The proposed research is relevant to public health and well aligned with the mission of NIAMS because it addresses the substantial need to improve effectiveness in prevention of ankle sprains, one of the most common musculoskeletal injuries that can significantly impact physical activity and quality of life. While external passive supports, such as ankle taping and bracing, are the most widely used approaches to prevent ankle sprains, their long-term use makes patients overly reliant on the passive and constant support, which leads to ankle muscle and soft tissue atrophy. Furthermore, this approach not only restricts inversion-eversion motion but also dorsiflexion-plantarflexion motion, which in turn may alter natural lower-extremity biomechanics. This project seeks to study a unique smart shoe system, using integrated scientific solutions of engineering, computing and behavioral science, to overcome these limitations and provide enhanced support for individuals at risk of ankle injury. Our specific aims are: (1) to design and implement a smart shoe system that integrates robust, real-time estimation of biomechanical data and activity recognition from wearable sensors with soft actuators capable of actively adjusting the stiffness of the ankle brace; (2) to quantify and model ankle stiffness and foot loading trajectory in healthy individuals as well as in people at risk of ankle sprains; (3) to integrate an injury prediction algorithm and a closed-loop feedback controller that provides active ankle support to prevent sprains; and (4) to refine the developed algorithms for free-living use and design an intuitive mobile user interface that provides summative injury risk metrics in real-time. We will validate and evaluate the proposed smart shoe system by closely engaging with clinical partners to ensure the system is tailored toward optimal clinical integration in mind. The smart shoe system is clinically significant because it will allow clinicians to better understand foot-ankle mechanics and their correlation to ankle injury risk during various physical activities and help them provide effective and summative feedback to the users in a timely manner to promote their adherence to ankle injury prevention strategies. Successful development of the system and rigorous assessment of its patient- and clinic-centered perceived utility will lay the groundwork for follow-up clinical trials specifically aimed at investigating the long-term effect of interventions on preserving/promoting ankle health and enhancing behavioral adherence to clinical recommendations.