Temporary dental fillers are critical for safeguarding teeth during the period between caries removal and permanent restoration. However, conventional fillers often lack sufficient antimicrobial properties to prevent bacterial colonization. To address this issue, the study researches on the development of antimicrobial Temporary Dental Nano-Fillers (TDNF) capable of targeting multiple cariogenic pathogens, including Streptococcus mutans, Lactobacillus casei, Candida albicans, and mixed-species planktonic cells/biofilms, which play a significant role in the progression of dental caries. The TDNF was formulated using a combination of Chloramine-T (CRT) and Cetylpyridinium Chloride (CPC), both known for their antimicrobial efficacy, and embedded in a nanoparticle matrix of hydroxyapatite (HAP) and silicon dioxide (SiO 2 ). The synergistic antimicrobial effect of CRT and CPC, with MIC 90 values of 12.5 and 6.25 ppm, respectively, displayed potent activity against S. mutans. Proteomic analysis, including gene ontology and protein−protein interaction network evaluations, further confirmed significant disruptions in S. mutans metabolic and stress response pathways, highlighting the bactericidal effectiveness of the formulation against S. mutans. Additionally, the formulation demonstrated sustained antimicrobial efficacy against other cariogenic pathogens such as L. casei, C. albicans and mixed-species planktonic cells and biofilms over a 16-day period. The TDNF (HAP+SiO 2 +CRT+CPC matrix) exhibited superior mechanical properties with a compressive strength of 237.7 MPa, flexural strength of 124.3 MPa, and shear bond strength of 52 MPa. Biocompatibility tests conducted on human oral squamous carcinoma cells (OECM-1) indicated over 95% cell viability, affirming its safety for preclinical or clinical applications. The multifunctional TDNF developed in this study successfully combines mechanical reinforcement with broad-spectrum antimicrobial efficacy, offering a promising interim solution in dental restorations. Its ability to protect against microbial colonization, while maintaining structural stability, positions it as an effective temporary material that enhances patient outcomes during the period before permanent restoration.
