Time- and Dose-Dependent Effects of Hyaluronidase on the Degradation of Different Hyaluronan-Based Fillers In Vitro

Background:Hyaluronidase (HYAL) is regarded as the standard for the management of complications associated with hyaluronan (HA)-based fillers. Therefore, the understanding of interactions of HA fillers and HYAL is essential. Methods:Nine different commercially available HA fillers (Belotero, Juvederm, and Restylane) with varying degrees of cross-linking were used for the analysis. Fluorescently dyed HA fillers were individually incubated with varying doses of HYAL [bovine HYAL (Hylase Dessau; Riemser Pharma, Germany); 5, 10, and 20 U/mL] or sodium chloride and monitored by time-lapse microscopy. HA filler degradation was assessed as a decrease in fluorescence intensity of HA filler plus HYAL compared to HA filler plus control, quantified by computerized image analysis. Results:HA fillers show significant differences in their reaction to HYAL. Levels of degradation of HA fillers are positively correlated with increasing concentrations of HYAL. At the highest concentration of HYAL (20 U/mL), all fillers except one (Belotero Volume) reached a significant level of degradation at 5 to 9 hours. Conclusions:In this study, the authors show that most HA fillers can be dissolved by HYAL in a dose- and time-dependent manner. Of note, the fillers' technology and degree of cross-linking seem to exert stronger effects on the degradability by HYAL as compared to the concentration of HA. CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, V.

Automated summary

This study found that almost all hyaluronic acid fillers can be dissolved by hyaluronidase in a dose- and time-dependent manner. The technology and degree of cross-linking of the fillers seem to have a stronger effect on degradability by hyaluronidase compared to the concentration of hyaluronic acid.