A combined in-silico and in-vitro evaluation of cyanoacrylate-based dental materials as an adhesive for applications in prosthodontics: molecular docking and cytocompatibility analysis

This study combined in-silico molecular docking with in-vitro cytocompatibility testing to evaluate the safety of cyanoacrylate adhesives. Molecular docking was performed for four cyanoacrylate monomers (ethyl, n-butyl, isoamyl, and 2-octyl) against key proteins associated with inflammation (IL-1β, IL-6, TNF-α, CRP), bone metabolism (BMP4), and tissue repair (NOTCH2, fibronectin). Docking scores and binding residues were analyzed using PyRx and BIOVIA Discovery Studio. Degradation products (formaldehyde, ethyl-2-cyanoacetate) were also evaluated. In-vitro cytocompatibility of isoamyl 2-cyanoacrylate was assessed on 3T3-L1 fibroblasts using MTT and LDH assays at concentrations of 25-200 μg/mL over 24 and 48 h. Docking scores ranged from -4 to -6 kcal/mol, suggesting weak to moderate binding and low likelihood of interference with protein function. Longer-chain cyanoacrylates showed weaker binding compared to ethyl cyanoacrylate, indicating more favorable stability and lower toxicity. Degradation products demonstrated reduced binding, though ethyl-2-cyanoacetate showed comparatively higher affinities than formaldehyde. In-vitro assays revealed cell viabilities above the ISO 10993-5 threshold at clinically relevant concentrations, with mild cytotoxicity only at higher concentrations and longer exposures. The combined findings provide a molecular and cellular basis for their clinical use, suggesting that longer-chain cyanoacrylates are likely safer adhesives for denture applications.