Combination of Biomaterials and Extracellular Vesicles from Mesenchymal Stem-Cells: New Therapeutic Strategies for Skin-Wound Healing

Hard-to-heal chronic wounds associated with aging and high-prevalence pathologies, such as diabetes, are a global health problem. Therefore, it is necessary to advance effective treatments to accelerate wound healing. Among these potential treatments are new therapies based on mesenchymal stem cells (MSC) and their secretomes, including extracellular vesicles (EV). They have an important therapeutic potential for the treatment of chronic ulcers, due to their immunomodulatory activity, as well as their ability to induce angiogenesis, cell proliferation and cell migration. The use of MSC-derived EV in regenerative medicine involves cell-free therapies that decrease risks associated with cell therapies, such as the potential development of tumors. However, the short half-life of MSC-EV is a limitation for their clinical use. A therapeutic strategy to increase the regenerative efficiency of EV in wounds is to encapsulate them in biomaterials. The latter must protect and progressively release EV in damaged tissues, optimizing healing. Biomaterials that can be used include hydrogels. These, in addition to acting as a vehicle for sustained application of EV, can create favorable environments for wound healing. Thus, the aim of this review is to critically describe the latest advances in the development of such therapeutic strategies. It highlights the significance and clinical potential of these new therapies, as well as the need to develop clinical trials, to ascertain their performance.