Visual, Ultrasonographic, and Microscopic Study on Hyaluronic Acid-Based Gel

September 2016 | Volume 15 | Issue 9 | Original Article | 1092 | Copyright © September 2016

Patrick Micheels MD,a Stéphanie Besse MD,b and Didier Sarrazin MDc

aPrivate practice, Geneva, Switzerland
bInstitut MedImage, Geneva, Switzerland
cLaboratoire Viollier-Weintraub, Geneva, Switzerland

BACKGROUND: Hyaluronic acid (HA) fillers are commonly used for enhancement of lips, and for softening fine lines and correcting skin depressions. Objective: This study sought to investigate whether the Vycross technology used for Volbella gel resulted in a cohesive gel, as documented in our previous studies with three other HA fillers (Restylane® NASHA [Q-MED, Uppsala, Sweden], Esthélis® Basic CPM™ [Anteis SA, Geneva, Switzerland], and Juvéderm® Ultra 3 using Hylacross technology [Allergan, Irvine, CA, USA]).
METHOD: The “resistance traction test” and “cohesiveness test” were conducted according to standard methods. Juvéderm® Volbella gel was injected into the buttock area, both in the superficial reticular and mid-reticular dermis. Tissue samples were analyzed at days 0, 15, and 90 by histology and immunohistochemistry, and visualized using electron microscopy. For Volbella gel, the same ultrasound devices as previously used were employed.
RESULTS: Prior to staining, Volbella gel presented resistance to spreading, suggesting a certain degree of cohesiveness. When smeared between two slides and following toluidine blue staining, the gel was visible through the microscope in the form of multiple tiny discrete particles, possibly resulting from gel desintegration. At 1/3 dilution with saline serum, Volbella gel disintegrated into several lumps, whereas at 1/1 dilution, Volbella gel appeared more cohesive. Yet when adding one drop 70% ethanol, the gel resembled a poorly defined magma, with numerous small lumps. On ultrasound, Volbella gel was found to leak in the hypodermis. On histological analysis, Volbella gel was visible as pools of variables sizes, particularly in the superficial and mid-reticular dermis, but also hypodermis.
CONCLUSION: Juvéderm Volbella gel appears to be a gel characterized by low-medium cohesiveness. The study findings, combined with our previous work, show that HA fillers using Vycross technology are not ideally suited for superficial use, unlike HA fillers using CPM technology.

J Drugs Dermatol. 2016;15(9):1092-1098.


Age-related facial changes have been characterized by a loss of hyaluronic acid (HA) and subcutaneous volume.1 On account of its excellent tolerance and hydroscopic properties, HA is an ideal candidate to create volume in soft tissues like the skin.2 Given that natural HA in the skin has an extremely rapid turn-over rate, commercially available HAs have been stabilized by means of different manufacturing techniques, resulting in products that vary in formulation and degree of cross-linking.
Numerous dermal HA fillers were manufactured using the patented cohesive polydensified matrix (CPM™) technology. This technology relies on the dynamic double cross-linking of monophasic HA strands with 1,4-butanediol diglycidyl ether (BDDE), leading to a product with variable cross-linking densities within the gel, denser areas ensuring voluminizing effects, and less dense areas the matrix cohesivity. This ensures optimal spreading of the gel into surrounding tissues allowing larger spaces to be filled with denser gel parts and finer tissue spaces to retain low-density gel, resulting in one continuous network. All these features were demonstrated by our research team in several ultrasonography and histology studies,3-6 with recently published data further confirming our own results.7
The patented Vycross™ (Allergan, Inc, Irvine, CA) technology incorporates short-chain HA together with long-chain HA, with the aim to improve the cross-linking efficiency of HA. Including short-chain HA allows more cross-linkers to attach to HA chains at both ends, thereby resulting in a longer product duration than fillers with only long-chain HA. As of 2015, there were three different HA gel types available relying on this technology: Juvéderm Volbella®, Juvéderm Voluma®, and Juvéderm Volift®.

Juvéderm Volbella

This injectable gel used in combination with lidocain is the subject of this paper. According to the Patient Information Leaflet, the gel is indicated for the treatment of any fine lines and me-