morphometrical analysis of the trabecular area. The organization of collagen fibers in the bone matrix and the histology of the tissue were evaluated using Picrosirius-polarization method and Masson's trichrome. After 7 days, there was a significant increase in the area of neoformed trabeculae in tibiae irradiated with 0.3 and 0.9 J compared to the controls. At a daily dose of 0.9 J (15 min of irradiation per day) the 7-day group showed a significant increase in trabecular bone growth compared to the 14-day group. However, the laser irradiation at the daily dose of 0.3 J produced no significant decrease in the trabecular area of the 14-day group compared to the 7-day group, but there was significant increase in the trabecular area of the 15-day controls compared to the 8-day controls. Irradiation increased the number of hypertrophic osteoclasts compared to non-irradiated injured tibiae (controls) on days 8 and 15. The Picrosirius-polarization method revealed bands of parallel collagen fibers (parallel-fibered bone) at the repair site of 14-day-irradiated tibiae, regardless of the dose. This organization improved when compared to 7-day-irradiated tibiae and control tibiae. These results show that low-level laser therapy stimulated the growth of the trabecular area and the concomitant invasion of osteoclasts during the first week, and hastened the organization of matrix collagen (parallel alignment of the fibers) in a second phase not seen in control, non-irradiated tibiae at the same period. The active osteoclasts that invaded the regenerating site were probably responsible for the decrease in trabecular area by the fourteenth day of irradiation.
Article
Full-text available
Acute wounds normally heal in a very orderly and efficient manner characterized by four distinct, but overlapping phases: hemostasis, inflammation, proliferation and remodeling. Specific biological markers characterize healing of acute wounds. Likewise, unique biologic markers also characterize pathologic responses resulting in fibrosis and chronic non-healing ulcers. This review describes the major biological processes associated with both normal and pathologic healing. The normal healing response begins the moment the tissue is injured. As the blood components spill into the site of injury, the platelets come into contact with exposed collagen and other elements of the extracellular matrix. This contact triggers the platelets to release clotting factors as well as essential growth factors and cytokines such as platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta). Following hemostasis, the neutrophils then enter the wound site and begin the critical task of phagocytosis to remove foreign materials, bacteria and damaged tissue. As part of this inflammatory phase, the macrophages appear and continue the process of phagocytosis as well as releasing more PDGF and TGF beta. Once the wound site is cleaned out, fibroblasts migrate in to begin the proliferative phase and deposit new extracellular matrix. The new collagen matrix then becomes cross-linked and organized during the final remodeling phase. In order for this efficient and highly controlled repair process to take place, there are numerous cell-signaling events that are required. In pathologic conditions such as non-healing pressure ulcers, this efficient and orderly process is lost and the ulcers are locked into a state of chronic inflammation characterized by abundant neutrophil infiltration with associated reactive oxygen species and destructive enzymes. Healing proceeds only after the inflammation is controlled. On the opposite end of the spectrum, fibrosis is characterized by excessive matrix deposition and reduced remodeling. Often fibrotic lesions are associated with increased densities of mast cells. By understanding the functional relationships of these biological processes of normal compared to abnormal wound healing, hopefully new strategies can be designed to treat the pathological conditions.
