3D Printed Curcuminoid-Loaded Nanocellulose–Alginate Scaffolds with Tunable Mechanical and Diffusion-Controlled Release Properties

Abstract

This study reports the fabrication of curcuminoid-loaded nanofibrillated cellulose (NFC)–alginate scaffolds via extrusion-based 3D printing, integrating supercritical CO2 extraction with biofabrication. NFC–alginate inks were pre-crosslinked with CaCl2 (1 to 10 mM) to tune structure and properties. Rheological analysis confirmed shear-thinning behavior suitable for extrusion printing. Mechanical testing revealed a non-linear dependence on crosslinking: optimal performance was achieved by Ink 2 (1 mM CaCl2 with curcuminoid extract), with tensile strength increasing from ~0.60 to ~0.80 MPa and Young’s modulus from ~1.5 to ~3.0 MPa relative (Ink 1, 10 mM CaCl2, without extract), reflecting the combined effect of extract incorporation and ionic pre-crosslinking rather than crosslinker concentration alone; higher crosslinking reduced stiffness (~1.15 MPa). SEM revealed porous architectures (Ink 1: 542 ± 63 μm; Ink 4: 398 ± 71 μm) with increasing structural heterogeneity upon curcuminoid incorporation. In vitro release exhibited biphasic, diffusion-dominated behavior, reaching ~50 to 60% in ethanol-containing media; PBS inclusion as a physiological reference confirmed minimal release (<5%), consistent with the known hydrophobicity and pH-dependent instability of curcuminoids and defining the physicochemical delivery boundaries of the system. The highest release (~372 ng/mL) was achieved at intermediate loading (10×). Kinetic modeling confirmed Higuchi-type diffusion as the dominant mechanism (R2 ≈ 0.90 to 0.99). These results establish a clear structure–property–release relationship and position the scaffolds as a tunable, diffusion-controlled delivery platform for hydrophobic bioactives in topical or formulation-assisted applications employing co-solvents or solubilizing excipients.