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• Dual-nanoparticle system enhances bioink performance for bone regeneration. • Nanodiamonds enhance printability and cell adhesion; Mg-hydroxyapatite supports osteogenesis. • Computational modeling with realistic geometry improves extrusion behavior prediction. • Novel bioink addresses the trade-off between printability and biological performance. Designing bioinks for bone tissue engineering (BTE) requires precise balancing of printability, stability and bioactivity. To address the trade-off between fabrication fidelity and osteogenic potential, we developed a novel multicomponent bioink composed of gelatin methacryloyl (GelMA), TEMPO-oxidized cellulose nanofibrils (TO-CNFs) and sodium alginate (SA), functionalized with a previously unexplored dual-nanoparticle (NP) system: nanodiamonds (NDs) and magnesium-doped nanohydroxyapatite (MgHA). Microstructural characterization confirmed spheroidal NDs (∼5 nm) and needle-like MgHA (∼200 × 50 nm), with aggregates forming co-localized organic–inorganic domains with NDs intercalated between MgHA particles. We evaluated the nanoparticles’ individual and combined effects on the rheology and printability of the inks, as well as on the structural integrity, biocompatibility and osteogenic performance of the 3D bioprinted constructs, hypothesizing complementary nanofiller functions. NDs improved printing fidelity and buildability, while MgHA supported osteogenic differentiation. The dual-loaded formulation demonstrated increased alkaline phosphatase (ALP) activity, Runx2 expression and biomineralization, compared to single-nanofiller formulations. These findings demonstrate that the complementary effects of the dual NP system, embedded in a hydrated polymer matrix, provide a promising platform with robust printability and enhanced bioactivity for extrusion-based BTE constructs
Nicolae et al. (Thu,) studied this question.