Article
Full-text available
Fetal epithelium retains the ability to re-epithelialize a wound in organotypic culture in a manner not dependent on the presence of underlying dermal substrata. This capacity is lost late in the third trimester of gestation or after embryonic day 17 (E(17)) in the rat such that embryonic day 19 (E(19)) wounds do not re-epithelialize. Moreover, wounds created in E(17) fetuses in utero heal in a regenerative, scar-free fashion. To investigate the molecular events regulating re-epithelialization in fetal skin, the wound-induced expression profile and tissue localization of activator protein 1 (AP-1) transcription factors c-Fos and c-Jun was characterised in E(17) and E(19) skin using organotypic fetal cultures. The involvement of mitogen-activated protein kinase (MAPK) signaling in mediating wound-induced transcription factor expression and wound re-epithelialization was assessed, with the effect of wounding on the expression of keratinocyte differentiation markers determined. Our results show that expression of AP-1 transcription factors was induced immediately by wounding and localized predominantly to the epidermis in E(17) and E(19) skin. c-fos and c-jun induction was transient in E(17) skin with MAPK-dependent c-fos expression necessary for the re-epithelialization of an excisional wound in organotypic culture. In E(19) skin, AP-1 expression persisted beyond 12 h post-wounding, and marked upregulation of the keratinocyte differentiation markers keratin 10 and loricrin was observed. No such changes in the expression of keratin 10 or loricrin occurred in E(17) skin. These findings indicate that re-epithelialization in fetal skin is regulated by wound-induced AP-1 transcription factor expression via MAPK and the differentiation status of keratinocytes.
Article
Full-text available
This study was carried out to investigate the influence of low-intensity polarized visible laser radiation on the acceleration of skin wound healing. Background Data: Low-level laser therapy (LLLT) at adequate wavelength, intensity, and dose can accelerate tissue repair. However, there is still unclear information about light characteristics, such as coherence and polarization. Some studies indicate that linearly polarized light can survive through long propagation distance in biological tissue. Three burns about 6 mm in diameter were created on the back of rats with liquid N(2). Lesion "L(//)" was irradiated by He-Ne laser (lambda = 632.8 nm), D= 1.0 J/cm(2), with linear polarization parallel to the spinal column of the rat. Lesion "L(inverted v)" was irradiated using the same laser and dose, but the light polarization was aligned perpendicularly to the relative orientation. Lesion "C" was not irradiated in order to be considered as control. The animals were sacrificed at day 3-17 after lesion creation. Samples were collected and prepared for histological analysis. Histological analysis showed that the healing of irradiated wounds was faster than that of non-irradiated wounds. Moreover, it was observed that skin wound repair is dependent on polarization orientation with respect to a referential axis as the animal's spinal column. Consequently, "L(//)" was completely healed after 17 days, whereas "L (perpendicular) " showed a moderate degree of healing after the same period. These results indicate that the relative direction of the laser polarization plays an important role in the wound healing process when highly coherent He-Ne laser is used.
Article
Full-text available
This study was conducted to analyze the effect of different irradiances of low-level laser therapy (LLLT) on angiogenesis after partial rupture of Achilles tendon of rats. Ninety-six animals were divided into three groups subject to treatment during 3, 5, and 7 days post-lesion. Thirty-two animals were used in each group. The groups were further divided into four subgroups with eight animals in each, receiving In-Ga-Al-P laser (660 nm) treatment at (1) mean output of 10 mW, (2) 40 mW during 10 sec, (3) a sham subgroup, and (4) a non-treatment subgroup. Each animal was subjected to a lesion of the Achilles tendon by dropping a 186-g weight from a 20-cm height over the tendon. Treatment was initiated 6 h post-injury for all the groups. Blood vessels were colored with India ink injection and were examined in a video microscope. Laser exposure promoted an increase in blood vessel count when compared to controls. The 40-mW group showed early neovascularization, with the greatest number of microvessels after three laser applications. The 10-mW subgroup showed angiogenesis activity around the same time as the sham laser group did, but the net number of vessels was significantly higher in the former than in the controls. After seven irradiations, the subgroup receiving 40 mW experienced a drop in microvessel number, but it was still higher than in the control groups. LLLT of different intensities seems to promote neovascularization in damaged Achilles tendons of rats after partial rupture compared to controls.
