Engineering Strain-Stiffening Granular Hydrogels for 3D-Printed Tissue-Mimicry

Biological tissues exhibit nonlinear strain-stiffening behavior with distinct toe (E_Toe) and heel (E_Heel) moduli essential for load-bearing function. However, synthetic materials lack a unified strategy and mechanistic basis for independently tuning E_Toe and E_Heel while maintaining high-fidelity 3D printability. Here, we introduce a 3D-printable strain-stiffening double-network granular hydrogel (SDGH) that enables region-specific control of E_Toe and E_Heel through modulation of secondary-network monomer concentration and microgel packing density, respectively. We elucidate the mechanism of strain-stiffening behavior using in situ microscopic imaging and mechanical analysis. To demonstrate utility, we direct-ink-write multilayered aortic valves using alternating soft and stiff inks. The printed valves, selected for their demanding mechanical and heterogeneous architecture, showed high geometric fidelity and excellent hemodynamic performance, achieving regurgitation <1.2% and surpassing ISO 5840 standards. This platform establishes a generalizable design framework for customized tissue mimetic organs for biomedical applications, particularly in synthetic surgical training material.