A systematic approach to improve printability and cell viability of methylcellulose-based bioinks.

Printability in 3D extrusion bioprinting encompasses extrudability, filament formation, and shape fidelity. Rheological properties can predict the shape fidelity of printed hydrogels. In particular, tan(δ), the ratio between loss (G'') and storage (G') modulus (G''/G'), is a powerful indicator of printability. This study explores the effect of different salt, sucrose, and MC concentrations on tan(δ), and therefore the printability of methylcellulose (MC) hydrogels. Salt and sucrose increased G', lowering tan(δ) and enabling printing of scaffolds with high shape fidelity. Conversely, MC concentration increased G'' and G', having a lesser effect on tan(δ). Shape fidelity of three formulations with similar G' but varying tan(δ) values were compared. Higher tan(δ) led to reduced height, while lower tan(δ) improved shape fidelity. Cell viability increased when reducing MC content, extrusion rate, and nozzle gauge. Higher MC concentration (G' > 1.5 kPa) increased the influence of needle size and extrusion rate on cell viability. Hydrogels with G' < 1 kPa could be extruded at high rates with small nozzles, minimally affecting cell viability. This work shows a direct relationship between tan(δ) and printability of MC-based hydrogels. Lowering the complex modulus of hydrogels, mitigates extrusion stress, thus improving cell survival.