Rating Cross-Linked Hyaluronic Acid Fillers

Last Updated On: May 20, 2025

Cross-linked hyaluronic acid filler undergoes a chemical modification process that stabilizes the structure of hyaluronic acid and increases its longevity in the skin.

Different dermal filler brands have come up with cross-linked hyaluronic acid (HA) products with varying HA concentrations, viscosity, effect duration, and injectability. These factors influence clinical performance and suitability for aesthetic indications.

This article rates and compares the leading cross-linked HA filler brands based on clinical research and injectability testing. 

Key Takeaways

• JUVÉDERM® fillers have consistent injectability. VOLBELLA® and VOLIFT® demonstrate the most stable injection force. 
• BELOTERO® fillers show significant variability in injection force, especially in lidocaine-containing versions, so clinicians need to adjust their technique to manage irregular flow.
• RESTYLANE® fillers consistently require less injection force than other brands and show minimal variability between versions with and without lidocaine. 
• A clinical study shows the most consistently smooth and predictable injectability for STYLAGE® fillers due to the IPN-Like® cross-linking technology.
• TEOSYAL RHA® fillers are easy to inject and require minimal pressure, but RHA® 1 shows inconsistency during injections. 

What Research Says About the Injectability of Cross-Linked HA Fillers

A clinical study conducted in 2024 evaluated the injectability of 28 commercially available cross-linked hyaluronic acid dermal fillers. 

The products included major brands such as JUVÉDERM®, RESTYLANE®, BELOTERO®, TEOSYAL RHA®, and STYLAGE®. ¹

The study analyzed both manual and automated injection methods:

• Manual injections. These were performed by three highly experienced clinicians using retro-tracing techniques in both the dermis and hypodermis, as well as bolus injections in the hypodermis.
• Automated extrusion. This was conducted using a texture analyzer instrument to quantify the force required to extrude each product.

The objective was to benchmark the injectability of each hydrogel product across different clinical conditions and techniques. 

For every product, injection type, and injector, qualitative assessments of injectability were documented to provide a comprehensive understanding of their performance in practice.

Based on the results of the study, we now rate the five leading cross-linked hyaluronic acid brands:

1. JUVÉDERM®

JUVÉDERM® products offered consistent injectability across practitioners, with low inter-injector variability. However, there was intra-brand variability due to differences in HA concentration, needle gauge, and cross-linking technology.

VOLBELLA® and VOLIFT®, with lower HA concentrations (15–17.5 mg/mL), showed the most stable injection force across all injectors. They are, therefore, reliable for delicate areas like tear troughs and medium folds. 

In contrast, VOLUX®, with the highest HA concentration (25 mg/mL), required more extrusion force appropriate for deep volumizing applications.

Fillers made with VYCROSS® technology (VOLBELLA®, VOLIFT®, VOLUMA®, and VOLUX®) showed more uniform viscoelastic properties, which points to tighter cross-linking and a firmer gel texture.

ULTRA 2 and ULTRA 3, which use HYLACROSS® technology, had higher tan delta values that suggest softer, more flexible gels.

The products studied and their use cases include: 

• VOLBELLA®: Fine lines; tear trough
• VOLIFT®: Medium folds; lips
• VOLUMA®: Facial volumizer
• VOLUX®: Jawline; chin
• ULTRA 2: Lip border; medium lines
• ULTRA 3: Lip volume; deep folds

2. BELOTERO®

The study included eight BELOTERO® fillers: 

1. BELOTERO® Soft
2. BELOTERO® Soft +
3. BELOTERO® Balance
4. BELOTERO® Balance +
5. BELOTERO® Intense
6. BELOTERO® Intense +
7. BELOTERO® Volume
8. BELOTERO® Volume +

BELOTERO® fillers contain cross-linked hyaluronic acid with lidocaine, but they showed noticeable variation in injection force within the same product and between different syringes. This means the pressure felt during injection can change more than with some other brands. 

Most BELOTERO® products use the CPM® technology, which tends to create less smooth and more irregular injection force curves, except for BELOTERO® Soft and Intense, which are more consistent.

Products with lidocaine required more force to inject compared to those without. Compared to other technologies like NASHA® in RESTYLANE® or VYCROSS® in JUVÉDERM®, the CPM® system showed more variability in how the gel flows during injection.

For BELOTERO®, clinicians should be prepared for some uneven resistance and adjust their technique accordingly to ensure smooth application.

3. RESTYLANE®

The following RESTYLANE® products were included in the study: 

• RESTYLANE®: 30G needle for medium lines
• RESTYLANE®: 29G needle for medium lines
• RESTYLANE® Lido: 30G needle for medium lines
• RESTYLANE® Lido: 29G needle for medium lines
• RESTYLANE® Lyft: 27G needle for deep folds; volumizer
• RESTYLANE® Lyft Lido: 27G needle for deep folds; volumizer

RESTYLANE® fillers showed injectability trends similar to BELOTERO®. However, RESTYLANE® consistently required less injection force across the range. 

The difference in force between versions with and without lidocaine was also less noticeable than what researchers saw with BELOTERO®. As expected, higher-gauge needles led to higher injection force. 

RESTYLANE® uses NASHA® technology, which differs from BELOTERO®’s CPM® technology. While all RESTYLANE® products contain 20 mg/mL of HA, BELOTERO® formulations vary between 20 and 26 mg/mL. 

Formulation-wise, RESTYLANE® gels tend to be less viscous and cohesive, making them easier to inject, except for the Soft variant. The Soft variant performs similarly to BELOTERO® on that front.

Interestingly, the injector who regularly used RESTYLANE® (PM) showed the most consistent injection force. This suggests that product familiarity reduces variability, even among trained professionals. 

