# Healing Effects of Photobiomodulation on Diabetic Wounds
## 4 Photobiomodulation for Diabetic Wound Healing  
Various studies have found PBM to be beneficial to diabetic wound healing (Table 1). PBM has promoted and sped up repair in non-healing ulcers. [PERSON] [49] reported on the use of different lasers with wavelengths in the visible to NIR spectra (532, 633, 810, 980, and 10,600 nm) and polychromatic LED clusters (510-872 nm, visible to infrared). Sreptozotocin-induced Sprague-Dawley rats were subjected to a full-thickness wound (102.5 \(\pm\) 9 mm\({}^{2}\)) or a burn (148 \(\pm\) 12.5 mm\({}^{2}\)) and then treated with PBM three times a week at different fluencies (5, 10, 20, and 30 J/cm\({}^{2}\)). It was concluded that the best treatment option for both diabetic wounds and burns was with a laser at a wavelength of 633 nm with 38.5% and 53.4% improvements, respectively. A dose (fluence) of 4.71 J/cm\({}^{2}\) for diabetic burns, and 2.35 J/cm\({}^{2}\) per dose for diabetic wound healing administered three times a week was recommended. [PERSON] and [PERSON] [50] irradiated diabetic wounded rats (632.8 nm, 4 mW/cm\({}^{2}\)) five times a week until the wounds healed. Irradiated diabetic wounds took 21 days to heal, whereas non-treated control wounds took 40 to 60 days to heal. Chronic diabetic wounds have shown decreased levels of cytokines and growth factors essential to wound healing [51]. PBM has been show to promote the synthesis and release of some of these under diabetic conditions, including EGF, IL-6, bFGF, platelet-derived growth factor (PDGF), and transforming growth factor beta 1 (TGF-81). [PERSON] et al. [43] demonstrated an increase in cell migration rate, proliferation, and viability in diabetic induced wounded fibroblast cells, which was ascribed to increased EGF, which in turn lead to activation of the receptor (EGFR) and the JAK/STAT pathway. They concluded that PBM at 660 nm (11 mW/cm\({}^{2}\), 5 J/cm\({}^{2}\)) is able to intensify and regulate cellular autocrine signaling, leading to increased cell proliferation and migration. [PERSON] and [PERSON] [52] irradiated human skin fibroblasts (632.8 nm; 0.66 mW/cm\({}^{2}\); 0.5, 1, and 2 J/cm\({}^{2}\)) in media that had different glucose concentrations (5.5 (physiological levels), 11.1, and 15 mM/L) and observed an increase in the release of intracellular cytokines IL-6 (at 0.5, 1, and 2 J/cm\({}^{2}\)) and bFGF (at 2 J/cm\({}^{2}\)). [PERSON] et al. [53] showed that PBM significantly augmented PDGF and up-regulated gene expression of FGF in diabetic mice skin fibroblasts when irradiated at a wavelength of 810 nm (10 mW/cm\({}^{2}\)) with a fluence of 1 J/cm\({}^{2}\). [PERSON] et al. [54] irradiated streptozotocin-induced Wistar rats to a wavelength of 630 nm (5, 10, and 20 mW/cm\({}^{2}\); 3.6 J/cm\({}^{2}\)) and found that PBM significantly altered TGF-81 and bFGF expression after 4 days. There was also an attenuation of the inflammatory response, greater reepithelial, mature granulation tissue (fibroblasts), and extensive collagen deposition, especially with irradiation of 20 mW/cm\({}^{2}\)[54]. Prolonged inflammation contributes to the pathophysiology of diabetic wound healing [55]. PBM has been shown to have anti-inflammatory effects under such conditions. [PERSON] and [PERSON] [56] treated incisions made with a diode laser or a scalpel on the left side of the dorsum in streptozotocin-induced Wistar rats with PBM (808 nm, 0.1W/cm\({}^{2}\), 10 J/cm\({}^{2}\)) for five sessions on alternative days. Rats were sacrificed at 10 (2 days after the last PBM treatment) and 20 days and the degree of reepithelialization and inflammation was investigated. There was a lower degree of reepithelialization and acute inflammation in the control group, with a significant increase in reepithelialization and diffuse acute inflammation in PBM treated groups. There was no statistically significant difference between the groups in inflammation and reepithelialization at day 20.