# Healing Effects of Photobiomodulation on Diabetic Wounds
## 3 Photobiomodulation (PBM)
### Cellular Effects of PBM  
PBM has been shown to affect cell functions, such as viability, proliferation, migration, and metabolism, in a variety of cell types, including fibroblasts, mast cells, osteoblasts, Schwann cells, stem cells, keratinocytes, and smooth muscle cells. It has been shown to promote tissue regeneration and speed up wound repair by reducing inflammation and stimulating cell migration and proliferation, ECM production, and release of essential growth factors, and increasing the mean breaking strength of the wound.  
[PERSON] and colleagues [39] evaluated various cellular responses in human endothelial cells (HECV) irradiated with an 808 nm diode laser (1 W/cm\({}^{2}\), 60 J/cm\({}^{2}\); or 0.95 W/cm\({}^{2}\), 57 J/cm\({}^{2}\)). Cellular viability, free radical-induced oxidative stress, nuclear factor kappa B (NF-\(\kappa\)B) activation, NO release, mitochondrial respiration, and wound healing repair were measured. Irradiated cells demonstrated increased proliferation and migration coupled with a moderate increase in ROS production without a significant increase in oxidative stress and oxidative stress-activated processes. PBM stimulated mitochondrial oxygen consumption and ATP production. There was no effect on cellular viability, however, PBM led to an increased wound healing rate. Their results demonstrated that NIR light led to a shift from anaerobic to aerobic metabolism. [PERSON] et al. [40] also showed PBM was effective in modulating oxidative stress and reducing inflammation in injured muscle. Irradiation (808 nm, 3.8 mW/cm\({}^{2}\), total energy 1.4 J) not only lessened oxidative and nitrative stress, but also reduced lipid peroxidation, nitrotyrosine formation, NO production, and the inflammatory response (NF-\(\kappa\)B, COX-2, TNF-\(\alpha\) and interleukin(IL)-1\(\beta\)) and amplified superoxide dismutase (SOD) gene expression. [PERSON] and colleagues [41] irradiated wounded rats with a wavelength of 670 nm (30 mW, 14.28 J/cm\({}^{2}\)) for 15 consecutive days. Histopathological analysis revealed a lower inflammatory infiltrate, as well as increased collagen. There was an increase in vascular endothelial growth factor (VEGF) and a decrease in tumor necrosis factor-alpha (TNF-\(\alpha\)).  
Growth factors have an important role during wound repair and are involved in regulating cell growth, division, differentiation, and migration, and are also concerned with various signaling pathways. Numerous studies have shown the beneficial effect of PBM on the increased production of various growth factors essential to wound healing. [PERSON] and colleagues [42] showed that irradiation of human gingival fibroblasts by an infrared laser (780 nm; 1 W/cm\({}^{2}\); 3 and 5 J/cm\({}^{2}\)) led to the increased production and secretion of basic fibroblast growth factor (bFGF). [PERSON] et al. [43] demonstrated an increase in cell migration rate, proliferation, and viability, as well as an increased release of epidermal growth factor (EGF) in wounded fibroblast cells, which lead to activation of the JAK/STAT signaling pathway.  
The effect of PBM in aged animals has also been shown to be effective. [PERSON] et al. [44] investigated PBMT (660 nm, 1.07 W/cm\({}^{2}\), 72 J/cm\({}^{2}\)) in cutaneous wound healing in aged rats (500 days). The study demonstrated that PBM is effective in the modulation of inflammatory mediators (IL-6, CINC-1, and VEGF) and matrix metalloproteinases and their inhibitors (MMP-3, MMP-9, and TIMP-2). There was also increased collagen production during different phases of tissue regeneration.