Background: Under physiological conditions, endothelial cells are the main regulator of arterial tone homeostasis and vascular growth, sensing and transducing signals between tissue and blood. Disease risk factors can lead to their unbalanced homeostasis, known as endothelial dysfunction. Red and near-infrared light can interact with animal cells and modulate their metabolism upon interaction with mitochondria’s cytochromes, which leads to increased oxygen consumption, ATP production and ROS, as well as to regulate NO release and intracellular Ca²⁺ concentration. This medical subject is known as photobiomodulation (PBM). We present a review of the literature on the in vitro and in vivo effects of PBM on endothelial dysfunction. Methods: A search strategy was developed consistent with the PRISMA statement. The PubMed, Scopus, Cochrane, and Scholar electronic databases were consulted to search for in vitro and in vivo studies. Results: Fifty out of >12,000 articles were selected. Conclusions: The PBM can modulate endothelial dysfunction, improving inflammation, angiogenesis, and vasodilatation. Among the studies, 808 nm and 18 J (0.2 W, 2.05 cm²) intracoronary irradiation can prevent restenosis as well as 645 nm and 20 J (0.25 W, 2 cm²) can stimulate angiogenesis. PBM can also support hypertension cure. However, more extensive randomised controlled trials are necessary.

Photobiomodulation therapy (PBMT) is an effective treatment modality, which has the significant advantage of enhancing a patient’s quality of life (QoL) by minimising the side effects of oral cancer treatments, as well as assisting in the management of potentially cancerous lesions. It is important to note that the major evidence-based documentation neither considers, nor tackles, the issues related to the impact of PBMT on tumour progression and on the downregulation of cellular proliferation improvement, by identifying the dose- and time-dependency. Moreover, little is known about the risk of this therapy and its safety when it is applied to the tumour, or the impact on the factor of QoL. The review aimed to address the benefits and limitations of PBMT in premalignant oral lesions, as well as the conflicting evidence concerning the relationship between tumour cell proliferation and the applied dose of photonic energy (fluence) in treating oral mucositis induced by head and neck cancer (H&N) treatments. The objective was to appraise the current concept of PBMT safety in the long-term, along with its latent impact on tumour reaction. This review highlighted the gap in the literature and broaden the knowledge of the current clinical evidence-based practice, and effectiveness, of PBMT in H&N oncology patients. As a result, the authors concluded that PBMT is a promising treatment modality. However, due to the heterogeneity of our data, it needs to undergo further testing in well-designed, long-term and randomised controlled trial studies, to evaluate it with diligent and impartial outcomes, and ensure laser irradiation’s safety at the tumour site.

Objective: Photobiomodulation is proposed as a non-linear process. Only the action of light at a low intensity and fluence is assumed to have stimulation on cells; whereas a higher light intensity and fluence generates negative effects, exhausting the cell's energy reserve as a consequence of a too strong stimulation. In our work, we detected the photobiomodulatory effect of an 808-nm higher-fluence diode laser [64 J/cm ² –1 W, continuous wave (CW)] irradiated by a flat-top handpiece on mitochondria activities, such as oxygen consumption, activity of mitochondria complexes I, II, III, and IV, and cytochrome c as well as ATP synthesis. Materials and methods: The experiments are performed by standard procedure on mitochondria purified from bovine liver. Results: Our higher-fluence diode laser positively photobiomodulates the mitochondria oxygen consumption, the activity of the complexes III and IV, and the ATP production, with a P/O = 2.6. The other activities are not influenced. Conclusion: Our data show for the first time that even the higher fluences (64 J/cm ² –1 W), similar to the low fluences, can photobiostimulate the mitochondria respiratory chain without uncoupling them and can induce an increment in the ATP production. These results suggest that the negative effects of higher fluences observed to date are not unequivocally due to higher fluence per se but might be a consequence of the irradiation carried by handpieces with a Gaussian profile.

The literature has supported the concept of mesenchymal stromal cells (MSCs) in bone regeneration as one of the most important applications in oro-maxillofacial reconstructions. However, the fate of the transplanted cells and their effects on the clinical outcome is still uncertain. Photobiomodulation (PBM) plays an important role in the acceleration of tissue regeneration and potential repair. The aim of this in vitro study is to evaluate the effectiveness of PBM with 808 nm diode laser therapy, using a flat-top hand-piece delivery system at a higher-fluence (64 J/cm²) irradiation (1 W, continuous-wave) on bone marrow stromal cells (BMSCs). The BMSCs of 3 old female Balb-c mice were analyzed. The cells were divided into two groups: irradiated group and control group. In the former the cells were irradiated every 24 h during 0 day (T0), 5 (T1), 10 (T2), and 15 (T3) days, whereas the control group was non-irradiated. The results have shown that the 64 J/cm² laser irradiation has increased the Runt-related transcription factor 2 (Runx2). Runx2 is the most important early marker of osteoblast differentiation. The higher-fluence suppressed the synthesis of adipogenic transcription factor (PPARγ), the pivotal transcription factor in adipogenic differentiation. Also, the osteogenic markers such as Osterix (Osx) and alkaline phosphatase (ALP) were upregulated with an increase in the matrix mineralization. Furthermore, western blotting data demonstrated that the laser therapy has induced a statistically valid increase in the synthesis of transforming growth factor β1 (TGF-β1) but had no effects on the tumor necrosis factor α (TNFα) production. The data has statistically validated the down-regulation of the important pro-inflammatory cytokines such as interleukin IL-6, and IL-17 after 808 nm PBM exposition. An increase in anti-inflammatory cytokines such as IL-1rα and IL-10 was observed. These in vitro studies provide for first time the initial proof that the PBM of the 808 nm diode laser therapy with flat-top hand-piece delivery system at a higher-fluence irradiation of 64 J/cm² (1 W/cm²) can modulate BMSCs differentiation in enhancing osteogenesis.

Bone defects are the main reason for aesthetic and functional disability, which negatively affect patient’s quality of life. Particularly, after tooth extraction, the bone of the alveolar process resorbs, limiting the optimal prosthetic implant placement. One of the major pathophysiological events in slowly- or non-healing tissues is a blood supply deficiency, followed by a significant decrease in cellular energy amount. The literature shows that photons at the red and infrared wavelengths can interact with specific photoacceptors located within the cell. Through this mechanism, photobiomodulation (PBM) can modify cellular metabolism, by increasing mitochondrial ATP production. Here, we present a review of the literature on the effect of PBM on bone healing, for the management of socket preservation. A search strategy was developed in line with the PRISMA statement. The PubMed and Scholar electronic databases were consulted to search for in vivo studies, with restrictions on the year (<50 years-old), language (English), bone socket preservation, and PBM. Following the search strategy, we identified 269 records, which became 14, after duplicates were removed and titles, abstract and inclusion-, exclusion-criteria were screened. Additional articles identified were 3. Therefore, 17 articles were included in the synthesis. We highlight the osteoblast–light interaction, and the in vivo therapeutic tool of PBM is discussed.

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.