Hyaluronidase, an enzyme that breaks down hyaluronic acid, has long been used to increase the absorption of drugs into tissue and to reduce tissue damage in cases of extravasation of a drug. With the increasing popularity of hyaluronic acid filler, hyaluronidase has become an essential drug for the correction of complications and unsatisfactory results after filler injection. For this reason, when performing procedures using hyaluronic acid filler, a sufficient knowledge of hyaluronidase is required. In order for hyaluronidase to dissolve a hyaluronic acid filler, it must interact with its binding sites within the hyaluronic acid. The reaction of a filler to hyaluronidase depends on the hyaluronic acid concentration, the number of crosslinks, and the form of the filler. Hyaluronidase is rapidly degraded and deactivated in the body. Therefore, in order to dissolve a hyaluronic acid filler, a sufficient amount of hyaluronidase must be injected close to the filler. If the filler is placed subcutaneously, injection of hyaluronidase into the filler itself may help, but if the filler is placed within a blood vessel, it is sufficient to inject hyaluronidase in the vicinity of the vessel, instead of into the filler itself. Allergic reactions are a common side effect of hyaluronidase. Most allergic reactions to hyaluronidase are local, but systemic reactions may occur in infrequent cases. Since most allergic responses to hyaluronidase are immediate hypersensitivity reactions, skin tests are recommended before use. However, some patients experience delayed allergic reactions, which skin tests may not predict.


In order for hyaluronidase to dissolve a hyaluronic acid filler, it must be able to access the intramolecular bonds within hyaluronic acid. The factors that interfere with access include the number of crosslinks between hyaluronic acid molecules and the concentration of hyaluronic acid. The more cross-linking, the more difficult it is for hyaluronidase to access its binding sites inside the hyaluronic acid filler. For this reason, fillers with extensive cross-linking require a long time to dissolve with hyaluronidase . In addition, the higher the concentration of hyaluronic acid, the slower it will be dissolved by hyaluronidase. Monophasic fillers are less soluble in hyaluronidase because they are less exposed to hyaluronidase than polyphasic fillers

As the side effects of fillers on blood vessels are known, many attempts have been made to effectively dissolve fillers inside blood vessels. DeLorenzi concluded in a 2014 paper that hyaluronidase could be injected subcutaneously without the need for intravascular injections to treat filler-induced vascular embolism. In an animal experiment, Wang et al. also found that subcutaneous injections of hyaluronidase were more effective than intravascular injections for preventing skin necrosis caused by hyaluronic acid filler embolism. The amount of hyaluronidase is important when injecting hyaluronidase in the vicinity of a blood vessel to dissolve filler inside the vessel. Lee et al.  reported that it was effective to inject 30–50 IU or more in one place in an animal test in 2020, and recommended injecting 100 IU or more at each location for a clear effect.