Biological Performance of a Nitrofurantoin-Based Triple Antibiotic Paste for Regenerative Endodontics.

INTRODUCTION: This study evaluated an experimental triple antibiotic paste (EXP) composed of nitrofurantoin (4 mg/g), ciprofloxacin (1 mg/g) and metronidazole (5 mg/g) for regenerative endodontic procedures (REPs), using calcium hydroxide [Ca(OH)2] as a reference. METHODS: EXP, commercial Hoshino pastes containing ciprofloxacin, metronidazole and minocycline at 1 or 5 mg/g, and a Ca(OH)2 paste were compared in human dental pulp stem cells exposed for 24 h to 0.2 g/mL extracts. Cytotoxicity was assessed by XTT, Neutral Red, Crystal Violet and qualitative Live/Dead imaging. The concentrations of 27 cytokines, chemokines and growth factors in culture supernatants were quantified by multiplex immunoassay. Data were analysed using Kruskal-Wallis with Dunn-Holm post hoc testing. RESULTS: EXP maintained approximately 75% metabolic activity and showed a less severe cytotoxic profile than the Hoshino formulations. In Neutral Red, EXP preserved significantly greater lysosomal integrity than Hoshino 1, Hoshino 5 and Ca(OH)2. Live/Dead imaging supported greater preservation of viable cells with EXP. Hoshino 5 significantly reduced IL-2, IL-5 and IL-8, whereas Ca(OH)2 increased IL-6 and reduced IL-1β, IL-15, IL-17, VEGF and MIP-1β. Hoshino 1 and EXP only differed from untreated control on IP-10, and no differences occurred among medicament-treated groups. CONCLUSION: The nitrofurantoin-based EXP paste demonstrated comparatively improved cytocompatibility toward DPSCs relative to the conventional Hoshino formulations and greater preservation of cell viability than the tested Ca(OH)2 paste under the present experimental conditions. Together with its previously demonstrated antimicrobial activity, these findings support EXP as a promising candidate for further investigation in REPs.