Abstract
Photobiomodulation (PBM) is, in its broadest sense, a form of light treatment that utilises non-ionising radiation energy or light sources devoid of thermality and
ablation to effectuate a photon-tissue interaction. According to the first law of
photobiology, for low-powered light to have biostimulatory effects, photons must be absorbed to elicit a photochemical or photophysical effect (Farivar et al., 2014).
Although numerous mechanisms of action of PBM are still not fully understood,
there are several recorded cellular and molecular effects. The first encompasses the absorption of light in the visible red or near-infrared (NIR) spectrum through the mitochondrial respiratory chain enzyme, cytochrome c oxidase (COX), which is
principal to the aerobic metabolism of organisms. Light penetrates the tissues and
leads to COX absorption of the incident photons. This triggers photochemical events, stimulating the production of adenosine 5’-triphosphate (ATP), nitric oxide (NO), and calcium ions (Ca2+) which leads to the generation of intracellular ROS,
cyclic adenosine monophosphate (cAMP) and several other molecules (Hamblin,
2018a; Mosca et al., 2019). PBM-mediated bioactivation of COX further initiates a cascade effect on gene transcription, cellular signalling, cell proliferation,
differentiation, migration, downstream protein synthesis, and enzyme activation.
However, the process is principally wavelength, fluence and irradiation time
dependent. PBM is a rapidly growing technology utilised in the treatment of a profusion of medical disorders that necessitate stimulation of tissue healing, repair
and restoration, pain mitigation, and inflammation attenuation.
Diabetes mellitus (DM) is correlated with impaired or delayed healing and is liable for approximately 15% of diabetic patients developing diabetic foot ulcers (DFUs).
It is estimated that 14-24% of these patients will require lower-extremity
amputations (Alavi et al., 2014; Frykberg et al., 2006). In diabetes, the biochemical microenvironment is compromised by the deregulation of growth factors involved
in initiating and sustaining the wound healing process, thus, resulting in increased
susceptibility to infection predominant in individuals with chronic wounds (Cho et
al., 2019). While the infiltrating cells fail to eradicate local pathogens and
v
promotion of cellular proliferation, an influx of proinflammatory cells is recruited
to the wound area, leading to altered immune function, prolonged inflammation,
and delayed wound healing. Furthermore, the exorbitant recruitment of
inflammatory cells is capable of producing several reactive oxygen species (ROS),
leading to the structural deformity of the extracellular matrix (ECM) (Demidova-
Rice et al., 2012). ROS stimulates matrix metalloproteinase (MMP) and serine protease generation, and also impairs growth factors, proteinase inhibitors, and
ECM. Diabetic wounds also display interrupted cell signalling pathways, including
the Janus kinase/signal transducer and activator of transcription (JAK/STAT)
pathway, which plays a critical role in the progression of wound healing.