Background: Injury of the trigeminal nerve in oral and maxillofacial surgery can occur. Schwann cell mitochondria are regulators in the development, maintenance and regeneration of peripheral nerve axons. Evidence shows that after the nerve injury, mitochondrial bioenergetic dysfunction occurs and is associated with pain, neuropathy and nerve regeneration deficit. A challenge for research is to individuate new therapies able to normalise mitochondrial and energetic metabolism to aid nerve recovery after damage. Photobiomodulation therapy can be an interesting candidate, because it is a technique involving cell manipulation through the photonic energy of a non-ionising light source (visible and NIR light), which produces a nonthermal therapeutic effect on the stressed tissue. Methods: The review was based on the following questions: (1) Can photo-biomodulation by red and NIR light affect mitochondrial bioenergetics? (2) Can photobiomodulation support damage to the trigeminal nerve branches? (preclinical and clinical studies), and, if yes, (3) What is the best photobiomodulatory therapy for the recovery of the trigeminal nerve branches? The papers were searched using the PubMed, Scopus and Cochrane databases. This review followed the ARRIVE-2.0, PRISMA and Cochrane RoB-2 guidelines. Results and conclusions: The reliability of photobiomodulatory event strongly bases on biological and physical-chemical evidence. Its principal player is the mitochondrion, whether its cytochromes are directly involved as a photoacceptor or indirectly through a vibrational and energetic variation of bound water: water as the photoacceptor. The 808-nm and 100 J/cm² (0.07 W; 2.5 W/cm²; pulsed 50 Hz; 27 J per point; 80 s) on rats and 800-nm and 0.2 W/cm² (0.2 W; 12 J/cm²; 12 J per point; 60 s, CW) on humans resulted as trustworthy therapies, which could be supported by extensive studies.

Photobiomodulation (PBM) consists of a photon energy transfer to the cell, employing non-ionizing light sources belonging to the visible and infrared spectrum. PBM acts on some intrinsic properties of molecules, energizing them through specific light wavelengths. During the evolution of life, semiconducting minerals were energized by sun radiation. The molecules that followed became photoacceptors and were expressed into the first proto-cells and prokaryote membranes. Afterward, the components of the mitochondria electron transport chain influenced the eukaryotic cell physiology. Therefore, although many organisms have not utilized light as an energy source, many of the molecules involved in their physiology have retained their primordial photoacceptive properties. Thus, in this review, we discuss how PBM can affect the oral microbiota through photo-energization and the non-thermal effect of light on photoacceptors (i.e., cytochromes, flavins, and iron-proteins). Sometimes, the interaction of photons with pigments of an endogenous nature is followed by thermal or photodynamic-like effects. However, the preliminary data do not allow determining reliable therapies but stress the need for further knowledge on light-bacteria interactions and microbiota management in the health and illness of patients through PBM.

The tremendous therapeutic potential of photobiomodulation therapy in different branches of medicine has been described in the literature. One of the molecular mechanisms for this treatment implicates the mitochondrial enzyme, cytochrome C oxidase. However, the efficacy and consistency of clinical outcomes with photobiomodulation treatments has been fiercely debated. This work was motivated by this need to improve photobiomodulation devices and delivery approaches. We designed a novel hand-piece with a flat-top beam profile of irradiation. We compared the beam profile versus a standard hand-piece and a fibre probe. We utilized isolated mitochondria and performed treatments at various spots within the beam, namely, the centre, left and right edge. We examined mitochondrial activity by assessing ATP synthesis with the luciferin/luciferase chemiluminescent method as a primary endpoint, while mitochondrial damage was assessed as the secondary endpoint. We observed a uniform distribution of the power density with the flat-top prototype compared to a wide Gaussian beam profile with the standard fibre and standard hand-piece. We noted increased production of ATP in the centre of all three beams with respect to the non-treated controls (p < 0.05). Both the fibre and standard hand-piece demonstrated less increase in ATP synthesis at the edges than the centre (p < 0.05). In contrast, ATP synthesis was increased homogenously in the flat-top handpiece, both in the centre and the edges of the beam. Fibre, standard hand-piece and the flat-top hand-piece prototype have discrete beam distribution characteristics. This significantly affected the mitochondrial activity with respect to their position within the treated areas. Flat-top hand-piece enhances the uniformity of photobiomodulation treatments and can improve the rigour and reproducibility of PBM clinical outcomes.