Article
Full-text available
To study the influence of HeNe laser irradiation on the collagen percentage in surgically-induced skin wounds in rats with and without alloxan-induced diabetes, by morphometric analysis of collagen fibers. 48 male Wistar rats were used, divided into groups: laser-treated diabetic (group 1); untreated diabetic (group 2); treated non-diabetic (group 3); and untreated non-diabetic (group 4). For groups 1 and 2, diabetes was induced by intravenous injection of alloxan (2,4,5,6-tetraoxypyrimidine; 5,6-dioxyuracil; Sigma), into the dorsal vein of the penis, at a rate of 0.1 ml of solution per 100 g of body weight. A wound was made on the back of all the animals. Groups 1 and 3 were treated with HeNe laser (4 J/cm2) for 60 s. One animal from each group was sacrificed on the 3rd, 7th and 14th days after wounding. Samples were taken, embedded in paraffin, stained with hematoxylin-eosin and Masson's trichrome, and morphometrically analyzed using the Imagelab software. The percentages of collagen fibers were determined from the samples from the euthanasia animals. The data were treated statistically using analysis of variance (ANOVA) and the Student t and Kruskal-Wallis tests. The significance level was set at 0.05 or 5%. The results obtained from the samples taken on the third, seventh and fourteenth days after wounding demonstrated that the laser-treated group presented a statistically significant (p<0.05) greater mean quantity of collagen fibers than in the non-treated group, both for diabetic rats (p = 0.0104) and for non-diabetic rats (p = 0.039). The low-power laser (632.8 nm) was shown to be capable of influencing the collagen percentage in skin wounds by increasing the mean quantity of collagen fibers, both for the diabetic and for the non-diabetic group.
Article
Full-text available
Wound healing is essential for maintaining the integrity of multicellular organisms. In every species studied, disruption of an epithelial layer instantaneously generates endogenous electric fields, which have been proposed to be important in wound healing. The identity of signalling pathways that guide both cell migration to electric cues and electric-field-induced wound healing have not been elucidated at a genetic level. Here we show that electric fields, of a strength equal to those detected endogenously, direct cell migration during wound healing as a prime directional cue. Manipulation of endogenous wound electric fields affects wound healing in vivo. Electric stimulation triggers activation of Src and inositol-phospholipid signalling, which polarizes in the direction of cell migration. Notably, genetic disruption of phosphatidylinositol-3-OH kinase-gamma (PI(3)Kgamma) decreases electric-field-induced signalling and abolishes directed movements of healing epithelium in response to electric signals. Deletion of the tumour suppressor phosphatase and tensin homolog (PTEN) enhances signalling and electrotactic responses. These data identify genes essential for electrical-signal-induced wound healing and show that PI(3)Kgamma and PTEN control electrotaxis.
Article
Full-text available
An essential feature of a healed wound is the restoration of an intact epidermal barrier through wound epithelialization, also known as re-epithelialization. The directed migration of keratinocytes is critical to wound epithelialization and defects in this function are associated with the clinical phenotype of chronic non-healing wounds. A complex balance of signaling factors and surface proteins are expressed and regulated in a temporospatial manner that promote keratinocyte motility and survival to activate wound re-epithelialization. The majority of this review focuses on the mechanisms that regulate keratinocyte migration in the re-epithelialization process. This includes a review of cell attachments via desmosomes, hemidesmosomes, and integrins, the expression of keratins, the role of growth factors, cytokines and chemokines, eicosanoids, oxygen tension, antimicrobial peptides, and matrix metalloproteinases. Also reviewed are recently emerging novel mediators of keratinocyte motility including the role of electric fields, and signaling via the acetylcholine and beta-adrenergic receptors. These multiple regulators impact the ability of keratinocytes to migrate from the wound edge or other epidermal reservoirs to efficiently re-epithelialize a breach in the integrity of the epidermis. New discoveries will continue to uncover the elegant network of events that result in restoration of epidermal integrity and complete the wound repair process.
