Effect of Recombinant Human Hyaluronidase on Conventional Hyaluronic Acid Fillers: An In Vitro Analysis

Hyaluronic acid (HA) fillers offer an advantage in being easily reversible with enzymatic hyaluronidase administration. Yet, there are no clear guidelines regarding the amount of hyaluronidase that should be administered given that commercially available fillers differ in constituent properties.

Six HA fillers were mixed with aliquots of human recombinant hyaluronidase (0 mL, 0.1 mL, 0.2 mL, and 0.3 mL). Filler dilution photography was obtained with the addition of various doses of hyaluronidase. Final filler and hyaluronidase mixture was then visualized on light microscopy at 40X magnification.

None of the fillers responded to the direct addition of hyaluronidase alone. Active mixing was required to stimulate the enzymatic effect. Restylane products which have equal concentrations at 20 mg/mL exhibited similar rates of dissolution. In contrast, Juvederm products, which differ in concentration, exhibited variable rates of dissolution. Juvederm Volbella (15 mg/mL) was the most easily dissolvable filler, in contrast, Juvederm Ultra (24 mg/mL) was the least easily dissolvable filler. Microscopically, Juvederm fillers appeared more refined whereas the Restylane fillers appeared more globular following hyaluronidase.

This study demonstrates the in vitro response of different HA fillers to hyaluronidase. Each filler exhibited a variable dose effect. HA concentration (mg/mL) was the critical variable in determining the rate of hydrolysis. Therefore, HA concentration may be an important factor when calculating the dose of hyaluronidase needed to reverse HA fillers. J Drugs Dermatol. 2025;24(3):303-306. doi:10.36849/JDD.8428.