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Objective: The main focus of this in vitro study was to highlight possible differences between outcomes of photobiomodulation performed in the presence or absence of growth factors derived from platelet-rich plasma.Background: Photobiomodulation has garnered increasing attention, thanks to a large number of controlled clinical trials that have proven its efficacy in various oral pathologies. Nevertheless, the mechanism of action is still a matter of debate.Materials and methods: The cell model used was Saos-2ATTC HTB-85, a human osteosarcoma cell line that retains an osteogenic potential matching that of osteoblastic cells. Photobiomodulation was performed with a 645 nm diode laser; we investigated three different fluence values (2, 5, and 10 J/cm(2)) delivered with 3 different irradiation times (1, 2, and 4 min). The design of the study included a case-control structure. Cell viability was assessed by resazurin reduction assay before laser irradiation. We assessed cell differentiation by Alizarin-red Sigma Aldrich assay 48 h after the last laser irradiation.Results: Results show that the combination of photobiomodulation and platelet-rich plasma can lead to a statistically significant increase in both proliferation and differentiation rates.Conclusions: Only a defined amount of energy, that is, a fluence of 5 J/cm(2) delivered in 2 min and of 10 J/cm(2) in 4 min, was proven to be the most effective in the presence of platelet-rich plasma to induce cell proliferation and calcium deposition.

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