Hyaluronidase, often referred to as the "filler dissolver," is an enzyme that has received considerable attention in both the medical and aesthetic fields. Its primary function is to degrade hyaluronic acid (HA), a major component of the extracellular matrix, thereby modulating tissue permeability and facilitating the dispersion of injected materials. This comprehensive article reviews the science behind hyaluronidase, its mechanisms of action, clinical applications, and considerations for safe and effective use.

Understanding Hyaluronidase: An Overview

Hyaluronidases are a family of enzymes that catalyze the hydrolysis of hyaluronic acid, a glycosaminoglycan abundant in connective tissue. By degrading HA, hyaluronidases reduce tissue viscosity and increase the permeability of the interstitial barrier. This property is particularly beneficial in medical procedures that require rapid dispersion of fluids or drugs.

Sources of Hyaluronidase

Hyaluronidase is found in a variety of organisms, including vertebrates, invertebrates, and microorganisms. Traditionally, commercial hyaluronidase has been extracted from bovine or ovine testes. However, due to the limited availability and high purification costs associated with these sources, researchers have explored alternative sources, such as recombinant hyaluronidases produced by microbial fermentation. This approach offers a more sustainable and cost-effective method for large-scale production. Creative Enzymes provides high-quality hyaluronidase from diverse sources.

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Mechanism of Action

Hyaluronidases act by hydrolyzing the glycosidic linkages within hyaluronic acid molecules. This enzymatic action reduces the viscosity of the extracellular matrix, thereby increasing tissue permeability. In medical applications, this property is used to enhance the absorption and dispersion of drugs or fluids administered.

Figure 1. Structure of hyaluronic acid and reaction mechanism of hyaluronidase. (Hong et al., 2025)

Biological Functions

Hyaluronidase plays several crucial roles in biological processes:

• ECM Remodeling: By degrading HA, hyaluronidase helps regulate the structure and function of the ECM, influencing cell migration, proliferation, and tissue repair.
• Inflammation and Immune Response: Hyaluronidase activity can modulate the inflammatory response by altering the local concentration of HA, which affects immune cell recruitment and cytokine production.
• Tissue Permeability: The enzyme enhances tissue permeability, allowing for the efficient diffusion of nutrients, drugs, and other molecules.

Clinical Applications of Hyaluronidase

The unique properties of hyaluronidase have led to its incorporation into various medical and aesthetic practices:

• Enhancement of Drug Delivery: By reducing the resistance of the extracellular matrix, hyaluronidase facilitates the spread and absorption of injected drugs, including local anesthetics. This application is particularly useful in ophthalmic surgeries and regional anesthesia.
• Management of Extravasation: In cases where intravenous medications inadvertently leak into surrounding tissues, hyaluronidase can be administered to promote the dispersion and absorption of the extravasated fluids, thereby mitigating tissue damage.
• Treatment of Edema: Hyaluronidase has been used to accelerate the absorption of excess fluid in conditions such as lymphedema due to its ability to increase tissue permeability.

Figure 2. The process of hyaluronic acid (HA) filler degradation when located inside a blood vessel, as a result of hyaluronidase solution infiltration in the perivascular space. (Hong et al., 2025)

Hyaluronidase in Aesthetic Medicine: The Filler Dissolver

The rise in popularity of hyaluronic acid fillers for facial augmentation has been accompanied by an increase in associated complications, such as overfilling, asymmetry, vascular occlusion, and formation of nodules. Hyaluronidase serves as an invaluable tool in these scenarios:

• Correction of Overfilling and Asymmetry: Excessive or uneven filler placement can lead to unnatural appearances. Hyaluronidase can selectively degrade the HA filler, allowing practitioners to fine-tune results or reverse the effects entirely.
• Management of Vascular Occlusion: Accidental injection of filler into blood vessels can cause ischemia and tissue necrosis. Prompt administration of hyaluronidase can dissolve the obstructing filler material, restoring blood flow and preventing serious complications.
• Treatment of Nodules and Granulomas: Delayed inflammatory reactions to HA fillers can manifest as palpable nodules or granulomas. Hyaluronidase injections can effectively reduce these formations by breaking down the filler material.