Article
Full-text available
It has recently been shown that nitrosyl complexes of hemoglobin (NO-Hb) are sensitive to low-level blue laser irradiation, suggesting that laser irradiation can facilitate the release of biologically active nitric oxide (NO), which can affect tissue perfusion. The aim of this study was to evaluate the therapeutic value of blue laser irradiation for local tissue perfusion after surgical intervention. Blood was withdrawn from a rat, exposed to NO and infused back to the same rat or used for in vitro experiments. In vitro, an increase of NO-Hb levels (electron paramagnetic resonance spectroscopy) up to 15 microM in rat blood did not result in the release of detectable amounts of NO (NO selective electrode). Blue laser irradiation of NO-Hb in blood caused decomposition of NO-Hb complexes and release of free NO. Systemic infusion of NO-Hb in rats affected neither systemic circulation (mean arterial pressure) nor local tissue perfusion (Doppler blood flow imaging system). In contrast, a clear enhancement of local tissue perfusion was observed in epigastric flap when elevated NO-Hb levels in blood were combined with local He-Cd laser irradiation focused on the left epigastric artery. The enhancement of regional tissue perfusion was not accompanied by any detectable changes in systemic circulation. This study demonstrates that blue laser irradiation improves local tissue perfusion in a controlled manner stimulating NO release from NO-Hb complexes.
Article
Full-text available
The keratins are the typical intermediate filament proteins of epithelia, showing an outstanding degree of molecular diversity. Heteropolymeric filaments are formed by pairing of type I and type II molecules. In humans 54 functional keratin genes exist. They are expressed in highly specific patterns related to the epithelial type and stage of cellular differentiation. About half of all keratins--including numerous keratins characterized only recently--are restricted to the various compartments of hair follicles. As part of the epithelial cytoskeleton, keratins are important for the mechanical stability and integrity of epithelial cells and tissues. Moreover, some keratins also have regulatory functions and are involved in intracellular signaling pathways, e.g. protection from stress, wound healing, and apoptosis. Applying the new consensus nomenclature, this article summarizes, for all human keratins, their cell type and tissue distribution and their functional significance in relation to transgenic mouse models and human hereditary keratin diseases. Furthermore, since keratins also exhibit characteristic expression patterns in human tumors, several of them (notably K5, K7, K8/K18, K19, and K20) have great importance in immunohistochemical tumor diagnosis of carcinomas, in particular of unclear metastases and in precise classification and subtyping. Future research might open further fields of clinical application for this remarkable protein family.
Conference Paper
BACKGROUND. Light-emitting diode (LED) photomodulation is a novel nonthermal technology used to modulate cellular activity with light. OBJECTIVE. We describe our experience over the last 2 years using 590 nm LED photomodulation within a dermatologic surgery environment. METHODS. Practical use of nonthermal light energy and emerging applications in 3,500 treatments delivered to 900 patients is detailed. RESULTS. LED photomodulation has been used alone for skin rejuvenation in over 300 patients but has been effective in augmentation of results in 600 patients receiving concomitant nonablative thermal and vascular treatments such as intense pulsed light, pulsed dye laser, KTP and infrared lasers, radiofrequency energy, and ablative lasers. CONCLUSION. LED photomodulation reverses signs of photoaging using a new nonthermal mechanism. The anti-inflammatory component of LED in combination with the cell regulatory component helps improve the outcome of other thermal-based rejuvenation treatments.
Conference Paper
Redox-regulated processes are relevant to wound healing. A balance between bioavailable nitric oxide (NO) concentration and a level of oxidative and nitroxidative stress in wounds may be crucial in wound repair. The highly beneficial effect of bioavailable NO is attributed to scavenging of superoxide, which is the main component of oxidative stress. Also, the high level of NO can influence angiogenesis and endothelial/skeletal muscle cell remodeling and proliferation. However, under conditions of excessive and prolonged production of O-2(-) in wounds, the supplementation of NO can be evolved in significant increase in nitroxidative stress due to production of peroxynitrite (ONOO-) and peroxynitrous acid (ONOOH). ONOOH can trigger a cascade of events leading to the generation of highly reactive and damaging radicals and oxidative species. These species (mainly CO3 center dot-, NO2+, NO2, N2O3, OH center dot) can impose significant damage in biological milieu and impair the process of wound healing. Therefore, a general strategy for an acceleration of the wound healing process may include an intervention(s) leading to the decrease in oxidative stress (treatment with antioxidants and/or prevention of O2(-) generation by uncoupled constitutive nitric oxide synthase, cNOS) and delivery of NO (treatment with NO donors, cNOS gene therapy). Here we briefly review the role of NO, and focus on O2(-) and ONOOH (major components of oxidative and nitroxidative stress respectively) in the normal and impaired process of wound healing.
