Tuning the mechanical properties of alginate dialdehyde-gelatin (ADA-GEL) bioinks for bioprinting approaches by varying the degree of oxidation.

Extrusion-based 3D bioprinting is one of the most promising and widely used technologies in bioprinting. However, the development of bioprintable, biocompatible bioinks with tailored mechanical and biological properties remains a major challenge in this field. Alginate dialdehyde-gelatin (ADA-GEL) hydrogels face these difficulties and enable to tune the mechanical properties depending on the degree of oxidation (% DO) of ADA. Here, we present a holistic approach for characterizing the influence of the % DO on the mechanical properties of ADA-GEL hydrogels under multiple loading modes, compression, tension, and torsional shear in the large-strain regime. We evaluate complex mechanical characteristics including nonlinearity, hysteresis, conditioning, and stress relaxation. We calibrate hyperelastic material models to determine the corresponding material parameters inversely. Our results confirm that decreasing the % DO of ionically crosslinked ADA-GEL hydrogels leads to an increase in stiffness, more distinct nonlinearity, more pronounced hysteresis, and minor preconditioning effects, while the relaxation behavior is slightly affected. The fabrication technique - molding or printing - does only slightly affect the complex mechanical properties and stress relaxation behavior. Ionically and enzymatically dual-crosslinked ADA-GEL hydrogels showed higher stresses during cyclic loading and less viscous effects during stress relaxation in all three loading modes. We conclude that the % DO and the crosslinking procedure are crucial parameters to tune the mechanical behavior of ADA-GEL hydrogels. Careful choice of these parameters might facilitate the fabrication of biomaterials that closely mimic the properties of native tissues for advanced tissue engineering applications.