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.

Replicating the nonlinear, pressure-dependent mechanical behavior of native arteries remains a central challenge in small-diameter vascular graft design, where compliance mismatch between synthetic grafts and host vessels is strongly linked to graft failure. Building on a silk fiber-reinforced alginate–polyacrylamide interpenetrating polymer network (IPN) hydrogel platform, we investigated whether biomimetic vascular structural motifs, specifically fiber reorientation and crimp, can be used as programmable design parameters to tune the tensile and pressure-dependent mechanical response of tubular constructs toward native coronary artery behavior. Three architectures were fabricated: a cross-plied (CP) baseline, a 25° reoriented configuration, and a crimped CP configuration. Under internal pressurization, fiber reorientation and crimp significantly increased compliance at low physiological pressures, with a consistent directional trend across the full pressure range, by extending the low-stiffness toe region preceding fiber recruitment while preserving tensile stiffness. Across the investigated pressure range, all architectures exhibited compliance within the reported range of native coronary arteries, with crimped constructs producing pressure–diameter behavior that most closely resembled young coronary arteries, whereas the CP baseline more closely resembled aged coronary arteries. These findings demonstrate that biomimetic structural motifs, without altering material composition, can serve as programmable design parameters for engineering vascular mechanics, enabling a single material platform to reproduce distinct physiological mechanical phenotypes through architecture alone.