Article
Injury to stratified epithelia causes a strong induction of keratins 6 (K6) and 16 (K16) in post-mitotic keratinocytes located at the wound edge. We show that induction of K6 and K16 occurs within 6 h after injury to human epidermis. Their subsequent accumulation in keratinocytes correlates with the profound reorganization of keratin filaments from a pan-cytoplasmic distribution to one in which filaments are aggregated in a juxtanuclear location, opposite to the direction of cell migration. This filament reorganization coincides with additional cytoarchitectural changes and the onset of re-epithelialization after 18 h post-injury. By following the assembly of K6 and K16 in vitro and in cultured cells, we find that relative to K5 and K14, a well-characterized keratin pair that is constitutively expressed in epidermis, K6 and K16 polymerize into short 10-nm filaments that accumulate near the nucleus, a property arising from K16. Forced expression of human K16 in skin keratinocytes of transgenic mice causes a retraction of keratin filaments from the cell periphery, often in a polarized fashion. These results imply that K16 may not have a primary structural function akin to epidermal keratins. Rather, they suggest that in the context of epidermal wound healing, the function of K16 could be to promote a reorganization of the cytoplasmic array of keratin filaments, an event that precedes the onset of keratinocyte migration into the wound site.
Article
New physical, pharmacological, biological, and surgical treatments offer the possibility of tailor made therapy Chronic wounds represent a major health burden and drain on resources. Recent advances in our understanding of chronic wound biology have led to the development of several new treatments that offer renewed hope to patients with ulcers and other chronic wounds. Defining the role of these new treatment, in the context of the increasing number of patients with chronic wounds, represents the next challenge. This review describes our view of the current and future developments in chronic wound management. ### Summary points Greater interest in wound healing is needed to ensure higher standards of basic care Precise identification of the systemic, local, and molecular factors underlying the wound healing problem in individual patients should allow better tailored treatment. Allogeneic skin grafting and bioengineered skin equivalents are being used successfully in patients with venous leg ulcers and diabetic patients with foot ulcers The material presented in this article has been compiled from the published literature (located by searching Medline, PubMed, Embase, and Zetoc with the search terms “wound healing,” “treatment and venous leg,” “treatment and diabetic foot,” and “treatment and pressure ulcer”) presentations at international meetings, and our own 30 years of clinical experience managing acute and chronic wounds. The management of chronic wounds places an enormous drain on healthcare resources; studies have calculated the cost of wounds to the NHS to be about £1bn a year.1 In the United Kingdom around 24 000 admissions a year are for patients with diabetic foot ulceration, thereby costing the NHS some £17m.2 Foot ulceration is the commonest complication of diabetes that requires hospitalisation, and in the United States management of this problem is estimated to cost $150m a year.3 Venous leg ulceration costs an estimated £400m annually in the …
Article
Background: Given the recent interest in light-emitting diode (LED) photomodulation and minimally invasive nonablative laser therapies, it is timely to investigate reports that low-level laser therapy (LLLT) may have utility in wound healing. Objectives: To critically evaluate reported in vitro models and in vivo animal and human studies and to assess the qualitative and quantitative sufficiency of evidence for the efficacy of LLLT in promoting wound healing. Method: Literature review, 1965 to 2003. Results: In examining the effects of LLLT on cell cultures in vitro, some articles report an increase in cell proliferation and collagen production using specific and somewhat arbitrary laser settings with the helium neon (HeNe) and gallium arsenide