Green-Synthesized titanium dioxide Nanoparticle–Modified glass ionomer cement: in vitro and in Silico assessment of Mechanical, Physical, and safety properties performance

Recurrent caries continues to pose a major problem in restorative dentistry. Although numerous antimicrobial agents have been added to restorative materials, their effectiveness and their influence on the materials' mechanical properties are still uncertain. This study investigated the physicomechanical performance of glass ionomer cement (GIC) modified with green-synthesized titanium dioxide nanoparticles prepared using Citrus aurantium seed extract (CA-TiO₂NPs). The novelty of this work lies in integrating a plant-mediated synthesis approach with systematic mechanical evaluation and preliminary in silico safety screening within a single proof-of-concept framework. CA-TiO₂NPs were synthesized via phytoreduction using C. aurantium seed extract and added to the powder phase of a conventional GIC at 5% and 10% w/w. Flexural strength was evaluated according to ISO 9917-2:2017, water sorption and solubility according to ISO 4049:2009, and Vickers microhardness according to ASTM E384. The major bioactive constituents identified by Gas Chromatography-Mass Spectrometry (GC-MS) were profiled. In addition, computational toxicological and ADME predictions were performed to provide early-stage safety indicators. While nanoparticle incorporation influenced selected mechanical parameters, flexural strength differences were not statistically significant. The 10% CA-TiO₂ NPs group exhibited the highest flexural modulus and microhardness (P < 0.0001) and lowest water sorption and solubility. Additionally. In silico pharmacokinetic and toxicological analyses suggested a favorable preliminary safety profile of the phytochemical constituents, supporting proof-of-concept evaluation rather than clinical validation. The combination of green synthesis and mechanical testing, together with screening-level toxic informatics of major extract-associated metabolites, supports a proof-of-concept for improving CA TiO₂ NPs -modified GIC properties while prioritizing safety-relevant endpoints for subsequent leachate and cytotoxicity testing. Clinical Significance: Computational integration strengthens the translational validity of green nanomaterial development by providing preliminary molecular-level safety indicators for phytochemical constituents potentially associated with the modified material.