Eosinophils respond to extracellular matrix treated muscle injuries but are not required for macrophage polarization

The immune response to decellularized extracellular matrix muscle injury is characterized by Th2 T cells, Tregs, M2-like macrophages, and an abundance of eosinophils. Eosinophils have previously been described as mediators of muscle regeneration but inhibit skin wound healing. In addition to response to wounding, a large number of eosinophils respond to biomaterial-treated muscle injury, specifically in response to decellularized extracellular matrix. ECM treatment of muscle wounds has been associated with positive outcomes in tissue regeneration, but the detailed mechanisms of action are still being evaluated. Here, we investigate the role of these eosinophils in terms of their immunologic phenotype and subsequent effect on the local tissue microenvironment. These cells have a mixed phenotype showing both type-2 and regulatory gene upregulation and regulate immune infiltration into the scaffold and wound microenvironment. Beyond the local tissue, ECM treatment was seen to induce a transient flux of eosinophils to the lungs but prevented a trauma-associated neutrophilia in the lungs of injured mice. We believe this local and systemic immunomodulation contributes to the regenerative effects of the material and such distal tissue effects should be considered in therapeutic design and implementation.