Does hyaluronidase destroy connective tissue

When hyaluronidase is used in appropriate dosages, it will not cause any permanent connective tissue damage, though temporary relaxation or loss of moisture may occur. It works by breaking down hyaluronic acid to the point of correcting issues like excessive or misplaced dermal fillers. Hyaluronidase injections should be performed by a professional who can control dosages carefully and ensure precise placement, preventing unnecessary impacts on connective tissue and avoiding potential side effects like skin depression and tissue relaxation. A thorough evaluation must be conducted before the procedure, which may include skin allergy testing to ensure safety.

What is Hyaluronidase

Hyaluronidase is an enzyme that specifically hydrolyzes a large-molecule substance known as hyaluronic acid. As a polysaccharide molecule, hyaluronic acid has a strong water retention capability and is widely distributed in the extracellular matrix of the dermis layer. It functions as a “natural sponge,” absorbing and locking in water to give skin fullness and elasticity. It also exists in synovial fluids of joints, the vitreous humor of eyes, and blood vessel walls for maintaining connective tissue structure and functional stability.

Through hydrolysis, hyaluronidase can depolymerize the long-chain polysaccharides in hyaluronic acid, transforming them into smaller molecules and thus accelerating its metabolism and clearance from tissues. Dissolving hyaluronic acid fillers is a major area of clinical interest in aesthetic medicine. Hyaluronidase can “reverse” or correct filler outcomes where placement is improper, there is excess volume, or in cases of local complications like vascular embolism and filler migration. Hyaluronidase is typically derived from bacterial secretion or animal tissue extracts, making it a highly bioactive enzyme protein.

How It Works

Hyaluronidase is an endoglycosidase enzyme that catalyzes the hydrolysis of β-1,4-glycosidic bonds within hyaluronic acid molecules, leading to the depolymerization of long-chain polysaccharides into smaller oligosaccharide fragments. This degradation greatly reduces the viscosity and hydration capability of hyaluronic acid, making it easier for the body to metabolize. Hyaluronic acid is hydrophilic, retaining water via hydroxyl groups on its polysaccharide chain structure. Hyaluronidase breaks these chains, weakening hyaluronic acid’s structural function and diminishing its water-binding capacity.

In aesthetic medicine, hyaluronidase degrades subcutaneously injected fillers, making the filler effect disappear. Typically, a few hours to days after a hyaluronidase injection, the hyaluronic acid at the filler site gradually degrades, to then be absorbed and metabolized by the body. Hyaluronidase thus serves as an essential tool not only for correcting fillers but also for treating filler complications. For instance, if a filler accidentally enters a blood vessel, hyaluronidase can immediately break it down, restoring blood flow and preventing severe outcomes such as tissue ischemic necrosis.

Action by hyaluronidase is unselective—it does not differentiate between natural hyaluronic acid in the body and that of injected fillers. Therefore, without precise dosage and location control, unintended breakdown of natural hyaluronic acid may affect normal tissue structure and function. In clinical practice, it’s essential to carefully regulate the dose and site of hyaluronidase to keep its action limited to the target area for dissolution.

Impact on Connective Tissue

Connective tissue is a complex structure made up of cells, fibers, and matrix, serving roles in support, connection, protection, and organ separation. It includes matrix components like hyaluronic acid, collagen, elastin, and other glycosaminoglycans. Together, these components create a highly organized network that imparts stability, elasticity, and repair capabilities to the tissue. Hyaluronic acid plays a central role in water balance, impact absorption, and lubrication between collagen and elastin fibers.

Hyaluronic acid’s primary function in connective tissue is to capture and store water for extracellular matrix volume and tension maintenance. Following hyaluronidase administration, local hyaluronic acid content drops rapidly, disrupting its moisture retention and structural support functions. Localized injections for clinical or aesthetic purposes temporarily relax connective tissue, often leading to decreased skin volume and elasticity. Because hyaluronic acid also contributes to cell signaling and tissue repair, hyaluronidase use temporarily suppresses these functions.

Hyaluronic acid’s distribution in connective tissue is sparse; therefore, proper hyaluronidase use typically does not cause long-lasting structural damage. Its effects are localized to the injection site, and newly synthesized hyaluronic acid will gradually replenish losses. However, frequent injections or high-dose hyaluronidase may result in prolonged tissue relaxation or depression in areas where hyaluronic acid levels are reduced, particularly in thin-skinned areas with low fat content.

