Abstract
Strain-stiffening hydrogels, which mimic the nonlinear mechanical behavior of biological tissues such as skin, arteries, and cartilage, hold transformative potential for biomedical applications. This study introduces immersion phase separation (IPS) 3-dimensional (3D) printing, an innovative technique that enables the one-step fabrication of strain-stiffening hydrogel scaffolds with intricate, hierarchical architectures. This technique addresses the long-standing challenge of balancing structural complexity and intrinsic mechanoresponsive behavior in traditional hydrogel fabrication methods. By leveraging dynamic hydrophobic interactions and solvent exchange kinetics, IPS 3D printing achieves multiscale control over pore architectures (5 to 200 μm) and anisotropic microchannels while preserving J-shaped stress-strain curves (fracture stress: ~0.7 MPa; elongation: >1,000%). The physically cross-linked network enables closed-loop recyclability (>95% material recovery) without performance degradation, while functional fillers (e.g., carbon nanotubes, copper, and hydroxyapatite) enhance properties such as electrical conductivity (2-orders-of-magnitude improvement) and real-time motion sensing capabilities. This platform facilitates the creation of patient-specific implants with tailored mechanical properties and paves the way for adaptive biohybrid devices that mimic the dynamic behavior of native tissues, holding promise for regenerative medicine, soft robotics, and advanced biomedical applications. IPS 3D printing uniquely resolves the trade-off between structural sophistication and functional biomimicry, establishing a paradigm for replicating dynamic biological tissues.