Alginate-gelatin-carboxymethylcellulose bioink designing and bioprinting to improve fibroblast cell niche

Most bioinks used in extrusion-based bioprinting are derived from natural hydrogels. Among these, alginate-gelatin blends are widely used but suffer from limited stability and suboptimal mechanical properties. In this study, a tricomponent bioink consisting of alginate, gelatin, and carboxymethylcellulose (CMC) is developed to address these limitations. To retain gelatin's cell-adhesive RGD sequences while minimizing rapid deterioration, the gelatin content was reduced compared to alginate-gelatin bioinks to preserve structural integrity and support cell attachment, spreading, and proliferation. The inclusion of CMC further enhanced the mechanical, rheological, and physical properties of the hydrogel. Four formulations with varying alginate and CMC concentrations were prepared and designated as D-1, D-2, D-3, and D-4. Among these, the D-4 formulation exhibited the highest compressive modulus and shear-thinning properties. NIH-3T3 fibroblasts were incorporated into each bioink formulation to assess cell viability, attachment, and proliferation. The D-4 bioprinted construct demonstrated a 21% increase in cell viability compared to the D-1 sample and a threefold increase in fibroblast proliferation relative to the control. These findings indicated that the alginate-gelatin-CMC bioink significantly improved the mechanical and biological performance over conventional alginate-gelatin formulations, offering a promising cell niche for skin tissue engineering applications.