Quantifying the Digestion of Cross-Linked Hyaluronic Acid Fillers With Hyaluronidase

Adverse events due to hyaluronic acid fillers (HAFs) may be treated with hyaluronidase, an enzyme that cleaves bonds within hyaluronic acid. This study reviews the efficacy of currently available hyaluronidase preparations in breaking down commercial, cross-linked HAFs.Three HAFs were used in this study (Restylane, Juvederm Voluma, and Belotero [BEL] Balance). A laser-based particle size analyzer (Malvern Mastersizer 3000) was used to calculate particle sizes in untreated HAFs (controls) and those treated with 450 units of hyaluronidase (Hylenex) for 5 and 30 minutes.Particle size analysis revealed that when Restylane was treated with hyaluronidase for 5 minutes, the average particle size reduced modestly, from 472 to 440 μm. At 30 minutes, the average particle size was 419 μm. For Juvederm, the average size of particles reduced from 703 μm in controls to 676 μm after treatment with hyaluronidase for 5 minutes and 635 μm after treatment for 30 minutes. For Belotero, the average size of control particles was 410 μm, reducing to 376 μm after treatment with hyaluronidase for 5 minutes and 345 μm after treatment for 30 minutes.After treatment with hyaluronidase for up to 30 minutes, there was only a modest breakdown of all 3 HAFs used. The results of this study raise questions regarding the efficacy of hyaluronidase in degrading cross-linked HAFs.