# Healing Effects of Photobiomodulation on Diabetic Wounds
## 4 Photobiomodulation for Diabetic Wound Healing
PBM at 830 nm (5 J/cm\({}^{2}\), 4.4 mW/cm\({}^{2}\)) resulted in a decrease in pro-inflammatory cytokines (TNF-\(\alpha\) and IL-18) and apoptosis in diabetic wounded fibroblast cells [35]. Irradiation of the same cells to 660 nm (11 mW/cm\({}^{2}\), 5 J/cm\({}^{2}\)) resulted in decreased apoptosis and IL-18 [57]. There was also an increase in cellular viability and proliferation. Hypoxic cells also responded to PBM at the same parameters, and showed increased viability and proliferation, as well as decreased TNF-\(\alpha\)[57]. During wound healing, the ECM is maintained by a balance between collagen production and ECM degradation to facilitate cellular migration and removal of debris. In the case of diabetes, this balance is negated; there is decreased ECM synthesis and increased ECM degradation [58]. [PERSON] and colleagues [59] irradiated diabetic Wistar rats (660 nm, 4 J/cm\({}^{2}\)) and found that PBM promoted healing by increasing collagen synthesis. [PERSON] et al. [60] irradiated 4 cm\({}^{2}\) wounds in diabetic mice daily for 5 days (supervised AsGa laser, 904 nm, 40 mW, 304.8 mW/cm\({}^{2}\), 18.288 J/cm\({}^{2}\)). It was shown that there was increased collagen production, organization and angiogenesis, and decreased oxidative and nitrosative stress. [PERSON] et al. [61] irradiated wounded mice that represented a model of type 2 DM. Mice received a full thickness wound using a 5 mm punch. It was determined that PBM at a wavelength of 660 nm (4.7 to 6.3 J/cm\({}^{2}\), with 25, 50, or 100 mW) increased granulation tissue formation in diabetic mice when irradiated daily for 7 days. [PERSON] et al. [62] ascertained irradiation of diabetic rats at 808 nm (5 J/cm\({}^{2}\)) led to swifter wound contraction, and increased fibroblasts, granulation tissue, and collagen deposition. This occurred using three different power densities of 0.1, 0.2, and 0.3 W/cm\({}^{2}\), however, better results were seen at 0.1 W/cm\({}^{2}\). [PERSON] et al. [63] irradiated wounded diabetic rats to a wavelength of 660 nm (50 mW, 4 J/cm\({}^{2}\)) and found that PBM reduced the genetic expression of proteinases MMP-2 and -9, and increased total collagen production, particularly collagen type-III. [PERSON] et al. [64] showed increased collagen production when diabetic wounded fibroblast cells were irradiated at 660 nm (10.22 mW/cm\({}^{2}\), 5 J/cm\({}^{2}\)). In similar studies, gene profiles showed that genes related to collagen (Collagen, type XI, and Collagen, type XIV) were up-regulated and various MMPs down-regulated (MMP-1, -2, -8, -12, -14, and -16) in response to laser irradiation. MMP inhibitors were also up-regulated (TIMP-1) [65]. When the same cells were irradiated at a different wavelength of 830 nm (10.76 mW/cm\({}^{2}\), 5 J/cm\({}^{2}\)) PBM produced a stimulatory effect on various cell adhesion molecules, namely, cadherins, integrins, selectins and immunoglobulins [66]. A study on the effect of PBM on _S. aureus_ infected wounds in diabetic rats was conducted by [PERSON] and colleagues [67]. Streptavidin-induced male Wistar rats received 4 cm full-thickness linear incisions on the dorsal midline which were contaminated with \(5\times 10^{7}\) CFU/mL of _S. aureus_. The wounds were then closed with sutures. On the third day post-wounding, wounds were irradiated daily for 5 consecutive days using a laser with a wavelength of 685 nm (15 mW, 3 J/cm\({}^{2}\), spot of 0.028 cm\({}^{2}\)); control rats were sham irradiated. PBM resulted in decreased bacterial numbers, with a significant decrease observed in the irradiated rats (\(0.51\times 10\pm 0.2\times 10\) CFU/mL) as compared to the controls (\(8.4\times 10^{7}\pm 1.8\times 10^{7}\) CFU/mL). PBM also resulted in significantly shorter wound length (on days 14 and 21), and a significant increase in the number of macrophages, new blood vessels, fibroblasts, and collagen deposition. The breaking strength of the scars was also significantly increased in PBM treated rats [67]. This study has shown the potential of utilizing PBM in the treatment of infected diabetic wounds.