**12. Conclusion**

Moreover, this treatment diminished the incidence of *S. epidermidis* and *S. aureus* [45]. It seems

It appears that LLLT not only has a great range of effects at the molecular, cellular, and tissue levels and also its specific modes of action may vary among different applications. Within the cell, there is strong evidence to suggest that LLLT causes the mitochondria [46] to enhance ATP production [27, 31], modification of reactive oxygen species (ROS), and induce transcription

LLLT also enhances the proliferation, maturation, and motility of fibroblasts, and increases the production of bFGF [48]. When a chromophore absorbs a photon of light (laser) in the treated cells, an electron in the chromophore has the potential to become excited and move from low‐ energy orbit to a higher energy orbit [49]. The system can then use this stored energy to achieve various cellular tasks. There are several pieces of data that suggest that a mitochondria chromophore is as the initial LLLT target. Radiation of tissue with light makes mitochondrial products such as ATP, nicotinamide adenine dinucleotide (NADH), proteins, and RNA, as well as a reciprocal augmentation in oxygen consumption to increase. Various in vitro experiments have showed that cellular respiration is upregulated when mitochondria are subjected to a He‐ Ne laser or other forms of illumination [50]. The relevant chromophore can be detected by matching the action spectra for the biological response to light in the NIR range to the absorption spectra of the four membrane‐bound complexes identified in mitochondria. This procedure demonstrates that complex IV or cytochrome *c* oxidase (CCO) is the essential chromophore in the cellular response to LLLT. CCO that consists of two copper and two heme‐ iron centers (components of the respiratory electron transport chain) is a large transmembrane protein complex [51]. The high‐energy electrons are passed from electron carriers through a series of transmembrane complexes (such as CCO) to the final electron acceptor which makes a proton gradient used to produce ATP. Therefore, the administration of light directly affects ATP production by influencing one of the transmembrane complexes in the chain. Especially,

Direct irradiation of the eyes, within 4–6 months after radiotherapy, hemorrhaging region,

Epilepsy, fever, malignancy, to the low back or abdomen during pregnancy or menstruation, embryo or fetus, over the gonads, epiphyseal lines in children confused or disoriented patient,

that special LLLT protocols have potential antimicrobial activity.

**10. Cellular and tissue mechanisms of LLLT**

408 Wound Healing - New insights into Ancient Challenges

LLLT increases ATP production and electron transport [52].

**11. Contraindications and precautions**

**11.1. Contraindications**

**11.2. Precautions**

locally to the endocrine glands [53].

factors [47].

The effects of LLLT depend on the physiological state of the target cells, type of laser, radiation wavelength, energy density, and number of laser sessions. The biostimulation efficiency of LLLT is also dependent on the delivered energy density, which appears to be restricted to a very narrow therapeutic window. Compared with CW LLLT devices, PW LLLT devices provide more laser parameters. By investigating different values of these parameters, research models can be more effectively studied in these devices (PWLLLT) in comparison with CW LLLT devices, with the purpose of achieving better outcomes [54]. There were different LLLT protocols for different tissues. Clinical applications of LLLT have significantly impacted medicine and attracted the interest of clinicians, the public, and the media. The use of LLLT in biological applications and medicine is growing rapidly; advances in LLLT research have dramatically improved the clinician's ability to safely and effectively treat various medical conditions. According to several studies if the general condition of patients (such as blood glucose level, hydration, Na level, etc.) is controlled, LLLT can be useful for the treatment of diabetic foot ulcer. Nevertheless, additional research is required to elucidate the exact mech‐ anism of laser photostimulations action at the cellular and molecular levels. Standardized treatment parameters of LLLT should be followed. Efforts should be made to evaluate precise dosimetry for skin wounds, DFUs, and burns.
