PROJECT SUMMARY An osseointegrated prosthesis is a novel alternative to a prosthesis socket that directly mounts the prosthesis to the residual limb through a bone anchored implant, which improves the load transmission between the ground and residual limb. Proper loading at the bone-implant interface is critical to long-term outcome as underloading can lead to implant loosening and overloading can lead to periprosthetic fracture. Preliminary outcome evidence is highly promising regarding improvements in function and quality of life following prosthesis osseointegration compared to a traditional socket; however, mechanical failure due to implant loosening or fracture persists in a small subset of this population, which can have devastatingly negative impacts on the patient. Although bone-implant loading has a direct impact on outcome, it cannot be measured in-vivo. As a result, finite element models are the most widely used surrogate to estimate bone-implant loading. However, these prior models have three primarily limitations that impede their clinical utility: 1) they have not included activities of daily living, 2) they have not incorporated muscle forces, and 3) they have not been developed for transtibial osseointegrated prostheses. The first goal of this proposal is to leverage an existing dataset that will develop a state-of-the-art modeling platform that will quantify bone-implant interface loading in patients with transfemoral and transtibial osseointegrated prostheses during activities of daily living. Rehabilitation following prosthesis osseointegration involves progression of mechanical loading through gradual increase in weight bearing and strengthening exercises designed to promote bone remodeling to prepare the bone and implant to sustain loads required for daily living. Further on in the healing stage, gait retraining is prescribed to retrain the movement patterns of the patient as they habituate to the new ability to directly load the residual bone. Although rehabilitation is pivotal to optimize patient outcome, it remains hindered by a lack of empirical data that results in protocols being not well defined, lacking validation, and not specific to amputation level. The second goal of this proposal will be to establish the effects of simulated rehabilitation on bone- implant interface loading in patients with transtibial and transtibial osseointegrated prostheses. This proposal will be the first to quantify dynamic bone-implant interface loading in osseointegrated prostheses while incorporating subject-specific movement, muscle, and joint forces (Aim 1) and to assess the effects of rehabilitation on these loading patterns (Aim 2). Because mechanical failures are largely due to pathologic loading at the bone-implant interface, understanding how it is altered by amputation level, activity, and rehabilitation following prosthesis osseointegration is critical to optimizing outcomes in this population. As prosthesis osseointegration...