In modern society, the healing of chronic wounds is still a major cause of discomfort for the patients and a financial burden for the care system. Current approaches use either organic tissue-engineered skin substitutes or stem cells based therapy. It has been shown that mesenchymal stem cells (MSCs) are able to improve the wound healing process by secreting factors with anti-inflammatory, anti-fibrotic and pro-angiogenic activities either as soluble molecules (growth factors, cytokines) or encapsulated within membrane vesicles (microparticles, exosomes). It has been shown that exosomes, the small membrane vesicles originating from the endocytic pathway, are the main mediators of MSCs paracrine effect. Their complex cargo (mRNA, microRNA and various anti-apoptotic and pro-angiogenic factors) has been found to induce migration and proliferation of fibroblasts as well as collagen synthesis. Thus, the combination of MSCs derived exosomes and organic biomaterials in order to enhance the healing process represents a novel approach for chronic wounds therapy, involving a cell-free use of MSCs paracrine activity.