Battlefield casualty and trauma often results in major injury to the extremities, one example of this is volumetric muscle loss VML injuries. While advances in prolonged field care have saved many Servicemembers lives, those with VML injures are left with long-term functional complications. Unlike more simple muscle injuries, VML injuries are not capable of undergoing significant self-repair. One factor limiting muscle function recovery is a lack of current treatments and rehabilitation techniques and lack of understanding of the secondary effects due to VML such as physical inactivity. We are investigating how early rehabilitation may improve muscle function following VML injury. We will test two specific aims 1 to determine if early rehabilitation approaches are sufficient to improve the function and quality of the remaining tissue after VML injury. And 2 to understand if injury-induced physical inactivity significantly impairs the quality of remaining tissue after VML injury and the responsiveness to rehabilitation. By studying and understanding early rehabilitation following injury we hope to improve healing of the muscle and effective rehabilitation. Additionally, we hope to elevate the wounded Servicemembers long-term quality of life. To date, we have identified mitochondrial dysfunction as a primary pathology of the remaining muscle after VML with long-term consequences, and the remaining muscle is resilient to traditional rehabilitation to correct this condition. Moving forward we are investigating new approaches and mitochondrial biogenesis targets.