Safety Concerns

Hyaluronidase is widely used in clinical settings and has a relatively good safety profile, though there are important safety considerations. First, overuse of hyaluronidase can lead to loss of tissue support due to localized tissue relaxation. Since hyaluronidase also degrades natural hyaluronic acid in the body, professionals must control dosage and injection site to prevent excessive skin relaxation or depression.

Another rare issue with hyaluronidase is allergic reactions. Allergic responses might include local redness, itching, or, in severe cases, anaphylactic shock. A skin test is usually conducted before the first injection to rule out hyaluronidase allergy risk. Allergic reactions relate to hyaluronidase’s protein nature, and if such a reaction occurs, injections should cease immediately and anti-allergy treatments should be administered.

Given its powerful dissolving ability, hyaluronidase may cause localized ischemic necrosis if accidentally injected into a blood vessel. In such cases, dissolution of hyaluronic acid in the vessel wall could form micro-thrombi or vascular spasms, leading to ischemia and necrosis in the skin. Practitioners must pay close attention to anatomical structure during procedures, using small doses and multi-point injections, if necessary, to gradually evaluate injection effects.

Can It Destroy Tissue

Hyaluronidase is not inherently destructive—its effects depend on dosage and injection control. While hyaluronidase targets hyaluronic acid, its unselective nature may lead to undesired effects on local tissue if improperly administered. Typically, standard hyaluronidase doses do not cause permanent tissue damage. However, miscalculated doses or incorrect sites could lead to temporary connective tissue damage.

In cases of excessive hyaluronidase, naturally occurring hyaluronic acid in connective tissue may break down too quickly, causing localized skin laxity, depression, or slight atrophy in subcutaneous tissue. Occasionally, direct blood vessel injection can cause embolism or even ischemic necrosis in local tissue, a serious risk associated with hyaluronidase use. Embolism may result in necrosis at the injection site and bring pain or permanent scarring.

Importantly, hyaluronidase’s dissolving effect is temporary. Connective tissue typically restores structure and function through the regeneration of hyaluronic acid and extracellular matrix molecules. Properly applied, hyaluronidase does not cause irreversible tissue loss.

Effects on Skin Structure

Hyaluronic acid is essential for skin hydration, with a molecular structure that captures large water amounts to maintain the skin’s moisturizing barrier for fullness and elasticity. Hyaluronidase degrades hyaluronic acid rapidly, reducing water support and flattening skin. As a result, decreased hydration and elasticity are observed in the injection site within hours to days after hyaluronidase treatment.

Hyaluronidase use will revert skin volume to its pre-filler state, altering areas treated with hyaluronic acid fillers in terms of volume and shape. In some cases, treated skin areas may appear thinner, especially in naturally thin regions with low-fat layers.

This effect is transient; as time passes, the skin’s own hyaluronic acid gradually regenerates, returning the skin structure to its pre-hyaluronidase condition. In some individuals, skin response may be slower due to physiological differences, possibly leading to extended recovery periods.

Is It Reversible

Hyaluronidase effects are highly reversible. Although it quickly depolymerizes hyaluronic acid, its depolymerization is limited, and new hyaluronic acid gradually replaces the initially dissolved hyaluronic acid. Hyaluronic acid synthesis occurs continuously in the body; thus, even if there’s localized loss of hyaluronic acid following hyaluronidase, natural metabolism will ultimately replenish and repair affected areas.

After hyaluronidase injection, the skin in the affected area goes through a recovery period. Recovery time varies by individual, depending on metabolic rate and skin hyaluronic acid synthesis rate. Generally, weeks to months allow the gradual return of hyaluronic acid content, restoring the skin’s hydration capacity and elasticity to normal levels.

In clinical practice, hyaluronidase is frequently used for aesthetic corrections and managing complications. For instance, if fillers yield unsatisfactory results or are misplaced, hyaluronidase can rapidly degrade the filler to correct the appearance. Thus, hyaluronidase serves well by successfully “reversing” undesired effects. Nonetheless, professional evaluation and precise dosage control are essential to prevent unnecessary skin damage and any long-term impact on connective tissue.