Hyaluronidase: from clinical applications to molecular and cellular mechanisms

Bettina Alexandra Buhren, Holger Schrumpf, Norman-Philipp Hoff, Edwin Bölke, Said Hilton, Peter Arne Gerber, Bettina Alexandra Buhren, Holger Schrumpf, Norman-Philipp Hoff, Edwin Bölke, Said Hilton, Peter Arne Gerber

Abstract

Over the past 60 years, hyaluronidase has been successfully utilized in ophthalmic surgery and is now being implemented in dermatosurgery as well as in other surgical disciplines. The enzyme is considered a "spreading factor" as it decomplexes hyaluronic acid (also called hyaluronan, HA), an essential component of the extracellular matrix (ECM). When applied as an adjuvant, hyaluronidase enhances the diffusion capacity and bioavailability of injected drugs. Therefore, the enzyme has been used as a local adjuvant to increase the diffusion capacity of local anesthetics, increasing the analgesic efficacy, and the anesthetized area particularly in the first minutes following injection, resulting in diminished intra- and postoperative pain. In aesthetic medicine, the off-label use of hyaluronidase is considered the gold standard for the management of HA-filler-associated complications. Here, we review the clinical use, underlying biological mechanisms, and future directions for the application of hyaluronidase in surgical and aesthetic medicine.

Figures

Fig. 1
Fig. 1
Hyaluronidase effectively degrades hyaluronan-based dermal fillers. The injection of hyaluronidase results in rapid degradation of the complex network of hyaluronan (HA)-fillers into HA fragments
Fig. 2
Fig. 2
Degradation of dermal hyaluronan by infiltration of hyaluronidase. Dermal fibroblasts play a major role in neo-synthesis of hyaluronan (HA) as an essential component of the extracellular matrix (ECM). The injection of hyaluronidase degrades HA, and subsequently renders the ECM more permeable, resulting in a greater diffusion capacity and bioavailability of injected drugs. In addition, applied hyaluronidase induces the de novo synthesis of HA in dermal fibroblasts to compensate potential transient hyaluronidase-induced HA deficits

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