Figure 3. Hydration and dissolution of monophasic HA fillers treated with varying concentrations of hyaluronidase. (Hong et al., 2025)

Dosage and Administration

The appropriate dosage of hyaluronidase varies depending on the specific clinical scenario:

• For Reversal of HA Fillers: Studies have demonstrated that injecting 75-150 U/mL (Wilde et al., 2024) can effectively dissolve the filler material.
• For Vascular Complications: In cases of vascular occlusion, higher doses of hyaluronidase may be required to rapidly dissolve the filler and restore perfusion. Prompt intervention is critical to prevent tissue necrosis.

Safety and Adverse Effects

While hyaluronidase is generally considered safe, potential adverse effects include:

• Allergic Reactions: Although rare, hypersensitivity reactions can occur. A history of allergies to bee or wasp stings may increase the risk of an allergic response to hyaluronidase.
• Localized Effects: Patients may experience temporary swelling, redness, or discomfort at the injection site.
• Unintended Dissolution: There is a risk of hyaluronidase diffusing to areas beyond the intended treatment site, leading to the breakdown of native hyaluronic acid and resulting in volume loss or skin laxity.

Guidelines and Recommendations

To ensure the safe and effective use of hyaluronidase in aesthetic practice, practitioners should adhere to follow guidelines:

• Patient Assessment: A thorough medical history and examination are essential to identify potential contraindications, such as known allergies to hyaluronidase or bee/wasp venom.
• Informed Consent: Patients should be informed of the potential risks, benefits, and alternatives to hyaluronidase treatment

Case Studies

Case 1: Hyaluronidase for Dermal Filler Complications: Review of Applications and Dosage Recommendations; Kroumpouzos and Treacy, 2024

Hyaluronidase (Hyal) plays a critical role in reversing complications associated with hyaluronic acid (HA) fillers, which has contributed to the widespread use of these procedures. However, there are differing opinions regarding the optimal treatment approach, particularly with regard to dosage for the management of filler complications. This study aims to clarify key aspects of Hyal treatment, such as timing, dosage, pre-treatment skin testing, and interactions with HA gels. A thorough review of the literature, including expert recommendations, indicates that while controlled data are limited, increasing clinical experience supports the efficacy and safety of Hyal.

For non-emergent complications such as Tyndall effect and non-inflamed nodules, lower doses of Hyal are generally effective, while emergent problems such as vascular occlusion and blindness require higher doses. The use of ultrasound guidance can increase the efficacy of treatments. In conclusion, hyaluronic acid is an important tool in the aesthetic practice that can safely treat most HA filler complications. Immediate, high-dose treatment is critical for emergent complications, and practitioners should be well versed in appropriate Hyal use and dosage protocols.

Figure 4. (A) Upper lip overfilling and edema that developed after HA filler overcorrection on the upper vermillion. (B) Complication resolved after injecting 150 iu recombinant human Hyal. As an allergic reaction was considered, intramuscular epinephrine (1:1000 solution) and 100 mg intravenous hydrocortisone therapy were also provided. (Kroumpouzos and Treacy, 2024)

Case 2: Resolve and Dissolve—An Ultrasound-Guided Investigation on the Effects of Hyaluronidase on Different Soft Tissue Fillers; Bravo et al., 2024

The increasing popularity of hyaluronic acid (HA)-based soft tissue fillers has led to an increase in associated complications, making hyaluronidase an important tool for managing adverse events. This study analyzed the response of various HA-based fillers to hyaluronidase injections using ultrasound imaging. Eleven fillers, categorized into structuring, volumizing, and lip volumizing groups, were injected into chicken breast tissue to simulate human application. Results showed that the most significant volume reduction—64.1%—occurred within the first hour and reached 81.7% at 24 hours. While there were no significant differences between filler groups for most parameters, fillers with higher G-prime values (structuring and volumizing) showed the greatest volume reduction. These results suggest that while hyaluronidase effectively degrades HA fillers regardless of their properties, its efficacy is enhanced in fillers with higher G-prime values.

Table 1. Differences between time periods for width, height and volume, stratified for each soft tissue filler group. Statistically significant differences (p < 0.05) are highlighted in bold. (Bravo et al., 2024)

In summary, hyaluronidase has rightly earned its reputation as the "magical filler dissolver," providing a safe and effective solution for modifying or reversing hyaluronic acid-based dermal fillers. Its precise enzymatic action allows for targeted corrections, ensuring optimal aesthetic results while minimizing complications

If you are looking for high-quality hyaluronidase for medical or aesthetic applications, Creative Enzymes is here to provide you with reliable, expertly sourced enzyme products. Contact us today to explore our range of hyaluronidase solutions and discover how they can support your professional needs.