Mechanically biomimetic silk Fiber–Reinforced IPN hydrogels for cardiovascular tissue engineering

Developing synthetic materials that replicate the nonlinear and anisotropic mechanical behavior of soft tissues remains a central challenge in tissue engineering. Here, we present a silk fiber-reinforced interpenetrating polymer network (IPN) hydrogel platform engineered to achieve a tunable balance of tensile strength, extensibility, and stiffness. By varying fiber orientation - longitudinal, transverse, and cross-plied (CP) - we introduced directional anisotropy that emulates key structure-function relationships observed in native fibrous tissues. The longitudinal and CP composites exhibited significantly enhanced mechanical performance, with ultimate tensile strengths of 8.1 ± 2.3 MPa and 6.8 ± 1.0 MPa, and elastic moduli of 28.2 ± 5.4 MPa and 25.8 ± 5.3 MPa, respectively - significantly larger than the unreinforced hydrogel and transverse configuration. Despite increased stiffness, these configurations maintained physiologically relevant ultimate strains: 46.5 ± 12.0% (longitudinal) to 63.5 ± 33.6% (transverse), closely matching values for native coronary arteries (54.0 ± 25.0%). The CP configuration further reproduced the nonlinear strain-stiffening and pressure-dependent compliance characteristic of coronary adventitia, with measured radial compliance (1.9-2.1 %/100 mmHg) within the range of human coronaries and saphenous veins. These findings demonstrate that coupling long-fiber alignment with IPN architecture enables controlled anisotropy and physiological mechanical fidelity, providing a robust framework for next-generation vascular grafts, adventitial wraps, and soft-tissue phantoms.