A Prospective, Multicenter, Randomized, Assessor-Blinded Study Assessing the Efficacy and Safety of Injectable Non-Cross-Linked Hyaluronic Acid for Improving Facial Skin Rejuvenation

Haiyan Cheng,1 Meng Jiang,1 Shan Zhong,1 Xinhai Liu,2 Dongsheng Cao,3 Qiuyuan Feng,4 Yongzhong Li,5 Wei Xu1 1Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Plastic Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Plastic and Wound Repair Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Department of Medical Aesthetics, Yixing People’s Hospital, Yixing, People’s Republic of China; 5Department of Plastic Surgery, Wuxi No. 2 People’s Hospital, Wuxi, People’s Republic of ChinaCorrespondence: Wei Xu, Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China, Tel +86‑137‑0129‑6490, Email 2403649155@qq.comObjective: To evaluate the efficacy and safety of an injectable non-cross-linked hyaluronic acid (NCHA) solution in improving facial skin appearance.Methods: This prospective, multicenter, randomized, no‑treatment–controlled, assessor-blinded, superiority clinical trial was conducted from December 2023 to July 2024 with 448 adults (224 per arm). The treatment group received full-face intradermal injections of NCHA (4 mL/session) at baseline, day 28, and day 56; the control group followed routine skincare and underwent the same injection protocol after day 84. The treatment group underwent skin hydration measurement, elasticity measurement (two objective assessments), global aesthetic improvement scale, skin roughness score, and fine line score (three subjective assessments) at baseline; day 28 and 56; and 7/14/28 days after the last injection (day 63/70/84). The control group completed the same assessments at baseline, 28, 56, 63, 70, and 84 days after randomization.Results: In the treatment group, 212 subjects (94.64%) completed the study, compared to 209 (93.3%) in the control group. Hydration increased steadily in the treatment group, exceeding that of the control at all post-treatment time points (P< 0.001). Elasticity improvements at 7/14/28 days after the final injection were significantly greater than those in the control group (P< 0.05). GAIS, ASRS, and AFLS all favored the treatment arm. Serious adverse events were not observed.Conclusion: Full‑face intradermal NCHA improved skin hydration, elasticity, texture, and fine lines with a favorable safety profile.Chinese Clinical Trial Registry: ChiCTR2300078169.Keywords: non-cross-linked hyaluronic acid, facial skin rejuvenation, efficacy, safety