Periapical inflammation is a common oral disease. With the progression of caries, microbiota and its secreted toxins intrude from the dentin tubules into the root canal and infect the pulp tissue (Siqueira, 2002). Then, the necrotic pulp tissue infects and contributes to the inflammation breaking through the apical barrier. Finally, the destruction of the periodontal membrane and the resorption of alveolar bone trigger inflammation of the periapical tissue (Ricucci & Siqueira, 2010). The periapical inflammation was resulted from the periapical bone destruction caused by microbial infection.

At present, root canal therapy (RCT) is the preferred method for the clinical treatment of periapical inflammation. With the continuous progress of modern RCT technology, the success RCT rate is as high as 85∼90 %, but there are still some failure cases despite the improvement of operation technology and imaging (Setzer et al., 2011; Sjögren et al., 1997). Persistent microbial infection is the main cause of RCT failure. In the post-treatment endodontic disease (PTED), Enterococcus faecalis (E. faecalis) with a high detection rate is considered to be the main pathogen of periapical inflammation (Delboni et al., 2017; Prada et al., 2019; Siqueira & Rôças, 2022). E. faecalis infection model of root canals in vitro presented the typical structure of biofilm formed by amorphous matrix and E. faecalis in 1/3 of the root tip using scanning electron microscopy (SEM) (Song et al., 2013). Studies have shown that E. faecalis colonized in dentin tubules will quickly form reinfection if it cannot contact with drugs directly (Zhang et al., 2015). In vitro experiments have also found that E. faecalis can withstand high-pressure environments such as high alkalinity and oligotrophic conditions, and can invade deep dentin tubules and live in root canals for a long time (Ran et al., 2015). There are evidences that E. faecalis can form the biofilm in the apical area to modulate host immune responses and synthesis toxic macromolecules (e.g. aggregators and surface proteins) and damage periapicular tissue (Chen et al., 2017; Kayaoglu & Ørstavik, 2004; Xu et al., 2018).

Meanwhile，fungal species were also isolated from about 3–18 % infected root canals (Siqueira & Sen, 2004). Candida, especially Candida albicans (C. albicans), was the dominant strain in isolated fungal species (Yoo et al., 2020). Recent studies have found a high co-detection rate of E. faecalis and C. albicans in oral and PTED samples (Dahlén et al., 2012; Kovac et al., 2013; Mergoni et al., 2018; Peciuliene et al., 2001). The interaction of E. faecalis and C. albicans may be responsible for the failure of RCT. In immunodeficient mice infected with C. albicans, E. faecalis was the main colonizing bacteria in the intestinal and oral mucosa (Bertolini et al., 2019). Compared with single bacteria, the dual species formed a thicker and more robust biofilm, which presented a greater tolerance to harmful stresses, such as starvation environments, mechanical shear forces, and bactericidal chemicals (Du et al., 2021, Krishnamoorthy et al., 2020).

The activity of osteoclasts is the direct reason for the periapical alveolar bone resorption in the periapical inflammation. The high expression of Receptor Activator of Nuclear Factor-κB Ligand (RANKL), the osteoclast activator, was associated with the severity of periapical inflammation, and the level of alveolar bone resorption was significantly increased in osteoporotic patients (Estrela et al., 2016). Ma et al. (Ma et al., 2024) found that vesicles of E. faecalis could increase the osteoclastic range of the inflammatory area of the root tip by promoting the infiltration of M1-type macrophages in the periapical tissue. Du et al. (Du et al., 2021) 's study in vivo showed that the coexistence of E. faecalis and C. albicans increased osteoclast resorption in periapical diseased areas. The results suggested that the active osteoclysis caused by microorganisms promoted the progression of periapical inflammation.

Dodecylmethylaminoethyl methacrylate (DMAEM) is a new type of tertiary amine (TA) material used in the oral cavity (Huang et al., 2022; Li et al., 2021; Liang et al., 2020; Shan et al., 2024; Shi et al., 2022; Yang et al., 2023). Since acidic pH stimulation could cause the TA structure to protonate into quaternary ammonium salts (QAMs), DMAEM monomer form could perform antibacterial effect in a pH-dependent manner (Chen et al., 2023a; Chen et al., 2022; Wang et al., 2021). For example, DMAEM-modified adhesive resin exhibited antibacterial effect against Streptococcus mutans UA159 (S. mutans), Streptococcus gordonii DL1 (S. gordonii), and Streptococcus sanguinis SK1 (S. sanguinis) only in acidic medium (Liang et al., 2020). The culture of S. mutans biofilm model in in acidic and neutral medium was used to verify the ability of reversible antibiofilm effect due to protonation and deprotonation of TA (Liang et al., 2020). Otherwise, DMAEM has been found exerting fungicidal activity by targeting the CHK1 two-component system in C. albicans with the similar structural and functional characteristics with quaternary ammonium under acidic pH (Li et al., 2024). At pH value of 5.5, DMAEM monomer could significantly decrease the bacteria count of S. mutans, Veillonella parvula (V. parvula), Prevotella denticola (P. denticola) and Leptotrichia wadei (L. wadei), the carious core microbiota, shift their composition and reduce the lactate production of biofilm. And under the acidic condition, DMAEM monomer presented the ability to inhibit enamel demineralization in vitro and vivo (Yang et al., 2023). DMAEM monomers could also inhibit the growth and virulence factor expression of E. faecalis and C. albicans in a pH-dependent manner, thus becoming a candidate drug for the treatment of periapical inflammation and candidiasis (Li et al., 2024; Shan et al., 2024). Based on the excellent antibacterial properties of DMAEM, novel oral synthetic materials containing DMAEM were applied in anti-oral disease. A resin infiltant containing BisGMA and TEGDMA was incorporated with DMAEM and could effectively inhibit the formation of enamel white spot, and then inhibit the early caries formation (Huang et al., 2022). DMAEM modified resin adhesive had obvious antibacterial effect in acidic environment, and inhibited the growth of dual-species (S. mutans and C. albicans) biofilm and enamel demineralization (Liang et al., 2020; Shi et al., 2022; Zhang et al., 2024). DMAEM@RA had a good potential to prevent caries and secondary caries.The resin-based sealants containing DMAEM could significantly reduce the metabolic activity of biofilm, decrease the production of lactic acid and exopolysaccharide, and reduce microleakage, thus preventing caries (Li et al., 2021). The root canal sealer containing DMAEM synthesized by Shan et al. (Shan et al., 2024) could inhibit E. faecalis and its biofilm growth while increasing the water absorption of the sealing material, which would be a good potential material for the treatment of periapical inflammation.

On this basis, the potential application of DMAEM monomer and sealers copolymerized with DMAEM in the treatment of periapical inflammation was investigated in this study. DMAEM monomer could significantly inhibit the growth of the dual-species biofilm formed by E. faecalis and C. albicans, mainly by inhibiting the expression of virulence genes of E. faecalis. The modified root canal sealer containing DMAEM had good biological activity, and inhibited the growth of E. faecalis and C. albicans in the dual-species biofilm. In particular, the modified root canal sealer containing DMAEM significantly inhibited the formation of osteoclasts and presented as a potential novel material for the treatment of periapical inflammation.