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1432 Lasers Med Sci (2018) 33:1431–1439 Invented in 1962, LED was at the beginning unable to produce a significant biological activity. First beneficial ef- fects for human health have been found by the National Aeronautics and Space Administration (NASA) with the de- velopment of LEDs producing a narrow spectrum of light in a non-coherent manner, able to deliver the appropriate wave- length and intensity required for the process. In the past 15 years, LED technology was continuously ameliorated. Red, blue, yellow, and near-infrared, also known as mono- chromatic infrared energy (MIRE), lights are today available. LED therapy is nowadays a US Food and Drug Administration (FDA)-approved cosmetic procedure, in which observed effects include increased ATP production, modulation of intracellular oxidative stress, the induction of transcription factors, alteration of collagen synthesis, stimula- tion of angiogenesis, and increased blood flow [21]. LED biological effects are strongly influenced by light parameters as by clinical therapy [15]. The possibility to act on all of these parameters makes LED therapy highly flexible and adaptable for the treatment of dif- ferent skin disorders; each one implicates different biological effects to be addressed. Several studies reported effectiveness and safety of LED therapy in photo-aged skin [22–26]. Therefore, narrowband LED therapy using blue light reveals its efficacy and safety as additional therapy for mild to moderate acne [27]. LED therapy efficacy was also reported for instance in wound- healing [28, 29] as in psoriasis [30–32] and rosacea [33–36]. Recent studies [37] also demonstrated the antimicrobial effect of blue light. This antimicrobial effect is a non- thermal photochemical reaction involving the simultaneous presence of visible light, oxygen, and photosensitizer. Once photosensitization has been activated by the proper light source, chemical reactions are triggered leading to the produc- tion of various reactive oxygen species (ROS) [38]. Antimicrobial efficacy of PDT has been verified against a wide range of pathogens also in biofilm forms [39]. Therefore, use of blue light (405 nm) followed by treatment with red light (603 nm) is under investigation in the treatment of skin disorder involving microbial agents. Evidence on the efficacy of LED therapy for antimicrobial purposes also sug- gests its possible application in modulating skin microbiome. This article will review the current LED-based therapeutic approach in different skin and hair disorders. Behind LED physiochemistry and photobiomodulation A typical LED system is based on a semiconductor chip upon a reflective surface. When electricity runs through the system, light is produced. From a radiometric point of view, LED emission curve is in the form of a Lambertian pattern in which all the light is emitted at angles less than 90°. The knowledge and definition of physical parameters are obligatory steps when setting-up PDT therapy. Maximization of LED therapy is strictly related to optimization of treatment parameters: (i) intensity and dosage, (ii) fluence rate, (iii) wavelength, (iv) pulsing or continuous mode, and (v) treat- ment duration [40]. Intensity or irradiance refers to the dose of energy delivered by the LED system per surface area of skin treated and is expressed in watts per square centimeter (W/ cm2). The optimal clinical intensity or irradiance is considered to be around 50–100 mW/cm2. Another key part of the process is the definition of the optical properties of the tissues [15]. Once these have been defined, the fluence rate at any position for a given source specification can be calculated by mean of radiation transport equation (RTE) (Fig. 1) [41]. This equation describes light propagation to the site of treatment in a given direction per unit solid angle per unit area perpendicular to that direction. Since the resolution of this equation is not possible in almost all cases, three alternative approaches have been introduced [15]. Therefore, when setting up these kinds of physical eval- uation, it is also important to consider the impact of the dif- ferent geometries, such as the surface and the interstitial mo- dality of irradiation, on the distribution of fluence rate [15]. Finding the appropriate combinations between the dose, the irradiance and the intensity of treatment are another im- portant parameters to be considered to achieve optimal effects on the targeted tissues. Each skin conditions will require a specific evaluation of these parameters. Different wavelengths can be produced depending on the composition of the semiconductor and LED system can deliv- er light either in continuous or in pulsed mode. Used wavelengths ranged from 400 to 1200 nm (Fig. 2); longer wavelengths are able to go deeper into tissues [42, 43]. Different cells and tissues absorb light at different wave- lengths, and this is strictly related to the penetration that the wavelengths have to achieve. Red light (630–700 nm) is able to reach dermis activating fibroblasts, increasing fibroblast growth factor expression as type 1 procollagen and matrix metalloproteinase-9 (MMP-9) [44]. Blue light (400–470 nm) has a lower potential for penetra- tion and reveals useful for skin conditions in the epidermis layer of the skin [45]. Yellow light (about 540 nm) is effective in skin conditions involving redness, swelling, and other ef- fects related to pigmentation [40]. Near-infrared light (700– Fig. 1 Radiation transport equation (RTE). L (r, Ω) is the radiant power transported at location r in a given direction Ω per unit solid angle per unit area perpendicular to that direction; Ω and Ω′are the propagation directions before and after elastic scattering; μs (Ω → Ω′) is the differential scattering coefficient; S(r, Ω, t) refers to the light source both internal and externalPDF Image | Photodynamic and photobiological effects of (LED) therapy
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