Effectiveness and Safety of Extracellular Vesicle-Based Therapies for Nonsurgical Facial Rejuvenation: A Systematic Review

BACKGROUND: Extracellular vesicle (EV)-based therapies have emerged as a novel modality in aesthetic medicine due to their proposed ability to modulate inflammation, stimulate collagen synthesis, and promote tissue regeneration. OBJECTIVES: To systematically evaluate the effectiveness and safety of EV-based interventions for nonsurgical facial rejuvenation in adult patients. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-adherent systematic review was conducted using MEDLINE, EMBASE, CENTRAL, Web of Science, and ClinicalTrials.gov (January 2000-June 2025). Eligible studies investigated EV therapies for facial rejuvenation outcomes. Risk of bias and methodological quality were assessed using tools appropriate to the study design. Certainty of evidence was evaluated using GRADE. Due to substantial heterogeneity, results were synthesized narratively. RESULTS: Sixteen studies encompassing 503 participants were included, comprising split-face studies, comparative trials, and single-arm studies. Most studies reported improvement in at least one skin quality outcome, including wrinkle severity, pigmentation, hydration, elasticity, or overall appearance. Comparative studies generally favored EV-treated areas. No serious adverse events were reported. Risk of bias was moderate to critical for most effectiveness outcomes. GRADE certainty was low or very low. CONCLUSIONS: EV-based therapies demonstrate preliminary signals of benefit and short-term safety for facial rejuvenation. However, methodological limitations, inconsistent outcome assessment, and short follow-up preclude definitive conclusions.