**2. Low-level laser and wound healing**

endothelial cells in the trauma site forming the granulation tissue. Turnover of collagen from type III to I restores skin integrity in the remodeling phase. Various factors can influence the quality of wound healing including nutrition, vitamin deficiencies, smoking, sex hormones, oxygenation, age, stress, diabetes, alcoholism, and medications such as glucocorticoid steroids,

Large varieties of treatment modalities have been used to enhance wound healing such as different medicines, surgical procedures, physical therapy, hyperbaric oxygen therapy, and physical modalities such as laser and shockwave. Some substances like honey have also proved to be beneficial in wound healing as a result of antiinflammatory and antibacterial features [2]. The ideal physical therapy modality is chosen based on the patient's factors, type of wound,

Electrical stimulation is another method of physical therapy used for accelerating wound healing. Electrotherapy works by stimulating cell migration, cell proliferation rate, and growth factor secretion via creating an electrical current. The anode attracts macrophages, neutrophils, and keratinocytes. The cathode attracts activated neutrophils, fibroblasts, myofibroblasts, and

Low‐level laser therapy (LLLT) is also a novel approach for treating wounds. Greatest benefits have been achieved through wavelengths of 632–1000 nm. The mechanism of action of LLLT is defined through wound contraction which accelerates the wound healing process [4].

Pulsed radiofrequency energy also promotes chronic wound healing by contracting the wound [5]. It has minimum side effects as well as the advantage of reducing wound pain.

Light‐emitting diode (LED) has somewhat similar effects as light amplification by stimulated emission of radiation (LASER) in expediting the process of wound healing by increasing

Shockwaves have also proved to be beneficial in overcoming chronic and intractable wounds such as diabetic ones with minimal adverse effects and long‐lasting results. The mechanism through which they work remains unknown; however, several factors are considered to be effective in this procedure including stimulation of microcirculation and metabolism, reduc‐

Photodynamic therapy (PDT) has also proved to be effective in wound healing. However, it

The effect of ultraviolet therapy on wound healing seems not promising and may even delay the process as it has shown to affect focal adhesion dynamics [9]. On the other hand, there are studies which suggest that ultraviolet C can be beneficial in expediting wound healing with

In this chapter, the authors tend to discuss physical modalities that are most used in the management of wound healing with a focus on lasers, shockwaves, photodynamic therapy,

fibroblasts and collagens and decreasing inflammatory cells in the trauma site [6].

tion of inflammatory cells, release of growth factors, and stimulation of stem cells [7].

seems to display best results when used in conjunction with lasers [8].

chemotherapeutic agents, and nonsteroidal antiinflammatory drugs [1].

previous therapies, and clinician's preference.

362 Wound Healing - New insights into Ancient Challenges

endothelial cells [3].

antibacterial effects [10].

UVB therapy, and lights.

In the recent years, it has been shown that the laser therapy had the potential to improve wound healing and reduce pain and inflammation [11].

The main indications of low‐reactive‐level laser therapy (LLLT) are reduction of pain and inflammation. It amplifies tissue repair, enhances regeneration of different nerves and tissues, and prevents tissue injury in situations where it is likely to occur [12, 13].

Low‐reactive‐level laser therapy (LLLT) enhances the activation of intracellular or extracellular chromophores and the initiation of cellular signaling by exposing cells or tissue to low levels of red and near infrared (NIR) light [11]. The biological effects of LLLT are decreased inflam‐ matory cells, increased fibroblast reproduction and angiogenesis, and stimulation of granula‐ tion tissue and augmented collagen synthesis [14].

LLLT assumes the use of photons at a nonthermal irradiation to alter biological activity. LLLT is composed of two sources: coherent light and noncoherent light sources (lasers) consisting of filtered lamps or light‐emitting diodes (LED) or, on occasion, a combination of both [13, 14].

The reason of the term "low level" is the use of low‐power contents compared to the other forms of laser therapy such as cutting, ablation, and thermally coagulating tissue.

The mechanism of LLLT on wound healing is not yet fully understood nevertheless it appears that LLLT has a wide area of effects at all the levels of molecular, cellular, and tissue ingredients. The main biological mechanism behind the effects of LLLT is proposed to be absorption of red and NIR light by mitochondrial components, in particular cytochrome c oxidase (CCO) which is concluded in the respiratory chain located within the mitochondria [15–17], and also in the plasma membrane of cells. Accordingly, a chain of events and various process carries out in the mitochondria [18] leading to wound healing.

Although LLLT is now used as a portable minimally invasive, easy‐to‐use, and cost‐effective modality to promote wound healing, it is also employed for treatment of diabetic lower extremity ulcer. However, it remains controversial in this therapy for two reasons. First, there are uncertainties about the basic molecular and cellular mechanisms responsible for appro‐ priate biological effects on the affected tissue. Second, there are significant variations in terms of parameters measuring: wavelength, irradiation or power density, pulse structure, coher‐ ence, polarization, energy, fluence, irradiation time, contact versus noncontact application, and repetition regimen. Lower level parameters can result in lower impact of the treatment and higher ones can lead to tissue injury [12, 14].

Inappropriate choice of light source and dosage can be the cause of negative results of many of the published studies on LLLT. In addition, eventual mismatch of the patient's skin to the application of LLLT were described, such as: improper preparation and oily debris that can interfere with the influence of the light source, and cause failure to account for skin pigmen‐ tation [19]. Unsuitable maintenance of the LLLT devices can reduce its efficiency and interfere with clinical results as well. It is important to notice that there is an optimal dose of light for any particular issues [14].

Nevertheless, many systematic reviews point that LLLT is an effective therapeutic modality on wound healing and diabetic foot ulcer recovery [20], but additional clinical studies must be performed in order to find out the best parameters of wavelength, dosage, and methodology and especially appropriate treatment protocol.
