Response of twelve different hyaluronic acid gels to varying doses of recombinant human hyaluronidase

Summary Purpose Hyaluronic acid (HA) fillers can be reversed with hyaluronidase, but their dose responses are not well characterized. We evaluated 12 fillers’ in vitro responses to varying doses of recombinant human hyaluronidase (RHH). Methods For the 12 HA gels, 0.2 mL aliquots were placed on six slides. Samples received no injection, saline injection, or RHH (2.5, 5, 10, or 20 units). The most resistant gels received 40 units of RHH on a seventh slide. Photos of gels were taken from bird's-eye and lateral views with a ruler at multiple time points. Results Restylane-L and Restylane Lyft were the most easily dissolvable HA fillers. Both demonstrated a significant response to 2.5 units RHH/0.2 mL. Juvederm Ultra, Belotero, Restylane Silk, and Restylane Defyne had moderate resistance to RHH. Restylane Refyne, Juvederm Ultra Plus, Vollure, Versa, and Voluma were most resistant, requiring more than 20 units RHH/0.2 mL for complete dissolution. Volbella was moderately resistant up to 20 units RHH but demonstrated pronounced dissolution with 40 units RHH. Conclusions This study visually and objectively demonstrates the in vitro response of HA to dissolution by hyaluronidase. Fillers were categorized into least, moderate, and most resistant to RHH. Interesting findings include markedly different degrees of liquefaction for products used for similar indications (such as Restylane Lyft being more liquefied than Voluma), and Belotero easily flattening but retaining texture. Combined with in vivo data, this may help calculate hyaluronidase doses needed for controlled, partial reversal of commercially available HA gels.