In Vitro Analysis of Hyaluronidase Degradation of Commercial Hyaluronic Acid Fillers: Considerations in Lip Augmentation

Background: Hyaluronic acid (HA) fillers are widely used for lip augmentation, but inadvertent intravascular injection may result in serious complications such as ischemia or necrosis. Timely degradation using hyaluronidase is crucial in such scenarios. Objectives: To evaluate the enzymatic degradation kinetics of 6 commercially available HA lip fillers using hyaluronidase, and to assess their relative susceptibilities in vitro. Methods: Six HA-based lip filler formulations (Luminera Hydryalix Lips, Yvoire Volume Plus, Restylane Kysse, Neauvia Intense Lips, Fillmed Artfiller Lips, and Juvederm Ultra 3) were incubated with hyaluronidase (167 U/mL) at 37°C. Degradation was quantified by measuring N-acetyl-D-glucosamine (NAG) release over time using the Morgan–Elson colorimetric assay. Absorbance was recorded at 585 nm, and degradation values were calculated through a standard calibration curve. Statistical analyses included one-way ANOVA with Tukey post hoc tests ( P <0.05). Results: Significant differences in degradation rates were observed at both 7 and 45 hours ( P <0.001). At 7 hours, Restylane Kysse exhibited the highest enzymatic degradation, followed by Yvoire Volume Plus and Neauvia Intense Lips. At 45 hours, the ranking remained similar. Luminera Hydryalix Lips and Juvederm Ultra 3 demonstrated the lowest degradation profiles. Conclusions: HA fillers vary in their susceptibility to hyaluronidase, likely due to differences in crosslinking and formulation. Fillers with higher degradability, such as Restylane Kysse, may be preferable in high-risk areas or emergency reversal situations. These findings underscore the importance of filler selection in clinical practice and warrant further in vivo studies.