Repair of skeletal muscle loss due to trauma, surgical resection or malformations represent a challenge for clinicians. Several attempts to create a bioscaffold to substitute skeletal muscle have been done and the use of extracellular matrix (ECM) from decellularized tissues to replenish volume muscle loss defects is one of the most promising approaches. However, the development of fibrosis still represents a major drawback. It is known that intercellular signals mediating tissue repair such as tissue renewal, vascularization and immune regulation, are convoyed via extracellular vesicles (EVs), biologically active nanoparticles secreted by the cells and composed of a lipid bilayer including cytoplasmic content. The aim of this work is to analyze the biological effects of EVs added to ECM scaffolds in a murine model of chronic volume muscle loss. ECM samples were obtained using a detergentenzymatic protocol and were embedded with EVs isolated either from Wharton Jelly mesenchymal stromal cells (MSC-EV) or from BJ fibroblast cell line (BJEV).