The knee joint plays a critical role in locomotion but is susceptible to overuse injuries, motivating the development of assistive exoskeletons. Current designs face a fundamental trade-off between achieving kinematic compatibility with the knee’s complex polycentric motion and providing effective variable-stiffness functionality for biomechanical support. This study presents a novel cable-driven multisegment exoskeleton to reconcile these competing requirements through an integrated biomimetic design. The proposed system employs redundant rotational joints and a linear guide rail to passively accommodate natural joint kinematics while enabling wide-range stiffness regulation (0–207 Nm/rad) via active cable length adjustment. This single-actuator approach achieves dynamic stiffness regulation, deterministic torque transmission with an effective moment arm exceeding 70 mm, and seamless state modulation within a low-profile structure (0.63 kg). Benchtop characterization confirmed precise stiffness control across the operational range (rmse ≤ 0.035 Nm/rad). Human subject experiments revealed significant muscular effort reduction during demanding tasks without compromising natural joint kinematics, including 23.9% decrease in peak vastus lateralis activation during incline walking and 29.2% reduction during squatting compared to unassisted conditions. These results validate the exoskeleton’s ability to reconcile anatomical compatibility with physiologically relevant stiffness regulation, representing a significant advance in knee assistive technology with broad applications in clinical rehabilitation and physical performance augmentation. This study bridges a critical gap in knee exoskeleton development, offering a unified solution for comfortable and effective assistance across dynamic tasks.
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