Selective recruitment of non-classical monocytes promotes skeletal muscle repair

Regeneration of traumatic defects in skeletal muscle requires the synchronized behavior of multiple cells that participate in repair. The inflammatory cascade that is rapidly initiated after injury serves as a powerful node at which to guide the progression of healing and influence tissue repair. Here, we examine the role that myeloid cells play in the healing of traumatic skeletal muscle injury, and leverage their pro-regenerative functions using local delivery of the immunomodulatory small molecule FTY720. We demonstrate that increasing the frequency of non-classical monocytes in inflamed muscle coincides with increased numbers of CD206+ alternatively activated macrophages. Animals treated with immunomodulatory materials had greater defect closure and more vascularization in the acute phases of injury. In the later stages of repair, during which parenchymal tissue growth occurs, we observed improved regeneration of muscle fibers and decreased fibrotic tissue following localization of pro-regenerative inflammation. These results highlight non-classical monocytes as a novel therapeutic target to improve the regenerative outcome after traumatic skeletal muscle injury.