Streamlined Facial Rejuvenation: A Randomized Split-Face Trial of Premixed Intradermal Botulinum Toxin Type A and Hyaluronic Acid Biorevitalization

Abstract Background Botulinum toxin type A (BoNT-A) effectively treats dynamic wrinkles but offers limited direct improvement in skin quality. Hyaluronic acid (HA)–based biorevitalization enhances hydration, firmness, and radiance; however, high-quality trials evaluating their combined use under controlled conditions are scarce. Objectives To compare the efficacy and safety of a single-session, premixed intradermal BoNT-A with HA biorevitalization (NCTF 135HA) versus BoNT-A alone for facial rejuvenation. Methods In this prospective, randomized, double-blind, split-face trial, 52 participants (73.1% female; mean age 44.5 ± 4.7 years) received BoNT-A + NCTF 135HA on one facial side and BoNT-A alone contralaterally. Outcomes at Day 60 included Wrinkle Severity Rating Scale (WSRS), visual analog scales for hydration, firmness, radiance, and tone homogeneity, and Global Aesthetic Improvement Scale (GAIS) scores from blinded evaluators and patients. Patient satisfaction and safety were also assessed. Results Mean WSRS reduction was greater with the combination (Δ = 2.33 ± 0.70) versus BoNT-A alone (Δ = 1.34 ± 0.59; d = 1.35, p < .001). Hydration increased significantly only on the combination side (Δ = 3.71 ± 1.48; d = 2.35, p < .001), with larger gains also in firmness (d = 2.11), tone homogeneity (d = 1.51), and radiance (d = 1.16; all p < .001). GAIS scores favored the combination (patients: 2.21 ± 0.67 vs 0.81 ± 0.79; evaluators: 2.02 ± 0.73 vs 0.54 ± 0.69; p < .001). At Day 60, 86.5% noticed a side-to-side difference, 94.2% would repeat, and 94.2% would recommend the combination; comfort was rated tolerable by 67.3%. Adverse events were mild and transient (pinpoint bruising 78.8%, tightness 11.5%, swelling/erythema 13.5%). Conclusions Premixed intradermal BoNT-A with NCTF 135HA achieved superior wrinkle reduction, enhanced skin quality, and greater patient satisfaction than BoNT-A alone, with minimal downtime and an excellent safety profile.