## 4 Discussion
### Antimicrobial Properties and Biocompatibility  
Finally, antimicrobial activity and biocompatibility were also examined as parameters in this systematic review. The biocompatibility of dental materials is a factor that must be considered in their manufacture, as it is important to avoid adverse reactions during treatment. The toxicity of acrylate-based resins is related to the possibility of unpolymerized monomers migrating and subsequently penetrating the oral cavity [15]. Therefore, it is important that this polymerization process of acrylate resins be carried out completely. It is also important to wash the dental materials in alcoholic solutions to remove unpolymerized monomers [35]. Regarding zirconia nanoparticles in resins, it has been described that their antimicrobial effect is related to the production of reactive oxygen species that inhibit the activity of microorganisms by forming pores in the cell wall, which increases cell permeability and causes cell death [13]. This article also described that the incorporation of zirconia nanoparticles, the type of resin, and the hydrophobicity of the resin affect the adhesion of C. _albicans_[13]. Regarding cell proliferation, it has been described that the cell counting method (CCK-8/WST-8) is a reliable, accurate, and practical method to determine the amount of biofilm for the studied microorganisms [13]. Several mechanisms involved in the inhibition of antimicrobial activity have been identified in the context of graphene nanoplatelet incorporation. In terms of physical damage to the microorganisms [14; 15], the graphene nanoplatelets rupture the cell membrane and cause cell death. Another proposed mechanism is the entrapment of microorganisms in the graphene layers, preventing cell nutrition. Finally, it has been described that the antifungal effect of graphene is due to the formation of oxygen radicals, which increase cytotoxicity. However, in vitro studies investigating the viability of the oral biofilm revealed that no toxicity occurred in oral cells, possibly due to the low concentration of incorporated graphene nanoparticles as well as the presence of the polycarboxylate functional group, which improves the biocompatibility of graphene [14]. With respect to silver-enriched mesoporous silica nanoparticles (Ag/MSN), it has been described that the toxicity of silver is related to the release of large amounts of ions that ultimately affect the release of oxygen radicals. Therefore, it is important to incorporate silver into mesoporous silica nanoparticles to reduce their toxicity. In this case, it was found that the cell viability of the groups with 1-2% Ag/MSN decreased compared to the others, possibly due to the release of monomers by the resin and silver ions. However, all species achieved a cell viability of greater than 75%, which is not considered a toxic effect according to ISO 10993-5 [15]. Regarding the mechanism of antimicrobial activity of Ag/MSN, it was mentioned that the amine group shows antimicrobial activity due to the interaction between the positive charge of the amine group and the negative charge of the cell membranes of the microorganisms. On the other hand, the amine group increases the hydrophobicity of the surface, which ultimately prevents the adhesion of microorganisms. The penetration of silver ions also leads to cell death because the cell membranes rupture [15]. For the ceramic nitrides Si3N4, Hf3N4, Zr3N4, and AIN contained in acrylic resins, the antibacterial activity of silicon and aluminum nitrides has been associated with the release of ammonia at the surface, while the mechanism for hafnium and zirconium nitrides hasnot yet been described, as further studies are needed to understand the mechanism of their antimicrobial activity [18]. The zwitterionic materials in the resins have a similar morphology to the lipid bilayers of cell membranes, with a hydrophilic head and a hydrophobic tail.