There is a dearth of therapies that are safe and effective for the treatment of volumetric muscle loss (VML), defined as the surgical or traumatic loss of muscle tissue, resulting in functional impairment. To address this gap in orthopedic care, we developed a porous sponge-like scaffold composed of extracellular matrix (ECM) proteins (e.g., gelatin, collagen, and laminin-111) and an immunosuppressant drug, FK-506. While the majority of VML injuries occur in orthopedic trauma cases, preclinical models typically study muscle injuries in isolation without a concomitant bone fracture. The goal of this study was to investigate the extent to which FK506 loaded biomimetic sponges support functional muscle regeneration and fracture healing in a composite trauma model involving VML injury to the tibialis anterior muscle and osteotomy (OST) to the tibia. In this model, implantation of the FK-506 loaded biomimetic sponges limited the extent of inflammation while increasing the total number of myofibers, mean myofiber cross-sectional area, myosin-to-collagen ratio, and peak isometric torque compared to untreated VML+OST muscles on Day 28. Although all tibia fractures were bridged by Day 28 post-injury, fracture healing was impaired in response to an adjacent VML injury. Sponge treatment increased bone callus volume, yet the bridged mineralized bone volume was not significantly different. Taken together, these results suggest that biomimetic sponges primarily benefitted muscle repair and may provide a promising therapy for traumatized muscle.