lasers, but none of the available studies address the mechanism, whether photothermal, photochemical, or photomechanical, whereby LLLT may be exerting its effect. Some studies, especially those using HeNe lasers, report improvements in surgical wound healing in a rodent model; however, these results have not been duplicated in animals such as pigs, which have skin that more closely resembles that of humans. In humans, beneficial effects on superficial wound healing found in small case series have not been replicated in larger studies. Conclusion: To better understand the utility of LLLT in cutaneous wound healing, good clinical studies that correlate cellular effects and biologic processes are needed. Future studies should be well-controlled investigations with rational selection of lasers and treatment parameters. In the absence of such studies, the literature does not appear to support widespread use of LLLT in wound healing at this time. Although applications of high-energy (10–100 W) lasers are well established with significant supportive literature and widespread use, conflicting studies in the literature have limited low-level laser therapy (LLLT) use in the United States to investigational use only. Yet LLLT is used clinically in many other areas, including Canada, Europe, and Asia, for the treatment of various neurologic, chiropractic, dental, and dermatologic disorders. To understand this discrepancy, it is useful to review the studies on LLLT that have, to date, precluded Food and Drug Administration approval of many such technologies in the United States. The fundamental question is whether there is sufficient evidence to support the use of LLLT.
Article
An essential feature of a healed wound is the restoration of an intact epidermal barrier through wound epithelialization, also known as re-epithelialization. The directed migration of keratinocytes is critical to wound epithelialization and defects in this function are associated with the clinical phenotype of chronic non-healing wounds. A complex balance of signaling factors and surface proteins are expressed and regulated in a temporospatial manner that promote keratinocyte motility and survival to activate wound re-epithelialization. The majority of this review focuses on the mechanisms that regulate keratinocyte migration in the re-epithelialization process. This includes a review of cell attachments via desmosomes, hemidesmosomes, and integrins, the expression of keratins, the role of growth factors, cytokines and chemokines, eicosanoids, oxygen tension, antimicrobial peptides, and matrix metalloproteinases. Also reviewed are recently emerging novel mediators of keratinocyte motility including the role of electric fields, and signaling via the acetylcholine and beta-adrenergic receptors. These multiple regulators impact the ability of keratinocytes to migrate from the wound edge or other epidermal reservoirs to efficiently re-epithelialize a breach in the integrity of the epidermis. New discoveries will continue to uncover the elegant network of events that result in restoration of epidermal integrity and complete the wound repair process.
Article
The ability to heal wounds is vital to all organisms. In mammalian tissues, alterations in intermediate filament (IF) gene expression represent an early reaction of cells surviving injury. We investigated the role of keratin IFs during the epithelialization of skin wounds using a keratin 6alpha and 6beta (K6alpha/K6beta)-null mouse model. In skin explant culture, null keratinocytes exhibit an enhanced epithelialization potential due to increased migration. The extent of the phenotype is strain dependent, and is accompanied by alterations in keratin IF and F-actin organization. However, in wounded skin in vivo, null keratinocytes rupture as they attempt to migrate under the blood clot. Fragility of the K6alpha/K6beta-null epidermis is confirmed when applying trauma to chemically treated skin. We propose that the alterations in IF gene expression after tissue injury foster a compromise between the need to display the cellular pliability necessary for timely migration and the requirement for resilience sufficient to withstand the rigors of a wound site.
