Immersion Phase Separation 3-Dimensional Printing for Strain-Stiffening Hydrogel Scaffolds

Muyuan Chai; Haolin Bu; Rui Zheng; Zhilu Yang; Xuetao Shi

doi:10.34133/research.0742

Immersion Phase Separation 3-Dimensional Printing for Strain-Stiffening Hydrogel Scaffolds

Research (Wash D C). 2025 Jun 17:2025:0742. doi: 10.34133/research.0742. eCollection 2025.

Authors

Muyuan Chai^{1

2

3}, Haolin Bu^{2

3}, Rui Zheng^{2

3}, Zhilu Yang¹, Xuetao Shi^{2

3

4}

Affiliations

¹ Dongguan Key Laboratory of Smart Biomaterials and Regenerative Medicine, The Tenth Affiliated Hospital, Southern Medical University, Dongguan 523059, P. R. China.
² National Engineering Research Centre for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, P. R. China.
³ School of Materials Science and Engineering, South China University of Technology, Guangzhou 510640, P. R. China.
⁴ Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou 510006, P. R. China.

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.