4. STYLAGE®

STYLAGE® fillers use IPN-Like® technology to produce cross-linked hyaluronic acid filler products. They also include mannitol as an antioxidant. They all showed excellent consistency and smooth flow during injection.

Here are the five STYLAGE® fillers studied with their uses: 

1. STYLAGE® S: Fine lines
2. STYLAGE® M: Medium folds; lip contour
3. STYLAGE® L: Deep folds; lip volumizer
4. STYLAGE® XL: Volumizer
5. STYLAGE® XXL: Cheeks; temples; jawline; chin volumizer

STYLAGE® S and M, used for fine lines, need the highest pressure among STYLAGE® fillers. Volumizing options like STYLAGE® XL and XXL, although not meant for intradermal injection, showed an average injection pressure and stable behavior when injected.

STYLAGE® also had very low variability in injection force, both between different syringes and different injectors. 

STYLAGE® L was the easiest to inject and required just 0.78 N of pressure. In contrast, STYLAGE® S required the most force at 1.68 N. The rest (M, XL, and XXL) fell in between, with forces ranging from about 1.1 to 1.4 N. 

Compared to other brands, STYLAGE® crosslinked hyaluronic acid fillers showed very reliable and smooth injectability, with excellent internal consistency and low variation across the product line. 

5. TEOSYAL RHA®

TEOSYAL RHA® fillers use the Preserved Network® cross-linking technology and all contain lidocaine. The studied fillers include:

• TEOSYAL RHA® 1
• TEOSYAL RHA® 2
• TEOSYAL RHA® 3
• TEOSYAL RHA® 4
• TEOSYAL Ultra Deep

TEOSYAL fillers were easy to inject and required low pressure, even for volumizing products like RHA® 3 and RHA® 4.

That said, injectability varied between RHA® types and even more between injectors. RHA® 3, for instance, required more pressure than RHA® 1 due to its higher HA content. 

Needle size also affected the experience; RHA® 3 with a 27G needle felt easier to push than RHA® 2 with a 30G needle.

RHA® 1 showed the most inconsistency with variable force, even within the same syringe. This means the injector felt fluctuations in pressure while injecting. 

Compared to other brands like STYLAGE®, TEOSYAL RHA® fillers didn’t deliver the smoothest injection profile. 

However, their viscoelastic properties remain low, which helps with easy flow and minimal pressure during injection. 

With the right technique, practitioners can achieve consistent results, especially with RHA® 2, 3, and 4.

Differences in Cross-Linked Hyaluronic Acid vs. Non-cross-Linked

HA fillers are broadly categorized into cross-linked and non-cross-linked formulations. 

Cross-linked HA fillers are chemically modified to enhance their viscosity and longevity. Their longevity is attributed to the cross-linking process, which slows down degradation and results in de novo synthesis of collagen in photodamaged skin. ²

However, the increased viscosity makes them more challenging to inject than non-cross-linked hyaluronic acid injections that have a more fluid consistency. They are usually administered into deeper dermal layers to address pronounced wrinkles and volume loss. 

Non-cross-linked hyaluronic acid fillers, in contrast, are mainly used for improving skin hydration and texture. Their effects are more transient, but they are also associated with a lower risk of adverse reactions due to closer resemblance to the body’s natural HA.

Final Words

It’s a good idea to consider the clinical evidence surrounding the ease and consistency of injectability when administering cross-linked hyaluronic acid injections. We hope this article proved helpful on that front.

To ensure you have access to authentic, high-quality cross-linked hyaluronic acid filler products, stock up your supply through Med Supply Solutions. 

All our products undergo stringent quality control measures and are safely and reliably shipped exclusively to licensed medical practitioners worldwide. Place your order today!

FAQs

Is Cross-Linked Hyaluronic Acid Safe?

Yes, FDA-approved cross-linked hyaluronic acid fillers are safe. Their safety is confirmed by the FDA Summary of Safety and Effectiveness Data, which mandates residual BDDE crosslinker levels below 2 ppm in all approved product batch specifications. ³

What Are the Benefits of Cross-Linked Hyaluronic Acid Filler?

Cross-linked hyaluronic acid filler produces longer-lasting results, better structural support, improved volume restoration, and slower degradation. 

Can Cross-Linked Hyaluronic Acid Be Dissolved?

Yes, cross-linked hyaluronic acid can eventually be dissolved with hyaluronidase. However, extensively cross-linked fillers resist enzymatic breakdown and dissolve more slowly than non-crosslinked counterparts.

References

1. Micheels P, Porcello A, Bezzola T, Perrenoud D, Quinodoz P, Kalia Y, Allémann E, Laurent A, Jordan O. Clinical Perspectives on the Injectability of Cross-Linked Hyaluronic Acid Dermal Fillers: A Standardized Methodology for Commercial Product Benchmarking with Inter-Injector Assessments. Gels. 2024; 10(2):101. https://doi.org/10.3390/gels10020101
2. Wang F, Garza LA, Kang S, et al. In Vivo Stimulation of De Novo Collagen Production Caused by Cross-linked Hyaluronic Acid Dermal Filler Injections in Photodamaged Human Skin. Arch Dermatol. 2007;143(2):155–163. doi:10.1001/archderm.143.2.155
3. Faivre, J., Pigweh, A. I., Iehl, J., Maffert, P., Goekjian, P., & Bourdon, F. (2021). Crosslinking hyaluronic acid soft-tissue fillers: current status and perspectives from an industrial point of view. Expert Review of Medical Devices, 18(12), 1175–1187. https://doi.org/10.1080/17434440.2021.2014320