Bioinspired Hydrogels with Broadly Programmable Mechanics for Soft‐Tissue Interfaces
Youchao Teng, TzuChun Chung, Katpady Akhil Tantry, Siyu Wu, Jing Tian, Yunqi Cui, Lanyu Li, Yongzan Zhou, Zhilei Zhang, Zhe Su, Gaili Cao, Kun‐Wei Yeh, Ruipeng Li, Xianghui Xiao, Adam F. G. Leontowich, Yuan‐Yu Hsueh, Zhao Pan, Kam C. Tam, Badri Narayanan, Song Li, Yimin. A. WuABSTRACT
Matching the mechanical properties of repair materials to tissue‐specific demands remains a major challenge in soft‐tissue repair. Here we report bioinspired anisotropic gelatin hydrogels formed by directional freezing and mechanically programmed through subsequent ionic treatment. By regulating intermolecular interactions while preserving the aligned, hierarchical porous architecture, this approach spans stiffnesses relevant to brain, kidney, tendon, and cartilage. Ion identity and treatment duration enable coordinated tuning of Young's modulus from 9.7 kPa to 3.59 MPa and tensile strength from 6 kPa to 14.25 MPa, together with broad regulation of viscoelasticity, extensibility, and fracture resistance. Multiscale SAXS/WAXS characterization, molecular simulations, and finite‐element analysis reveal that ion‐regulated chain association and hierarchical anisotropic organization collectively govern directional load transfer and mechanical reinforcement. Sodium citrate‐treated AGE‐SC 36H reaches a Young's modulus of 3.59 MPa, a tensile strength of 14.25 MPa, and a fracture energy of 413,305 J m − 2 , while subsequent microbial transglutaminase (MTG) stabilization improves cyclic mechanical retention and resistance to swelling and enzymatic degradation under aqueous conditions. In a rat Achilles tendon model, AGE‐SC 36H (MTG) promotes organized collagen remodeling and improves functional recovery over surgical repair alone. Overall, ionic regulation offers a general strategy for programming anisotropic hydrogel mechanics across material classes.