Effect of a New Hyaluronic Acid Hydrogel Dermal Filler Cross-Linked With Lysine Amino Acid for Skin Augmentation and Rejuvenation

Abstract Background Hyaluronic acid (HA) fillers are the most popular filler agents for skin rejuvenation. Although 1,4-butanediol diglycidyl ether is regarded as a relatively safe cross-linker, it still exhibits certain cytotoxicity. Objectives We presented here an amino acid–cross-linked HA (ACHA) which was obtained by an amidation reaction with lysine and HA. This study aimed to investigate ACHA's efficacy and safety for skin augmentation and rejuvenation. Methods Rheology, compressive tests, and swelling experiments were conducted to investigate ACHA's mechanical and viscoelastic properties. The effects of ACHA on the human keratinocytes (HaCaT) cells and the human dermal fibroblast (HDF) were investigated by Transwell and wound healing assays. Its impacts on the epithelial thickness and collagen synthesis were further examined in a mouse experimental model. We recruited 50 patients with moderate to severe nasolabial folds (NLFs). The patients were randomly allocated to receive ACHA or Restylane injections. The resulting retention rates of HA and the Wrinkle Severity Rating Scale and Global Aesthetic Improvement Scale outcomes were evaluated and compared. Results ACHA exhibited good viscoelasticity. It not only promoted migration and proliferation of HaCat and HDF and secretion of various growth factors but also increased skin thickness and promoted the generation of collagen. Patients who received ACHA had more residual volume 12 months after treatment. ACHA exhibited a promising augmentation effect in NLF correction with few adverse reactions. Conclusions ACHA has shown promise as a biomaterial with excellent biocompatibility and viscoelastic characteristics in both research and the clinic. See the abstract translated into Hindi, Portuguese, Korean, German, Italian, Arabic, Chinese, and Taiwanese online here: https://doi.org/10.1093/asj/sjad169. Level of Evidence: 2