Article
Background Given the recent interest in light-emitting diode (LED) photomodulation and minimally invasive nonablative laser therapies, it is timely to investigate reports that low-level laser therapy (LLLT) may have utility in wound healing.Objectives To critically evaluate reported in vitro models and in vivo animal and human studies and to assess the qualitative and quantitative sufficiency of evidence for the efficacy of LLLT in promoting wound healing.Method Literature review, 1965 to 2003.Results In examining the effects of LLLT on cell cultures in vitro, some articles report an increase in cell proliferation and collagen production using specific and somewhat arbitrary laser settings with the helium neon (HeNe) and gallium arsenide lasers, but none of the available studies address the mechanism, whether photothermal, photochemical, or photomechanical, whereby LLLT may be exerting its effect. Some studies, especially those using HeNe lasers, report improvements in surgical wound healing in a rodent model; however, these results have not been duplicated in animals such as pigs, which have skin that more closely resembles that of humans. In humans, beneficial effects on superficial wound healing found in small case series have not been replicated in larger studies.Conclusion To better understand the utility of LLLT in cutaneous wound healing, good clinical studies that correlate cellular effects and biologic processes are needed. Future studies should be well-controlled investigations with rational selection of lasers and treatment parameters. In the absence of such studies, the literature does not appear to support widespread use of LLLT in wound healing at this time. Although applications of high-energy (10–100 W) lasers are well established with significant supportive literature and widespread use, conflicting studies in the literature have limited low-level laser therapy (LLLT) use in the United States to investigational use only. Yet LLLT is used clinically in many other areas, including Canada, Europe, and Asia, for the treatment of various neurologic, chiropractic, dental, and dermatologic disorders. To understand this discrepancy, it is useful to review the studies on LLLT that have, to date, precluded Food and Drug Administration approval of many such technologies in the United States. The fundamental question is whether there is sufficient evidence to support the use of LLLT.WILLIAM POSTEN, MD, DAVID A. WRONE, MD, JEFFREY S. DOVER, MD, FRCPC, KENNETH A. ARNDT, MD, SIRUNYA SILAPUNT, MD, AND MURAD ALAM, MD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS.
Article
The medical literature describes numerous in vitro and in vivo wound-healing models. The selection of an animal model depends on a number of factors including availability, cost, ease of handling, investigator familiarity, and anatomical/functional similarity to humans. Small mammals are frequently used for wound healing studies, however, these mammals differ from humans in a number of anatomical and physiological ways. Anatomically and physiologically, pig skin is more similar to human skin. The many similarities between man and pig would lead one to believe that the pig should make an excellent animal model for human wound healing. The purpose of this paper is to review the existing literature for evidence of this supposition and determine how well the various models correlate to human wound healing. Studies of wound dressings, topical antimicrobials, and growth factors are examined. Over 180 articles were utilized for this comparative review. Our conclusion is that the porcine model is an excellent tool for the evaluation of therapeutic agents destined for use in human wounds.
Article
This paper briefly reviews the authors' experimental and clinical use of lasers over a 20-year period, during which laser effects on 15 biological systems were studied. Low-energy laser radiation was found to have a stimulating effect on cells, and high-energy radiation had an inhibiting effect. The application of lasers to stimulate wound healing in cases of nonhealing ulcers is recommended.
Article
Low doses of laser were found to stimulate the regeneration not only of mechanically induced wounds but also of burns. The wound-healing stimulated by laser radiation involves an increased rate of epithelial growth, which may eventually be the starting point of neoplastic growth.
Article
Dermal wound repair events can be temporally, albeit arbitrarily, grouped into inflammation, granulation tissue formation, and tissue remodeling. These phases are not mutually exclusive but rather overlap in time. This review follows the chronology of dermal wound repair, that is, inflammation, granulation tissue formation, and tissue remodeling.
