Abstract

Biophysical and biochemical data on hyaluronan (HA)-based dermal fillers strongly support their optimal use and design to meet specific requisites. Here, four commercially available (in Europe) HA “volumetric” fillers, among the most used in the clinical practice, have been characterized in vitro. Analyses revealed the highest amounts of water-soluble HA reported so far and provided hydrodynamic data for these soluble polymeric fractions. Volumetric gels exhibit a wide range of rigidity with most of them showing G’ values around 200-300Pa. They greatly differ in cohesivity. 1mL of gel hydrates up to 2.4–3.2mL. The products completely solubilize due to Bovine Testicular Hyaluronidase (BTH)’s action, thus predicting in vivo complete resorption. For the first time, filler degradation due to reactive oxygen species (ROS) was studied by rheological measurements and a rank in stability was established. Studies using Human Dermal Fibroblasts (HDF) indicated a positive biological response to the HA networks. Further, gel capacity to prompt collagen I, elastin and aquaporin3 synthesis was demonstrated, thus suggesting a positive effect on skin elasticity and hydration, besides the physical volumetric action. The findings are the first wide assessment of features for the volumetric class of HA-fillers and include first data on their resistance to degradation by ROS and biological effects on HDF. The study represents a valuable contribution to the understanding of HA-fillers, useful to optimize their use and manufacture.

Highlights

  • Hyaluronan (HA)-based hydrogels, obtained by crosslinking the biopolymer with 1,4 butandiolediglycidylether (BDDE), are the most commonly used dermal fillers in aesthetic medicine procedures for facial rejuvenation [1,2,3,4]

  • Aliaxin SV (ASV), the most concentrated in total HA, was the most concentrated in soluble HA, followed by Teosyal RHA4 (TRH4) and, by Juvederm Voluma (JV) while Restylane Lift (RL) is the gel with the lower water-soluble HA content

  • JV proved the less concentrated in water-insoluble HA, while even if differing for the total HA concentration, ASV, RL and TRH4 were comparable for the insoluble HA amount (p>0.05)

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Summary

Introduction

Hyaluronan (HA)-based hydrogels, obtained by crosslinking the biopolymer with 1,4 butandiolediglycidylether (BDDE), are the most commonly used dermal fillers in aesthetic medicine procedures for facial rejuvenation [1,2,3,4]. Diverse proprietary manufacturing technologies (i.e., Vycross, NASHA, CMP etc.) have been developed and are currently employed for HA filler production [3,5,6]. Hyaluronan-based dermal fillers: The biophysical properties that translate into a “volumetric” effect

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