Published in Aesthetic Surgery Journal on July 15, 2025, this multicenter, double-blind, split-face RCT enrolled 140 subjects (70 per arm) with moderate-to-severe nasolabial folds. Each person got a cold-crosslinked HA (Evolysse Form or Evolysse Smooth) in one fold and traditionally crosslinked Restylane-L in the contralateral fold, then 12 months of follow-up with optional retreatment. Split-face is the strength here: same patient, same aging, two gels.

At month 6 on the Wrinkle Severity Rating Scale, Evolysse Form was both noninferior and statistically superior to Restylane-L (mean difference -0.27, p<.001), with Evolysse Smooth at -0.22 (p<.001). Blinded responder rates at month 6 ran 45.2% for Form versus 38.7% for Restylane-L, and 51.6% for Smooth versus 35.5%. The gap held at a year: GAIS responders at month 12 were 73.8% for Form versus 60.7% for Restylane-L. Safety was comparable, with mild-to-moderate injection-site swelling and tenderness resolving in about a week and no serious treatment-related events.

The lesson worth keeping: crosslinking chemistry, not just particle size or G-prime, measurably affects how long a result lasts. Head-to-head against a familiar benchmark HA, the cold-crosslinked gel held nasolabial correction better at both 6 and 12 months. For the patient who keeps asking how to stretch time between touch-ups, that is a concrete, data-backed reason to favor a cold-crosslinked HA in the NLF.

Source: Aesthetic Surgery Journal — https://pmc.ncbi.nlm.nih.gov/articles/PMC12260371/