Abstract
Critical limb ischemia (CLI) poses a substantial and intricate challenge in vascular medicine, necessitating the development of innovative therapeutic strategies to address its multifaceted pathophysiology. Conventional revascularization approaches often fail to adequately address the complexity of CLI, necessitating the identification of alternative methodologies. This review explores uncharted territory beyond traditional therapies, focusing on the potential of two distinct yet interrelated entities: cell-derived extracellular vesicles (EVs) and artificial nanovesicles. Cell-derived EVs are small membranous structures naturally released by cells, and artificial nanovesicles are artificially engineered nanosized vesicles. Both these vesicles represent promising avenues for therapeutic intervention. They act as carriers of bioactive cargo, including proteins, nucleic acids, and lipids, that can modulate intricate cellular responses associated with ischemic tissue repair and angiogenesis. This review also assesses the evolving landscape of CLI revascularization through the unique perspective of cell-derived EVs and artificial nanovesicles. The review spans the spectrum from early preclinical investigations to the latest translational advancements, providing a comprehensive overview of the current state of research in this emerging field. These groundbreaking vesicle therapies hold immense potential for revolutionizing CLI treatment paradigms.