Development of fully synthetic bio-inspired extracellular vesicles for regenerative wound healing

Wound care constitutes a growing clinical and economic burden, with the global market predicted to exceed €28.6B annually by the end of 2024. This represents a 71% increase in wound prevalence and a 48% increase in management cost in the last decade. Despite advances in our understanding of the cellular and molecular mechanisms involved in wound healing, the rapid growth of these markets alone underlines the need for new therapeutic approaches to address the growing incidence of chronic and non-healing wounds and the ongoing development of scar tissue and fibrosis -which increase the risk of severe complications, significantly impact patient quality of life, and extend the burden on healthcare systems. Extracellular vesicles (EVs) from mesenchymal stromal cells (MSCs) and MSC-like cells, have already been proven to significantly enhance wound healing and inhibit scar formation. Despite their potential, the inherent complexity, source-based variability of these cell-based therapies, as well as a lack of conclusive information regarding their mechanisms of action, has significantly impeded their clinical translation. This proposal outlines the characterization of natural EVs from both novel and established MSC sources; the identification of key biological and biophysical factors underpinning their potential to support wound healing and reduce fibrosis; and the application of this knowledge to design, optimize, and validate bio-inspired fully synthetic extracellular vesicles (fsEVs) as a novel treatment to improve clinical wound healing outcomes.