Article
Injury to stratified epithelia causes a strong induction of keratins 6 (K6) and 16 (K16) in post-mitotic keratinocytes located at the wound edge. We show that induction of K6 and K16 occurs within 6 h after injury to human epidermis. Their subsequent accumulation in keratinocytes correlates with the profound reorganization of keratin filaments from a pan-cytoplasmic distribution to one in which filaments are aggregated in a juxtanuclear location, opposite to the direction of cell migration. This filament reorganization coincides with additional cytoarchitectural changes and the onset of re-epithelialization after 18 h post-injury. By following the assembly of K6 and K16 in vitro and in cultured cells, we find that relative to K5 and K14, a well-characterized keratin pair that is constitutively expressed in epidermis, K6 and K16 polymerize into short 10-nm filaments that accumulate near the nucleus, a property arising from K16. Forced expression of human K16 in skin keratinocytes of transgenic mice causes a retraction of keratin filaments from the cell periphery, often in a polarized fashion. These results imply that K16 may not have a primary structural function akin to epidermal keratins. Rather, they suggest that in the context of epidermal wound healing, the function of K16 could be to promote a reorganization of the cytoplasmic array of keratin filaments, an event that precedes the onset of keratinocyte migration into the wound site.
Article
The healing of an adult skin wound is a complex process requiring the collaborative efforts of many different tissues and cell lineages. The behavior of each of the contributing cell types during the phases of proliferation, migration, matrix synthesis, and contraction, as well as the growth factor and matrix signals present at a wound site, are now roughly understood. Details of how these signals control wound cell activities are beginning to emerge, and studies of healing in embryos have begun to show how the normal adult repair process might be readjusted to make it less like patching up and more like regeneration.
Article
The purpose of this study was to determine irradiation parameters of a 780 nm low power CW diode laser (6.5 mW) leading to enhanced proliferation of cultured normal human keratinocytes (NHK). The possible role of reactive oxygen species (ROS) in this response was evaluated. NHK were exposed to a single dose of 0 to 3.6 J/cm2 (0-180 sec) of irradiation. Proliferation parameters studied were: incorporation of 3H-thymidine during 6-24 hr following irradiation; percentage of dividing cells and number of cells, 24 hr and 48 hr following irradiation, respectively. Proliferation of NHK exposed to 0.45-0.95 J/cm2 was significantly enhanced by 1.3-1.9-folds relative to sham-irradiated controls, as inferred from parameters studied. Exposure to other energy densities was considerably less effective in enhancing proliferation parameters. Added enzymatic antioxidants, superoxide dismutase or catalase, scavenging superoxide anions and H2O2, suppressed this enhanced proliferation. Added scavengers (alpha-tocopherol acetate, scavenging lipid peroxidation, or sodium azide, histidine, mannitol, scavenging singlet oxygen, superoxide anions, and hydroxyl radicals, respectively), or N-acetyl cysteine, the thiol-reducing agent, suppressed the response, but to different extents. The results indicate that 780 nm low power diode laser irradiation enhanced keratinocytes proliferation in vitro, with an apparent involvement of ROS in this response, and comparably, might be used to promote their proliferation in vivo to enhance wound healing.
Article
Recently, we demonstrated a large induction of inducible nitric oxide synthase (iNOS) during cutaneous wound repair. In this study, we established an in vivo model in mice to investigate the role of NO during the wound healing process. During excisional repair, mice were treated with L-N6-(1-iminoethyl)lysine (L-NIL), a selective inhibitor of iNOS enzymatic activity. Compared with control mice, L-NIL-treated animals were characterized by a severely impaired reepithelialization process, as the hyperproliferative epithelia at the wound edges appeared to be delayed and characterized by an atrophied morphology. Immunohistochemical labeling for detection of proliferating cells (BrdU-, Ki67-staining) revealed a strong reduction in proliferating keratinocyte cell numbers during the process of re-epithelialization after inhibition of iNOS activity during repair. Western blot analysis of total wound lysates from PBS- and L-NIL-treated mice clearly demonstrated a reduction in proliferating cell nuclear antigen, representing a marker for cell proliferation, in lysates isolated from L-NIL-treated mice. The dependency between keratinocyte proliferation and NO availability observed during wound repair in vivo is further supported by the observation that proliferation of the keratinocyte cell line (HaCaT) is stimulated by low concentrations of NO-donors also in vitro. In summary, our data demonstrate that the presence of a functionally active iNOS is a crucial prerequisite for normal wound reepithelialization.