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Non-Crosslinked hyaluronic acid (HA) vs Crosslinked hyaluronic acid (HA): What’s the Difference?

Non-Crosslinked hyaluronic acid (HA) vs Crosslinked hyaluronic acid (HA): What’s the Difference?

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Hyaluronic Acid (HA) is a foundational ingredient in modern aesthetic and regenerative medicine. From injectable dermal fillers and PRP-enhanced treatments to microneedling serums, HA plays a key role in improving hydration, structure, and tissue recovery. But not all HA works the same way. The two most common forms—crosslinked and non-crosslinked HA—have different properties, uses, and benefits.

In this article, we’ll explore the differences between these two forms, how they behave in the body, and how to choose the right one depending on your treatment goal.

What Is Hyaluronic Acid?

Hyaluronic Acid (HA) is a naturally occurring glycosaminoglycan, a type of long-chain sugar molecule that plays a crucial role in maintaining hydration and structural support in the human body. It is found in high concentrations in the skin, synovial fluid of joints, eyes, and connective tissue, where it helps retain moisture, lubricate tissues, and facilitate cellular repair. In the skin, HA resides mainly in the dermis and extracellular matrix, acting as a sponge that traps water and keeps the skin plump, elastic, and resilient.

One of HA’s most remarkable features is its exceptional water-binding capacity—just one molecule of HA can hold up to 1,000 times its own weight in water. This makes it an essential molecule not only for skin hydration but also for maintaining joint function, wound healing, and tissue regeneration. As the body ages, natural HA levels decline, leading to dryness, volume loss, and visible signs of aging such as fine lines and wrinkles.

Because of its biocompatibility, versatility, and regenerative potential, HA has become a cornerstone ingredient in both topical skincare (serums, moisturizers) and injectable therapies (like dermal fillers and skin boosters). However, not all HA is created equal. Its effectiveness depends heavily on its molecular weight, concentration, and—most importantly—its structural form. This is where the distinction between crosslinked and non-crosslinked HA becomes critical. The way HA is modified determines its behavior in the body, including how long it lasts, how it integrates into tissue, and what kind of results it delivers.

Understanding these differences is essential when selecting HA-based treatments or products, especially in professional settings such as aesthetic clinics or regenerative therapy practices. The next sections will explore exactly how these two types of HA differ, and which one is best suited for specific treatment goals.

what is ha

What Is Crosslinked Hyaluronic Acid?

Crosslinked Hyaluronic Acid (HA) is a structurally modified form of hyaluronic acid designed to enhance its longevity, cohesion, and lifting ability when used in injectable treatments. In its natural state, HA is rapidly broken down by enzymes in the body (like hyaluronidase), which limits its use in procedures that require lasting volume or support. To overcome this limitation, manufacturers chemically “crosslink” HA molecules—linking individual HA chains together into a cohesive, stable 3D network.

This crosslinking process is typically achieved using BDDE (1,4-butanediol diglycidyl ether), a widely accepted crosslinking agent that is safe and biocompatible when purified correctly. BDDE bridges the gaps between HA molecules, resulting in a thicker, gel-like substance that is more resistant to degradation. The degree of crosslinking (light, moderate, or high) can be adjusted to produce HA gels with different densities and textures, each tailored for specific clinical applications—from fine line filling to deep structural augmentation.

Because of this enhanced structure, crosslinked HA remains in the tissue much longer than non-crosslinked forms, typically lasting between 6 to 18 months, depending on the product and the treatment area. It is this durability and moldability that make crosslinked HA ideal for dermal fillers used in facial contouring, lip enhancement, and wrinkle correction. However, due to its thicker nature, it also requires greater injection precision, and carries a slightly higher risk of swelling or lump formation if not used appropriately. When used by trained professionals, though, crosslinked HA delivers predictable, long-lasting results that are both restorative and natural-looking.

📌 Common Applications:

  • Dermal fillers for cheeks, lips, jawline, and nasolabial folds
  • Facial contouring and volume restoration
  • Long-lasting wrinkle correction

✅ Key Characteristics:

  • Thicker, gel-like consistency
  • Long-lasting effects (6–18 months, depending on formulation)
  • Ideal for deep dermis or subcutaneous injection
  • Requires precision to avoid swelling or lumping

At IPPOCARE, our HA dermal fillers are formulated with crosslinked HA to deliver predictable, sculpting effects with safe, CE-certified ingredients.

Hyaluronic Acid Dermal Filler-ippocare_4

What Is Non-Crosslinked Hyaluronic Acid?

