Radiofrequency Microneedling Combined With Topical Extracellular Vesicle Preparation for Facial Rejuvenation: A Randomized Split-Face Controlled Study

Abstract

OBJECTIVE: To evaluate whether adding a topical extracellular vesicle (EV) preparation after radiofrequency microneedling (RFMN) improves objective and patient-centered outcomes for facial rejuvenation in a randomized split-face design. METHODS: Sixty adults underwent paired facial treatment from January 16, 2023, to March 15, 2026; 1 side received RFMN followed by topical EV preparation, and the contralateral side received RFMN alone. Outcomes were assessed at baseline, week 4, and week 12 in an unblinded study design. The primary endpoint was the paired between-side difference in change in wrinkle severity score at week 12. Secondary endpoints included texture, pore visibility, erythema, melanin index, corneometer hydration, patient Global Aesthetic Improvement Scale (GAIS), investigator GAIS, and local reactions. RESULTS: The mean age was 43.6 (7.9) years, and 50 participants (83.3%) were women. At week 12, wrinkle improvement was 12.59 (2.58) points on the RFMN+EV side and 9.28 (2.35) points on the RFMN side, giving a paired mean difference of 3.32 points (95% CI: 2.55-4.08). Texture, pore, erythema, melanin, hydration, and GAIS outcomes numerically favored RFMN+EV, while local reactions were transient and predominantly mild. CONCLUSIONS: The findings suggest a short-term incremental benefit signal for topical EV application after RFMN; however, the unblinded design, 12-week follow-up, and absence of histologic or molecular biomarkers require cautious interpretation.