Stem cell-derived extracellular vesicles and artificial nanovesicles: a translational framework for cell-free wound...

Chronic nonhealing wounds remain a major clinical challenge, driven by persistent inflammation, impaired angiogenesis, defective extracellular matrix remodeling, and incomplete functional restoration. While stem cell therapies can modulate these processes, their clinical use is limited by low engraftment, variability, and safety concerns. Stem cell-derived extracellular vesicles (SC-EVs) and artificial nanovesicles (SC-ANVs) have emerged as cell-free alternatives that aim to capture key paracrine functions of stem cells. In this review, we evaluate these vesicle-based approaches within a problem-oriented framework linking molecular and cellular effects to clinically meaningful outcomes. SC-EVs and SC-ANVs influence inflammation, angiogenesis, and tissue regeneration in preclinical wound models; however, current evidence is largely limited to improvements in wound closure and histological parameters. We highlight that proof of concept for clinically relevant endpoints, such as durable function, reduced scarring, and recurrence prevention, remains insufficient. Key translational challenges, including delivery, dosing, and endpoint selection, are discussed, along with a framework for future studies required to establish therapeutic efficacy. Collectively, SC-EVs and SC-ANVs represent emerging platforms whose clinical potential depends on rigorous validation against defined clinical benchmarks.