Efficacy and Safety of Cross‐Linked Sodium Hyaluronate for the Treatment of Moderate‐to‐Severe Neck Wrinkles: A Prospective, Multicenter, Randomized, Single‐Blind Clinical Trial

Background The increasing prevalence of skin aging has highlighted neck wrinkles as a significant factor affecting facial esthetics. While nonsurgical treatments such as botulinum toxin and hyaluronic acid (HA) fillers are widely applied to facial wrinkle management, clinical evidence supporting their use for neck wrinkles remains scarce. Cross‐linked sodium hyaluronate (cross‐linked HA), known for its superior stability and extended duration of effect, may offer enhanced clinical benefits for the treatment of neck wrinkles. Objective This study aimed to assess the efficacy and safety of cross‐linked HA gel for the treatment of moderate‐to‐severe neck wrinkles through a prospective, multicenter, randomized, single‐blind, parallel‐controlled clinical trial and to compare its performance against HiBody, a non–cross‐linked HA gel. Methods A total of 192 Chinese patients with moderate‐to‐severe neck wrinkles, as assessed using the modified Allergan Transverse Neck Lines Scale (Grades 2‐3), were enrolled in the study. Patients were randomly assigned to the experimental group (cross‐linked HA gel) or the control group (HiBody) and received injection therapy accordingly. The primary endpoint was the effectiveness rate posttreatment. Secondary endpoints included the Global Aesthetic Improvement Scale (GAIS), patient satisfaction, and the incidence of treatment‐related adverse events. Data were collected at baseline and at 30 and 60 days posttreatment. Results A total of 185 patients completed the treatments and follow‐ups. The experimental group (cross‐linked HA gel) demonstrated an effectiveness rate of 90.43% (85/94), which was significantly higher than 79.12% (72/91) in the control group, with a difference of 11.30%. Analysis of the GAIS revealed that the proportion of patients rated as “significantly improved” or “very significantly improved” was significantly higher in the experimental group compared to the control group ( p < 0.0002). Regarding safety, the experimental group showed superior comfort levels, requiring no additional anesthesia during treatment, with a lower incidence of adverse events reported. Conclusion Cross‐linked HA gel is effective and safe for the treatment of moderate‐to‐severe neck wrinkles. Compared to non–cross‐linked HA gel, cross‐linked HA gel not only provides longer‐lasting results but also enhances patient comfort due to the inclusion of lidocaine. This study underscores the clinical utility of cross‐linked HA gel and provides a solid foundation for its broader application in the management of neck wrinkles. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2500102839