## 1 Introduction  
Over the years, considerable effort has been made to find new prognostic and predictive biomarkers for oral pathologies, to develop new technologies for identifying and controlling etiological factors and to use new methods in the treatment and follow-up of oral diseases [1; 2; 3; 4]. Most prevalent oral conditions, such as dental caries and periodontal and peri-implant disease, are plaque-related. Pulpal and periapical pathology are the consequence of intracanal bacteria and their products. Mechanical preparation of root canals targets the removal of infected dentin and the enlargement of canals to favor irrigant penetration during the disinfecting process. However, literature data reveal that complete bacterial removal is not constantly achieved with current conventional chemical disinfectants [1; 2; 3; 4; 5; 6; 7; 8]. The antiseptic properties of dental lasers and ozone have been analyzed and extensively discussed in the literature in recent years [1; 2; 3; 4; 5; 6; 7; 8]. Their bactericidal, fungicidal and virucidal effects have been highlighted since the early twentieth century [9; 10]. Since then, lasers and ozone have had a wide applicability in several medical fields, including dentistry. Chemomechanical debridement of the infected root canals, especially on teeth with persistent apical periodontitis, is a modern minimally invasive treatment. It is extremely attractive for both dental practitioner and patient because it is painless and does not require any anesthesia. A correct decontamination of the endodontic space is the key to success in the treatment of chronic apical periodontitis. The intervention procedures include the reduction of bacterial microflora by mechanical removal of pulp tissue and the infected residual smear layer [11]. It is unanimously accepted that anaerobic gram-negative bacteria are involved in infections of root canals and the periapical area. _Enterococcus faecalis_ (_E. faecalis_) plays an important role in endodontic and periapical infections, especially due to its highly pathogenic characteristics [12]. While some studies have considered _E. faecalis_ to be one of the most common pathogens involved in persistent root infections, other studies have shown the contrary. [PERSON] et al. identified in 2015 the presence of _E. faecalis_ in only 14% of the evaluated cases of persistent apical periodontitis. The samples were obtained by cryopulverization and tested by polymerase chain reaction (PCR) [13]. The low frequency of _E. faecalis_ in the root apex makes its involvement in endodontic treatment failures questionable. Nevertheless, _E. faecalis_ proved to be one of the most resilient contaminants, showing resistance to antimicrobial and disinfecting agents, such as chlorhexidine, NaOCL, ethylenediamine tetraacetic acid (EDTA), citric acid, halogens and hydrogen peroxide [11; 12; 13; 14]. Additionally, for most of these agents toxicity in high concentrations is a significant factor. The main goal of combining endodontic ozone therapy with diode laser therapy is to significantly reduce or eradicate the microbial load on the complex root canal system, facilitating the completion of the mechanical debridement. The three-dimensional obturation is meant to prevent bacterial recolonization [15; 16]. Compared to laser therapy, which is a radiative technique, ozone therapy uses a highly instable chemical compound (O\({}_{3}\)) that is much more oxidizing than oxygen. Ozone is naturally produced in the upper layer of the atmosphere, as a result of ultraviolet energy or lightning. Clinically, an ozone generator produces an electrical discharge field that increases the energy of oxygen molecules (O\({}_{2}\)), causing atom separation and temporary recombination of oxygen atoms in triatomic molecules. Ozone has a remarkable antimicrobial capacity, and bacteria do not become resistant to its action, which is an enormous advantage when compared to antibiotic therapy [17].