Photobiomodulation (PBM) is a form of low-dose light therapy that acts through energy delivery from non-ionizing sources. During the recent two decades, there has been tremendous progress with PBM acceptance in medicine. However, PBM effects on potential stimulation of existing malignant or pre-malignant cells remain unknown. Thus, the primary endpoint was to assess the safety of PBM treatment parameters on head and neck squamous cell carcinoma (HNSCC) proliferation or survival. The secondary endpoint was to assess any putative anti-cancer effects of PBM treatments. Cell viability, energy metabolism, oxidative stress, and pro- and anti-apoptotic markers expression were investigated on a Human Head and Neck Squamous Cell Carcinoma cellular model (OHSU-974 FAcorr cell line). PBM therapy was administered through the 810 nm diode laser (GaAlAs) device (Garda Laser, 7024 Negrar, Verona, Italy) at the powers of 0, 0.25, 0.50, 0.75, 1.00, or 1.25 W in continuous wave (CW) mode for an exposure time of 60 s with a spot-size of 1 cm² and with a distance of 1.86 cm from the cells. Results showed that 810-nm PBM affected oxidative phosphorylation in OHSU-971 FAcorr, causing a metabolic switch to anaerobic glycolysis. In addition, PBM reduced the catalase activity, determining an unbalance between oxidative stress production and the antioxidant defenses, which could stimulate the pro-apoptotic cellular pathways. Our data, at the parameters investigated, suggest the safeness of PBM as a supportive cancer therapy. Pre-clinical and clinical studies are necessary to confirm the in vitro evidence.

Diminished facial movement and marked facial asymmetry can lead to a consistent psychological burden. Bell′s palsy (BP) is one of the most common causes of facial nerve illness, which comes with unilateral acute facial paresis. Nowadays, no clear guidelines for treating BP are available. We carried out a case series study to test the efficacy of photobiomodulation (PBM) therapy in patients with BP non-responsive to standard treatment. The study was experimentally performed at the Department of Surgical and Diagnostic Sciences, University of Genoa (Genoa, Italy), in accordance with case report guidelines. Patients were referred to our department by colleagues for evaluation to be included in the case series because no consistent improvement was observed at least 3 months from the diagnosis of BP. All the patients interrupted their pharmacological therapy before the initiation of PBM therapy. PBM therapy (808 nm, 1 W irradiated in continuous-wave for 60 s on spot-size 1 cm²; 1 W/cm²; 60 J/cm²; and 60 J) was administered every 2 days until complete resolution. Evaluation of the House-Brackmann scale was performed before and after treatments. Fourteen patients were screened as eligible for the study. Patients were Caucasians (36% females and 64% males) with a mean age ± standard deviation of 56.07 ± 15.21 years. Eleven patients out of 14, who experienced BP a maximum of 6 months, completely recovered through PBM. The three patients that did not show improvement were those who had experienced BP for years. PBM could be a supportive therapy for the management of BP in patients non-responsive to standard treatment. However, randomized controlled trials are necessary to sustain our encouraging results, exclude bias, and better explain the boundary between the time from diagnosis and the recovery of BP through PBM therapy.

Tooth extraction is followed by a sequence of elaborate local changes affecting hard and soft tissues. Dry socket (DS) can occur as intense pain around and in the extraction site, with an incidence from 1–4% after generic tooth extraction to 45% for mandibular third molars. Ozone therapy has gained attention in the medical field because of its success in the treatment of various diseases, its biocompatible properties and its fewer side effects or discomfort than drugs. To investigate the preventive effect of the sunflower oil-based ozone gel Ozosan^® (Sanipan srl, Clivio (VA), Italy) on DS, a double-blind split-mouth randomized placebo-controlled clinical trial was conducted according to the CONSORT guidelines. Ozosan^® or the placebo gel were put in the socket, and the gels were washed off 2 min later. In total, 200 patients were included in our study. The patient population comprised 87 Caucasian males and 113 Caucasian females. The mean age of the included patients was 33.1 ± 12.4 years. Ozosan reduced the incidence of DS after inferior third molar extraction from 21.5% of the control to 2% (p < 0.001). Concerning the dry socket epidemiology, the incidence was not significantly correlated with gender, smoking or mesioangular, vertical or distoangular Winter’s classification. Post hoc power calculation showed a power of 99.8% for this data, with alpha = 0.001.