Comparison of the Degradability of Hyaluronic Acid by Ovine and Recombinant Human Hyaluronidase

Aesthet Surg J. 2025 Sep 16;45(10):1086-1093. doi: 10.1093/asj/sjaf127.

Abstract

Background: The mainstay of treatment for adverse events to hyaluronic acid filler is the use of hyaluronidase (HYAL); however, the dose and dilution are not standardized.

Objectives: The objective of this study was to examine differential dilutions and concentrations of HYAL, and to compare the effectiveness of ovine and human HYAL.

Methods: Fillers were selected for study based on a variety of rheologic factors. A 0.2-mL dose of product was selected for use based on previous studies. Degradation was assessed by comparing both ovine and recombinant HYAL over a range of concentrations and dilutions.

Results: In the 2:1 dilution group, Restylane Lidocaine (Galderma, Lausanne, Switzerland) was degraded by 100 U of ovine HYAL after 50 minutes. No other filler was completely degraded; Restylane Lyft (Galderma) was partially degraded after 1 hour of treatment with 100 U of HYAL. In both the 3:1 and 4:1 dilution groups, Restylane Shaype (Galderma) and Restylane Lyft fillers were most susceptible to degradation, dissolving within 30 minutes with 100 U of recombinant HYAL and within 40 minutes with 100 U of ovine HYAL. Juvéderm and RHA4 fillers were the most resistant, requiring 300 U of HYAL for degradation within 1 hour. Beyond a 3:1 dilution ratio, no further improvement was observed.

Conclusions: This study demonstrates that 300 U of hyaluronidase is sufficient to degrade 0.2 mL of the most resistant hyaluronic acid fillers within 1 hour. Importantly, a minimum dilution of 3:1 should be used to provide adequate fluid for dissolving filler. Ovine HYAL appears to be just as effective as recombinant HYAL in terms of dissolving product.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cosmetic Techniques*
  • Dermal Fillers* / administration & dosage
  • Dermal Fillers* / chemistry
  • Dermal Fillers* / metabolism
  • Humans
  • Hyaluronic Acid* / administration & dosage
  • Hyaluronic Acid* / analogs & derivatives
  • Hyaluronic Acid* / chemistry
  • Hyaluronic Acid* / metabolism
  • Hyaluronoglucosaminidase* / chemistry
  • Hyaluronoglucosaminidase* / metabolism
  • Lidocaine / chemistry
  • Recombinant Proteins / chemistry
  • Sheep

Substances

  • Hyaluronic Acid
  • Hyaluronoglucosaminidase
  • Dermal Fillers
  • Recombinant Proteins
  • Restylane
  • Lidocaine