In Vitro Analysis of Dissolution of 18 HA-based Dermal Fillers with Tailored Hyaluronidase Dosing to Achieve Urgent Reversal of Vascular Complications

Abstract

Introduction: Hyaluronidase (HYAL), a hyaluronic acid-degrading enzyme, is commonly used “off-label” as part of the gold standard management of hyaluronic acid (HA) dermal filler complications. It is paramount that injectors be cognizant to diagnose and treat filler complications, particularly vascular emboli, where there may be a narrow window for timely treatment. There is a paucity of studies, however, that provide HYAL dosage guidelines in the setting of acute vascular obstruction that are specific to each of the 18 reversible HA-based dermal fillers commercially available on the current US market. Differences in resistance to HYAL degradation is based on variation in cross-linking technique, concentration of HA, and cohesive properties that each filler may possess. This in vitro study investigates optimal dosage parameters of HYAL to achieve gross dissolution of every reversible HA-based filler commercially available to better improve outcomes after filler-induced vascular complications. Methods: Standardized in vitro analysis using 0.5-mL aliquots of all 18 commercially available HA-based fillers included all Restylane products (Lyft, Restylane-L, Silk, Refyne, Defyne, Kysse, Contour), Juvederm products (Volbella, Vollure, Voluma, Ultra XC, Ultra Plus XC), Revanesse products (Versa+, Lips+), Teoxane products (RHA 2, RHA 3, RHA 4), and Belotero. Hylenex, recombinant human HYAL, was used in 150 IU increments for total quantities of either 300, 450, 600, or 750 IU to achieve timed assessment of the gross dissolution of filler using photographic and videographic documentation. Inert dye was used to improve filler visibility against the HYAL. Mechanical integration of HYAL into the filler mimicked massage technique commonly implemented to incorporate HYAL into the perivascular soft tissue to help relieve a filler-induced vascular obstruction. Results: The cross-linking technology utilized by each HA-filler manufacturer played a significant role in the readiness of filler dissolution with HYAL. Fastest dissolution times ranged from 11 seconds to approximately 32 minutes, with a strong correlation with Restylane products dissolving the fastest, followed by Juvederm & Revanesse products. The slowest to achieve gross dissolution were Belotero and the RHA series. Discussion: All 18 HA-based fillers achieved complete gross dissolution within the first 32 minutes, however, due to differences in cross-linking technology and molecular properties, there was large variation in in vitro HYAL-induced degradation that can be extrapolated clinically to help reverse urgent vascular obstruction. This may also help beginner injectors strategically choose the HA-based dermal fillers that have the fastest degradation response to HYAL. Further in vivo studies are necessary to integrate these into clinical practice.