Comparative Analysis of Hyaluronidase-Mediated Degradation Among Seven Hyaluronic Acid Fillers in Hairless Mice

Abstract

Purpose Hyaluronic acid (HA) is the most common injectable dermal filler used for soft-tissue augmentation, and can be removed non-surgically by directly injecting hyaluronidase. In this study, the hyaluronidase-mediated degradation of different types of HA fillers implanted subcutaneously at the back of hairless mice having filler residence time of four days or three months were compared. Methods Two sites at the back of female hairless mice were subcutaneously implanted with 0.1-mL of one of the seven HA fillers (NLL, NL, NDL, NVL, and ND, JUV X+ , and RES LYFT ) and injected with 30 IU or 60 IU hyaluronidase per 0.1-mL filler after reaching a filler residence time of 4 or 91 days, respectively. Filler bolus projection was measured using three-dimensional optical imaging over a 72 h period, and the implantation sites were histologically examined 2 weeks after hyaluronidase injection. Results Following hyaluronidase injection, all seven HA fillers showed a rapid decrease of filler volume within 24 h, and complete degradation was confirmed by histological examination after 2 weeks. There was no significant difference in filler volume reduction rate among the seven HA fillers, and no evidence of macroscopic or microscopic adverse effects were observed at the implantation sites. Conclusion All seven HA fillers show comparable susceptibility to hyaluronidase-mediated degradation. HA fillers with prolonged filler residence time may require a higher dose of hyaluronidase to achieve efficient degradation owing to tissue integration.

Bridging a Century-Old Problem: The Pathophysiology and Molecular Mechanisms of HA Filler-Induced Vascular Occlusion (FIVO)—Implications for Therapeutic Interventions

“…The intravascular half-life of hyaluronidases is short, spanning only 2–3 min because of the presence of plasma glycoprotein inhibitors [ 70 ]. In tissues, hyaluronidases have a more prolonged activity, remaining active for 24–48 h; nevertheless, some murine studies have shown a complete drop in activity after 3–6 h [ 71 , 72 ]. For this reason, hyaluronidase re-dosing every 1–6 h has been recommended in cases of FIVO [ 73 ].…”

Physico-Chemical Characterization and In Vitro Biological Evaluation of a Bionic Hydrogel Based on Hyaluronic Acid and l-Lysine for Medical Applications

“…The degradation kinetic of the hydrogel is another crucial parameter that must be evaluated, in order to understand its lifetime in the body after implantation (for example, in aesthetic medicine or tissue regeneration applications) but also to evaluate its reversibility upon minimally invasive injection of hyaluronidases. Even if one of the purposes of the crosslinking process is to increase the HA hydrogel’s resistance to endogenous hyaluronidases, the physicochemical features of the polymer must allow rapid degradation if inappropriate applications occur [ 35 ]. Therefore, understanding the susceptibility of this new material to hyaluronidase-mediated degradation is a valid way to complete its safety assessment and its chemical characterization.…”

A Prospective, Observational Registry Study to Evaluate Effectiveness and Safety of Hyaluronic Acid-Based Dermal Fillers in Routine Practice: Interim Analysis Results with One Year of Subject Follow-Up

“…Albeit chemically modified, HA fillers can be promptly degraded upon injection of highdose hyaluronidase, which represents a key advantage of HA over other injectable materials from a safety perspective, especially to manage serious adverse events such as vascular compromise. 9,10 Additionally, the degree of HA modification, and the crosslinking technology used, can both impact the rheological properties of the final product, allowing to fine tune its strength and malleability. 11 As a result, multiple filler formulations, rheologically adapted to specific treatment areas and patient needs, have emerged over the past two decades.…”