## 1 Introduction  
A biological aim of endodontic treatment is the elimination of bacterial biofilms alongside a rigorous removal of pulpal remnants and smear layers from the root canal walls, followed by the hermetic sealing of the root canals [1; 2; 3; 4; 5; 6; 7; 8]. For endodontic treatment success, it is specifically important that the radicular system is regarded as a three-dimensionalentity, including not only the main canal but also lateral canals, ramifications, loops, isthmuses, and deltas [1; 8; 9]. These root canal complexities may give refuge to biofilms, pulp remnants, and dentin debris that may become a source of re-infection after root canal treatment is completed [10; 11; 12]. Thus, an important step of endodontic treatment is root canal chemo-mechanical preparation, i.e., irrigation and instrumentation aimed to reach difficult-to-access areas to the maximum possible extent [1; 9; 13; 14]. At the same time, instrumentation results in the formation of an amorphous layer consisting of dentin debris, remnants of odontoblastic processes, pulp tissue, and bacteria known as the smear layer [15; 16]. The surface smear layer is usually 1-2 \(\upmu\)m thick, but it may form smear plugs in the dental tubules up to 40 \(\upmu\)m deep [6; 16]. These plugs decrease dentin permeability and prevent the penetration of antiseptic and dissolving agents into the dental tubules [15; 16; 17]. The removal of this layer enhances the antibacterial effectiveness of chemo-mechanical treatment by allowing antiseptic solutions to penetrate deeper into the dentin and also provides stronger bonding of sealer to the root canal walls [15; 18; 19]. Smear layer elimination is mainly achieved by meticulous irrigation of the root canal system and may be enhanced by the use of different activation techniques [20; 21; 22; 23; 24]. In order to effectively remove the smear layer, the irrigation protocol should include medicaments affecting its organic and inorganic components [18; 19; 25]. Sodium hypochlorite (NaOCI) in different concentrations is considered to be a gold standard in root canal irrigation due to its antimicrobial and tissue-dissolving properties [26; 27; 28; 29]. However, it provides limited activity against the inorganic part of the smear layer [25; 30; 31; 32]. Therefore, smear layer removal should be accomplished by irrigation with NaOCI combined with decalifying (chelating) substances [33; 34]. Chelating agents react with calcium ions in the dentin wall and form soluble calcium compounds, which may be easily rinsed off [35]. Sodium hypochlorite's proteolytic activity is directly proportional to its concentration [1; 29]. It can also be potentiated by laser-assisted irrigation and ultrasonic activation [2] and frequent refreshing of the solution [29]. On the other hand, the presence of dentin powder [36] and the use of some chelating substances have been reported to hamper sodium hypochlorite's proteolytic activity [37; 38; 39; 40; 41; 42]. Various chelating substances have demonstrated different inhibiting potentials towards the NaOCI effect [43; 44; 44]. Ethylene-diaminetetraacetic acid (EDTA) is the most widely used chelating agent [45; 46; 47; 48]; however, the use of NaOCI combined with EDTA has been found to cause demineralization and collagen rearrangement of root canal dentin, i.e., peritubular and intertubular dentin erosion [41; 49; 50]. Moreover, a protocol involving alternating use of EDTA and NaOCI alters the ability of the latter to dissolve organic matter. EDTA, being a strong chelator, actively reacts with NaOCI, leading to a decrease in its proteolytic activity due to the loss of free available chlorine (hypochlorite ion and hypochlorous acid) that is responsible for protein breakdown [14; 37; 38; 39; 40; 51]. Other strong chelating agents, such as citric [41] and maleic [52; 53] acids, demonstrated similar inhibiting effects when combined with NaOCI. To overcome the aforementioned issue, a \"continuous chelation\" approach was proposed.