This study aimed to assess the mechanical and biocompatibility properties of dental resin reinforced with different nanoparticle additives. Temporary crown specimens were 3D-printed and grouped based on nanoparticle type and amount, including zirconia and glass silica. Flexural strength testing evaluated the material’s ability to withstand mechanical stress using a three-point bending test. Biocompatibility was tested using MTT and dead/live cell assays to assess effects on cell viability and tissue integration. Fractured specimens were analysed using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) for fracture surface examination and elemental composition determination. Results show that adding 5% glass fillers and 10–20% zirconia nanoparticles significantly improves the flexural strength and biocompatibility of the resin material. Specifically, the addition of 10%, 20% zirconia, and 5% glass silica by weight significantly increases the flexural strength of the 3D-printed resins. Biocompatibility testing reveals cell viabilities greater than 80% in all tested groups. Reinforced 3D-printed resin holds clinical potential for restorative dentistry, as zirconia and glass fillers have been shown to enhance mechanical and biocompatibility properties of dental resin, making it a promising option for dental restorations. The findings of this study may contribute to the development of more effective and durable dental materials.

Clinical Relevance: Fluoride containing resin composites and especially those containing pre reacted glass ionomer fillers could be employed to great benefit in treating high caries risk patients in situations where glass ionomers may be unsuitable; particularly in high load bearing or aesthetically critical locations.