Non-crosslinked Hyaluronic Acid (HA) refers to the unmodified, naturally occurring form of HA, where individual HA molecules are not chemically bound to one another. Unlike crosslinked HA, which is processed into a dense, gel-like structure for volumizing purposes, non-crosslinked HA maintains its free-flowing, liquid consistency, making it ideal for hydration-based and regenerative therapies.

Because there are no chemical crosslinks, this form of HA is rapidly metabolized by the body—typically lasting from a few days to a few weeks. However, what it lacks in longevity, it makes up for in biocompatibility and integration. Non-crosslinked HA spreads easily through tissue layers, is highly hydrophilic, and provides instant moisture retention, improving skin suppleness, glow, and elasticity. It also plays a supporting role in wound healing and tissue repair by enhancing cell migration and modulating inflammation.

Clinically, non-crosslinked HA is used in treatments where the goal is hydration rather than structure. It’s commonly found in skin boosters, mesotherapy solutions, microneedling serums, and increasingly, in PRP tubes—such as IPPOCARE’s PRP + HA tube, which contains 2mL of non-crosslinked HA (16mg/mL). When combined with platelet-rich plasma, non-crosslinked HA serves as a biological scaffold, helping distribute growth factors more evenly and prolonging their regenerative effects. It’s especially beneficial in delicate areas like the under-eye region, or on the scalp, where tissue sensitivity demands a lighter, more natural formulation.

Thanks to its purity, softness, and hydrating capability, non-crosslinked HA is the preferred choice for treatments focused on skin quality improvement, post-inflammatory healing, and natural tissue regeneration—offering visible results with minimal risk or downtime.

📌 Common Applications:

  • Skin boosters or mesotherapy
  • PRP tubes, like IPPOCARE’s PRP + HA tube
  • Microneedling serums and superficial injections
  • Scalp and under-eye rejuvenation

✅ Key Characteristics:

  • Watery, smooth texture
  • Shorter duration (several days to a few weeks)
  • Promotes deep tissue hydration and glow
  • Suitable for sensitive or delicate areas

At IPPOCARE, our PRP + HA tubes contain 2mL of non-crosslinked HA at 16mg/mL, ACD anticoagulant, and a gel separator. This formulation blends seamlessly with PRP during centrifugation—no calcium chloride or external activators needed.

Hyaluronic Acid-ippocare

FeatureCrosslinked HANon-Crosslinked HA
TextureThick, structured gelLight, fluid solution
Duration6–18 monthsDays to weeks
Primary UseFacial sculpting and filler treatmentsHydration, skin glow, PRP synergy
Injection DepthDeep dermis or subcutaneousSuperficial or intradermal
Risk of SwellingHigher, especially in high-motion areasMinimal
PRP-CompatibleNot recommendedYes — ideal for PRP enhancement

Why Non-Crosslinked HA Is Ideal for PRP Tubes

When used in PRP tubes, non-crosslinked HA enhances the hydrating and regenerative properties of PRP. It binds water, stabilizes platelets, and helps deliver growth factors more evenly. This synergy is especially effective in:

  • Under-eye rejuvenation
  • Skinbooster-style facial glow treatments
  • Scalp PRP for hair restoration

Unlike crosslinked HA, which is too dense for smooth plasma integration, non-crosslinked HA disperses naturally into tissue and does not require additional injectables or activators.

👉 Explore IPPOCARE’s PRP Tube with HA →

PRP-tube+HA-details-onetube

Why Crosslinked HA Is Best for Dermal Fillers

Crosslinked HA is the gold standard for facial volumizing treatments. Its gel-like structure allows it to hold form and resist breakdown over time. When injected into deeper facial planes, it can:

  • Restore lost cheek volume
  • Define the jawline or chin
  • Fill deep nasolabial folds and marionette lines
  • Enhance lips with shape and projection

At IPPOCARE, our dermal fillers use crosslinked HA in varying densities to match each indication—ensuring natural results, long duration, and smooth injection experience.

👉 Discover IPPOCARE Dermal Fillers →

Hyaluronic Acid Dermal Filler-ippocare_4_types

Both non-crosslinked and crosslinked Hyaluronic Acid are essential tools in modern medical aesthetics—but they serve very different purposes.

  • Crosslinked HA is best for structural results—lifting, contouring, and restoring volume over months.
  • Non-crosslinked HA is ideal for hydration-focused treatments, regenerative applications, and enhancing PRP therapy.

At IPPOCARE, we offer both:
Crosslinked HA fillers for long-lasting, sculpted results
PRP + HA tubes with non-crosslinked HA for natural glow and regenerative synergy

Understanding the differences helps you offer tailored, effective treatments—and achieve results your patients will love.

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