Tailoring mechanical and functional properties of 3D-printed nanocellulose-alginate scaffolds via alternative ionic crosslinkers

Renewable polysaccharides combined with advanced 3D printing enable precise, biomimetic scaffolds for tissue engineering (TE). Alginate hydrogels offer excellent biocompatibility and rapid gelation but lack mechanical strength and bioactivity. Adding nanofibrillated cellulose (NFC) improves rheological and structural properties, yet research has mostly focused on conventional calcium-based crosslinking. This study evaluates insoluble divalent metal carbonate crosslinkers (Mg²⁺, Ca²⁺, Zn²⁺, Sr²⁺) in NFC–alginate inks printed via direct-ink-writing (DIW) 3D printing. Rheological tests confirmed shear-thinning behavior dominated by the polymer matrix, facilitating extrusion printing. Improved dimensional and mechanical stability resulted from gradual metal ion release and in situ crosslinking triggered by acetic acid in an ethanol–water medium. Sr²⁺-crosslinked scaffolds achieved the highest tensile strength (3.5 MPa) and modulus (16%), outperforming Ca²⁺, Mg²⁺, and Zn²⁺. Sr²⁺ and Ca²⁺ also showed superior ion retention (>75%) and dimensional stability. SEM/EDX analysis confirmed compact matrices with uniform ion distribution. Cytocompatibility assays revealed that Sr²⁺ and Ca²⁺ scaffolds maintained high human cell viability (>80%), while Zn²⁺ was cytotoxic (